EFFECTS OF ACUTE SUPERIOR CERVICAL GANGLIONECTOMY ON CEREBRAL BLOOD FLOW AND METABOLISM IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS SUBJECTED TO CEREBRAL ISCHAEMIA

1. The effects of acute bilateral superior cervical ganglionectomy on cerebral blood flow and metabolism were investigated in stroke-prone spontaneously hypertensive rats (SHRsp), before and during cerebral ischaemia. 2. The resting cerebral blood flow was comparable between the control and denervated animals. 3. There was no significant difference in cerebral blood flow or concentration of tissue energy metabolites (adenosine triphosphate [ATP], lactate and pyruvate) between the sham-operated control and denervated animals during ischaemia. 4. The results suggest that sympathetic innervation of cerebral vessels originating from superior cervical ganglia may not play a major role in the progression of cerebral ischaemia in SHRsp.     

Synergistic renal protection by combining alkaline-diuresis with lipid peroxidation inhibitors in rhabdomyolysis: possible interaction between oxidant and non-oxidant mechanisms

BACKGROUND AND PURPOSE.: Heme-proteins, besides causing renal tubular obstruction, maycontribute to rhabdomyolysis-induced renal injury through aheme-iron-mediated lipid peroxidation process. In the presentstudy, we compared the combined therapy of a lipid peroxidationinhibitor, 21-aminosteroid (21-AS) and fluid-alkaline-mannitol(FAM) diuresis with either of them alone to determine the efficacyof the combination therapy and to delineate the roles of lipidperoxidation and cast formation. METHODS AND RESULTS.: Employing Raman spectroscopy, we confirmed in vitro the abilityof 21-AS to inhibit iron-induced fatty acid peroxidation. 21-ASwas then administered to rats developing renal failure fromglycerol-induced rhabdomyolysis. Although 21-AS inhibited rhabdomyolysis-inducedplasma and renal lipid peroxidation, renal protection was incomplete.Administration of FAM to inhibit cast formation afforded a betterrenal protection. However, when these therapies were combinedto inhibit both lipid peroxidation and cast formation, therewas a synergistic renal functional protection. This was accompaniedby a maximum inhibition of renal and plasma lipid peroxidation,as well as, renal tubular necrosis and cast formation. Comparedto combination therapy, FAM therapy alone, despite identicalvolume, was accompanied by a higher tubular necrosis and castformation. CONCLUSIONS.: That combining a lipid peroxidation inhibitor with fluid-alkalinediuresis in rhabdomyolysis further lowers renal lipid peroxidation,tubular necrosis and cast formation and synergistically limitsrenal dysfunction (i) supports a role for lipid peroxidationin the pathophysiology of rhabdomyolysis ARF, (ii) underscoresthe role of intratubular heme retention, a cause for tubularobstruction as well a source for prodigious amount of iron,likely involved in the lipid peroxidation, and (iii) raisesthe possibility of interactions between non-oxidant and oxidantmechanisms.     

Small round and spindle cell sarcoma with neuronal differentiation and oncocyte-like features of the thoracic wall: A case report with histological,immunohistochemical and ultrastructural examinations

A case of small round and spindle cell sarcoma with neuronal differentiation and oncocyte-like features is presented. The tumor was encountered in a 32 year old Japanese woman with an initial presentation of palpable tumor in the left lateral region of the thorax. The resected tumor was a partially well encapsulated whitish medullary one and consisted of small round and spindle tumor cells, together with so-called rhabdoid cells in the small round cell area. Although pseudorosettes were often observed, true rosette formation could not be detected anywhere. Ultrastructurally, despite a histologic variety of tumor cells, most tumor cells possessed numerous mitochondria, some of which occasionally contained abnormal filamentous or crystalloid structures. Various amounts of microfilaments were present in most tumor cells and microtubules were present in a few. A minority of small round cells possessed a small number of neurosecretory granules, especially in short cytoplasmic processes. A positive immunoreaction for neuron specific enolase was found by immunohistochemical examination in several small round tumor cells and for neurofilaments in lesser numbers. Despite the lack of S-100 protein, MB2 was detected in both small round and spindle cells. On the basis of these findings, the tumor of the present case corresponds to malignant peripheral nerve sheath tumor with neuronal differentiation and oncocytic features.     

Inhibitory effect of polymyxin B on catecholamine secretion from cultured bovine adrenal medullary cells

Incubation of cultured bovine adrenal medullary cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of Ca2+/phospholipid-dependent protein kinase (protein kinase C), was associated with increased secretion of catecholamine (CA) from the cells. Polymyxin B (PMB, 30-300 microM), a preferential inhibitor of protein kinase C, inhibited the TPA-induced secretion of CA. PMB also inhibited CA secretion induced by other secretagogues, the Ca2+ ionophore ionomycin (10 microM), 56 mM K+ or acetylcholine (ACh). Ionomycin, 56 mM K+ or ACh increased the concentration of intracellular free Ca2+ ([Ca2+]i) (measured using the fluorescent calcium indicator quin2), whereas TPA did not increase [Ca2+]i. PMB blocked the increase in [Ca2+]i induced by 56 mM K+ or ACh at concentrations similar to those inhibiting the secretion of CA. In contrast, PMB did not affect ionomycin-induced increase in [Ca2+]i. These results strongly suggest that CA secretion induced by TPA or ionomycin is mediated via activation of protein kinase C. The results further indicate that in 56 mM K+- or ACh-evoked CA secretion, PMB inhibits the secretion by blocking Ca2+ influx into the cells.     

Neurotoxicity of Clostridium perfringens Epsilon-Toxin for the Rat Hippocampus via the Glutamatergic System

The neurotoxicity of epsilon-toxin, one of the major lethal toxins produced by Clostridium perfringens type B, was studied by histological examination of the rat brain. When the toxin was injected intravenously at a lethal dose (100 ng/kg), neuronal damage was observed in many areas of the brain. Injection of the toxin at a sublethal dose (50 ng/kg) caused neuronal damage predominantly in the hippocampus: pyramidal cells in the hippocampus showed marked shrinkage and karyopyknosis, or so-called dark cells. The dark cells lost the immunoreactivity to microtubule-associated protein-2, a postsynaptic somal and dendric marker, while acetylcholinesterase-positive fibers were not affected. Timm’s zinc staining revealed that zinc ions were depleted in the mossy layers of the CA3 subfield containing glutamate as a synaptic transmitter. The cerebral blood flow in the hippocampus was not altered significantly before or after administration of the toxin, as measured by laser-Doppler flowmetry, excluding the possibility that the observed histological change was due to a secondary effect of ischemia in the hippocampus. Prior injection of either a glutamate release inhibitor or a glutamate receptor antagonist protected the hippocampus from the neuronal damage caused by epsilon-toxin. These results suggest that epsilon-toxin acts on the glutamatergic system and evokes excessive release of glutamate, leading to neuronal damage.     

Extraskeletal myxoid chondrosarcoma arising from the retroperitoneum

A case of extraskeletal myxoid chondrosarcoma is presented. The tumor occurred in the retroperitoneum and systemic metastases were found at autopsy. The primary and metastatic tumors were soft and strikingly myxoid on gross appearance. Microscopic observation revealed undifferentiated malignant tumor having large amounts of myxoid substance and a small amount of well-differentiated chondrosarcoma element in the primary lesions. The authors obtained an immunohistochemical result that the tumor cells showed positivity for alpha-1-antitrypsin and alpha-1-antichymotrypsin. Regarding S-100 protein, the well-differentiated chondrosarcoma element revealed intense positivity, whereas the poorly differentiated myxoid areas were not positive except for a few tumor cells. This is the first case, to our knowledge, of extraskeletal myxoid chondrosarcoma arising from the retroperitoneum, and immunohistologic findings suggest that alpha-1-antitrypsin and alpha-1-antichymotrypsin may be available markers in poorly differentiated chondrosarcomas showing a negative reaction for S-100 protein.     

Clear cell hepatocellular carcinoma with abundant myxoid stroma.

A case of the clear cell variant of hepatocellular carcinoma with an abundant myxoid stroma is presented. The tumor occurred in a 55-year-old Japanese man, and swelling of the scrotum was the initial symptom. The patient underwent high-level orchiectomy, and the pathologic diagnosis was a metastatic tumor on the surface of the processus vaginalis and intact testis. Extensive examination failed to show a primary site. Subsequent autopsy revealed a large hepatic tumor and metastatic nodules with a prominent myxoid appearance in multiple organs. Histologically, each tumor consisted of uniform small tumor cells with clear cytoplasm attributed to abundant accumulation of glycogen particles, and an abundant myxoid stroma was also present. The tumor cells were positive for keratin, alpha 1-antitrypsin, alpha 1-antichymotrypsin, liver ferritin, prealbumin, and fibrinogen, but lacked alpha-fetoprotein. These findings indicated that this case was hepatocellular carcinoma of the clear cell type with a prominent myxoid stroma.