text:
Sudan frees woman on death row for apostasy
Filed under: Lone Nile of Sudan — Leave a comment
KHARTOUM, Sudan (AP) — A Sudanese woman sentenced to death for apostasy was freed Monday by a Khartoum court, and has rejoined her Christian husband with their two young children, her lawyer and state media said.
State news agency SUNA said the Court of Cassation threw out the death sentence against 27-year-old Meriam Ibrahim after defense lawyers presented their case. Her lawyer, Eman Abdul-Rahim, told The Associated Press that Ibrahim left prison and was with her husband. Her 18-month-old son, Martin, had been with her in jail, where she gave birth last month to a second child.
Ibrahim, whose father was Muslim but who was raised by her Christian mother, was convicted of apostasy for marrying a Christian. Sudan's penal code forbids Muslims from converting to other religions, a crime punishable by death.
Ibrahim married a Christian man from southern Sudan in a church ceremony in 2011. As in many Muslim nations, Muslim women in Sudan are prohibited from marrying non-Muslims, though Muslim men can marry outside their faith. By law, children must follow their father's religion.
The sentence drew international condemnation, with Amnesty International calling it "abhorrent." The U.S. State Department said it was "deeply disturbed" by the sentence and called on the Sudanese government to respect religious freedoms.
On Monday, U.S. Rep. Chris Smith, who had met with the Sudanese Ambassador to discuss Ibrahim's case, described the release as "a huge first step." "But the second step is that Ms. Ibrahim and her husband and their children be on a plane heading to the United States," he added. It's not clear whether Ibrahim had planned to travel to the United States.
Sudan introduced Islamic Shariah law in the early 1980s under the rule of autocrat Jaafar Nimeiri, contributing to the resumption of an insurgency in the mostly animist and Christian south of Sudan. The south seceded in 2011 to become the world's newest nation, South Sudan.
Sudanese President Omar Bashir, an Islamist who seized power in a 1989 military coup, has said his country will implement Islam more strictly now that the non-Muslim south is gone. A number of Sudanese have been convicted of apostasy in recent years, but they all escaped execution by recanting their new faith.
In Washington, State Department spokeswoman Marie Harf, praised the decision to free Ibrahim and called on the government to repeal the laws to help demonstrate to the Sudanese people that their government intends to respect their fundamental freedoms and universal human rights."
Associated Press writer Matthew Lee contributed from Washington.
Tags: Lone Nile of Sudan
Bashir bans political party meetings without permission
KHARTOUM – Sudan's President Omar al-Bashir has issued a decree banning political parties from holding meetings without permission from the authorities, the official SUNA news agency reported.
The decree comes just a week after Bashir assured a meeting of party leaders they had freedom to operate in the run-up to a "national dialogue" he has promised to hold to address urgent demands for change in his 25-year regime.
"No political party has the right to hold meetings and conferences inside their areas without first obtaining permission from the relevant authorities," SUNA late on Monday reported the decree as reading.
At the April 6 meeting in Khartoum, Bashir assured party leaders they were free to conduct activities inside or outside their offices, "according to law".
A day later, however, the Reform Now party said security agents had prevented it from holding a discussion forum and had detained the leader of its student wing, Emad Al-Dien Hashim.
Reform Now was formed in December by Bashir's ex-adviser Ghazi Salahuddin Atabani after the ruling National Congress Party ousted him.
Critics have said Bashir's political dialogue is just a way for the elite to hang on to power without properly addressing the country's problems.
An alliance of small opposition parties has refused to join the dialogue, which Bashir announced in January, unless the government meets several conditions.
These include declaring a ceasefire with the country's armed rebels, and abolishing all laws that restrict freedoms.
The Revolutionary Front, which comprises insurgent groups from Kordofan, Blue Nile and Darfur, on Sunday rejected participation in the dialogue, describing it as a "farce".
Link: http://middle-east-online.com/english/?id=65404.
Sudan to release political prisoners
Mon Apr 7, 2014
Sudan is set to free some political prisoners and allow political parties to be active without restrictions as part of national reconciliation efforts.
President Omar al-Bashir made the announcement in a meeting with representatives of more than 50 parties and groups on Sunday, DPA reported.
Bashir said he had given orders to release all political prisoners "who have not committed criminal offenses" and ordered local authorities to allow political parties to exercise their activities inside and outside their headquarters without any restrictions.
Bashir also pledged to help create a suitable atmosphere for a comprehensive national dialog.
The Sudanese leader called on media to contribute to the success of the national dialog.
The release of the prisoners is the latest move by Bashir to push the national dialog forward. It was followed by a December 2013 cabinet shuffle, which analysts said was aimed at calming down protesters, who took to the streets in September after the government slashed fuel subsidies.
Sudan lost billions of dollars in oil revenues after South Sudan gained independence two years ago, taking with it some 75 percent of crude production of the formerly united country.
Sudan has been plagued by running inflation and a weakening currency since then.
Source: PressTV.
Link: http://edition.presstv.ir/detail/357493.html.
Sudan: DUP Calls for Establishing a National Transitional Government
Khartoum — The Sudanese Democratic Unionist Party (DUP) led by Mohamed Osman al-Mirghani has laid out its view on the national dialogue initiative announced by the Sudanese president Omer Hassan Al-Bashir earlier this year.
Leader of the Democratic Unionist Party (DUP) Mohamed Osman al-Mirghani (Al-Sharq Al-Awsat)
In a televised address to the nation late last January, the Sudanese president Omer Hassan al-Bashir announced a four-point plan for reform "to stop the war and bring peace, free political society, fight against poverty and revitalize national identity".
He further called on political forces and even rebel groups should they lay down arms to engage in dialogue to agree on the implementation items to achieve these objectives.
The DUP urged the government to declare general amnesty for the rebel groups in Darfur, South Kordofan, and Blue Nile besides allowing public freedoms and declaring an immediate ceasefire as of today as an essential part of the requirements for creating environment conducive for dialogue.
The DUP is a major partner in the "broad-based" government of the National Congress Party (NCP) but its vision has matched with that of the opposition parties which rejected the government's call for national dialogue.
The DUP stated at a press conference on Monday seven requirements for creating the appropriate atmosphere for dialogue, calling the government to implement them immediately.
These requirements include releasing political detainees and forming an independent committee in line with international standards to investigate all abuses besides removing the damages and injustices.
The DUP's spokesperson, Ibrahim al-Mirghani, said they proposed dividing the dialogue agendas into three main categories including national principles, urgent national issues, and the implementation mechanisms, underscoring the need for establishing a national interim government to carry out tasks of the transitional period.
He said the transitional period should be governed by a provisional constitution or a constitutional declaration until drafting the interim constitution and the new elections law.
Al-Mirghani stressed the need for inviting regional and international organizations to monitor the national dialogue process including the Arab League, African Union, the European Union, and the United Nations.
He mentioned eleven agreements to be used as references for the dialogue on top of which is the agreement signed between the government and the rebel SPLM-N in June 2011 besides the New Dawn Charter which was signed by various opposition parties and rebel groups and rejected by the government.
The spokesperson also pointed to the 2005 Cairo Agreement which was signed by the government and the ex-opposition alliance, National Democratic Alliance (NDA) as well as the Comprehensive Peace Agreement (CPA) protocol on the Two Areas.
He further demanded that political parties commit themselves to five requirements including stopping the negative media campaigns besides staying away from setting preconditions.
Al-Mirghani denied inconsistency in their position as partners in the government and their demands from it to meet certain requirements.
"Being partners in the government doesn't mean we merged with the NCP and it doesn't prevent us from announcing our own reform proposal", he added
He asserted his party is still considering a recommendation for pulling out of the government.
Following the September 2013 protests against lifting fuel subsidies, al-Mirghani established a committee to look into whether or not the DUP should continue in the NCP-dominated cabinet.
The panel unanimously recommended that the party withdraw from the government. The decision is not binding however, and the DUP chief can overrule it.
The DUP left opposition ranks and joined the "broad-base" government of the NCP in December 2011, citing the "need to save the country" in the words of al-Mirghani himself.
The decision of one of Sudan's biggest opposition parties to join the government has created a great deal of internal dissent that saw many members quitting in protest.
Source: allAfrica.
Link: http://allafrica.com/stories/201404010920.html?viewall=1.
Somali parliament votes out prime minister
NAIROBI, Kenya (AP) — Somalia's parliament voted to oust the country's prime minister on Saturday, capping a long feud between the president and prime minister, an official said.
Parliament Speaker Mohamed Sheikh Osman Jawari said 153 members voted to oust Abdiweli Sheikh Ahmed from office. Eighty members voted for him to stay. The vote took place after several recent rowdy sessions of parliament over the issue. Legislators who supported Ahmed heckled those who voted him out.
Somali President Hassan Sheikh Mohamoud had a falling out with Ahmed and wanted him to vacate his office. Ahmed said he accepted the vote but said he had been diligent in executing his constitutional mandate.
"We must eradicate a culture of impunity, disregard for the law and corruption if Somalia is to make meaningful progress. My administration has been relentless in our pursuit for reform and we leave a solid foundation that carries the hopes and aspirations of all Somalis," Ahmed said in a statement.
The United States and the U.N., among others, have warned that the political infighting in Somalia is putting at risk the recent security gains made in the country. Nicholas Kay, the U.N. representative to Somalia, said the country needs "unity of political purpose" between its institutions and leaders "and a significant period of stability." He said leaders need to prevent such political crises and instability in the future.
Security has improved in Somalia in recent years but the federal government remains weak and ineffective and wields little power outside the capital Mogadishu. A recent U.N. Monitoring Group report on Somalia said significant amounts of the federal budget are siphoned off through corruption.
Somali-American who helped Mogadishu govt killed
MOGADISHU, Somalia (AP) — Gunmen shot and killed a Somali-American from Minnesota who had left a well-paying job in the U.S. to help the fledgling city government in Mogadishu, an official and relative said Wednesday.
Abdullahi Ali Anshur, 60, was an engineer helping the Mogadishu government with urban planning and drainage systems. He was killed after armed militants from the Islamic extremist group al-Shabab stopped his vehicle and sprayed it with bullets on Monday, police Capt. Mohamed Hussein said.
Anshur was buried in Mogadishu on Wednesday. He had left his work in Minnesota to help Mogadishu's municipal government, said a relative who insisted on anonymity for security reasons. Anshur had held a similar job in Mogadishu more than two decades ago before the Somali government collapsed in the early 1990s.
His daughter in Minnesota, Maryan Ali, said she had just communicated with her father over the weekend, and he told her things were going well. He traveled for work frequently, and was heading from Kenya to Mogadishu.
She said her dad was a noble man, with a kind heart, who worked hard to help whomever he could. "He always encouraged us to work hard and to help whoever you can help … especially your community to better ourselves. He was a great mentor."
Many Somalis who fled the country's chaos for the U.S. and Europe have recently returned to Mogadishu to use their expertise to help the country move past decades of war and Anshur's killing has sent shock waves through that community. One British-Somali man who returned to Mogadishu to open a cafe called Anshur's death discouraging.
"Insecurity is the biggest threat for now," said Ahmed Mohamed. A Somali-American in Mogadishu, Hussein Ali, said such attacks leave U.S. and European Somalis scared and disappointed. "It makes many of us contemplate leaving Mogadishu," he said.
Ali said her father got his bachelor's degree at the University of Somalia, then got a scholarship to pursue a master's degree in the U.S. He graduated from California State University, Fresno, in the mid-1980s, then went back to Somalia to work until the civil war broke out, Ali said.
He managed a public housing unit in St. Paul, Minnesota, and was well-known in Minnesota's large Somali community. He returned to Mogadishu last year. "What happened to my dad was such a shock to us," Ali said. "We would never have expected something like that. Life surprises you."
Al-Shabab, an ultra-conservative Islamic militant group that wants to run Somalia by its strict interpretation of Shariah law, once ruled nearly all of Mogadishu. The group was forced out of the capital in 2011 but continues to carry out insurgent attacks and targeted murders.
In a separate incident, armed assailants shot and killed a freelance journalist in the central Somali town of Galkayo on Tuesday evening. Three journalists have been murdered in targeted killings this year, according to the National Union of Somali Journalists, which condemned the shooting. Journalists face attacks by al-Shabab, government figures and powerful businessmen, the group said.
Ali said many people like her father believe rebuilding Somalia is worth the risk. "They do what they feel like they can do to help rebuild that country to how it used to be, or maybe even better," Ali said. "That's the motivation for everybody — don't just sit around, if you want change to happen, you've got to get up and do something."
Associated Press writer Amy Forliti contributed to this report from Minneapolis.
Somalia Closes Nine Embassies
Somalia has closed nine of its embassies due to lack of funds, Minister of Foreign Affairs Abdirahman Duale Beyle said Wednesday (October 8th).
Beyle announced in July that the government intended to reduce its diplomatic missions from 37 to 31. He did not name all the embassies closed, but said those in Burundi and Germany were among them, Somalia's RBC Radio reported.
The Ministry of Foreign Affairs carried out the closures after discussions with the cabinet, Beyle said. He attributed the closures to limited resources for staff at the embassies.
Link: http://allafrica.com/stories/201410100634.html.
In Qatar, migrant workers paid to be sports 'fans'
Filed under: Gulf Land of Qatar — Leave a comment
DOHA, Qatar (AP) — The men grappled with each other to board the quickly filling bus. Others wriggled in through the windows, scaling the outside, using the large wheels as footholds and leaving scuff-marks on the white exterior with their shoes.
These weren't refugees fleeing disaster. They were migrant workers in 2022 World Cup host Qatar, fighting to earn a few dollars. The job: Pretend to be a sports fan. Qataris boast they're mad for sports. The ruling emir of the oil-and-gas rich Gulf nation is so fond of football he bought Paris Saint-Germain, now France's powerhouse team. Lobbying World Cup organizer FIFA in 2010, his royal mother said: "For us, football is not just a mere game or a sport among many. It is THE sport."
Pitching successfully in November to track and field's governing body to host its world championships in 2019, Qatar bid presenter Aphrodite Moschoudi said: "Qatar has a true passion for sports. Everything in our country revolves around sport."
Or, when passion is lacking, around money. When the world's second-richest people per capita can't find time or be bothered to fill their sports arenas, migrant workers are paid to take their place. Thirty Qatar riyals — equivalent to $8 — won't buy a beer in the luxury waterside hotel in Doha, the capital, where Qatari movers-and-shakers unwind. But for this pittance, workers from Africa and Asia sprint under blinding sun in the Doha industrial zone where they're housed and surround a still-moving bus like bees on honey. They sit through volleyball, handball and football, applaud to order, do the wave with no enthusiasm and even dress up in white robes and head-scarves as Qataris, to plump up "home" crowds.
The Associated Press squeezed aboard one of three buses that ferried about 150 workers, through dense traffic of luxury cars and past luxury villas they'll never be able to afford, to be fake fans at the Qatar Open of international beach volleyball in November.
The FIVB, volleyball's governing body, trumpeted on its website that the tournament, part of its World Tour, "brought out the crowds." But migrants from Ghana, Kenya, Nepal and elsewhere, who work in Qatar as bus and taxi drivers for the state-owned transport company and for other employers, told the AP they were there for money, not volleyball.
Word of payment filtered around their crowded dormitories. At 2:30 p.m., clumps of men on their off-day gathered outside, inhaling dust stirred up by passing forklifts and trucks. Someone spotted the first bus far down the street that cuts through the bleak-scape of construction and piled dirt. The bus filled instantly. A second and third bus — and more frantic scrambling — followed.
Breathing heavily, men squeezed into seats, three on one side of the aisle, two on the other. There were no safety belts and the ceiling fans didn't turn. One man without a seat squatted on the floor. To shouts of "get down!" he made himself small when a policeman was spotted on the journey.
One by one, from memory, the men reeled off their employee numbers — no names — to a man who methodically shuffled down the aisle, jotting down the details on a crumpled piece of paper. This ensured he'd later know who to pay, workers said.
At the Al Gharafa Sports Club, we disembarked and formed a line. An official in Qatari robes counted us in, with taps on the shoulder. French volleyballers Edouard Rowlandson and Youssef Krou were winning their bronze-medal match as we filled seats, making the arena appear almost full.
"Bizarre," Rowlandson said when told of the hired spectators. "But we prefer that to playing in front of nobody." Ahmed al-Sheebani, executive secretary of the Qatar Volleyball Association, rebuffed the AP's questions, reaching over to switch off this reporter's voice recorder.
Reached later by phone, FIVB media director Richard Baker thanked the AP for making it aware of the fake fans and said the federation will "seek clarification" from Qatari organizers. "It's news to us," he said.
But not to Qatar's government. A survey of 1,079 Qatar residents published this January by the Ministry of Development Planning and Statistics suggested that paid fans may be turning Qataris off sport. The ministry said two-thirds of Qataris surveyed did not attend any football matches during the previous season and two-thirds of respondents cited "the spread of paid fans" as a "significant reason" keeping audiences away.
At the volleyball, some for-hire spectators were offered less than others. Security guards and office boys from Kenya said a promise of 20 riyals ($5.50) each drew 40 people onto their bus. A Nigerian manservant said he, too, was getting just 20.
Numerous workers said they regularly make up numbers at sports events. Qatar league football games pay 20 or 25 riyals, they said. A Kenyan said he made 50 riyals at handball. An added bonus: the volleyball arena had free Wi-Fi, allowing workers to get news and emails from home. They pulled out smartphones, ignoring a crowd organizer waving a plastic hand who urged them to clap to Daft Punk's "Get Lucky."
Thirty riyals buys food for three days when you're eating just once a day to save money for families back home, workers said. And watching sports, some said, is less tedious than whiling away off-duty hours in Doha's back-of-beyond industrial zone.
"Shaking my body all over … being in the crowd and shouting and dancing" was great fun for Adu, a trainee bus driver from Ghana who gave just his first name. "Being there and getting paid is a plus for me."
Afterward, the transport company workers waited nearly three hours in the dark, on barren land near the arena, for return buses. Contacted separately later by phone, three of them confirmed they got 30 riyals each in cash, either on the bus back or in their dormitories.
On an hourly basis, that came out at just over $1 per hour.
Tags: Atmariar Gulf, Gulf Land of Qatar


text:
Investor Pumps Dogecoin On Tik Tok But Describes A Technical Ponzi Scheme
Investor Pumps Dogecoin On Tik Tok But Describes A Technical Ponzi Scheme. Photo by STRF/STAR MAX/IPx 2021 1/30/21: Dogecoin with Dogecoin logos photographed off an Apple iMac.
Written by Dana Sanchez
A Dogecoin fan pumped the hugely popular meme coin on Tik Tok, and an observer reposted the video on Twitter with an accompanying comment saying that the man had just flawlessly described a Ponzi scheme.
The unnamed Dogecoin enthusiast was keen to share what he said was "an incredible investment opportunity right now."
The goal is for Dogecoin to reach $1, the Tik Tok investor said.
"If we get more people to buy it, the value goes up, right?" the Tik Tok investor said. "As soon as the value goes up, I make more money, they make more money. Oh wow, so let's get more people to buy it and then the value goes up and we all make more money. So it's one of those things where it's like, if we do that enough times we can get to a dollar, which is the goal."
Mans just flawlessly described a ponzi 😭pic.twitter.com/zObh5m2vJi
— TikTok Investors (@TikTokInvestors) December 4, 2021
Dogecoin was trading at $0.17 as of this writing. Its price rose as much as 33 percent on Dec. 14 after Tesla CEO Elon Musk, a fan, sent out a new market-moving tweet saying he would accept dogecoin as payment for some of his merchandise. Dogecoin rose from around $0.15 to more than $0.21 following Musk's tweet, before falling back, but not all the way back.
"Everybody's jumping around like 'Oh, to the moon, to the moon, to the moon. Let's get it to a dollar,'" the Tik Tok investor said. ("To the moon" is a slogan used by Dogecoin fans and high-profile crypto enthusiasts such as Tesla CEO Elon Musk.) "So it's encouraging. It's teamwork. It's putting effort into it. It's telling everyone who knows, shouting it from the top of the mountain, 'Everybody buy Dogecoin because then everybody gets rich.' Do you see what I'm saying?"
Dogecoin is a payment system created in 2013 as a joke to make fun of the speculation in cryptocurrencies. Based on a viral internet meme of a Shiba Inu dog, it is considered the first meme coin. Dogecoin's price stayed relatively flat for eight years at around 10 thousandths of a cent per coin until January 2021, when its price started going up. By April 2021, price action was increasing significantly.
Dogecoin reached an all-time high of $0.7376 on May 08, 2021, according to Coinmarketcap. In the process, its market cap rose higher than companies such as Twitter and Ford. "But it doesn't have any utility, and it doesn't have any paid staff," Motley Fool reported.
The Tik Tok dogecoin investor described how he thinks dogecoin can make everyone rich. "Everybody is just encouraging each other to get it to a dollar and every time it gets a little closer, we cheer: 'Oh it went up a cent. Oh it went up another.' Everybody gets all amped up about it, you know what I mean? So it's almost like we're all in this together, all a part of a team and we're all trying to get it to a certain goal."
"Mans just flawlessly described a ponzi," @TikTokInvestors tweeted.
Ponzi schemes are named for Charles Ponzi, who was arrested on Aug. 12, 1920, in Boston for faking investments. In his scheme, early investors were paid with money from later investors, making Ponzi's enterprise appear legitimate. Ponzi promised investors a 50 percent profit within 45 days and 100 percent profit within 90 days. Early investors got what they were promised and Ponzi soon had investors begging him to take their money.
Subsequent Ponzi schemes have proved that "too good to be true" can be too hard to resist. Bernie Madoff promised his investors a steady return on their investments via the asset management arm of his firm, which pretended to trade in securities using his "unique" strategy of picking winning bets. Madoff delivered through the recession in the 1990s and the 9/11 terrorist attacks of 2001 until the 2008 financial crisis put an end to his "big lie." How the Ponzi scheme worked is that money given to Madoff by newer investors was used to pay older investors while Madoff manufactured counterfeit returns. In 2008, older investors pulled out, new ones evaporated and banks stopped lending. When Madoff's Ponzi scheme unraveled, investors lost as much as $65 billion.
People begged Madoff to take their money. Madoff said that he waved red flags that should have been obvious to even an unsophisticated investor, according to New York Magazine. "They were all told by me, 'Don't invest any more money than you could afford to lose. This is the stock market. There's always stuff that can happen. Brokerage firms can fail. I could go crazy and do something stupid. If you want a [safe thing], put your money in government bonds.' So everybody understood this … Everyone was greedy. I just went along. It's not an excuse," Madoff said.
Madoff died in prison on April 14, 2021, at age 82 after being sentenced in 2009 to serve 150 years. He pulled off the largest Ponzi scheme in history.
All this ponzi stuff is coming to an end. That goes for the shitcoins, private tech/vc, NFT, & stocks. https://t.co/dUdpWYULg8
— Jamarlin Martin (@JamarlinMartin) December 5, 2021

redpajama_set_name: RedPajamaCommonCrawl


text:
Home » IANS » Bahrain GP: Hamilton claims 11th win of the season
Bahrain GP: Hamilton claims 11th win of the season
Bahrain, Nov 29 (IANS) Seven-time world champion Lewis Hamilton took his 11th win over the 2020 season at the Bahrain Grand Prix and Red Bull pair Max Verstappen and Alex Albon took second and third place respectively in a race that started with a horror crash for Haas' Romain Grosjean.
The crash, in which Grosjean plunged into the barriers at high speed in the first lap and his car exploded into flames and split in two, led to a lengthy red flag period.
Following a subsequent Safety Car period at the restart after Racing Point's Lance Stroll was rolled over after contact with AlphaTauri's Daniil Kvyat, it was a relatively simple evening's work for Mercedes' Hamilton – crowned world champion last time out at the Turkish Grand Prix – whose victory never looked seriously under threat from Verstappen, despite the Dutchman shadowing him for much of the race.
However, it was not Verstappen's team mate Albon who looked set for the third podium place but Racing Point's Sergio Perez. However, just as the Mexican was looking set for a second podium in as many races, his car had to stop with a suspected power unit issue three laps from the end that promoted Albon up to third, giving the Thai driver his second career podium as the race finished behind a Safety Car brought out as Perez's car was recovered.
Perez's retirement was great also news for McLaren, who claimed fourth and fifth, Lando Norris leading home Carlos Sainz, while their 22-point haul saw them move ahead of the point-less Racing Point to P3 in the constructors' standings.
rkm/sdr/
Kamala Harris becomes America's first woman Vice President (Lead)
Nearly 80% believe India's actions can bolster Tibetan cause: Survey
WhatsApp investment tips' land two in trouble with SEBI
ALERT: Joe Biden sworn in as US President
Kamala Devi Harris sworn in as Vice President
Joe Biden's presidential inauguration ceremony underway
IPL's top wicket-taker Malinga quits franchise cricket
ALERT: Kamala Devi Harris sworn in as Vice President of the US
Two-third Indians acknowledge Dalai Lama as country's eminent spiritual figure


text:
È stato Primo ministro del Togo dal dicembre 2007 al settembre 2008.

Dal 2008 al 2011 ha ricoperto il ruolo di Ministro della salute.

Note

Collegamenti esterni

Primi ministri del Togo

redpajama_set_name: RedPajamaWikipedia


Calculating the hash code of a C# image is useful in many image processing applications. A hash code can be used to compare two images for perfect equality or can be used to make sure an image remains unmodified.
As we will see, calculating the hash code of a bitmap is no different than getting the hash value of any piece of data.
A hash code is a value generated from a separate starting value (the seed value). A hash code is usually a fixed length for any given size data. So for example, if we are talking about bytes, a seed value that is 1-byte long and a seed value that is 300-bytes long will result in a hash value of the same length.
As you might guess, this means that it is possible for two different seed values to have the same hash value. (There are complicated math proofs for this, but just think about it, it is not too difficult to understand how this happens). When two different seed values result in the same hash value, that is called a collision.
Here is where we introduce the concept of hashing algorithms. A hashing algorithm, as used commonly with data encryption, is a process that takes a seed value and transforms it into a hash value. Good algorithms will use certain math properties to minimize the chance of collisions. Popular algorithms are the MD5 and SHA hashing algorithms. These algorithms are very good at reducing the number of collisions.
Of course, there are a ton of hashing algorithms, some better than others. SHA for example is a family of many different algorithms, not a single algorithm. For those interested in the topic, as of early 2010, there is a public competition to create the new SHA-3 algorithm.
Luckily for C# developers, the .NET Framework comes with implementation of widely-used hashing algorithms.
So how do we calculate the hash code of an image? The trick is to remember that an image is stored in a computer in bits, just like any other piece of data. If we can get the bytes that represent the given image, we can calculate the hash value of those bytes. As long as the image-to-byte transformation is consistent, the resulting hash value will always be the same for a given image.
As it so happens, converting a bitmap to bytes is a trivial problem. This article describes two of many ways to turn an image into bytes in C#. Just remember that whatever method you use, you have to make sure it is the same method every time.
This will not work. At least not in the purpose of image processing. Why? Because the GetHashCode function will return a hash value for the bitmap object. This is used in C# programming to compare when two references are pointing to the same object (since they will return the same hash value calculated on the object). You might have two separate images that are identical, but because the are each represented by an object, the GetHashCode values will be completely different.


Examine your gift card balance by logging in into your Big Eagle account. Be sure that to examine the stability of your Big Eagle gift card by following the link or phone quantity offered here for Big Eagle. While you're achieved searching for groceries and offers, sell any unused or partially used Big Eagle reward cards on for cash.
Get points in the direction of free reward playing cards with Granny Rewards. Enroll in the present day and obtain 100 factors for signing up and points along with your buy. All designated logos and types are the property of their respective homeowners.
On this site you won't discover the feedback of unbiased experts or quotes from magazines and online media. Our specialists are our users. Read comments left by users who found CureIt! to be actually useful. It's also possible to check out the cardboard stability in retailer.
Declare your 100 factors by verifying your electronic mail address. Gift Card Granny has despatched you an e mail with instructions. No claims of affiliation are made in regards to the shops on this site. A Large Eagle present card is good in the direction of groceries, prescription drugs, photos, dry cleaning and far more. Check your Big Eagle reward card steadiness utilizing one of many options under.
Test Giant Eagle present card steadiness online, over the telephone or in store. To verify Giant Eagle gift card steadiness select an possibility proven under. All designated trademarks and types are the property of their respective owners. No claims of affiliation are made about the shops on this site.
Be sure to verify the stability of your Large Eagle reward card by following the link or cellphone quantity provided here for Big Eagle. If you're done searching for groceries and deals, sell any unused or partially used Big Eagle reward cards on for money.
Sign up right this moment and receive a hundred factors for signing up and points with your buy. Get factors in direction of free gift playing cards with Granny Rewards. Our consultants are our customers. Read feedback left by customers who found CureIt!
Below are a few of our best giant eagle gift card balance graphic that you can download and print.


text:
The Scientific World Journal
For authorsFor reviewersFor editorsTable of Contents
The Scientific World Journal / 2014 / Article
AbstractIntroductionMaterials and MethodsResultsDiscussionConclusionAcknowledgmentsReferencesCopyright
Volume 2014 |Article ID 909586 | 11 pages | https://doi.org/10.1155/2014/909586
Effect of Noni (Morinda citrifolia Linn.) Fruit and Its Bioactive Principles Scopoletin and Rutin on Rat Vas Deferens Contractility: An Ex Vivo Study
Vijayapandi Pandy ,1 Megala Narasingam,1 Thubasni Kunasegaran ,1 Dharmani Devi Murugan,1 and Zahurin Mohamed1
1Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
Academic Editor: Valdir Cechinel Filho
Received18 Feb 2014
Revised24 May 2014
Accepted26 May 2014
Published22 Jun 2014
This study examined the effect of methanolic extract of Morinda citrifolia Linn. (MMC) and its bioactive principles, scopoletin and rutin, on dopamine- and noradrenaline-evoked contractility in isolated rat vas deferens preparations. MMC (1–40 mg/mL), scopoletin (1–200 μg/mL), and rutin hydrate (0.6–312.6 μg/mL) dose-dependently inhibited the contractility evoked by submaximal concentrations of both dopamine and noradrenaline, respectively. Haloperidol and prazosin, reference dopamine D2, and α1-adrenoceptors antagonists significantly reversed the dopamine- and noradrenaline-induced contractions, respectively, in a dose-dependent manner. Interestingly, MMC per se at higher doses (60–100 mg/mL) showed dose-dependent contractile response in rat vas deferens which was partially inhibited by high doses of haloperidol but not by prazosin. These results demonstrated the biphasic effects of MMC on dopaminergic system; that is, antidopaminergic effect at lower concentrations (<40 mg/mL) and dopaminergic agonistic effect at higher concentrations (>60 mg/mL). However, similar contractile response at high doses of scopoletin (0.5–5 mg/mL) and rutin hydrate (0.5–5 mg/mL) per se was not observed. Therefore, it can be concluded that the bioactive principles of MMC, scopoletin, and rutin might be responsible for the antidopaminergic and antiadrenergic activities of MMC.
Morinda citrifolia Linn. (family: Rubiaceae) is also known as noni, Indian mulberry, hog apple, and cheese fruit. The fruit, flower, leaves, bark, and root of M. citrifolia have been used for diverse medicinal purposes as traditional plant-based medicine. In fact, the fruits of this plant have benefited the Polynesians over 2000 years as an alternative medicine for antibacterial, antiviral, antifungal, antitumor, anthelmintic, analgesic, hypotensive, anti-inflammatory, and immune-enhancing effects [1].
The decoction or infusions of roasted mature unripe fruits have been recommended to relieve the symptoms of nausea and vomiting [2]. It has also been reported that noni fruit extract showed prokinetic and antiemetic activity on the intestinal transit being delayed by apomorphine (a potent agonist of dopamine D2 receptor) in mice and on the apomorphine-induced emesis in dogs, respectively. These actions are attributed to antidopaminergic effect of noni fruit extract [3]. In contrast, Pu et al. (2004) found that gastric emptying was significantly inhibited in rats which were treated with noni juice (0.25, 1, or 4 mL/kg) for 7 days [4]. These opposing effects on gastric emptying observed for noni by two different research groups might be due to the difference in the type of fruit extract and the concentration used in these experiments [5].
Our recent report revealed that the acute treatment of methanolic extract of M. citrifolia (MMC 1, 3, 5, and 10 g/kg, p.o.) significantly decreased the apomorphine-induced cage climbing behaviour and methamphetamine-induced stereotypy behaviour in mice in a dose-dependent manner which demonstrated the antidopaminergic effect of noni fruit extract [6]. Furthermore, it was also reported that the administration of M. citrifolia fruit extract significantly increased the brain levels of serotonin, dopamine, and noradrenaline in rats [7]. Similarly, other neurochemical analysis of noni-treated rats (1 mL/day, p.o.) for 15 days revealed significant changes in noradrenergic, dopaminergic, or serotonergic systems in amygdala, hippocampus, and substantia nigra [8]. Besides that, in some preliminary studies noni's capability in lowering blood pressure [9] and its vasodilatory properties [10] have been reported. However, the possible modes of action(s) of noni on the cardiovascular system are lacking [11].
Studies have shown that noni fruit contains a number of active constituents including rutin (3,3′,4′,5,7-pentahydroxyflavone-3-rhamnoglucoside), a flavonoid and scopoletin (6-methoxy-7-hydroxycoumarin), a coumarin derivative. Rutin has been reported to exert numerous pharmacological activities including antioxidant, anticarcinogenic, neuroprotective, and anticonvulsant activity [12–15]. Scopoletin has been reported to exhibit antioxidant, analgesic, and anti-inflammatory effects [16, 17]. In addition, scopoletin has been recommended as a marker constituent for the quality control and pharmacokinetic study of noni products [18]. It has also been demonstrated that scopoletin and rutin, respectively, showed antidepressant activity mediated by its interaction with α1- and α2-adrenoceptors [19, 20]. However, there has hitherto been no report demonstrating the interaction of rutin and scopoletin on the dopaminergic system.
Thus, the present study aimed to investigate the intervention of noni (Morinda citrifolia Linn.) and its bioactive principles, scopoletin and rutin, on the dopaminergic and noradrenergic systems using isolated rat vas deferens preparations.
2.1. Plant Collection and Identification
The fresh unripe fruits (dark green) of M. citrifolia were collected in January 2012 from Malacca, Malaysia. The plant material was taxonomically identified and authenticated by Rimba Ilmu, Institute of Biological Sciences, University of Malaya, and the voucher specimen (KLU 47738) was deposited at Rimba Ilmu for future reference. The fruits were cut into thin slices and shade dried. The shade dried fruit slices were pulverized in a mechanical grinder to obtain a coarse powder.
2.2. Preparation of M. citrifolia Fruit Extract
The methanolic extract of M. citrifolia (MMC) was prepared using cold extraction with sonication. The coarse fruit powder (1.8 kg) was soaked with 10L of methanol (Scharlau, Spain, isocratic HPLC grade) for 20 h followed by sonication using a water bath sonicator at 30°C for another 4 h. The resultant solution was evaporated under vacuum in a rotary evaporator to obtain a dry mass extract (yield: 14.36% w/w). The dried solvent-free crude methanolic extract of M. citrifolia was stored at 4°C in an air-tight, labelled, amber-coloured container until further use.
2.3. Chromatography Conditions and Instrumentation
MMC prepared as above was subjected to 1100 HPLC instrument (Agilent Technologies, California, USA) equipped with auto sampler and a fraction collector. Chromatographic separations were carried out on an Agilent Zorbax ODS C18 (4.6 × 250 mm, 5 μm, 70 A) and column temperature was maintained at 25°C. Mobile phase composed of methanol and 1.0% acetic acid in water was used. Elution was performed with a flow rate of 1 mL/min. The injection volume was 30 μL and the detection wavelength was 365 nm. Prior to injection, all samples were filtered through 0.20 μm syringe filter into HPLC sample vial to remove any remaining particles.
HPLC-purified MMC was further subjected to LCMS analysis. The system comprised of Agilent 1290 Infinity LC system coupled to Agilent 6520 Accurate-Mass Q-TOF mass spectrometer with dual ESI source used to analyse the samples. The LC separation was carried out by an Agilent Zorbax SB-C18 Narrow-Bore (2.1 × 150 mm, 3.5 μm). LC parameters are autosampler temperature, 25°C; injection volume, 0.5 μL; column temperature, 25°C; and flow rate of 0.21 mL/min. A gradient system composed of solvents A (0.1% formic acid in water) to B (0.1% formic acid in 100% methanol) was employed. Mass spectra data were acquired using the following settings: ESI capillary voltage was set at 4000 V (+) ion mode and 4000 V (−) ion mode and fragmentor at 125 V. The liquid nebulizer was set to 45 psig and the nitrogen drying gas was set to a flow rate of 10 L/min. Drying gas temperature was maintained at 300°C. The vaporizer temperature was maintained at 300°C. The ionization interface was operated in both positive and negative modes. Data was acquired at a rate of 1.03 spectra/s with a stored mass range of 100–3200 m/z for positive mode and 115–3200 m/z for negative mode. Data was collected using Agilent MassHunter Workstation Data acquisition software. LCMS data files were processed by Agilent MassHunter Qualitative Analysis B.05.00 software. Feature finding was achieved using the molecular feature extraction (MFE) and correlation algorithms, which locates the groups of covariant ions in each chromatogram. In positive-ion mode this included adducts (H+, Na+, K+, and +NH4) and in negative ion mode it included adducts (−H and +Cl).
2.3.1. Tentative Compound Identifications
The Agilent METLIN (METLIN_AM_PCDL-N-130328.cbd) database was used to make tentative identifications from the mass lists created in Agilent Mass Profiler software. This database includes masses, chemical formulas, and structure information for various compounds. All features were searched against the METLIN database according to match m/z value. A list of identified compounds was generated.
2.3.2. Quantification of Scopoletin and Rutin in MMC by LCMS/MS Analysis
Primary stock solution of rutin and scopoletin standard was prepared by dissolving the compounds in methanol to achieve the desired concentration of 0.5 mg/mL. Working standards solution was prepared by serial dilution of primary stock solution using methanol. Peak area was plotted against the corresponding concentrations to obtain calibration plot. A MMC stock solution was prepared at the concentration of 10 mg/mL in methanol. All the samples prepared were filtered through a 0.22 nylon filter (Bioflow, Malaysia) and were transferred to autosampler vial for LCMS/MS quantification analysis. The concentration of each constituent was expressed in μg/mg of dry samples.
The LCMS/MS quantification analysis was performed using Agilent 1290 infinity UHPLC, coupled with Agilent 6410 Triple quad LCMS. The mass detector was equipped with electrospray ionization (ESI) interface and controlled by MassHunter software. 2 μL of all the samples prepared was loaded on a 2.1 mm (i.d) Narrow-BoreSB-C18 (length 150 mm) analytical column (particle size 3.5 mM) used with a flow rate of 0.5 mL/min in a solution A (0.1% formic acid in water) and solution B (100% acetonitrile with 0.1% formic acid). The total gradient time for the LCMS run was 11 min. The ionization conditions were adjusted at 350°C and 4000 V for capillary temperature and voltage, respectively. The nebulizer pressure was 45 psi and the nitrogen flow rate was 11 L/min.
2.4. Animals
Sprague-Dawley male rats (250–300 g), obtained from the laboratory animal centre, University of Malaya, were used in this study. The rats were housed in polycarbonate cages in a group of four animals under standard laboratory conditions at temperature of °C and 12/12 h light/dark cycle (light on from 8 am to 8 pm). Animals were fed with standard laboratory food pellets and water ad libitum. Animal Care and Use Committee, University of Malaya, Kuala Lumpur, approved the experimental protocol (ACUC Ethics number FAR/27/01/2012/PV (R)) and care of the animals was taken as per guidelines of the Council for International Organization of Medical Sciences (CIOMS) on animal experimentation [21].
2.5. Drugs and Chemicals
Dopamine hydrochloride, L-noradrenaline, prazosin hydrochloride, haloperidol, rutin hydrate, dimethyl sulfoxide (Sigma-Aldrich), and scopoletin (Friendemann Schmidt Chemicals) were used. All the drug solutions were prepared fresh in double distilled water. Dopamine hydrochloride and L-noradrenaline were dissolved in double distilled water containing ascorbic acid (0.125% w/v). The stock solution of different concentrations of MMC, rutin hydrate, and scopoletin was prepared using DMSO (0.1% v/v). All reagents were of isocratic HPLC grade unless stated otherwise. HPLC grade water was prepared by reverse osmosis and further purified.
2.6. Effect of MMC, Scopoletin, and Rutin Hydrate on Dopamine or Noradrenaline-Evoked Contractile Response in Isolated Rat Vas Deferens
The rats were sacrificed by CO2 inhalation and pairs of vas deferens were dissected out and fixed on a wax plate with fine nail. After carefully removing blood vessels and connective tissues, the epididymal portions of the vas deferens (length, 1 cm) were cut from the preparation, mounted with silk thread on to a hook in a 10 mL organ bath, and immersed in Krebs-Henseleit (K-H) solution gassed with 95% O2 plus 5% CO2 to achieve a pH of 7.3-7.4; the temperature was 37°C. Preparations were stretched to a preload tension of 500 mg and equilibrated for 60 min during which time the bath solution was changed every 15 min. Isometric tension was recorded by a force transducer (Grass Instrument Co., Quincy, MA, USA) and the output was amplified and recorded continuously using the PowerLab recording system (AD Instruments, Sydney, Australia). The K-H solution contained (mM) NaCl 119, KCl 4.7, CaCl2 2.5, MgSO4 1.0, NaHCO3 25, KH2PO4 1.2, EDTA 0.03, and D-glucose 11.1 as previously described [22]. After the equilibration period, the contractile responses of vas deferens tissues were tested for viability by the repeated addition of high KCl solution (high K, 80 mM).Once reproducible contractions were obtained with high K, a full noncumulative dose-response curve was obtained by a stepwise increase in concentrations of the agonist (noradrenaline (NA) or dopamine (DA)). DA (0.4–102.4 μg/mL) and NA (0.1–12.8 μg/mL) were tested. Each dose was applied for 30s and then washed thoroughly (at least three times) before the next higher dose was added [23].
From the dose-response curves of DA/NA, a submaximal dose of each agonist was selected for further studies. In the presence of DMSO (0.001% v/v) or the various concentrations of MMC (1–40 mg/mL, 5 min incubation), scopoletin (1–200 μg/mL, 5 min incubation), and rutin hydrate (0.6–312.6 μg/mL, 5 min incubation) in ascending order, the contractile response of the chosen submaximal dose of DA/NA was recorded. Decrease in response with respect to the vehicle control (DMSO) represents inhibitory effect of the extract/bioactive compounds on the corresponding agonist. The % contraction of the chosen submaximal dose of DA (25.6 μg/mL) or NA (3.2 μg/mL) over high KCl solution (high K, 80 mM) in presence of DMSO/MMC/scopoletin/rutin hydrate was calculated. The same set of experiments was also repeated in presence of reference drugs, haloperidol (dopamine D2-receptor blocker) and prazosin HCl (α1-adrenoceptor blocker) as positive controls.
In order to examine the nature of antagonism (reversible or irreversible) by MMC on DA/NA-evoked contractile response in isolated rat vas deferens, log dose-response curves of DA/NA in absence and presence of MMC (1–20 mg/mL, 10 min incubation) were carried out. Similarly, the effect of MMC (1–40 mg/mL, 10 min incubation) on high K- (80 mM) evoked contractility in rat vas deferens was also studied.
In a separate experiment, contractile response of MMC (20–100 mg/mL) per se was tested. The contractile response of MMC per se was recorded for 5 min and washed thoroughly with fresh K-H solution (at least three times in 5 min interval) before the next higher dose of MMC was added. Following that, contractile response of submaximal dose of MMC (80 mg/mL) was recorded in presence of prazosin HCl (0.01, 0.1, and 1.6 μg/mL) and haloperidol (12.8, 128, and 500 μg/mL), respectively. Similarly, the contractile responses of scopoletin (0.5–5 mg/mL) and rutin hydrate (0.5–5 mg/mL) per se on rat vas deferens were also studied.
2.7. Statistical Analysis
The concentrations indicated in the text or in the figures represent the final tissue-bath concentration of the respective drugs. The responses were recorded as mean ± standard error of mean (S.E.M) and "" indicates number of rats used for each set of data. The statistical significance of differences between treatments was evaluated by unpaired Student's -test when comparing means of two groups and one-way analysis of variance (ANOVA) and Dunnett post hoc test for more than two group comparisons. A value of was considered as statistically significant.
3. Results
3.1. Phytochemical Characterization of the MMC
MS parameters were optimized by individual standards of 10 mg/L of target compounds that were injected by infusion in full scan in positive and negative modes. For scopoletin, ESI negative ion mode provided the best response where unprotonated molecular ion [M-H]− peak was observed at m/z 191.0342 (Figure 1(a)). Rutin was detected only in negative mode. The unprotonated molecular ion [M-H]− peak of rutin was observed at m/z 609.1472 (Figure 1(b)).
MFE zoomed mass spectrum of (a) scopoletin and (b) rutin obtained from MMC.
The other components identified in full scan in positive modes are monosaccharides: D-glucoheptose, fagomine, and L-galactose; disaccharides: D-(+)-cellobiose and palatinose; polysaccharides: levan and hyaluronic acid; glycosides: paromomycin, gentamicin C1a, netilmicin, and antibiotic JI-20A; sugar acid: isovalerylglucuronide; sugar alcohol: mesoerythritol, erythritol, and 1,4-dideoxy-1,4-imino-D-arabinitol; quinone: 4-bromo-3,5-cyclohexadiene-1,2-dione; heterocycles: naltrindole, scopoletin, and piperonyl butoxide; aromatic: benzidine; cyclic: beta-2,3,4,5,6-pentachlorocyclohexanol; polycyclic: corrinoid; fatty acids: 4-hydroxy-valeric acid, 8S-hydroxy-hexadecanoic acid, 2,3-dinor-TXB2, arachidic acid (d3), and 7-hydroxy tetranor iloprost; fatty acyls: n-valeryl acetic acid, 12-hydroxy-10-octadecynoic acid, and 9,10-dioxo-octadecanoic acid; fatty alcohol: 2,2,9,9-tetramethyl-decan-1,10-diol and dolichyl phosphate; sterol lipids: cholestan-3α-ol,3α,6α,7α,12α-tetrahydroxy-5β-cholan-24-oic acid, alpha-tocopheronic acid, and (24R)-1α,24-dihydroxy-22-oxacholecalciferol; glycerides: 1-monopalmitin; terpenes and others: tetrahydrocortisone, cucurbitacin A, and C25:3 6,7-epoxy highly branched isoprenoid; amine: 1-naphthylacetylspermine; amino acid: Tyr Met, Thr Ser Asn, Arg Ser, N-acetyl-leucyl-leucine, Ala His Ala, His Arg Asn, Thr Gln Tyr, Thr Tyr Tyr, Gln His Gly, and Leu Ala Arg; amide: fenothiocarb sulfoxide.
On the other hand, adduct in LC-MS in negative mode provided the following: nucleoside: azacitidine; glucuronic acid: isovalerylglucuronide; carbohydrate acid: arabinonic acid; polysaccharides: levan; fatty acid: 2-hydroxy-6-oxo-6-(2-hydroxyphenyl)-hexa-2,4-dienoate; steroids: fluocinolone and dexamethasone phosphate; fatty acyls: 18-hydroxy-9S,10R-epoxy-stearic acid, 7-keto-stearic acid, 2,4-dimethyl-tetradecanoic acid, and DL-9-hydroxy stearic acid; terpenes: antirrhinoside and monotropein; heterocyclic compounds: etanidazole, 5-acetylamino-6-amino-3-methyluracil, nifuradene, 3,7-dimethyluric acid, xanthine, hypoxanthine, scopoletin, rutin, and dioclein; alkaloid: atalanine; amino acid derivatives: fructoselysine 6-phosphate.
3.2. Quantification of Scopoletin and Rutin in MMC by LCMS/MS Analysis
The concentration of scopoletin and rutin in MMC was found to be 18.95 μg/mg and 1.66 μg/mg, respectively.
3.3. Effect of MMC, Scopoletin, and Rutin Hydrate on DA- or NA-Evoked Contractile Response
Dopamine and noradrenaline produced concentration-dependent contractions of epididymal segments of the isolated rat vas deferens preparation are shown in Figures 2(a) and 2(b).
Log dose-response curve of (a) dopamine and (b) noradrenaline (NA) employing isolated rat vas deferens preparation ( ).
After incubation of the tissue preparation with MMC (1–40 mg/mL), scopoletin (1–200 μg/mL), and rutin hydrate (0.6–312.6 μg/mL) for 5 min, the contractile responses to the selected submaximal dose of NA (3.2 μg/mL) and DA (25.6 μg/mL) were significantly reduced in dose-dependent manner (Figures 3(a), 3(b), and 3(c) and Figures 4(a), 4(b), and 4(c)).
Effect of (a) MMC (1–40 mg/mL), (b) scopoletin (1–200 μg/mL), and (c) rutin hydrate (0.6–39.1 μg/mL) on NA- (3.2 μg/mL) evoked contraction expressed as % contraction over 80 mM High K. and compared to DMSO (0.001% v/v); .
Effect of (a) MMC (1–30 mg/mL), (b) scopoletin (1–200 μg/mL), and (c) rutin hydrate (0.6–312.6 μg/mL) on dopamine- (25.6 μg/mL) evoked contraction in isolated rat vas deferens preparations expressed as % contraction over 80 mM High K. , , and compared to DMSO (0.001% v/v); .
3.4. Log Dose-Response Curve of NA/DA in Absence and in Presence of MMC
As shown in Figures 5(a), 5(b), 6(a), and 6(b), the log dose-response curves of NA and DA were dose-dependently shifted rightward in the presence of MMC (1–20 mg/mL). The maxima of the agonists (NA/DA) curves were also progressively depressed by MMC in a dose-dependent manner. The values of the calculated area under the curve (AUC) of NA and DA were significantly decreased by MMC dose-dependently.
Log dose-response curve of (a) noradrenaline (NA) and (b) area under curve in absence and in presence of MMC, expressed as % contraction over 80 mM High K. and compared to DMSO (0.001% v/v); .
Log dose-response curve of (a) dopamine (DA) and (b) area under curve in absence and in presence of MMC, expressed as % contraction over 80 mM High K. and compared to DMSO (0.001% v/v); .
3.5. Effect of MMC on 80 mM High K-Evoked Contractile Response
MMC (1–40 mg/mL) did not alter 80 mM High K-evoked contractile response in rat vas deferens preparations (data not shown).
3.6. Effect of Haloperidol or Prazosin HCl on DA or NA-Evoked Contractile Response
While incubating the vas deferens preparation with haloperidol (1.6–12.8 μg/mL) for 5 min, the contractile responses to the selected submaximal dose of DA (25.6 μg/mL) were significantly reduced in dose-dependent manner (Figure 7). Prazosin HCl (0.01 μg/mL) showed 100% inhibition on NA response (data not shown).
Effect of haloperidol (1.6–12.8 μg/mL) on dopamine- (25.6 μg/mL) evoked contraction on isolated rat vas deferens preparation. compared to DMSO (0.001% v/v); .
3.7. Effect of High Doses of MMC, Scopoletin, and Rutin Per Se on Contractility of Rat Vas Deferens
Remarkably, MMC per se at higher doses (60, 80, and 100 mg/mL) significantly increased the contractility of vas deferens in a dose-dependent manner (Figure 8). However, the bioactive principles of MMC, scopoletin, and rutin, respectively, at higher doses (0.5–5 mg/mL) did not show any contractile response (data not shown) in rat vas deferens.
Contraction evoked by MMC (20–100 mg/mL) per se expressed as % contraction over 80 mM High K. compared to DMSO (0.001% v/v); .
3.8. Effect of Haloperidol or Prazosin HCl on High Dose MMC-Evoked Contractile Response
Haloperidol (12.8–500 μg/mL) significantly decreased the contractility induced by high dose MMC (80 mg/mL) (Figure 9(a)). On the other hand, prazosin HCl even at higher concentration (1.6 μg/mL) pretreatment could not alter the contractile response of high doseMMC (Figure 9(b)).
Effect of haloperidol (a) (HAL 12.8, 128, and 500 μg/mL) and (b) prazosin (PRZ 0.01, 0.1, and 1.6 μg/mL) on MMC (80 mg/mL) per se induced contractility expressed as % contraction over 80 mM High K. compared to DMSO (0.001% v/v); .
The isolated rodent vas deferens is an established research model for functional and molecular investigation of normal and altered autonomic (sympathetic) neuroeffector coupling [24]. It has also been suggested that dopamine may be a neurotransmitter in the rat vas deferens and that excitatory dopamine receptors are located on the smooth muscle [25–27]. Boadle-Biber and Roth (1975) reported that a high proportion of newly formed catecholamine in the rat vas deferens was present as dopamine as compared to noradrenaline [28]. Relja et al. (1982) reported that dopamine receptors are present in rat vas deferens, based on the binding of [3H] haloperidol to the plasma membranes [29]. Besides that, Ohmura et al. (1992) indicated the occurrence of two distinct α1-adrenoceptor subtypes in the rat vas deferens [30].
The preliminary phytochemical analysis of the methanol extract of M. citrifolia showed the presence of carbohydrate, alkaloids, saponin, glycosides, tannins, flavonoids, and steroids [31]. Phytochemical studies using high performance liquid chromatographic (HPLC) fingerprint profile of the MeOH extracts of noni fruit revealed three major peaks representing scopoletin, rutin, and quercetin together with several minor peaks. These are major bioactive constituents of noni responsible for various pharmacological activities [32, 33]. The present phytochemical analysis results are consistent with earlier findings and confirmed the presence of scopoletin and rutin (retention times: 14.51 and 15.86 min, resp.). Furthermore, we estimated the concentration of these constituents in MMC using LCMS/MS analysis and it has been found that MMC is enriched with scopoletin (18.95 μg/mg) and rutin (1.66 μg/mg). Hence, in the present study, scopoletin and rutin were used to establish its interaction with dopaminergic and noradrenergic systems.
In the present study, we observed that MMC (<40 mg/mL), scopoletin (100, 200 μg/mL), and rutin hydrate (156.3, 312.6 μg/mL) caused a significant concentration-dependent inhibition of contraction evoked by dopamine in the isolated rat vas deferens preparations, thus indicating antidopaminergic activity of MMC, scopoletin, and rutin hydrate (Figures 4(a), 4(b), and 4(c)). It has been observed that MMC [1–20 mg/mL; equivalent to scopoletin (18.95–379 μg/mL) and rutin (1.66–33.2 μg/mL)] dose-dependently decrease the slope as well as maxima of the agonists (DA/NA) curves (Figures 5(a), 5(b), 6(a), and 6(b)) and suggested that the antagonistic effect of MMC (<40 mg/mL) on dopaminergic and noradrenergic system might be irreversible. Furthermore, MMC (<40 mg/mL) did not alter the contraction induced by high K (80 mM KCl) in rat vas deferens. This observation excludes the possibility of the observed inhibitory effect of MMC (<40 mg/mL) on rat vas deferens being due to direct muscle relaxing effect of MMC. The reference drug, haloperidol (dopamine D2 receptor blocker, 1.6–12.8 μg/mL), also showed dose-dependent inhibition on dopamine-induced contractile response in rat vas deferens. Conversely, MMC per se at higher doses (60, 80, and 100 mg/mL) exhibited significant dose-dependent contractile response. Interestingly, contractility evoked by MMC per se was significantly inhibited by high doses of haloperidol (128–500 μg/mL). Thus, the present results have demonstrated the biphasic effect of MMC on dopaminergic system, with dopaminergic antagonistic effect at lower concentrations (<40 mg/mL) and dopaminergic agonistic effect at higher concentrations (>60 mg/mL). However, the main bioactive principles of noni, scopoletin, and rutin per se at higher doses (0.5–5 mg/mL) did not show any contractile response in rat vas deferens. Therefore, it can be postulated that the antidopaminergic effects of MMC might be mediated by its active principles, scopoletin and rutin. Nevertheless, these active principles might not be involved in the high dose contractile response of MMC per se. There is a possibility that some other bioactive phytoconstituents of MMC could be involved in the high dose contractile response of MMC.
M. citrifolia has been used as an antiemetic agent in patients considered with high risk for postoperative nausea and vomiting (PONV) after various types of surgery. The 600 mg dose of noni extract (equivalent to 20 g of dried noni fruit/8.712 μg of scopoletin) was the minimum dose that could effectively reduce the incidence of postoperative nausea in the early postoperative period [34]. However, these studies could not reveal the possible mechanism of action of M. citrifolia for its antiemetic action. In our recent published report, we suggested the antipsychotic and antiemetic activities of M. citrifolia might be mediated by antidopaminergic mechanism [6]. Another recent report on neurochemical analysis revealed the alterations in the monoaminergic system in the noni-treated rats (1 mL/day, p.o., for 15 days), compared to the control rats. It was found that the reduction in these neurotransmitters including noradrenaline in the amygdala and the hippocampus, serotonin in the amygdala, DOPAC in the hippocampus and the substantia nigra, and HVA in the substantia nigra of the noni group might be responsible for anxiolytic effects of noni juice [8]. Conversely, it has been demonstrated that ethyl acetate fraction of crude methanol extract of M. citrifolia at a daily dose of 200 and 400 mg/kg which was administered to the rats for 15 days significantly increased the brain levels of serotonin, dopamine, and noradrenaline [7]. This opposing effect of noni on monoamine levels in two different studies could be due to the difference in the doses of noni used for these studies. Lower doses of noni might inhibit monoaminergic system whereas higher concentrations could stimulate monoaminergic system. The enhancement in brain monoamines after 15-day treatment of ethyl acetate fraction of crude methanol extract of M. citrifolia might be due to the presence of enrichment of active constituents in the ethyl acetate fraction. The higher concentration of active constituents in the ethyl acetate fraction when compared to crude MMC could activate the monoaminergic system. The present results are in good agreement with these earlier findings; that is, MMC can act as a dopaminergic antagonist at lower concentrations (<40 mg/mL) and as a dopaminergic agonist at higher dose (>60 mg/mL). However further receptor-ligand binding assays are necessary to confirm the biphasic effects of M. citrifolia on dopaminergic system.
In the present study, MMC showed antiadrenergic effect at lower concentrations [<30 mg/mL; equivalent to scopoletin (<568.5 μg/mL) and rutin (<49.8 μg/mL)] in the isolated rat vas deferens preparation. Besides that, scopoletin (50, 100, 200 μg/mL) and rutin hydrate (9.8, 19.5, 39.1 μg/mL) caused a significant concentration-dependent inhibition of contraction evoked by noradrenaline (Figures 3(a), 3(b), and 3(c)). The reference drug, prazosin HCl (adrenergic α1 receptor blocker), completely reversed the noradrenaline-evoked contractility in the isolated rat vas deferens even at lower concentration of 0.01 μg/mL. A recent research report suggested that the spasmolytic and vasodilator effects of M. citrifolia root extract are mediated possibly through blockade of voltage-dependent calcium channels and release of intracellular calcium and justified traditional medicinal usage of M. citrifolia in diarrhoea and hypertension [11]. These studies also demonstrated the vasorelaxant activity of M. citrifolia by inhibiting contractile response of α1 adrenoceptors agonist, phenylephrine (1 μM), in endothelium-intact rat aortic preparations [11]. The present results are consistent with these earlier findings and suggest that the antihypertensive effect of M. citrifolia might be partially mediated by α1 adrenoceptors blocking effect. The present study results also revealed the antiadrenergic activity of scopoletin and rutin, respectively, in rat vas deferens. Therefore, it can be postulated that α1 adrenoceptors blocking effect of MMC could be mediated by its bioactive principles, scopoletin and rutin. An earlier report revealed the predominance of α-adrenoceptors in the testicular (epididymal) segment of the vas deferens compared with the urethral (prostatic) segment [35]. A nerve-stimulation evoked postjunctional receptor for NA is the α1A-adrenoceptor, acting via inositol trisphosphate (IP3) leading to increase in intracellular Ca2+ and the slow component of nerve-mediated contraction [36]. However, the possibility that there are differences between neurogenic and exogenously applied NA has been raised [37]. They showed that contractions to exogenous NA involved both α1A and α2A/D adrenoceptors. Hence the antiadrenergic effect of MMC (<30 mg/mL) and its bioactive principles, scopoletin and rutin, could be mediated by both α1A and α2A/D adrenoceptors. The contractile response of high dose of MMC (80 mg/mL) was not inhibited by α1-adrenoceptor blocker, prazosin, even at higher concentration (1.6 μg/mL). Therefore, the contractility response of high dose of MMC might not be mediated through adrenergic mechanism. The biphasic effect of MMC observed in the present study using rat vas deferens preparation could be exhibited only at the dopaminergic system.
In conclusion, MMC showed biphasic effect on dopaminergic system, that is, antidopaminergic effect at lower dose (<40 mg/mL) and dopaminergic agonistic effect at higher dose (>60 mg/mL) in the isolated rat vas deferens preparation. Additionally, MMC (<30 mg/mL) showed the antiadrenergic activity in the rat vas deferens. Furthermore, antidopaminergic and antiadrenergic activities of scopoletin (<200 μg/mL) and rutin hydrate (<312.6 μg/mL), respectively, have been established. It has been postulated that the bioactive principles of noni, scopoletin and rutin, could be responsible for the antidopaminergic and antiadrenergic activities of MMC. However, the mechanism of high dose contractile response of MMC on rat vas deferens could not be explained in the present study. Further, in vivo animal behaviour studies are warranted to confirm the biphasic effect of noni on dopaminergic system. Studies in this direction are currently under way in our laboratory.
This study was supported by University of Malaya Research Grants (PG015-2012B and RG495-13HTM) and HIR MOHE Project no. UM.C/625/1/HIR/MOHE/MED/05 (H-20001-E000088).
S. Nayak and R. Shettigar, "Morinda citrifolia: a review," Journal of Pharmacy Research, vol. 3, no. 8, pp. 1872–1874, 2010. View at: Google Scholar
W. Ekpalakorn, S. Supjaroen, P. Keawkomol, K. Chompuwiset, P. Limangkoon, and W. Boonchui, "A clinical study of Morinda citrifolia Linn.in the treatment of nausea and vomiting," in Office of the Primary Health Care, Ministry of Public Health. Research Reports on Medicinal Plants, Medicinal Plants and Primary Health Care Project, pp. 40–41, Veteran Administration Printing, Bangkok, Thailand, 1987. View at: Google Scholar
A. Chuthaputti, P. N. Pattaloong, U. Permpipat, and Y. Techadamrongsin, "Study on antiemetic activity of Morinda citrifolia fruits," Thai Journal of Pharmaceutical Science, vol. 20, pp. 195–202, 1996. View at: Google Scholar
H.-F. Pu, W.-J. Huang, W.-M. Tseng et al., "Effects of juice from Morinda citrifolia (Noni) on gastric emptying in male rats," Chinese Journal of Physiology, vol. 47, no. 4, pp. 169–174, 2004. View at: Google Scholar
S. Mahattanadul, W. Ridtitid, S. Nima, N. Phdoongsombut, P. Ratanasuwon, and S. Kasiwong, "Effects of Morinda citrifolia aqueous fruit extract and its biomarker scopoletin on reflux esophagitis and gastric ulcer in rats," Journal of Ethnopharmacology, vol. 134, no. 2, pp. 243–250, 2011. View at: Publisher Site | Google Scholar
V. Pandy, M. Narasingam, and Z. Mohamed, "Antipsychotic-like activity of Noni (Morinda citrifolia Linn.) in mice," BMC Complementary and Alternative Medicine, vol. 12, article 186, 2012. View at: Publisher Site | Google Scholar
P. Muralidharan and J. Srikanth, "Anti epileptic activity of Morinda citrifolia linn fruit extract," E-Journal of Chemistry, vol. 7, no. 2, pp. 612–616, 2010. View at: Google Scholar
S. Kalandakanond-Thongsong and J. Charoenphandhu, "Anxiolytic-like effects of noni juice (Morinda citrifolia L.) On the respective changes of neurotransmitters in rat brain in the elevated plus-maze test," Thai Journal of Veterinary Medicine, vol. 42, no. 3, pp. 275–280, 2012. View at: Google Scholar
Dang-Van-Ho, "Treatment and prevention of hypertension and its cerebral complications by total root extracts of Morinda citrifolia," Pressemédicale, vol. 63, no. 72, p. 1478, 1955 (French). View at: Google Scholar
I. Runnie, M. N. Salleh, S. Mohamed, R. J. Head, and M. Y. Abeywardena, "Vasorelaxation induced by common edible tropical plant extracts in isolated rat aorta and mesenteric vascular bed," Journal of Ethnopharmacology, vol. 92, no. 2-3, pp. 311–316, 2004. View at: Publisher Site | Google Scholar
A. H. Gilani, S.-U. Mandukhail, J. Iqbal et al., "Antispasmodic and vasodilator activities of Morinda citrifolia root extract are mediated through blockade of voltage dependent calcium channels," BMC Complementary and Alternative Medicine, vol. 10, article 2, 2010. View at: Publisher Site | Google Scholar
C. la Casa, I. Villegas, C. Alarcón de la Lastra, V. Motilva, and M. J. Martín Calero, "Evidence for protective and antioxidant properties of rutin, a natural flavone, against ethanol induced gastric lesions," Journal of Ethnopharmacology, vol. 71, no. 1-2, pp. 45–53, 2000. View at: Publisher Site | Google Scholar
K. H. Janbaz, S. A. Saeed, and A. H. Gilani, "Protective effect of rutin on paracetamol- and CCl4-induced hepatotoxicity in rodents," Fitoterapia, vol. 73, no. 7-8, pp. 557–563, 2002. View at: Publisher Site | Google Scholar
F. Pu, K. Mishima, K. Irie et al., "Neuroprotective effects of quercetin and rutin on spatial memory impairment in an 8-arm radial maze task and neuronal death induced by repeated cerebral ischemia in rats," Journal of Pharmacological Sciences, vol. 104, no. 4, pp. 329–334, 2007. View at: Publisher Site | Google Scholar
M. Nassiri-Asl, S. Shariati-Rad, and F. Zamansoltani, "Anticonvulsive effects of intracerebroventricular administration of rutin in rats," Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 32, no. 4, pp. 989–993, 2008. View at: Publisher Site | Google Scholar
C.-Y. Shaw, C.-H. Chen, C.-C. Hsu, C.-C. Chen, and Y.-C. Tsai, "Antioxidant properties of scopoletin isolated from Sinomonium acutum," Phytotherapy Research, vol. 17, no. 7, pp. 823–825, 2003. View at: Publisher Site | Google Scholar
T.-N. Chang, J.-S. Deng, Y.-C. Chang et al., "Ameliorative effects of scopoletin from Crossostephium chinensis against inflammation pain and its mechanisms in mice," Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 595603, 10 pages, 2012. View at: Publisher Site | Google Scholar
B. F. Issell, A. Franke, and R. M. Fielding, "Pharmacokinetic study of noni fruit extract," Journal of Dietary Supplements, vol. 5, no. 4, pp. 373–382, 2008. View at: Publisher Site | Google Scholar
J. C. Capra, M. P. Cunha, D. G. Machado et al., "Antidepressant-like effect of scopoletin, a coumarin isolated from Polygala sabulosa (Polygalaceae) in mice: evidence for the involvement of monoaminergic systems," European Journal of Pharmacology, vol. 643, no. 2-3, pp. 232–238, 2010. View at: Publisher Site | Google Scholar
D. G. Machado, L. E. B. Bettio, M. P. Cunha et al., "Antidepressant-like effect of rutin isolated from the ethanolic extract from Schinus molle L. in mice: evidence for the involvement of the serotonergic and noradrenergic systems," European Journal of Pharmacology, vol. 587, no. 1–3, pp. 163–168, 2008. View at: Publisher Site | Google Scholar
N. Howard-Jones, "A CIOMS ethical code for animal experimentation," WHO Chronicle, vol. 39, no. 2, pp. 51–56, 1985. View at: Google Scholar
Y. Huang, "Inhibition of contractions by tricyclic antidepressants and xylamine in rat vas deferens," European Journal of Pharmacology, vol. 327, no. 1, pp. 41–47, 1997. View at: Publisher Site | Google Scholar
P. Vijayapandi, A. Vamsi Krishna, B. Srikanth et al., "In vitro anticholinergic and antihistaminic activities of Acorus calamus Linn. leaves extracts," African Journal of Traditional, Complementary and Alternative Medicines, vol. 10, no. 1, pp. 95–101, 2013. View at: Google Scholar
T. D. Westfall and D. P. Westfall, "Pharmacological techniques for the in vitro study of the vas deferens," Journal of Pharmacological and Toxicological Methods, vol. 45, no. 2, pp. 109–122, 2001. View at: Publisher Site | Google Scholar
A. Simon and E. F. Van Maanen, "Dopamine receptors and dopaminergic nerves in the vas deferens of the rat," Archives Internationales de Pharmacodynamie et de Thérapie, vol. 222, no. 1, pp. 4–15, 1976. View at: Google Scholar
F. M. Tayo, "Occurrence of excitatory dopaminoceptors in the rat and guinea-pig vas deferens," Clinical and Experimental Pharmacology and Physiology, vol. 6, no. 3, pp. 275–279, 1979. View at: Google Scholar
A. Badia, P. Bermejo, and F. Jane, "Pre- and postsynaptic effects of sulpiride in the rat isolated vas deferens," Journal of Pharmacy and Pharmacology, vol. 34, no. 4, pp. 266–268, 1982. View at: Google Scholar
M. C. Boadle-Biber and R. H. Roth, "Formation of dopamine and noradrenaline in rat vas deferens: comparison with guinea pig vas deferens," British Journal of Pharmacology, vol. 55, no. 1, pp. 73–78, 1975. View at: Google Scholar
M. Relja, Z. Lackovic, and N. H. Neff, "Evidence for the presence of dopaminergic receptors in vas deferens," Life Sciences, vol. 31, no. 23, pp. 2571–2575, 1982. View at: Publisher Site | Google Scholar
T. Ohmura, M. Oshita, S. Kigoshi, and I. Muramatsu, "Identification of α1-adrenoceptor subtypes in the rat vas deferens: binding and functional studies," British Journal of Pharmacology, vol. 107, no. 3, pp. 697–704, 1992. View at: Google Scholar
S. Ramesh, M. Radhakrishnan, R. Anburaj, R. Elangomathavan, and S. Patharajan, "Physicochemical, phytochemical and antimicrobial studies on Morinda citrifolia L. fruits at different maturity stages," International Journal of Pharmacy and Pharmaceutical Sciences, vol. 4, no. 5, pp. 473–476, 2012. View at: Google Scholar
S. Deng, B. J. West, A. K. Palu, B.-N. Zhou, and C. J. Jensen, "Noni as an anxiolytic and sedative: a mechanism involving its gamma-aminobutyric acidergic effects," Phytomedicine, vol. 14, no. 7-8, pp. 517–522, 2007. View at: Publisher Site | Google Scholar
S. D. Pachauri, S. Tota, K. Khandelwal et al., "Protective effect of fruits of Morinda citrifolia L. on scopolamine induced memory impairment in mice: a behavioral, biochemical and cerebral blood flow study," Journal of Ethnopharmacology, vol. 139, no. 1, pp. 34–41, 2012. View at: Publisher Site | Google Scholar
S. Prapaitrakool and A. Itharat, "Morinda citrifolia Linn. for prevention of postoperative nausea and vomiting," Journal of the Medical Association of Thailand, vol. 93, no. 7, pp. S204–S209, 2010. View at: Google Scholar
L. Vardolov and J. N. Pennefather, "Regional variation in the distribution of α adrenoreceptors in the vas deferens of the rat," Archives Internationales de Pharmacodynamie et de Thérapie, vol. 221, no. 2, pp. 212–222, 1976. View at: Google Scholar
V. Honner and J. R. Docherty, "Investigation of the subtypes of α1-adrenoceptor mediating contractions of rat vas deferens," British Journal of Pharmacology, vol. 128, no. 6, pp. 1323–1331, 1999. View at: Google Scholar
L. Cleary, C. Vandeputte, and J. R. Docherty, "Investigation of postjunctional α1- and α2-adrenoceptor subtypes in vas deferens from wild-type and α2A/D-adrenoceptor knockout mice," British Journal of Pharmacology, vol. 138, no. 6, pp. 1069–1076, 2003. View at: Publisher Site | Google Scholar
Copyright © 2014 Vijayapandi Pandy et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
5755 Views | 1249 Downloads | 19 Citations