An ultrastructural study of gold thioglucose lesion formation in the ventromedial hypothalamus: subnecrotic gold thioglucose dose.

In an ultrastructural study of gold thioglucose (GTG) lesion formation in the mouse ventromedial hypothalamus (VMH), a single intraperitoneal subnecrotic dose of GTG (100 mg/kg) was used to induce a VMH microlesion, visible only by electron microscopy. Definitive neuronal alterations were not evident until eight hours after GTG injection. Large pericapillary processes, probably dendrites, displayed a loss of cytoplasmic density and distention, while the capillary endothelium appeared normal. Some intercellular distention also was apparent. By 24 hours after GTG administration, degenerating neurons were visible. Swollen and disrupted synaptic profiles were seen. However, no vascular damage was evident. These results support the evidence that GTG is a neurotoxin for structures in the mouse VMH.

Glucose analog effects on glucose oxidation in the ventromedial hypothalamus.

The effect of the glucose analogs 2-deoxyglucose (2DG), glucosamine (GLA), mannoheptulose (MAN), and gold thioglucose (GTG) on glucose utilization in the mouse ventromedial hypothalamus (VMH) was assessed by using an in vitro incubation system. The amount of 14C-CO2 generated from uniformly labelled 14C-glucose was measured in VMH tissue cubes. MAN and GTG did not alter glucose oxidation at any of the concentrations compared with controls. GLA inhibited glucose utilization but only when the amount of GLA was 3 times that of glucose in the medium. However, this difference was not significant. The 2DG inhibited glucose oxidation significantly (50%; P less than 0.005), but only when 2DG was used in a quantity three-fold greater than glucose. These results imply that the VMH, a reputed central area for controlling feeding behavior, may possess a high affinity for glucose, which is not effectively altered by competitive inhibitors.

The effect of digitoxose on feeding behavior.

The effect of digitoxose (DIG) on food intake, gold thioglucose (GTG) lesion formation in the ventromedial hypothalamus (VMH), and VMH glucose oxidation in vitro was investigated in mice. DIG significantly decreased the amount of food ingested during the day compared to controls (p less than 0.01). DIG had no effect on nocturnal feeding. GTG lesion formation in the VMH and VMH glucose oxidation were not altered by DIG treatment. These results suggest that DIG alters daytime feeding behavior by affecting extrahypothalamic or peripheral glucoreceptor sites.

Resistance of the gerbil hypothalamus to gold thioglucose lesion formation.

Mongolian gerbils do not develop ventromedial hypothalamic (VMH) lesions, as seen in mice, when challenged with gold thioglucose (GTG, 800, 1600 and 3600 mg/kg IP). Insulin administration or bilateral adrenalectomy, procedures which sensitize nonresponsive mice to GTG, have no effect in the gerbil given GTG. These findings suggest that the gerbil VMH differs significantly in structure and/or function compared with the mouse by not possessing glucoreceptive cells sensitive to GTG.

Systemic phlorizin prevents gold thioglucose necrosis in the ventromedial hypothalamus.

Intraventricular and intrahypothalamic infusions of phlorizin (PHL) are known to cause hyperphagia and to prevent gold thioglucose (GTG) lesion formation in the ventromedial hypothalamus (VMH), respectively. In this study, PHL, administered IP in a large dose (900 mg/kg), completely inhibited GTG necrosis in the VMH. PHL did not cause excessive urinary excretion of GTG. This evidence suggested that systemic PHL must be injected in a high concentration to alter the hypothalamic response to GTG. In vitro measurements of VMH glucose oxidation substantiated this idea. Only at a high concentration of PHL was glucose oxidation significantly depressed in the VMH (p less than 0.001). Small amounts of PHL elevated VMH glucose oxidation (p less than 0.001). Since PHL is an inhibitor of glucose transport, these data support the concept of a hypothalamic glucostatic modulation for the control of food intake.

Myofiber damage accompanying intramuscular parasitism by Sarcocystis muris.

Myofiber degeneration which results from Sarcocystis infection exhibits a number of fine structural features suggestive of other myopathies and several well-defined fine structural features not characteristic of other myopathies. Some of these fine structural features are similar to those observed in intramuscular infections of Trichinella spiralis, another muscle parasite. Major alterations of the myofibrillar contractile apparatus occur at the periphery of the membrane bound parasitophorous vacuole which include splitting and fragmentation of the myofibrils at the longitudinal ends of the parasitophorous vacuole and Z line dissolution at the radial periphery. Membranous structural elements including mitochondria, sarcoplasmic reticulum and T system components become disarrayed as the myofibrils degenerate. Some minor hypertrophy of the sarcoplasmic reticulum occurs in conjunction with initial fragmentation of the myofibrils bu no major dilation or hypertrophy has been observed. There is a distinctive membranous organization of the interface of the parasitophorous vacuole. The presence of pycnotic and fragmenting nuclei, sarcolemmal invaginations with accompanying fibrous connective tissue invasion and large areas of undifferentiated cytoplasm suggest the ultimate necrosis and destruction of infected myofibers. The similarity between morphological features of myofibrillar degeneration accompanying intramuscular Sarcocystis muris infections and those associated with a variety of myopathies resulting from other causes suggests that a common mechanism of muscle response to damage might result in the observed structural degeneration.

Glucose oxidation in the ventromedial hypothalamus is not affected by insulin or ouabain but depressed by alloxan treatment.

Insulin is apparently not required for VMH glucose oxidation in vitro. Ouabain, an inhibitor of the Na-K pump ATPase, does not prevent VMH glucose oxidation in vitro. These data suggest (a) the VMH does not exhibit a cotransport phenomenon of glucose with the Na-K pump mechanism, and (b) glucose oxidation in the VMH is not insulin dependent. Alloxan-diabetes was induced to increase tissue insulin sensitivity. A comparison of glucose oxidation rates in alloxan-diabetic VMH tissue and normal VMH tissue, supplemented only with saline, indicated a highly significant (p < 0.001) depression of glucose oxidation in the alloxan-treated tissue. Cell membranes in the VMH are perhaps altered by alloxan.

Some cellular changes associated with triton WR-1339 accumulation in rat hepatocytes.

Electron microscopic morphological and cytochemical techniques were used to follow the sub-cellular events that accompanied Triton WR-1339 accumulation in hepatocytes. Localization of two lysosomal enzymes, acid phosphatase and aryl sulfatase, clearly established the lysosomal nature of the Triton WR-1339 containing electron-lucid structures that appear in hepatocytes following treatment with this compound.

The ultrastructure of the cyst wall of a murine Sarcocystis.

Electron microscope studies of the cyst wall of a murine Sarcocystis-like organism of Mus musculus indicate that the sarcocyst wall is a degenerate muscle cell. The degenerate muscle cell contains nuclei, mitochondria, ribosomes, and myofibrils in disarray with the A-bands thickened. Surrounding the outside of the muscle cell there is a layer of fibrous material, and occasional fibroblasts are seen. The parasites are found within a parasitophorous vacuole in the muscle cell. There are short-finger-like projections extending into the vacuole from the muscle cell. The ground substance of the vacuole is fairly homogeneous, but somewhat more electron dense between the finger-like projections.