Effects of acute barbiturate administration, tolerance and dependence on brain GABA system: comparison to alcohol and benzodiazepines

Central nervous system depressants, e.g., barbiturates, alcohol and benzodiazepines, have a wide spectrum of activity in humans and animals. Evidence accumulated suggests that some of the pharmacological actions exerted by these agents may be mediated through GABA system by mimicking GABAergic transmission. This review attempts to summarize the evidence available as to how the GABA system plays a part in the barbiturate actions and the development of tolerance to and physical dependence on barbiturates. The comparisons of the effects of alcohol, barbiturates and benzodiazepines at different steps of GABA synapse are also presented. Furthermore, the results which have been reported in the literature are inconsistent. This may be due to differences in: (a) animal models used; (b) brain regions used; (c) protocols (dose, duration, form and route of administration, etc.) used in treating animals and/or (d) techniques (pharmacological, biochemical, physiological, etc.) used.     

Inhibition of hepatic glucose production by SDZ 51641

The new oral hypoglycemic agent SDZ 51641 was evaluated in nondiabetic rats and a rat model of human non-insulin-dependent diabetes mellitus. Diabetes was induced with a single injection of 37.5 mg/kg streptozocin, and the rats exhibited hyperglycemia in the fed state with normal insulin levels. Treatment of nondiabetic animals with 100 mg/kg SDZ 51641 given orally significantly decreased serum glucose and ketone levels within 4 h without affecting insulin levels. Nonesterified fatty acids increased more than twofold during the same period. Its effect on ketone and fatty acid levels suggests that SDZ 51641 acts as an inhibitor of fatty acid oxidation. Diabetic rats treated with SDZ 51641 exhibited a significant acute hypoglycemic response, which was more pronounced after 3 days of treatment. The compound also significantly decreased serum cholesterol and triglyceride levels 27 and 53%, respectively. When endogenous hepatic glucose production was assessed in nondiabetic and diabetic animals via continuous infusion of [3-3H]glucose, we found that hepatic glucose production was elevated 43% in diabetic compared with control animals. When diabetic rats were treated with 100 mg/kg SDZ 51641, hepatic glucose production decreased to normal levels within 6 h. Hyperinsulinemic-euglycemic clamp studies indicated that SDZ 51641 had no effect on insulin-stimulated glucose utilization. Measurement of [1-14C]oleate oxidation in isolated hepatocytes demonstrated that SDZ 51641 inhibited long-chain fatty acid oxidation in a concentration-dependent manner. The compound was ineffective at inhibiting long-chain fatty acid oxidation in epitrochlearis or soleus muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anatomic relationship of the oculomotor nuclear complex and medial longitudinal fasciculus in the midbrain.

PURPOSETo compare the MR characteristics of the oculomotor nucleus with its appearance on anatomic images.METHODSSpecimens of cadaveric brains were imaged in a 3.0-T MR imager equipped with a 3.0-cm solenoid coil. The specimens were sectioned, stained, and examined histologically. On anatomic sections, the oculomotor nuclei, medial longitudinal fasciculus, red nuclei, and oculomotor nerve were identified. The MR images were then compared with the anatomic sections.RESULTSThe oculomotor nuclei, medial longitudinal fasciculus, red nuclei, and oculomotor nerve could be identified on MR images by their size, shape, signal intensity, and location.CONCLUSIONMR images show the anatomic relationship of the oculomotor nerve complex, medial longitudinal fasciculus, and related structures in the brain stem.     

EMG myokymia as a cause of ptosis in hypothyroidism

Ptosis is known to be associated with thyroid disorders. We describe two biochemically corrected hypothyroid patients presenting with isolated bilateral ptosis. EMG of the orbicularis oculi showed continuous grouped motor unit potentials. In the absence of obvious aetiology, it is hypothesised that focal demyelination of terminal branches to the orbicularis oculi may play a role in the generation of the discharges.     

Production of monoclonal antibody against granulomonopoietic enhancing activity (GM-EA)

The granulomonopoietic enhancing activity (GM-EA) is a novel myelopoietic synergizing factor which acts as an enhancing factor for the proliferation and/or maturation of myelopoietic progenitor cells (CFU-GM) in combination with various types of colony-stimulating factors. In the present study, we report the production of a mouse anti-human GM-EA monoclonal antibody (mAb) designated 63A which is of the IgG1 subclass and has kappa light chains. This mAb can be used to quantitate GM-EA using a solid-phase enzyme-linked immunoabsorbent assay (ELISA) and is shown to have no cross-reaction with other myeloid synergizing factors. Furthermore, 63A mAb can significantly neutralize the colony-enhancing activity of GM-EA when added to CFU-GM assay cultures. In addition to being a convenient tool for the assay of GM-EA, 63A mAb may also be valuable for the exploration of the full potential of this enhancing factor in myelopoiesis.     

Mental object rotation in Parkinson's disease.

Deficits in visual-spatial ability can be associated with Parkinson's disease (PD), and there are several possible reasons for these deficits. Dysfunction in frontal-striatal and/or frontal-parietal systems, associated with dopamine deficiency, might disrupt cognitive processes either supporting (e.g., working memory) or subserving visual-spatial computations. The goal of this study was to assess visual-spatial orientation ability in individuals with PD using the Mental Rotations Test (MRT), along with other measures of cognitive function. Non-demented men with PD were significantly less accurate on this test than matched control men. In contrast, women with PD performed similarly to matched control women, but both groups of women did not perform much better than chance. Further, mental rotation accuracy in men correlated with their executive skills involving mental processing and psychomotor speed. In women with PD, however, mental rotation accuracy correlated negatively with verbal memory, indicating that higher mental rotation performance was associated with lower ability in verbal memory. These results indicate that PD is associated with visual-spatial orientation deficits in men. Women with PD and control women both performed poorly on the MRT, possibly reflecting a floor effect. Although men and women with PD appear to engage different cognitive processes in this task, the reason for the sex difference remains to be elucidated.     

Blunt abdominal trauma causing a 'degloving injury' to the colon

A case of an unusual degloving injury of the descending colon resulting from a crushing injury to the mid-torso is reported. The diagnosis was made at laparotomy for associated injuries. The colon was stripped of its muscle layers and mesentery for 10 cm without perforation.