Classification of some GABA antagonists with regard to site of action and potency in slices of rat cuneate nucleus

Compounds reported to be GABA antagonists have been studied quantitatively on dorsal funiculus fibres and terminals in the rat cuneate nucleus in vitro. The potencies of the antagonists against the GABA analogue muscimol were determined as pA₂ values. Distinction was made between three different sites of antagonist action within the GABA receptor and ionophore complex. Competitive antagonists, presumed to act at the GABA receptor, and their pA₂ values were bicuculline (5.98), bicuculline methochloride (5.88), strychnine (5.29) and tubocurarine (4.95). Antagonists which were not competitive and acted predominantly at the ‘picrotoxin site’ on the ionophore were picrotoxin (6.19), picrotoxinin (6.03), isopropylbicyclophosphate (5.82) and leptazol (2.89). A third type of antagonism was shown by frusemide. Attention is drawn to the picrotoxin site and its likely importance in the regulation of GABA-mediated inhibition by drugs.     

Hereditary hyperuricemia and renal disease

Hyperuricemia and gout have long been known to run in families. As well as an apparently multifactorial genetic component to classic gout itself, 2 rather unusual sex-linked single-gene disorders of purine biosynthesis or recycling have been defined: deficiency of the enzyme hypoxanthine-guaninephosphoribosyl transferase (HPRT), and overactivity of PPriboseP synthase. Both result in overproduction of urate, hyperuricemia, and secondary overexcretion that may lead to acute or chronic renal damage. Familial juvenile hyperuricemic nephropathy (FJHN) and autosomal-dominant medullary cystic kidney disease (ADMCKD) are more common but less well-defined hyperuricemic conditions resulting from a decrease in the fractional excretion of filtered urate, with normal urate production. Although having features in common, ADMCKD is distinguished in particular by the presence of medullary cysts. One major group of both disorders is associated with mutations in the gene for uromodulin, but this accounts for only about one third of cases, and genetic heterogeneity is present. Whether the genes involved in these latter disorders contribute to the polygenic hyperuricemia and urate underexcretion of classic gout remains unexplored.     

The effect of a neoprene sleeve on knee joint position sense

The aims of the study were, first, to assess the effect of a neoprene knee brace on prop rioceptive acuity of normal subjects and, second, to assess the relationships between a variety of tests of proprioceptive acuity. Twenty healthy, physically active subjects had absolute error scores measured while carrying out three different established tests of proprioceptive ability (active tracking, active reproduction, and perceived angle tests) under two conditions, either with or without the presence of a neoprene sleeve. The neoprene sleeve significanltly improved the degree of error scores in all tests. For the active tracking, test accuracy was improved by 28% (p = 0.004), the angle reproduction test showed a 23% increase in accuracy (p = 0.029), and the accurancy of the perceived angle test improved by 27% (p = 0.035). The relationship between magnitude of error scores between the test all showed nonsignificant low correlation. The findings of this study support the previous literature, which indicates that the application of a knee sleeve improves proprioceptive acuity. The study also indicates that when testing proprioceptive acuity, a test battery should be used because of the limited correlatiotn between any of the tests used.