used a mouse model to cre-lox knockout the Prkar1a gene specifically from cells of the adrenal cortex and observed that the mice subsequently developed Cushing syndrome that is independent of the pituitary. They also observed that the mutation caused increased PKA activity.The R1α loss caused the adult adrenal gland became hyperactive and hyperplastic on both sides, as seemingly the foetal adrenal cells within it were not maintained and thus expanded. This established tumoral growths. This mouse KO model phenocopies what happens in human cases of PPNAD.Inactivation of PDE11A4, located at 2q31-5, has also been identified in PPNAD patients without PRKAR1α mutations. PDE11A4 is the gene encoding phosphodiesterase 11A4, another participant of the cAMP signalling pathway. Diagnosis
Diagnosis usually occurs upon investigation of a cause for already suspected Cushings syndrome. High levels of cortisol observed in patients with PPNAD are not suppressed upon administration of dexamethasone (dexamethasone suppression test), and upon MRI or CT imaging, the pituitary will show no abnormalities. Measuring ACTH will confirm that the cause of the patients Cushings syndrome is ACTH independent. The nature of Cushings syndrome itself is periodic, which can make diagnosing PPNAD increasingly difficult.Diagnosis of PPNAD can be difficult to determine preoperatively as CT scan findings can be variable i.e. appear normal or suggest unilateral adrenal lesions therefore impeding the correct diagnosis.
Dextran is a complex branched glucan (polysaccharide derived from the condensation of glucose), originally derived from wine. IUPAC defines dextrans as "Branched poly-α-d-glucosides of microbial origin having glycosidic bonds predominantly C-1 → C-6". Dextran chains are of varying lengths (from 3 to 2000 kilodaltons). The polymer main chain consists of α-1,6 glycosidic linkages between glucose monomers, with branches from α-1,3 linkages. This characteristic branching distinguishes a dextran from a dextrin, which is a straight chain glucose polymer tethered by α-1,4 or α-1,6 linkages. Occurrence
Dextran was discovered by Louis Pasteur as a microbial product in wine, but mass production was only possible after the development by Allene Jeanes of a process using bacteria. Dental plaque is rich in dextrans. Dextran is a complicating contaminant in the refining of sugar because it elevates the viscosity of sucrose solutions and fouls plumbing.Dextran is now produced from sucrose by certain lactic acid bacteria of the family lactobacillus. Species include Leuconostoc mesenteroides and Streptococcus mutans. The structure of dextran produced depends not only on the family and species of the bacterium but on the strain. They are separated by fractional precipitation from protein-free extracts using ethanol. Some bacteria coproduce fructans, which can complicate isolation of the dextrans. Uses
Dextran 70 is on the WHO Model List of Essential Medicines, the most important medications needed in a health system.Medicinally it is used as an antithrombotic (antiplatelet), to reduce blood viscosity, and as a volume expander in hypovolaemia. Microsurgery
These agents are used commonly by microsurgeons to decrease vascular thrombosis.