Regulation of G proteins by chronic antidepressant drug treatment in rat brain: tricyclics but not clorgyline increase Go alpha subunits.

The effect of long-term (3-week) administration of various antidepressant drugs on the steady-state concentrations of G protein alpha subunits, Gs alpha, Gi alpha, and Go alpha, has been investigated in rat brain using an enzyme-linked immunosorbent assay. Tricyclic antidepressants and clorgyline decreased Gs alpha and, to a lesser extent, Gi alpha in several brain regions, while Go alpha was increased by tricyclics but not clorgyline. We conclude that long-term treatment with antidepressant drugs exerts differential effects on G protein alpha subunits, and that antidepressant efficacy may potentially be based on functional modifications of signal transduction.     

Non-immune therapy of IgA glomerulonephritis

Summary: The involvement of the IgA immune system and complement components in IgA glomerulonephritis (IgAGN) has prompted the use of immunosuppressive drugs in therapy, but none has so far been shown to alter the natural course of the disease. Because most patients with IgAGN present during the chronic phase of their illness, at the time when the initiating immune events may no longer be active, nonimmune therapy which targets the common pathway of progressive renal injury is likely to be more useful. There is increasing evidence that angiotensin-converting enzyme inhibitors (ACEI) reduce proteinuria and renal injury in patients with IgAGN, and this effect may be observed in both normotensive and hypertensive patients. Yet to be determined is whether this effect is specific for ACEI and whatever other effective antihypertensive drugs may achieve a similar result. Fish oil has recently been shown to retard the progression of renal failure in patients with aggressive IgAGN, but a narrow therapeutic window appears to exist for this form of treatment. Antiplatelet agents on their own appear to be ineffective but in combination with anticoagulation (low dose warfarin) have been shown to have an antiproteinuric effect and may preserve renal function in patients with progressive disease. Future directions of non-immune therapy of IgAGN include evaluation of the renoprotective effect of angiotensin II receptor antagonists, free-radical scavengers and antilipid drugs. More work should also be done to identify factors which put the patients at risk of developing progressive disease and which predict therapeutic response, as has been done recently with the identification of the deletion polymorphism of the angiotensin-converting enzyme gene as a marker of progressive disease and therapeutic response to ACEI in patients with IgAGN.     

Myosin VIIA gene: heterogeneity of the mutations responsible for Usher syndrome type IB

Usher syndrome is recognized as the most frequent cause of hereditary deaf-blindness. Usher syndrome type I (USH1), the most severe form of the disease, is characterized by profound congenital sensorineural deafness, constant vestibular dysfunction, and retinitis pigmentosa of prepubertal onset. This form is genetically heterogeneous and five loci (USH1A-E) have been mapped thusfar. However, only the gene responsible for USH1 B (which accounts for approximately 75% of USH1 cases) has been characterized. It encodes a long-tailed unconventional myosin, myosin VIIA, with a predicted 2215 amino acid sequence. Primers covering the complete myosin VIIA coding sequence as well as the 3' non coding sequence were designed, allowing direct sequence analysis of each of the 48 coding exons and flanking splice sites in seven patients affected by USH1. Four novel mutations were thereby identified. The possibility should now be considered of a sequence-based prenatal diagnosis in some of the families affected by this very severe form of Usher syndrome.      

Gamma-hydroxybutyric acid in the treatment of alcohol withdrawal syndrome in patients admitted to hospital

Gamma-hydroxybutyric acid is a gamma-aminobutyric acid analogue which can be found in the human brain and is believed to be a neurotransmitter in the central nervous system. In animal experiments as well as in humans gamma-hydroxybutyric acid has been shown to alleviate the symptoms of the alcohol withdrawal syndrome. 299 patients, who were admitted to hospital for reasons primarily unrelated to their alcohol dependence, were treated with gamma-hydroxybutyric acid when symptoms of the alcohol withdrawal syndrome occurred. Gamma-hydroxybutyric acid was usually given at a daily dose of 50 mg/kg in 3 divided doses, the clinical course of the patients was followed for 7 days or until discharge from hospital. Patients were 214 men and 82 women aged 18-87 years. The reasons for admission to hospital were frequently internal diseases, neurological/psychiatric problems, trauma or surgery. At the start of gamma-hydroxybutyric acid treatment, tremor was present in 81% of patients, sweating in 76% and unrest in 92%. Symptoms occurred 1-72 hours after admission. The efficacy of gamma-hydroxybutyric acid to ameliorate or suppress the symptoms of the alcohol withdrawal syndrome was judged to be excellent in 57%, good in 34%, fair in 18%, insufficient in 3% of patients. Drug tolerance was judged to be excellent in 79%, good in 17%, fair in 2% and poor only in 1% of patients. Adverse events were rare and mild. It is concluded that gamma-hydroxybutyric acid is an attractive alternative to tranquilizers in the management of the alcohol withdrawal syndrome in hospital.