Squalestatin 1, a potent inhibitor of squalene synthase, which lowers serum cholesterol in vivo.

Squalestatin 1 is a member of a novel family of fermentation products isolated from a previously unknown Phoma species (Coelomycetes). Squalestatin 1 is a potent, selective inhibitor of squalene synthase, a key enzyme in cholesterol biosynthesis; in vitro, 50% inhibition of enzyme activity is observed at a concentration of 12 +/- 5 nM (range of 4-22 nM). Squalestatin 1 inhibits cholesterol biosynthesis from [14C]acetate by isolated rat hepatocytes (50% inhibition at 39 nM) and by rat liver in vivo. In marmosets, a species with a lipoprotein profile similar to that of man, squalestatin 1 lowers serum cholesterol by up to 75%. This compound will allow further investigation of the control of the sterol biosynthesis pathway and could also lead to the development of new therapies for elevated serum cholesterol.

Auditory evoked response in patients of diabetes mellitus.

Brainstem auditory evoked response (BAER) and the mid latency response (MLR) were recorded in 25 diabetic men and compared with a group of 25 control subjects. The threshold of hearing was higher (P less than 0.001) in the patients. The BAER peak latencies were also significantly prolonged in both the ears; however, the degree of prolongation was more prominent in the right ear. The interpeak latencies of waves I-III were also prolonged (P less than 0.01) in the left ear, with non significant increase noticed in the right ear also. The wave V amplitude was lower (P less than 0.05) in diabetics. The MLR, on the other hand, was not affected in patients. These findings suggest functional impairment in the auditory pathway in patients of diabetes mellitus.

Hypothalamo-pituitary axis by magnetic resonance imaging in isolated growth hormone deficiency patients born by normal delivery.

Magnetic resonance imaging was performed using a 1.5 Tesla magnet in 22 children (14 boys and 8 girls) between 5-20 yr of age with isolated GH deficiency (IGHD), born by normal vaginal delivery without any birth asphyxia or trauma. A total of 22 children (10 boys and 12 girls) without short stature and endocrine disease were evaluated as controls. The IGHD group had a height velocity less than 4 cm/yr and delayed bone age. The peak GH levels were less than 10 micrograms/L (mean, 2.4 micrograms/L). The height of the pituitary gland ranged from 3-7.5 mm in controls. An intact stalk was observed in 21 children with IGHD, with nonvisualization in 1. An apparently thin stalk was seen in 6. The posterior lobe identified by the hyperintensity signal, had a mean diameter of 1.84 mm and was located in a normal position in 21 children. An ectopic posterior pituitary hyperintensity was present in 1 patient. The anterior pituitary was hypoplastic in 17 children, with partial empty sella in 13. A total of 5 children had associated brain anomalies, such as Arnold Chiari malformation, craniovertebral malformation with basilar impression, degenerative plaques around posterior horn of lateral ventricle and parietal area, and infarcts in caudate nucleus and putamen. These findings suggest that IGHD was not related to transection or compression of the stalk.

MR observations on the effects of praziquantel in neurocysticercosis.

Eight patients with neurocysticercosis treated with praziquantel (PZQ) were studied with serial MR imaging to demonstrate the early effects of the drug in brain lesions. Increase in cyst size and appearance of pericystic edema were observed as early as 24 hr, followed by gradual degeneration of the scolex and cyst contents. Cysts showed varied degree of response to the drug and in their rate of disappearance. MRI was found to be a sensitive technique to objectively document early changes in the parasite and patterns of response to the cysticidal drug in brain cysticercosis.

Effect of vitamin C deficiency and excess on the liver: a histopathological and biochemical study in guinea pigs fed normal or high cholesterol diet.

When guinea pigs were kept on a restricted vitamin C intake of only 0.5 mg daily, their serum ascorbic acid fell to 0.16 +/- 0.06 mg/d1 in 16 weeks as compared to 0.73 +/- 0.11 in control. This was associated with significant increase in liver cholesterol and triglycerides. When they were simultaneously challenged with a high cholesterol load, this fat accumulation was markedly exaggerated. The weight of the liver now increased by almost two-and-half times. Liver cholesterol rose to 12.90 +/- 2.63 mg/gm as compared to 3.23 +/- 0.56 mg/gm with low vitamin C alone. Histopathology showed marked distension and vacuolation of hepatocytes, focal necrosis and fibroplasia. Administration of excess vitamin C (100 mg daily) significantly countered these changes. The vitamin C-lipid relationship has important clinical bearings and liver could be an important site of vitamin C action.