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Biomedical subjects

S Shapira

Publications and source records attributed to S Shapira.

29 records · Page 2Linked to original sources

A goldfish model for evaluation of the neurotoxicity of omega-conotoxin GVI A and screening of monoclonal antibodies.

The neurotoxicity of omega-conotoxin (omega-CgTx), a potent neuronal voltage-sensitive calcium channel blocker, was measured using a new bioassay. omega-CgTx was administered intraperitoneally (ip) to goldfish weighing approximately 1.6 g, and dose-related changes were observed over a 2-hr period. omega-CgTx induced time- and dose-dependent abnormal swimming behavior (ASB) and mortality. The antitoxin activity of the antibodies was investigated in vivo by either (1) preincubation of the antibody with omega-CgTx at 4 degrees C overnight, or (2) pretreatment with antibody, 30 min before omega-CgTx injection in a 10:1 antibody/omega-CgTx molar ratio. The LD50 dose of omega-CgTx in goldfish was 5 nmol/kg ip, and preincubation of monoclonal antibody (50 nmol/kg ip) with omega-CgTx (5 nmol/kg ip) significantly (p less than 0.05) reduced mortality, ASB, and toxicity time. The antitoxin activity of the monoclonal antibodies evidenced in the goldfish bioassay was further tested in the conscious rat. In the rat, the increases in mean arterial pressure and heart rate induced by omega-CgTx (0.03 nmol/rat icv) were significantly (p less than 0.02 and p less than 0.01, respectively) attenuated by preincubation of the toxin with the antibody (0.3 nmol/rat). We conclude that the goldfish bioassay provides a simple, accurate, and inexpensive in vivo model for the study of the toxicity of omega-CgTx.

Animals↗

Percutaneous transluminal angioplasty of proximal subclavian artery stenosis after left internal mammary to left anterior descending artery bypass surgery.

A patient is described who underwent percutaneous transluminal angioplasty, through a brachial approach, of a high grade stenosis at the proximal portion of the left subclavian artery 1.5 years after coronary artery bypass grafting including left internal mammary to left anterior descending artery anastomosis. Symptoms of class IV angina, vertebrobasilar insufficiency and occupational arm claudication that developed after bypass surgery were promptly relieved after balloon dilation. Percutaneous transluminal angioplasty of the subclavian artery can be performed safely and provides an alternative to carotid-subclavian or axillary-axillary bypass surgery for treatment of internal mammary artery graft malfunction.

Angioplasty, Balloon↗

Selective hippocampal lesion following omega-conotoxin administration in rats.

Histopathological evaluation of rat brains 3 days following unilateral i.c.v. injections of omega-conotoxin GVIA (omega-ctx), 0.032 and 0.1 nmol/kg, was performed. An isolated unilateral lesion confined to the injected hemisphere was found in the hippocampal CA3 neurons. Morphometric analysis of these cells revealed a significant reduction in cell area in both dose groups compared to i.c.v. injected vehicle, and to the contralateral hemisphere. These data indicate a specific degenerative process and suggest that CA3 cells possess omega-ctx-sensitive Ca2+ channels which are essential to their viability.

Animals↗

Effects of CBDP and MEPQ on the toxicity and distribution of [3H]-soman in mice.

Soman poisoning presents a problem in terms of its detailed pathophysiology and its detoxification mechanism(s). The present study was designed to evaluate the role of carboxylesterases (CaE) and cholinesterase (ChE) in the distribution and detoxification of soman in vivo. Mice were injected (i.v.) with 0.06-1.0 LD50 of [3H]-soman, 60 min following pretreatment with either 2-O-cresyl-4H-1:2:3 benzodioxa-phosphorine-2-oxide (CBDP), which blocks CaE or 7-(methylethoxyphosphinyloxy)-1-methyl quinolinium iodide (MEPQ), which selectively inhibits intravascular ChE. One hour after [3']-soman administration animals were sacrificed and whole body autoradiography was performed. High concentrations of [3H]-soman were found in lung and kidney in control mice, and low concentrations were found in central nervous system. Pretreatment with CBDP caused a 93% decrease in radioactive labelling in the lung, and a minor decrease in overall labelling, whereas pretreatment with MEPQ did not change the distribution pattern of [3H]-soman. It is concluded that lung is a major target organ for soman detoxification and that it exerts this effect by means of enzymatic reaction with soman through the abundant amounts of CaE which are present in the lung. Intravascular ChE has little (if any) effect on the distribution and detoxification of soman in vivo.

Animals↗

Integrated autonomic and behavioral responses to L/N Ca2(+)-channel blocker omega-conotoxin in conscious rats.

omega-Conotoxin (omega-ctx) was used as a probe for studying the putative role of brain L/N-type Ca2+ channels in regulation of autonomic functions. Rats were injected intracerebroventricularly (icv) with omega-ctx, and hemodynamic, biochemical and behavioral variables were monitored. omega-Ctx (0.032-10 nmol/kg) caused a persistent, dose-dependent shaking behavior, complex thermoregulatory changes, and motor deficits lasting up to 48 h. Cardiovascular responses to omega-ctx included tachycardia (+71 +/- 16%, P less than 0.01) and elevated arterial blood pressure (+16 +/- 1%, P less than 0.05) associated with increased circulating levels of norepinephrine and epinephrine. Higher doses, 1 or 10 nmol/kg, resulted in circulatory shock and death. Central administration of 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8), diltiazem (100 or 1,000 nmol/kg), neomycin (100 nmol/kg, each), nifedipine (10 nmol/kg), and CdCl2 (100 nmol/kg), which represent intracellular, non-specific N-, L-, and L/N-type Ca2(+)-channel blockers, respectively, did not cause any behavioral or hemodynamic effects, whereas the L-channel agonist BAY K 8644 (100 nmol/kg icv) caused a mild transient pressor response. Pretreatment with the gamma-aminobutyric acid (GABA) agonist muscimol (icv) or a combined intravenous pretreatment with propranolol and N-methylatropine blocked the omega-ctx effects. Our data suggest that omega-ctx actions in the brain involve central GABAergic mechanisms modulated by yet a different type of Ca2+ channels not characterized by any of the known voltage-operated Ca2+ channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

[Continuous intercostal nerve block for chronic pain].

21 ambulatory patients with acute or chronic pain localized to the chest, were treated successfully by continuous intercostal block. They included 6 women and 15 men, aged 39-70. Treatment was initiated in the outpatient clinic and continued at home for usually 5-6 days. Between 15-20 ml of 0.5% marcaine were continuously injected over the course of 6-12 hours through a catheter introduced into the intercostal space by a Touhy needle. 76% of the patients had substantial relief of pain during the block and required only minimal systemic medication. During a 3 month follow-up after cessation of the block, up to 65% were still pain-free. Results were poor or only fair in those with malignancy and long-standing intercostal neuralgias. There were no serious side-effects during treatment. This method is an important new tool in the treatment of pain.

Acute Disease↗

Distribution of 3H-soman in mice.

3H-soman (specific activity 10 Ci/mMol), a potent irreversible cholinesterase inhibitor, was administered IV to mice in a dose of one LD-50, which corresponds to 0.25 mCi/mouse. Animals were sacrificed at 5 min, 2 h and 24 h, and whole body autoradiography was performed. High levels of radioactivity in lung and skin were observed at all time intervals after injection. The central nervous system showed very low concentrations of radioactivity, which remained so for 24 h post-injection. Considerable accumulation of 3H-soman in the urine and gall-bladder, and in the intestinal lumen, may indicate these as pathways of soman excretion. Quantitative determinations of radioactivity in various tissue samples were consistent with the above-mentioned findings. It is concluded that the nature of the persistent binding of soman to lung and skin is striking, and may indicate the existence of specific sites for soman depots.

Animals↗

Transdermal therapeutic system scopolamine (TTSS), dimenhydrinate, and placebo--a comparative study at sea.

The efficacy of transdermally administered scopolamine was compared with the efficacy of oral dimenhydrinate and placebo therapy in the prevention of motion sickness at sea. Medication was administered on a controlled double blind basis to 140 subjects. A placebo effect reduced the motion sickness incidence (MSI) from 57.69% in the control group to 43.47%. Administration of dimenhydrinate reduced the MSI to 22.22% and the use of Transdermal Therapeutic System Scopolamine (TTSS) further reduced the MSI to 16.66%. TTSS afforded 61.67% protection against motion sickness at sea, compared to 48.88% protection with dimenhydrinate.

Administration, Topical↗

Hypopharyngeal injury as a result of attempted endotracheal intubation.

Perforation of the hypopharynx due to traumatic attempted endotracheal intubation usually occurs during resuscitation efforts under poor conditions, but may occur even under optimal conditions due to improper technique. The implication of the appearance of subcutaneous emphysema in the neck, cyanosis, or pneumothorax during or following attempts at endotracheal intubation should be known. Direct laryngoscopy may be helpful in establishing the injury but early radiological examination is necessary for diagnosis of the site and extent of the perforation. The radiological contribution appears to be decisive in the choice of treatment. The radiological findings and the considerable morbidity observed in 6 cases of hypopharyngeal injury are described.

Adult↗