Activation of muscarinic and serotonergic receptors results in phosphoinositide hydrolysis but not in mobilization of calcium in sympathetic neurons.

The effects of various neurotransmitters on phosphoinositide hydrolysis, mobilization of Ca2+ and release of [3H]-norepinephrine ([3H]-NE) were studied in cultures of sympathetic neurons of chick embryos. [3H]-inositol-1,4,5-triphosphate ([3H]-IP3) was increased in sympathetic neurons by acetylcholine (ACh), muscarine and serotonin (5-HT). Dopamine and norepinephrine did not stimulate phosphoinositide hydrolysis. Intracellular concentration of free Ca2+ ([Ca2+]i) was measured in Indo-1-loaded sympathetic neurons at rest and after addition of test agents. Measurements were made in the cell body and growth cone regions since Ca2+ mobilization is known to be different in different regions of the sympathetic neurons. ACh (nicotinic component was blocked by hexamethonium) and 5-HT failed to increase the [Ca2+]i, in the cell body as well as in the growth cone. The spontaneous release of [3H]-NE was not affected by ACh and 5-HT. Caffeine increased the [Ca2+]i only in the cell body but not in the growth cone and had no effect on the release of [3H]-NE. These results suggest that an IP3-insensitive but caffeine-sensitive pool of Ca2+ is present only in the somatic region of sympathetic neurons and is not coupled to the transmitter release.     

Hyperfractionated radiation therapy and concurrent 5-fluorouracil, cisplatin and mitomycin-C in head and neck carcinoma. A pilot study.

Seventeen patients were entered into a Phase I/II trial of concurrent hyperfractionated radiation therapy (7,440 cGy total dose; 120 cGy b.i.d.) combined with constant infusion of 5-fluorouracil (5-FU) (1,000 mg/m2/24 hours for 72 hours) and cisplatin (DDP) (50 mg/m2) for a total of three cycles. Thirteen patients had Stage IV disease; three, Stage III disease; and one, Stage II hypopharyngeal disease. Thirteen of 17 patients had positive cervical lymph nodes, and the mean size of the largest lymph node was 5.5 x 5.1 cm. The patients were not treated with planned adjunctive surgery except for one patient who had a radical neck dissection for massive, rapidly growing cervical adenopathy, which recurred promptly within 1 month before the initiation of protocol therapy. After the initial six patients were entered, mitomycin-C (Mito 8 mg/m2) was added during the second cycle. All the patients completed the planned course of radiotherapy with a median dose of 7,440 cGy and a mean dose of 7,248 cGy except for two patients who died--one from toxicity and the other, suicide. The predominant toxicity was mucositis, which was grade 3/4 in 11 of 15 patients, resulting in an average interruption of radiation therapy of 12 days. Weight loss was significant and was on the average 12% of baseline weight. Hematological toxicity was mild in the 5-FU/DDP group (only one grade 3 toxicity of six) and severe in the 5-FU/DDP/Mito-treated patients (five of eight patients having grade 3/4 toxicity including one leukopenic pneumonitis death). Additional toxicity included one parapharyngeal cellulitis, which responded to antibiotics. Noncompliance with the complex regimen was only seen in three patients. One patient refused b.i.d. radiation therapy, and one patient refused further chemotherapy after the first cycle. Additionally, one patient who had a severe ethanol withdrawal reaction during the first cycle of 5-FU/DDP did not receive further chemotherapy. The complete response rate of both primary site and neck by the protocol regimen alone was 71%. However, two patients, one from each group, did undergo salvage neck dissection, and the locoregional control is currently 73%, with a mean follow-up time of 18.4 months. The feasibility of combining hyperfractionated radiation therapy with aggressive concurrent chemotherapy was demonstrated. The response and local control rate justifies the added toxicity of concurrent chemotherapy and radiation therapy.     

The experimental treatment of cyanide poisoning with a methemoglobin solution]

The stroma-free methemoglobin solution proved to be an effective antidote against acute cyanide poisoning in experiment. The poisoning was induced by intraperitoneal administration to rats of cyanide solutions in doses of 5, 10 and 15 mg/kg. Methemoglobin solutions were injected intravenously in doses of 2 and 4 g/kg. All the rats given methemoglobin solution after the administration of cyanide survived. Spectrophotometry of rat urine demonstrated rapid excretion of methemoglobin cyanide.     

Serum levels of alpha-tocopherol (vitamin E) in Parkinson's disease.

To elucidate the possible role of vitamin E in the pathogenesis of Parkinson's disease (PD), we compared serum levels of alpha-tocopherol (vitamin E), measured by high-performance liquid chromatography, and the vitamin E/cholesterol ratio of 42 Parkinson's disease (PD) patients using their spouses as the control group. The serum levels of vitamin E did not differ significantly between the groups (13.84 +/- 0.56 micrograms/ml for PD and 14.80 +/- 0.57 micrograms/ml for controls), nor did the vitamin E/cholesterol ratio (0.64 +/- 0.03 for both groups). There was no influence of antiparkinsonian therapy on vitamin E or the vitamin E/cholesterol ratio. Serum levels of the vitamin E and vitamin E/cholesterol ratio did not correlate with age, age at onset, scores of the Unified Parkinson's Disease Rating Scale or the Hoehn and Yahr staging in the PD group. These results suggest that serum vitamin E concentrations do not play a role in the pathogenesis of PD.     

Regional expression of c-fos and heat shock protein-70 mRNA following hypoxia-ischemia in immature rat brain.

Cerebral ischemia induces the expression of a number of proteins that may have an important influence on cellular injury. The purpose of this study was to compare the regional effects of hypoxia-ischemia on the expression of the proto-oncogene, c-fos, and the heat shock protein-70 (HSP-70) gene in developing brain. Unilateral hypoxia-ischemia was produced in the brain of immature rats (7, 15, and 23 days after birth) using a combination of carotid artery ligation and systemic hypoxia (8% O2). After recovery for 2 and 24 h, the regional expression of c-fos and HSP-70 mRNA was determined using in situ hybridization. Littermates were permitted to recover for 1 week for assessment of histologic injury. Hypoxia-ischemia increased the expression of both c-fos and HSP-70 mRNA, but the topography of expression varied with the age of the animal as well as the mRNA species. In the 7-day-old group, expression of c-fos at 2 h increased in multiple regions of the ipsilateral hemisphere in nearly one-half of the animals, while HSP-70 mRNA was not expressed until 24 h and, then, predominantly in the hippocampus. In 15- and 23-day-old rats, expression of c-fos was increased at 2 h in the entorhinal cortex and in the dendritic field of the upper blade of the hippocampal dentate gyrus, while HSP-70 mRNA was prominently expressed in neocortex and the cell layers of the hippocampus. Interestingly, the strong expression of HSP-70 mRNA in dentate granule cells did not occur in the innermost layer of cells.(ABSTRACT TRUNCATED AT 250 WORDS)