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Biomedical subjects

S Reznik

Publications and source records attributed to S Reznik.

8 recordsLinked to original sources

Massive acute thymic haemorrhage and cerebral haemorrhage in an intrauterine fetal death.

Massive acute thymic haemorrhage in the neonate occurs extremely rarely and is associated with haemorrhagic disease of the newborn. A 30 year old woman with an unremarkable previous obstetric history presenting at 37 weeks and 4 days gestation with the complaint of loss of fetal movement was found to have a male fetus with findings at necropsy of massive acute thymic haemorrhage, acute intracranial haemorrhage, and hydrops fetalis. This is the first report of massive acute thymic haemorrhage in utero. Massive thymic haemorrhage should be added to the reported causes of lethal non-immunological hydrops.

Acute Disease↗

The effect of diazepam in the recovery of rabbits from acute acetaminophen intoxication.

We have recently shown that diazepam can reduce mortality of acute iron overdose in rats. The mechanism for that effect is not yet defined. Our objective in the present study was to assess whether diazepam can similarly reduce mortality of experimental acute acetaminophen intoxication. Survival of rabbits was compared among four groups receiving 3 g/kg (body weight) of acetaminophen (LD40) orally each, followed by: 1) nothing (group I), 2) one oral dose of 140 mg/kg N-acetylcystein (NAC) an hour later (group II), 3) intramuscular injection of 7 mg/kg diazepam (group III), 4) intramuscular injection of 7 mg/kg diazepam and one oral dose of 140 mg/kg NAC an hour later (group IV). 37.5% of rabbits in group I died after 16 hours, whereas none of the rabbits in group III died, (p = 0.04). No animal died during the 96-hour observation period in groups II and IV. Two and four hours post drug administration, acetaminophen plasma concentrations (APC) were significantly lower among rabbits in group III than in group I (p = 0.0007 and 0.01, respectively) and significantly lower among rabbits in group IV than in those in group II (p<0.0001 and p = 0.03, respectively). Acetaminophen plasma concentrations 2 hours after drug administration were also significantly lower among rabbits in group III than in those in group II (p = 0.0002). Seven and 24 hours after dosage, APC tended to be higher among rabbits in group III than in those in group I, but not significantly so. Administration of diazepam without NAC did not prevent liver and renal dysfunction. We conclude that early administration of diazepam in acute experimental acetaminophen overdose in rabbits reduced APC and mortality, probably by slowing intestinal motility, which resulted in delayed acetaminophen absorption from the gastrointestinal tract.

Acetaminophen↗

Antibody to transforming growth factor beta reduces collagen production in injured peripheral nerve.

Epineurial scarring in peripheral nerve after injury inhibits normal axonal regeneration primarily due to fibroblast deposition of type I collagen. The transforming growth factor beta (TGF-beta) family is an important class of signaling molecules that has been shown to stimulate fibroblasts to produce collagen. The aim of this study was to design a prototypic therapeutic system in which the neutralization of TGF-beta in crushed rat sciatic nerve would decrease collagen formation. A total of 45 experimental Lewis rats were used. Group 1 animals (20 rats) sustained a unilateral crush injury to the sciatic nerve with injection of phosphate buffer solution. Group 2 animals (20 rats) sustained a unilateral crush injury to the sciatic nerve with injection of phosphate-buffered saline and goat, anti-rat, panspecific TGF-beta antibody. Group 3 control animals (five rats) underwent only exposure of sciatic nerve with injection of antibody. All animals were killed at 14 days and sciatic nerve specimens were harvested at that time. Slides of experimental tissue were processed using a 35S-labeled oligomer for procollagen alpha-1 mRNA, then dipped in photographic emulsion and examined by darkfield autoradiography. Morphometric analysis of pixel counts was then performed. A significant reduction in total pixel count per high-power field and in total number of fibroblasts per high-power field was found in crushed rat sciatic nerve treated with anti-TGF-beta antibody when compared with those treated only with phosphate-buffered saline. These findings are consistent with successful reduction in procollagen induction after a crush injury by topical administration of blocking antibody against transforming growth factor beta. The concept of growth factor blockade for therapeutic collagen reduction is attractive in the context of nerve injury, and the current article provides a model for future clinical application.

Animals↗

"Skinny lips".

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Communication↗

Endopeptidase 24.15 from rat testes. Isolation of the enzyme and its specificity toward synthetic and natural peptides, including enkephalin-containing peptides.

Endopeptidase 24.15, a metalloendopeptidase (EC 3.4.24.15) with an Mr of about 70,000, was purified to homogeneity from rat testes. The enzyme cleaves preferentially bonds on the carboxyl side of hydrophobic amino acids. Secondary enzyme-substrate interactions at sites removed from the scissile bond are indicated by the finding that a hydrophobic or bulky residue in the P3' position greatly contributes to substrate binding and catalytic efficiency. The isolated enzyme is inhibited by metal chelators and by thiols. Loss of enzymic activity after dialysis against EDTA can be restored by low concentrations of Zn2+ and Co2+ ions. The rate of reaction of the Co2+ enzyme with a synthetic substrate was higher than that of the Zn2+ enzyme. These results are consistent with the classification of the enzyme as a metalloendopeptidase. N-Carboxymethyl peptides that fulfil the binding requirements of the substrate recognition site of the enzyme act as potent competitive inhibitors. Biologically active peptides such as luteinizing hormone-releasing hormone, bradykinin and neurotensin are cleaved at sites consistent with the specificity of the enzyme deduced from studies with synthetic peptides. Dynorphin A (1-8)-peptide, beta-neoendorphin, metorphamide, and Metenkephalin-Arg6-Gly7-Leu8 are rapidly converted to the corresponding enkephalins. The testis enzyme is catalytically and immunologically closely related to the previously identified brain enzyme.

Animals↗

Activity of 5-fluorouracil, mitomycin C, and methyl CCNU in inoperable adenocarcinoma of pancreas.

Twenty-two patients with inoperable adenocarcinoma of the pancreas were treated with 5-fluorouracil (5-FU), mitomycin C (Mito-C), and 1(-2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU). Fifteen were evaluable by completing 2 months of therapy. Two patients achieved a complete remission with the above combination. A partial remission seen in four other patients, which produced a response rate of 40% of evaluable, and 27% of entered, patients. Three had stable disease. The average time to progression in this study was 8 months. This combination was well tolerated and no deaths were secondary to drug therapy. Mucositis, leukopenia, thrombocytopenia, and hyperpigmentation were the significant toxicities seen in this study. These observations are worthy of further investigation.

Adenocarcinoma↗

Inhibition of endopeptidase 24.15 slows the in vivo degradation of luteinizing hormone-releasing hormone.

Endopeptidase (EP) 24.15 cleaves the Tyr5-Gly6 bond of luteinizing hormone-releasing hormone (LHRH) (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2), and is the primary LHRH degrading enzyme in pituitary and hypothalamic membrane preparations. Potent and specific inhibitors were used to identify the enzymes involved in the in vivo degradation of LHRH. After i.c.v. administration of LHRH, only about 1% of the peptide was recovered from brain after 1 hr. Concurrent administration of LHRH and N-[1-(RS)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (cFP-AAF-pAB), a specific inhibitor of EP 24.15, led to a more than 10-fold increase in LHRH recovery. Administration of N-[1-(RS)-carboxy-3-phenylpropyl]-Phe-pAB (cFP-F-pAB) or captopril, inhibitors of "enkephalinase" (EP 24.11) and angiotensin converting enzyme, respectively, did not significantly increase LHRH recovery. Intravenous administration of LHRH and either cFP-F-pAB or cFP-AAF-pAB but not captopril, led to an increase in the half-life of LHRH from 10 min to 15 and 20 min, respectively. Concurrent administration of both inhibitors resulted in a dramatic 8-fold increase in the half-life of LHRH, similar to values reported for "superactive" analogs of LHRH which are rendered resistant to enzymatic degradation by introduction of a D-amino acid in position 6. Concentrations of plasma LHRH 65 to 80 min after administration of inhibitors were 100- to 200-fold higher than those in controls. The potentiating effect of cFP-F-pAB resulted from inhibition of the in vivo degradation of cFP-AAF-pAB by EP 24.11.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hepatic arterial and systemic chemotherapy for the treatment of primary and secondary malignancies of the liver.

Twenty-two patients with metastatic and primary cancer of the liver were treated with 5-fluoro-2'-deoxyuridine (5FUDR), Mitomycin C (Mito C), and 1 (-2-chlorethyl)-4(methyl-cyclohexyl)-1-nitrosourea (MeCCNU). 5FUDR 0.3 mg/kg/day was administered as a continuous infusion via the hepatic artery. Mito C (10 mg/M2) and MeCCNU (50 mg/M2) were given I.V. and orally, respectively, every 8 weeks. Remission of the neoplastic lesions within the liver was seen in 10 patients (4CR, 6PR). Five patients had stabilization of their lesion neoplasm for at least 4 months. The response rate in this study was 6/15 (40%) in patients with colon cancer metastatic to the liver. Toxicity was mainly hematologic and hepatic. Three patients experienced a platelet count below 25,000 and/or white blood count below 1000. Fifteen patients had hepatic toxicity showing elevation in SGOT and SGPT. The SGOT and SGPT returned to normal when the 5FUDR was discontinued. The combination of 5FUDR intraarterially, and Mito C and MeCCNU systemically, demonstrated activity in malignancies of the liver. This study proved that chemotherapy can be administered systemically and regionally with acceptable toxicity.

Administration, Oral↗