text:
Ladogal
Danazol
Antigonadotropic,Endocrine Therapy,Endocrine-Metabolic Agent,Sex Hormones And Modulators Of The Genital System
Angioedema,Infertility,Pain,Menorrhagia,Hereditary Angioedema,Edema,Premenstrual Syndrome,Precocious Puberty,Fibrocystic Breast Disease,Surgery,Endometriosis
Medically reviewed by Oliinyk Elizabeth Ivanovna, PharmD. Last updated on 2020-04-08
AnargilDanametLozanaDanazolKupdinaDzolLadogalDanatrolElleBenzol (Danazol)DanasinDanocrineAzolDanolDanazol EipicoDanazol AstarDorinkKodazolAzol (ENDOCRINE THERAPY)Bonzol
Danazol PolfarmexDanalolDanazantDanazol HualianGynadomCyclomenDanazol Tai YuDanoniceGonablokDanalDanodiolDanogenDanzolGong Fu Yi KangVabonDanazol JelfaВеро-ДаназолДанолCycloladyDanamin
The information provided in Name of the medicinal product of Ladogal is based on data of another medicine with exactly the same composition as the Ladogal. . Be careful and be sure to specify the information on the section Name of the medicinal product in the instructions to the drug Ladogal directly from the package or from the pharmacist at the pharmacy.
The information provided in Qualitative and quantitative composition of Ladogal is based on data of another medicine with exactly the same composition as the Ladogal. . Be careful and be sure to specify the information on the section Qualitative and quantitative composition in the instructions to the drug Ladogal directly from the package or from the pharmacist at the pharmacy.
The information provided in Therapeutic indications of Ladogal is based on data of another medicine with exactly the same composition as the Ladogal. . Be careful and be sure to specify the information on the section Therapeutic indications in the instructions to the drug Ladogal directly from the package or from the pharmacist at the pharmacy.
Capsules are solid
Ladogal capsules are recommended for the treatment of:
Endometriosis: treatment of endometriosis-associated symptoms or/and to reduce the extent of endometriosis foci. Danazol may be used either in conjunction with surgery or, as sole hormonal therapy, in patients not responding to other treatments.
Benign fibrocystic breast disease: symptomatic relief of severe pain and tenderness. Danazol should be used only in patients not responsive to other therapeutic measures or for whom such measures are inadvisable.
Ladogal is indicated for the treatment of endometriosis amenable to hormonal management.
Fibrocystic Breast Disease
Most cases of symptomatic fibrocystic breast disease may be treated by simple measures (e.g., padded brassieres and analgesics).
In infrequent patients, symptoms of pain and tenderness may be severe enough to warrant treatment by suppression of ovarian function. Ladogal is usually effective in decreasing nodularity, pain, and tenderness. It should be stressed to the patient that this treatment is not innocuous in that it involves considerable alterations of hormone levels and that recurrence of symptoms is very common after cessation of therapy.
Hereditary Angioedema
Ladogal is indicated for the prevention of attacks of angioedema of all types (cutaneous, abdominal, laryngeal) in males and females.
The information provided in Dosage (Posology) and method of administration of Ladogal is based on data of another medicine with exactly the same composition as the Ladogal. . Be careful and be sure to specify the information on the section Dosage (Posology) and method of administration in the instructions to the drug Ladogal directly from the package or from the pharmacist at the pharmacy.
Ladogal capsules should be given as a continuous course, dosage being adjusted according to the severity of the condition and the patient's response. A reduction in dosage once a satisfactory response has been achieved may prove possible. In fertile females, Ladogal capsules should be started during menstruation, preferably on the first day, to avoid exposing a pregnancy to its possible effects. Where doubt exists, appropriate checks should be made to exclude pregnancy before starting medication. Females of child-bearing age should employ non-hormonal contraception throughout the course of treatment.
In endometriosis the recommended dosage is 200mg to 800mg daily in a course of treatment lasting normally three to six months. Dosage should be increased if normal cyclical bleeding still persists after two months therapy, a higher dosage (not exceeding 800mg per day) may also be needed for severe disease.
In benign fibrocystic breast disease, treatment should commence at a dose of 300mg daily, a course of treatment normally lasting 3 to 6 months.
Elderly: Ladogal is not recommended.
Children: Ladogal is not recommended.
The capsules are for oral administration.
In moderate to severe disease, or in patients infertile due to endometriosis, a starting dose of 800 mg given in two divided doses is recommended. Amenorrhea and rapid response to painful symptoms is best achieved at this dosage level. Gradual downward titration to a dose sufficient to maintain amenorrhea may be considered depending upon patient response. For mild cases, an initial daily dose of 200 mg to 400 mg given in two divided doses is recommended and may be adjusted depending on patient response.
Therapy should begin during menstruation. Otherwise, appropriate tests should be performed to ensure that the patient is not pregnant while on therapy with Ladogal. (See CONTRAINDICATIONS and WARNINGS.) It is essential that therapy continue uninterrupted for 3 to 6 months but may be extended to 9 months if necessary. After termination of therapy, if symptoms recur, treatment can be reinstituted.
The total daily dosage of Ladogal for fibrocystic breast disease ranges from 100 mg to 400 mg given in two divided doses depending upon patient response. Therapy should begin during menstruation. Otherwise, appropriate tests should be performed to ensure that the patient is not pregnant while on therapy with Ladogal. A nonhormonal method of contraception is recommended when Ladogal is administered at this dose, since ovulation may not be suppressed.
In most instances, breast pain and tenderness are significantly relieved by the first month and eliminated in 2 to 3 months. Usually elimination of nodularity requires 4 to 6 months of uninterrupted therapy. Regular menstrual patterns irregular menstrual patterns and amenorrhea each occur in approximately one-third of patients treated with 100 mg of Ladogal. Irregular menstrual patterns and amenorrhea are observed more frequently with higher doses. Clinical studies have demonstrated that 50% of patients may show evidence of recurrence of symptoms within one year. In this event, treatment may be reinstated.
The dosage requirements for continuous treatment of hereditary angioedema with Ladogal should be individualized on the basis of the clinical response of the patient. It is recommended that the patient be started on 200 mg, two or three times a day. After a favorable initial response is obtained in terms of prevention of episodes of edematous attacks, the proper continuing dosage should be determined by decreasing the dosage by 50% or less at intervals of one to three months or longer if frequency of attacks prior to treatment dictates. If an attack occurs, the daily dosage may be increased by up to 200 mg. During the dose adjusting phase, close monitoring of the patient's response is indicated, particularly if the patient has a history of airway involvement.
The information provided in Contraindications of Ladogal is based on data of another medicine with exactly the same composition as the Ladogal. . Be careful and be sure to specify the information on the section Contraindications in the instructions to the drug Ladogal directly from the package or from the pharmacist at the pharmacy.
1. Pregnancy
2. Breast feeding
3. Markedly impaired hepatic, renal or cardiac function
4. Porphyria
5. Active thrombosis or thromboembolic disease and a history of such events
6. Androgen dependent tumour
7. Undiagnosed abnormal genital bleeding
8. Hypersensitivity to danazol or to any of the excipients
9. Concomitant administration with simvastatin
Ladogal should not be administered to patients with:
Undiagnosed abnormal genital bleeding.
Markedly impaired hepatic, renal, or cardiac function.
Pregnancy. (See WARNINGS.)
Breast feeding.
Porphyria-Ladogal can induce ALA synthetase activity and hence porphyrin metabolism.
Androgen-dependent tumor.
Active thrombosis or thromboembolic disease and history of such events.
Hypersensitivity to danazol.
The information provided in Special warnings and precautions for use of Ladogal is based on data of another medicine with exactly the same composition as the Ladogal. . Be careful and be sure to specify the information on the section Special warnings and precautions for use in the instructions to the drug Ladogal directly from the package or from the pharmacist at the pharmacy.
Special warnings
In the event of virilisation, Ladogal should be withdrawn. Androgenic reactions generally prove reversible, but continued use of Ladogal after evidence of androgenic virilisation increases the risk of irreversible androgenic effects.
Ladogal should be stopped if any clinically significant adverse event arises, and particularly if there is evidence of papilloedema, headache, visual disturbances or other signs or symptoms of raised intracranial pressure, jaundice or other indication of significant hepatic disturbance, thrombosis or thromboembolism.
Whilst a course of therapy may need to be repeated, care should be observed as no safety data are available in relation to repeated courses of treatment over time. The long-term risk of 17-alkylated steroids (including benign hepatic adenomata, hepatocellular focal nodular hyperplasia, peliosis hepatis and hepatic carcinoma), should be considered when danazol, which is chemically related to those compounds, is used.
Data, from two case-control epidemiological studies, were pooled to examine the relationship between endometriosis, endometriosis treatments and ovarian cancer. These preliminary results suggest that the use of danazol might increase the baseline risk of ovarian cancer in - patients treated for endometriosis.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
In view of its pharmacology, known interactions and side effects, particular care should be observed when using Ladogal in patients with hepatic or renal disease, hypertension or other cardiovascular disease and in any state which may be exacerbated by fluid retention as well as in diabetes mellitus, polycythaemia, epilepsy, lipoprotein disorder, and in those who have shown marked or persistent androgenic reaction to previous gonadal steroid therapy.
Caution is advised in patients with migraine.
Until more is known, caution is advised in the use of Ladogal in the presence of known or suspected malignant disease (see also contra-indications). Before treatment initiation, the presence of hormone-dependent carcinoma should be excluded at least by careful clinical examination, as well as if breast nodules persist or enlarge during danazol treatment.
In addition to clinical monitoring in all patients, appropriate laboratory monitoring should be considered which may include periodic measurement of hepatic function and haematological state. For long-term treatment (> 6 months) or repeated courses of treatment, biannual hepatic ultrasonography is recommended.
Danazol should be initiated during menstruation.6 Fertility, Pregnancy and Lactation).
The lowest effective dose of Ladogal should always be sought.
Use of danazol in pregnancy is contraindicated. A sensitive test (e.g., beta subunit test if available) capable of determining early pregnancy is recommended immediately prior to start of therapy. Additionally a non-hormonal method of contraception should be used during therapy. If a patient becomes pregnant while taking danazol, administration of the drug should be discontinued and the patient should be apprised of the potential risk to the fetus. Exposure to danazol in utero may result in androgenic effects on the female fetus; reports of clitoral hypertrophy, labial fusion, urogenital sinus defect, vaginal atresia, and ambiguous genitalia have been received. (See PRECAUTIONS: Pregnancy, Teratogenic Effects.)
Thromboembolism, thrombotic and thrombophlebitic events including sagittal sinus thrombosis and life-threatening or fatal strokes have been reported.
Experience with long-term therapy with danazol is limited. Peliosis hepatis and benign hepatic adenoma have been observed with long-term use. Peliosis hepatis and hepatic adenoma may be silent until complicated by acute, potentially life-threatening intraabdominal hemorrhage. The physician therefore should be alert to this possibility. Attempts should be made to determine the lowest dose that will provide adequate protection. If the drug was begun at a time of exacerbation of hereditary angioneurotic edema due to trauma, stress or other cause, periodic attempts to decrease or withdraw therapy should be considered.
Danazol has been associated with several cases of benign intracranial hypertension also known as pseudotumor cerebri. Early signs and symptoms of benign intracranial hypertension include papilledema, headache, nausea and vomiting, and visual disturbances. Patients with these symptoms should be screened for papilledema and, if present, the patients should be advised to discontinue danazol immediately and be referred to a neurologist for further diagnosis and care.
A temporary alteration of lipoproteins in the form of decreased high density lipoproteins and possibly increased low density lipoproteins has been reported during danazol therapy. These alterations may be marked, and prescribers should consider the potential impact on the risk of atherosclerosis and coronary artery disease in accordance with the potential benefit of the therapy to the patient.
Before initiating therapy of fibrocystic breast disease with Ladogal, carcinoma of the breast should be excluded. However, nodularity, pain, tenderness due to fibrocystic breast disease may prevent recognition of underlying carcinoma before treatment is begun. Therefore, if any nodule persists or enlarges during treatment, carcinoma should be considered and ruled out.
Patients should be watched closely for signs of androgenic effects some of which may not be reversible even when drug administration is stopped.
Because Ladogal may cause some degree of fluid retention, conditions that might be influenced by this factor, such as epilepsy, migraine, or cardiac or renal dysfunction, polycythemia and hypertension require careful observation. Use with caution in patients with diabetes mellitus.
Since hepatic dysfunction manifested by modest increases in serum transaminases levels has been reported in patients treated with Ladogal, periodic liver function tests should be performed (see WARNINGS and ADVERSE REACTIONS).
Administration of danazol has been reported to cause exacerbation of the manifestations of acute intermittent porphyria. (See CONTRAINDICATIONS.)
Laboratory monitoring of the hematologic state should be considered.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Current data are insufficient to assess the carcinogenicity of danazol.
Pregnancy, Teratogenic Effects
(See CONTRAINDICATIONS.) Pregnancy Category X. Ladogal administered orally to pregnant rats from the 6th through the 15th day of gestation at doses up to 250 mg/kg/day (7-15 times the human dose) did not result in drug-induced embryotoxicity or teratogenicity, nor difference in litter size, viability or weight of offspring compared to controls. In rabbits, the administration of Ladogal on days 6-18 of gestation at doses of 60 mg/kg/day and above (2-4 times the human dose) resulted in inhibition of fetal development.
Nursing Mothers
(See CONTRAINDICATIONS.)
Safety and effectiveness in pediatric patients have not been established.
Clinical studies of Ladogal did not include sufficient numbers of subjects aged 65 and over to determine the safety and effectiveness of Ladogal in elderly patients.
The information provided in Effects on ability to drive and use machines of Ladogal is based on data of another medicine with exactly the same composition as the Ladogal. . Be careful and be sure to specify the information on the section Effects on ability to drive and use machines in the instructions to the drug Ladogal directly from the package or from the pharmacist at the pharmacy.
Ladogal has no or negligible influence on the ability to drive and use machines.
The information provided in Undesirable effects of Ladogal is based on data of another medicine with exactly the same composition as the Ladogal. . Be careful and be sure to specify the information on the section Undesirable effects in the instructions to the drug Ladogal directly from the package or from the pharmacist at the pharmacy.
Blood and lymphatic system disorders
Increase in red cell and platelet count. Reversible polycythaemia, leucopoenia, thrombocytopenia, eosinophilia and splenic peliosis.
Androgenic effects:
Acne, weight gain, increased appetite, seborrhoea, hirsutism, hair loss, voice change, which may take the form of hoarseness, sore throat or of instability or deepening of pitch. Hypertrophy of the clitoris, fluid retention.
Other endocrine effects:
Menstrual disturbances in the form of spotting, alteration of the timing of the cycle and amenorrhoea. Flushing, vaginal dryness, changes in libido, vaginal irritation and reduction in breast size.
Modest reduction in spermatogenesis.
Increased insulin resistance, increase in plasma glucagon, mild impairment of glucose tolerance.
Increase in LDL cholesterol, decrease in HDL cholesterol, affecting all subfractions, and decrease in apolipoproteins AI and AII.
Induction of aminolevulinic acid (ALA) synthetase, and reduction in thyroid binding globulin, T4, with increased uptake of T3 but without disturbance of thyroid stimulating hormone or free levothyroxine index.
Emotional lability, anxiety, depressed mood and nervousness.
Dizziness, headache, vertigo, benign intracranial hypertension, migraine.
Aggravation of epilepsy, carpal tunnel syndrome.
Visual disturbances such as blurring of vision, difficulty in focusing, difficulty in wearing contact lenses and refraction disorders requiring correction.
Respiratory, thoracic and mediastinal disorders
Pleuritic pain, interstitial pneumonitis.
Nausea, epigastric pain.
Hypertension, palpitations and tachycardia.
Thrombotic events including sagittal sinus, cerebrovascular thrombosis as well as arterial thrombosis. Myocardial infarction.
Isolated increases in serum transaminase levels, cholestatic jaundice, benign hepatic adenomata and pancreatitis. Peliosis hepatitis as well as malignant hepatic tumour observed with long term use.
Hepatocellular injury, hepatic failure, jaundice hepatocellular, hepatocellular focal nodular hyperplasia.
Rashes, which may be maculopapular, petechial or purpuric and may be accompanied by fever or may take an urticarial form and may be accompanied by facial oedema. Sun-sensitive rash.
Inflammatory erythematosus nodules, changes in skin pigmentation, exfoliative dermatitis and erythema multiforme.
Musculoskeletal and connective tissue disorders
Backache and muscle cramps which can be severe, with elevation of creatine phosphokinase levels. Muscle tremors, fasciculation, limb pain, joint pain and joint swelling.
Renal and urinary disorders
Haematuria with prolonged use in patients with hereditary angioedema.
General disorders and administration site conditions
The following events have been reported in association with the use of Ladogal:
Androgen like effects include weight gain, acne and seborrhea. Mild hirsutism, edema, hair loss, voice change, which may take the form of hoarseness, sore throat or of instability or deepening of pitch, may occur and may persist after cessation of therapy. Hypertrophy of the clitoris is rare.
Other possible endocrine effects are menstrual disturbances including spotting, alteration of the timing of the cycle and amenorrhea. Although cyclical bleeding and ovulation usually return within 60-90 days after discontinuation of therapy with Ladogal, persistent amenorrhea has occasionally been reported.
Flushing, sweating, vaginal dryness and irritation and reduction in breast size, may reflect lowering of estrogen. Nervousness and emotional lability have been reported. In the male a modest reduction in spermatogenesis may be evident during treatment. Abnormalities in semen volume, viscosity, sperm count, and motility may occur in patients receiving long-term therapy.
Hepatic dysfunction, as evidenced by reversible elevated serum enzymes and/or jaundice, has been reported in patients receiving a daily dosage of Ladogal of 400 mg or more. It is recommended that patients receiving Ladogal be monitored for hepatic dysfunction by laboratory tests and clinical observation. Serious hepatic toxicity including cholestatic jaundice, peliosis hepatis, and hepatic adenoma have been reported. (See WARNINGS and PRECAUTIONS.)
Abnormalities in laboratory tests may occur during therapy with Ladogal including CPK, glucose tolerance, glucagon, thyroid binding globulin, sex hormone binding globulin, other plasma proteins, lipids and lipoproteins.
The following reactions have been reported, a causal relationship to the administration of Ladogal has neither been confirmed nor refuted; allergic: urticaria, pruritus and rarely, nasal congestion; CNS effects: headache, nervousness and emotional lability, dizziness and fainting, depression, fatigue, sleep disorders, tremor, paresthesias, weakness, visual disturbances, and rarely, benign intracranial hypertension, anxiety, changes in appetite, chills, and rarely convulsions, Guillain-Barre syndrome; gastrointestinal: gastroenteritis, nausea, vomiting, constipation, and rarely, pancreatitis and splenic peliosis; musculoskeletal: muscle cramps or spasms, or pains, joint pain, joint lockup, joint swelling, pain in back, neck, or extremities, and rarely, carpal tunnel syndrome which may be secondary to fluid retention; genitourinary: hematuria, prolonged posttherapy amenorrhea; hematologic: an increase in red cell and platelet count. Reversible erythrocytosis, leukocytosis or polycythemia may be provoked. Eosinophilia, leukopenia and thrombocytopenia have also been noted. Skin: rashes (maculopapular, vesicular, papular, purpuric, petechial), and rarely, sun sensitivity, Stevens-Johnson syndrome and erythema multiforme; other: increased insulin requirements in diabetic patients, change in libido, myocardial infarction, palpitation, tachycardia, elevation in blood pressure, interstitial pneumonitis, and rarely, cataracts, bleeding gums, fever, pelvic pain, nipple discharge. Malignant liver tumors have been reported in rare instances, after long-term use.
The information provided in Overdose of Ladogal is based on data of another medicine with exactly the same composition as the Ladogal. . Be careful and be sure to specify the information on the section Overdose in the instructions to the drug Ladogal directly from the package or from the pharmacist at the pharmacy.
Available evidence suggests that acute overdosage would be unlikely to give rise to immediate serious reaction.
In the case of acute overdose consideration should be given to reducing the absorption of the drug with activated charcoal and the patient should be kept under observation in case of any delayed reactions.
The information provided in Pharmacodynamic properties of Ladogal is based on data of another medicine with exactly the same composition as the Ladogal. . Be careful and be sure to specify the information on the section Pharmacodynamic properties in the instructions to the drug Ladogal directly from the package or from the pharmacist at the pharmacy.
Pharmacotherapeutic group: sex hormones and modulators of the genital system, antigonadotropins and similar agents, ATC code: G03XA01
Danazol, 17a-pregna-2,4-dien-20-yno(2,3-d)-isoxazol-17-ol, is a synthetic steroid derived from ethisterone. Its pharmacological properties include:
1. Relatively marked affinity for androgen receptors, less marked affinity for progesterone receptors and least affinity for oestrogen receptors. Danazol is a weak androgen but in addition antiandrogenic, progestogenic, antiprogestogenic, oestrogenic and antioestrogenic actions have been observed.
2. Interference with the synthesis of gonadal steroids, possibly by inhibition of the enzymes of steroidogenesis, including 3β hydroxysteroid dehydrogenase,17β hydroxysteroid dehydrogenase, 17 hydroxylase, 17, 20 lyase, 11β hydroxylase, 21 hydroxylase and cholesterol side chain cleavage enzymes, or alternatively by inhibition of the cyclic AMP accumulation usually induced by gonadotrophic hormones in granulosa and luteal cells.
3. Inhibition of the mid-cycle surge of FSH and LH as well as alterations in the pulsatility of LH. Danazol can also reduce the mean plasma levels of these gonadotrophins after the menopause.
4. A wide range of actions on plasma proteins, including increasing prothrombin, plasminogen, antithrombin III, alpha-2 macroglobulin, C1 esterase inhibitor, and erythropoietin and reducing fibrinogen, thyroid binding and sex hormone binding globulins. Danazol increases the proportion and concentration of testosterone carried unbound in plasma.
5 The suppressive effects of danazol on the hypothalmic-pituitary-gonadal axis are reversible, cyclical activity reappearing normally within 60-90 days after therapy.
The information provided in Pharmacokinetic properties of Ladogal is based on data of another medicine with exactly the same composition as the Ladogal. . Be careful and be sure to specify the information on the section Pharmacokinetic properties in the instructions to the drug Ladogal directly from the package or from the pharmacist at the pharmacy.
Danazol is absorbed from the gastrointestinal tract, peak plasma concentrations of 50-80ng/ml being reached approximately 2-3 hours after dosing. Compared to the fasting state, the bioavailability has been shown to increase 3 fold when the drug is taken with a meal with a high fat content. It is thought that food stimulates bile flow which facilitates the dissolution and absorption of danazol, a highly lipophilic compound.
The apparent plasma elimination half life of danazol in a single dose is approximately 3-6 hours. With multiple doses this may increase to approximately 26 hours.
None of the metabolites of danazol, which have been isolated, exhibits pituitary inhibiting activity comparable to that of danazol.
Few data on excretion routes and rates exist. In the monkey 36% of a radioactive dose was recoverable in the urine and 48% in the faeces within 96 hours.
The information provided in Pharmacotherapeutic group of Ladogal is based on data of another medicine with exactly the same composition as the Ladogal. . Be careful and be sure to specify the information on the section Pharmacotherapeutic group in the instructions to the drug Ladogal directly from the package or from the pharmacist at the pharmacy.
sex hormones and modulators of the genital system, antigonadotropins and similar agents, ATC code: G03XA01
The information provided in Preclinical safety data of Ladogal is based on data of another medicine with exactly the same composition as the Ladogal. . Be careful and be sure to specify the information on the section Preclinical safety data in the instructions to the drug Ladogal directly from the package or from the pharmacist at the pharmacy.
There are no preclinical data of relevance to the prescriber, which are additional to those already included in other sections of the SmPC.
The information provided in Incompatibilities of Ladogal is based on data of another medicine with exactly the same composition as the Ladogal. . Be careful and be sure to specify the information on the section Incompatibilities in the instructions to the drug Ladogal directly from the package or from the pharmacist at the pharmacy.
The information provided in Special precautions for disposal and other handling of Ladogal is based on data of another medicine with exactly the same composition as the Ladogal. . Be careful and be sure to specify the information on the section Special precautions for disposal and other handling in the instructions to the drug Ladogal directly from the package or from the pharmacist at the pharmacy.
Ladogal price
The approximate cost of Danazol 100 mg per unit in online pharmacies is from 0.85$ to 1.5$, per package is from 83$ to 865$.
The approximate cost of Danazol 50 mg per unit in online pharmacies is from 0.65$ to 1.13$, per package is from 56$ to 113$.
The approximate cost of Danazol 200 mg per unit in online pharmacies is from 1.07$ to 1.64$, per package is from 90$ to 614$.
https://www.drugs.com/search.php?searchterm=ladogal
https://pubmed.ncbi.nlm.nih.gov/?term=ladogal


text:
Астри́льд масковий (Estrilda nigriloris) — вид горобцеподібних птахів родини астрильдових (Estrildidae). Ендемік Демократичної Республіки Конго. Масковий астрильд раніше вважався підвидом смугастого астрильда, однак був визнаний окремим видом.

Опис
Маскові астрильди досягають довжини 11 см. Вони є дуже схожими на смугастих астрильдів, однак вирізняються чорною, а не червоною "маскою" на обличчі, а також коротшим дзьобом.

Поширення і екологія
Маскові астрильди мешкають в басейні річки  та в районі озера  на півдні ДР Конго, зокрема в Національному парку . Вони живуть на високотравних луках та в чагарникових заростях, зустрічаються зграями. Вид не спостерігався з 1950 року.

Примітки

Джерела
 Jürgen Nicolai (Hrsg.), Joachim Steinbacher (Hrsg.), Renate van den Elzen, Gerhard Hofmann: Prachtfinken – Afrika. Serie Handbuch der Vogelpflege, Eugen Ulmer Verlag, Stuttgart 2007, ISBN 978-3-8001-4964-3.
 Peter Clement, Alan Harris, John Davis: Finches and Sparrows. An Identification Guide. Christopher Helm, London 1993, ISBN 0-7136-8017-2.

Астрильдові
Птахи, описані 1928
Птахи Демократичної Республіки Конго
Ендемічна фауна Демократичної Республіки Конго

redpajama_set_name: RedPajamaWikipedia


Carers do have a need for self-care, but striking a balance is key. The term 'lunch is for wimps' is synonymous with taking a break being seen as a form of weakness, an assumption that no rest means being more productive. That may be so for the very few, but not for all, and it does not guarantee that quantity of work achieved equates to quality of life. We all strive to do our best while contributing a great deal to society as well as to the community. In doing so, we can easily lose sight of our own wellbeing.
The Joint Health and Wellbeing Strategy 2013-2018 gives added concern that "Croydon is in the bottom 10% of areas for satisfaction with the ability to see a GP quickly". This gives more incentive than ever to improve social, mental and physical health; this can be achieved in a variety of ways. Some of the steps to improve your health provided by the consultation for carers can be adapted, improvised and applied to all.
They include making sure that your GP practitioner and other professionals are up to date with your general health checks, especially if you are a carer, plus ensuring that you have respite breaks. As well as physical activity, it is also good to slow down and have a rest. Make time for yourself – for at least 10-30 minutes every day. Keep your mind active and learn new things. This includes trying new activities and hobbies, or even reacquainting yourself with what you used to enjoy doing in the past. Join groups that have interests similar to yours. Meet up with friends and family, or they could come and see you. Chats on the phone can curb isolation; get out there and speak to your neighbours.
My journey towards self-care has not been an easy road and is ongoing still, but it has led me to meet a variety of people who are not only generous with their time and knowledge, but who are also very good at what they do, with the added bonus of being great listeners. It has encouraged me to resume my art after a long hiatus. Volunteering has brought me here to the Croydon Citizen and to the Click Clock Gallery.
The Click Clock Gallery, based in the Clocktower Café, has been displaying a variety of artwork of all mediums for all ages for some time now, which makes what was once a blank canvas (the walls) an exciting feature. The 'Photo of the Month' competition, which started last May, is proving to be very popular. Other artistic outlets such as the Studio Upstairs, RISE, Turf Projects and the Elizabeth James Gallery further add to a growing creative scene in the borough, which I am happy to be a part of.
In a world that relies so heavily on technology, it's no easy decision to switch off – but we are not machines, and must remember not to treat ourselves as if we were. Simply taking care of yourself, while creating an environment of self-care, makes a massive difference.


S25-10HA-313K, Aluminum Sprocket, 10 tooth - AndyMark Inc.
S25-10HA-313K, 7075 Aluminum Sprocket, 25 Series, 10 tooth, 313 Key Bore Fits the 8mm shaft of a 2.5 in. CIM Motor, with a 2mm keyway.
Overall Hub And Sprocket Width: 0.50"
I ordered this with a 2nd option for the application that we needed it for. We ended up using the other one, but if this is anything like the one we ended up using, I am sure it is great. It's nice to have it around for possible use in future years.


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redpajama_set_name: RedPajamaGithub


"Cries and Echoes" is an ambitious collection of four substantial works for solo instruments and electronics, composed by Priscilla McLean and performed by several accomplished musicians. The works are all accompanied by her original video collages. Her compositions eschew traditional harmony and rhythmic relationships, in favor of creating a sequence of textures and moods. Electronics and taped sounds are used to extend and modify the music, so it has a much richer, more multilayered texture than a normal instrumental solo.
The haunting "Desert Voices" uses the electronically altered sounds of the Midi Violin to create aural landscapes. The composition has an open ended structure in which layered motifs come and go at regular intervals, in the same way that the sounds of birds, wind, and water recur in a natural landscape. Clusters of high notes are layered over sounds that resemble Tibetan throat singing, and a poignant repeated melody suggests a bird cry. At one point, a complex melody is built up entirely from the harmonics of a single note. These sounds are mixed with a collage of desert wildlife sounds, wind, an Australian didgeridoo, and whispered poems in Navajo. The rhythmically free, graphic notation employed by McLean allows some personal interpretation from the player, and Jonathan Aceto dramatically realizes the sense of stark, elemental drama of a desert landscape.
The images accompanying the music are slides of the desert: bizarre rock formations, gorgeous cacti and agaves, and dramatically lit banks of clouds. The images slowly cross fade, in a sequence which makes intelligent use of similar shapes and colors. These beautiful images make a perfect accompaniment for the music. The non-developmental, cyclical nature of the music might cause one to get lost if one listened to it on its own, but combined with the images, it creates a powerful sense of the haunting spirituality of a desert.
Xakaalawe (Flowing) is another landscape piece, also quite beautiful. Charlie Tokarz plays a variety of woodwinds, augmented by McLean on voice and electronics. Long, sustained chords create a sense of spaciousness and expectation. On top, we hear textures of sparkling, discordant tones and lonely outcries. We hear a lot of flowing water. The use of whispering and the open, textural feeling will remind some listeners of George Crumb, but more with a more lush feeling. Woodwind ostinatos contribute to the overall feeling of a never-ending flow.
The images are a collage of scenes from the Rocky Mountains, showing waterfalls, pools, and grazing elk. The images are layered on top of one another in a very awkward, technically unsophisticated video montage. Despite this, the images themselves are so beautiful, and so completely at one with the mood and structure of the music, that they create an awe-inspiring sense of the power of a particular landscape.
The 'cello solo "Cries and Echoes," ably realized by Ronald Feldman, spends a lot of time in a mood of anxiety, with long, sliding notes layered on top of edgy tremolos of indeterminate pitch. There are also spooky arpeggios of discordant plucked notes. Occasional bowed passages create a lyrical mood of plangent longing, quoting obliquely from a Bach suite. The accompanying images are an awkwardly composed montage of Feldman playing the 'cello, and travelling shots of the trunk of a tree. These images did not particularly enhance the music.
"Caverns of Darkness, Rings of Light" for solo tuba, expertly played by James Gourlay, was less to my personal taste. To my ear, it sounded as if McLean's primary intention here is to explore the different kinds of sounds which a tuba is capable of making, both through "extended playing" techniques, and through electronic manipulation of sounds. I am one of those listeners who prefers music to have some kind of expressive element to it: some way in which the music seems to refer to feelings, movement, images, or some other type of human experience. Certainly the sounds in this piece are interesting, and the fact that a tubist is able to produce them is also interesting. As a listener, however, I need more than interesting sounds. I want the music to make me feel something.
The images in the video are all of the tuba itself, in an awkward and primitive style of video collage. While these images reinforce the idea that the point of the piece is to explore the tuba itself, I didn't find that they added appreciably to my experience of the sound.
Priscilla McLean is a skilled, original composer with considerable musical gifts. As a filmmaker, however, she is clearly just beginning to find her voice. If McLean could learn to manipulate and juxtapose images with the same precision and expressiveness with which she amasses layers of sonic textures, she could create audio/visual works of great force.
I enjoyed your review (sort-of), but must correct the many misspellings of my name. It is PRISCILLA McLEAN, not Priscilla MClean or Patricia MClean. But thanks for your honest comments!
I've gone through and corrected the spellings for you.


Fiction Southeast – Interview with Sherrie Flick, author of Whiskey, etc.
Sherrie Flick's new colle ction Whiskey, Etc.—flash, micros, short-shorts—has been getting rave reviews. Kim Chinquee calls her writing "deliciously intoxicating." Flick's flash chapbook I Call This Flirting is legendary. She is also a novelist (Reconsidering Happiness) and has written food essays for the Wall Street Journal, Pittsburgh Post-Gazette and Ploughshares. What we wanted to know is—how does she write such great stories?
Question #1: What's the best response to your book so far?
It's too long since our paths crossed but I did want to write and tell you how much I liked and admired the stories in Whiskey, Etc. You are a mistress of voice – Sweet Thang! – and detail – the Microwave. And I love how much you can do in a small space – like Dinner Party or the Paper Boy which has one of the great opening sentences. … You have a wonderful ability to entertain the reader and indeed even to make fun of the characters without ever deriding their hopes and desires. Your sentences sing.
I also received a fantastic congratulatory bottle of Rowan's Creek Kentucky Bourbon from my friend and former student Kyle Wolf. She drove it from Kentucky to my book release party.
Did you start out writing flash fiction? Obviously you're a talented writer in several genres.
When I was an undergraduate I had never heard the term "flash fiction" because I don't think it had been "named" yet. I do remember one fine day at a local bookstore when I spotted that green-covered anthology edited by Tom Hazuka and James Thomas called Flash Fiction and yearned like anything to be one of the people in there.
But I'm getting ahead of myself. I started off as a poet. In fact, I went to the University of New Hampshire to study with Charles Simic. In retrospect, this all makes sense. Charles Simic is the perfect prose poemy poet for someone like me to work with. But line breaks baffled me. I felt I couldn't be a poet because I didn't understand line breaks. When you're 18, 19 years old this is how you make decisions sometimes, you know?
So, I took some fiction workshops and diligently wrote the 15-20 page stories that my professors liked. Then one day my friend Guy gave me a book by Raymond Carver. Then I discovered Gordon Lish's The Quarterly. And thus discovered Diane Williams and so many other great flash writers. Then I started writing these short compressed stories and I felt a kind of coming home. My first published piece of writing was a flash fiction called "It's Bob, Let's Say, or John" published in Quarterly West in fall, 1990. I'd found my people and my place.
I think Margot Livesey is right on about your writing. "You are a mistress of voice"—I love that. Ta-Nehisi Coates said in The Atlantic blog (June 11, 2013) that voice is the most important thing in fiction because "if you like the person telling you the story—which is to say the voice, not the author—you generally will let them tell you a story." Is voice something that comes naturally to you, or is it a lyric impulse, or long practice in writing, or is it tempered from staying close and personal with the characters, their feelings, what they notice in the moment? The language in the narration always seems right for them. I never get the sense you are writing for the language itself.
I think I've always had a knack for getting inside a voice–or maybe I should say for getting inside voices that can tell stories in an intimate way. I always loved the blurb that John McNally wrote for I Call This Flirting, which reads in part: "These are late-night stories, told after midnight, a femme fatale whispering sad and unraveled and lusty tales into your ear." I love the idea that every character you ever write has a secret they're whispering to you. Sometimes those secrets are revealed to the reader. Other times they are just what drives me forward to create.
I think my initial interest in poetry informs the lyrical, rhythmic quality of my prose. I can hear a kind of meter as I write–or I strive toward it might be a better way of saying it? As I draft I do so much reading aloud. So, some of the voice is instinctual and some comes from practice and revision.
The way I look at it, all the craft elements are connected. I've been really interested in setting the past few years and how character and voice can rise from setting. Many of the stories in Whiskey, Etc. were drafted with this in mind. So I'm really happy that you noticed that about the figurative language. It's a package deal when the stories are working–character works with voice, which works with setting, which adds to point of view, etc. I would like for it all to be seamless, of course.
I want to borrow one other phrase from Livesey's note, that "You have a wonderful ability to … make fun of the characters without ever deriding their hopes and desires." How do you come by this ability? Or do you have to like characters that you write about? Or do you ever get inspired by characters even if they're hatable? Or do you just let the situation guide you? I love your characters. Some are cheaters, irresponsible, selfish, manipulative … yet my feeling is just, bring them on.
This question is a tough one. I guess first, I don't feel like I make fun of my characters. I do inhabit them while I'm writing. When I was a student in workshops people said they didn't like some of my characters, especially women who behaved badly. That comment always bothered me because I feel like the interior life of anyone is worth examining. I guess mining that territory when it's a selfish or irresponsible person can be uncomfortable to readers. I don't have pity for my characters, even when they can't redeem themselves. I sort of feel like we're all unredeemable on some level. At any rate, I don't have a desire to make excuses for them. I've never thought about my characters in this exact way so I'm working through it as I'm typing this answer. I should note that sometimes my characters are based on people I've known, sometimes they arise from the scene I'm setting, but usually they're a hybrid of me, you, and everyone else I've ever met.
That's interesting, that characters arise from the scene you're setting. Is that sometimes how stories start for you? Stuart Dybek says he generates a story by looking through his journal for some memory or image or other jotting (Richard Brautigan called such things in his journal "lint") and picks one that has an emotional charge for him. Based on that piece of "lint" he starts a scene or narrative description, then a second character comes in with dialogue and the story takes off, it's in gear. Maybe anything could serve as a prompt, whether it's "lint," or just a group of random words, or maybe a song (like your great story "Sweet Thang"—was that from that oldie Chaka Kahn song "Sweet Thing"?). I see I've made this a double question—first, where do you get your story idea, then what do you typically do to develop it?
It was a fascinating exercise, though failure is built into it. We always seem to turn to judgment, but how long can we hold it off? At any rate, from this came many stories. Setting first, then characters and tension rising up. I'm still trying to process and think about this.
But it's not my only method. I'm often inspired by an object or a snippet of dialogue I've heard. I just need a little nudge to get going on a story. Once I have something down, which I've written pretty organically and pretty quickly, then I begin to shape it on a sentence level–refining characterization and setting as I go. I find that for me tension and plot arise next. I follow after. I revise forever.
During another little stint of daily exercises I tried to incorporate whatever song was playing on the radio when I started to write. This is way harder than it sounds. But another story in Whiskey, Etc., "Relationship," came this way, so I guess it was worth it.
At the time of this interview you are teaching a 10-day summer MFA fiction workshop at Chatham University. Your course description has a sentence that intrigues me: "The plan is to think inside and outside the fiction box in every way possible." Could you just give us some specifics on what you mean by that?
Yes, we're having the session out at the school's Eden Hall Farm campus, which is about 50 minutes north of Pittsburgh. It's beautiful. There's even a white stag on the grounds. Magical.
I'm focusing on short stories in my workshop and also on generative exercises. I'm really open to what students want to define as a story. We have a range of work from fantasy to flash to standard realism to magic realism. Yesterday, we took one student's story and acted it out while she read it aloud slowly, like stage directions. This helps with continuity issues (the actors can only do/say what's on the page), helps show simultaneous action (or lack thereof), and helps to confirm that the dialogue contains action and internal thoughts. Everyone was laughing but we were also critiquing as we went.
This workshop has a lot of moving parts and the students leave it with many, many starts and drafts of stories. I figure they can do the hard work of finishing after we're out of this intensive. For example, I might give students the first and last lines of a story and they have ten minutes to connect them, or give the students two objects that they have to include in a scene. Then I might throw a bag of short story collections onto the table, and we spend an hour just looking at and reading aloud first sentences. I want them to understand the importance of the reader's first encounter with the story. I also think if you really learn how setting can work for you, then you can learn character and plot. It's the same with an object–if you can get an object to represent a person, then you have enhanced characterization and all of this leads to effective compression, which is my favorite part of writing. Taking the big, huge world and bringing it down to a thimble.
It's good to see how you generate stories. How did you put together Whiskey Etc? It's such a rich, full book. So was I Call This Flirting, a dozen years ago, when a flash fiction chapbook was a rarity. There are more opportunities now—would you tell up and coming writers to go for chapbooks, then gather them to make a larger book? Maybe it's best just to write and not worry about a book, but if they want a plan, would it help to work with themes, or maybe a recurring cast of characters? There seems to be interest in flash fiction novellas now.
Yes, I think there's a lot of interesting hybrid work happening right now and it seems to me that flash lends itself to the novella or short novel form. I love Christine Schutt's Florida, for instance. I have a roving interest in writing something in that direction.
Ordering and putting together my chapbook taught me a lot about how to order a collection. It was my training ground. With Whiskey, Etc. I first thought of using overlapping characters, that is, to link some stories across sections with the same people, but that definitely didn't work. Then I tried the reverse, to not overlap character names at all, which is how it stands now. But, of course, changing the name can change the character, which changes the story, and so more revision was called for. I don't recommend working this way. But I did want to break it into sections, somehow, because I feel that flash reads better when there are some resting points built in. To do this I scrolled through the stories and started highlighting common themes, ideas, and objects, and then I sorted them by those themes. I tried for a good balance of obvious with subtle, and a rhythm between stories within each section. This might sound like it took a long time. And it did! I spent a great deal of time reading the full manuscript aloud to my dog. I wrote some new stories to fill in some sections that just seemed too short to work on their own.
How has very short fiction changed, as a "genre," since you started? Where do you see it going? You're still a young writer yet you've been part of it, almost since Flash Fiction came out, as writer, as teacher, as impresario of a flash reading series. It goes by so many names now—flash, nano, micro—is it getting shorter? Have approaches or attitudes changed? Has your own writing changed? You write other kinds of prose now—is there any conflict with your continuing to write very short stories as well?
One of the main changes I've seen with flash fiction is that academia has accepted it. Because of that I have to think that's it's trickling its way into the canon or into a broader definition of what fiction can be. Back in the late 80s when I first started writing flash, my fiction professors were very unhappy with me. Some refused to workshop my tiny stories and others just talked expansion and narrative arcs and plot. I see both professors and students now who are open to experimentation and to taking on critiques of stories in a more complex way.
On my own writing, my early pieces of flash were focused more on atmosphere and relaying an emotion and on one tiny slice of life than on, say, character development. In Whiskey, Etc., the super tiny "This Was It" is the only story from that time period that has made it this far. As I've practiced compression and experimented and written a ton of flash stories I've learned to relay the world more effectively and with more complication. I would say more recent stories like "Canoe" or "Sweet Thang" or "Forever" have much more character development and setting, and go beyond one moment to explore larger and deeper parts of the characters' lives.
I don't see a conflict with flash and the other genres/forms I work in. I can put on my journalism hat or essay hat or novel hat and feel that my experience writing flash helps me in all those arenas. If I turn in a 1300 word article for a magazine, maybe something about gardening, and the editor says that they've lost some space and could I bring it down to 900 words? I say: no problem. I love to cut. Compression came in handy with my novel when I wanted to relay a change in geography quickly so I could get into the action of my characters. Everyone can benefit from trying to write flash, to relay our complex world in approximately 700 words. It's an effective and rewarding challenge.
Robert Shapard's fiction and essays have appeared in New England Review, Kenyon Review, The Literary Review, World Literature Today, New World Writing, Juked, World Riot, and Hobart, and have won National Endowment for the Arts, the Council of Literary Magazine and Presses and Fiction Network Awards. He edits the flash fiction book series for W.W. Norton, the latest of which is Flash Fiction International (2015).
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Once inside Hospice I walked to Dad's room, his door ajar, and saw him no longer tubed up and Mom atop him, fancy, in one of her party dresses with a Jackie O pillbox hat and two-inch heels, whispering in his ear as she moved back and forth in a rocking motion; her eyes closed, her hands caressing his face. I watched him draw his last breath just as she stopped moving. She rolled off, lying still next to his stillness with her arm across his chest, bodies touching as one, a single tear rolling down his cheek onto hers.


text:
Mirco Miori (born 28 August 1995) is an Italian football player who currently plays for ASD Adrense.

Career

Club career
He made his Serie C debut for Südtirol on 7 March 2015 in a game against Real Vicenza.

In February 2020, Miori joined Swiss club FC Emmenbrücke.

References

External links

1995 births
People from Romano di Lombardia
Living people
Italian footballers
Italian expatriate footballers
F.C. Südtirol players
Piacenza Calcio 1919 players
Alma Juventus Fano 1906 players
U.S. Triestina Calcio 1918 players
Serie C players
Serie D players
Association football goalkeepers
Italian expatriate sportspeople in Switzerland
Expatriate footballers in Switzerland
Sportspeople from the Province of Bergamo
Footballers from Lombardy