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V Lynch

Publications and source records attributed to V Lynch.

31 records · Page 2Linked to original sources
PubMed1990

An approach to trapping gamma-glutamyl radical intermediates proposed for vitamin K dependent carboxylase: alpha,beta-methyleneglutamic acid.

The vitamin K dependent carboxylase activates the glutamyl gamma-CH of substrate peptides for carboxylation by producing a gamma-glutamyl free radical, a gamma-glutamyl carbanion, or through a concerted carboxylation. We propose to intercept the putative gamma-glutamyl free radical by the intramolecular rearrangement of a substrate containing the alpha,beta-cyclopropane analogue of glutamic acid. The rearrangement of cyclopropylcarbinyl radicals into 2-butenyl radicals is rapid, exothermic, and considered diagnostic of free-radical formation. 1-Amino-2-(carboxymethyl)cyclopropane-1-carboxylate, the beta-cyclopropane analogue of glutamic acid, was synthesized starting from diethyl alpha-ketoglutarate. The alpha-keto ester was first treated with benzonitrile in sulfuric acid, to yield diethyl alpha,alpha-dibenzamidoglutarate. The alpha,alpha-dibenzamido acid was cleaved to produce the alpha,beta-dehydroamino acid and benzamide on treatment with p-toluenesulfonic acid in hot benzene. Diazomethane addition to the dehydroamino acid resulted in cycloaddition of diazomethane and production of the pyrazoline, which upon irradiation lost N2 to give the protected cyclopropane-containing amino acid analogue. Acidic hydrolysis of the N-benzoyl-alpha,beta-methyleneglutamate diethyl ester resulted in the production of the unprotected amino acid, alpha,beta-methyleneglutamic acid, in high yield. A single dehydroamino acid and a single methyleneglutamic acid isomer were produced in this synthesis; both are identified as the Z isomer, the former by NMR using the nuclear Overhauser effect and the latter through X-ray crystallographic analysis of N-benzoyl-alpha,beta-methyleneglutamate diethyl ester. Saponification of a N-protected methyleneglutamic acid dialkyl ester using limiting alkali was shown to selectively yield the alpha-alkyl ester gamma-acid. The reaction was used to produce alpha,beta-cyclopropane-containing analogues of the carboxylase substrates N-t-Boc-L-glutamic acid alpha-benzyl ester and N-benzoyl-L-glutamic acid alpha-ethyl ester. The cyclpropane-containing analogues were tested and found to be neither substrates for nor inhibitors of the rat liver microsomal vitamin K dependent carboxylase. The inability of the enzyme to recognize these substrate analogues is attributed to the alpha-alkyl substitution, which apparently abolishes substrate binding.

Animals↗
PubMed1984

Upper airway obstruction caused by massive subcutaneous emphysema.

Acute upper airway obstruction is a potentially life-threatening event. The most common causes include foreign body inhalation, thermal injury, inflammation, angioedema and trauma. Airway obstruction caused by submucosal extension of subcutaneous emphysema has only been previously reported once. We report the case of a patient who suffered a respiratory arrest as a result of hypopharyngeal and laryngeal swelling associated with massive subcutaneous emphysema.

Airway Obstruction↗
PubMed1982

Behavioral and biochemical changes induced by lithium and L-tryptophan in muricidal rats.

Lithium (0.5--12 meq/kg) and L-tryptophan (100--800 mg/kg) inhibited the muricidal (mouse killing) response in isolated, male, Long Evans rats and did so both in an acute (single dose) and on an longer-term intraperitoneal treatment basis. The response was dose-dependent. There was no concomitant motor impairment at doses effective in inhibiting the muricidal response. Plasma lithium levels were positively correlated with the percentage inhibition of muricidal behavior. When lithium and L-tryptophan were administered in combination in their smallest effective doses, the behavioral interaction was synergistic in the acute and addictive in the longer-term treatment. The effects of pharmacological treatment on the inhibition of muricidal behavior were: lithium and L-tryptophan greater than L-tryptophan greater than - lithium. The results of biochemical assays showed that these compounds fore- and hindbrain serotonin turnover. The biochemical action of lithium and L-tryptophan in combination on brain serotonergic pathways was again clearly more potent than that which occurred after treatment with either lithium or L-tryptophan alone. The magnitude of the biochemical changes paralleled those of psychopharmacological changes. These data show an interaction between lithium and L-tryptophan both in the repression of aggressive behavior in rats and in the alteration of centrally acting serotonergic function. These data further elucidate a mechanism of action through central serotonergic function for a psychotherapeutic agent, lithium, and for aggressive behavior, muricide.

Aggression↗
PubMed1972

Amino acid metabolism during starvation in human pregnancy.

To evaluate the factors regulating gluconeogenesis in pregnancy, plasma amino acid levels were determined during the course of an 84-90 hr fast in physically healthy women studied during wk 16-22 of gestation (before undergoing therapeutic abortion), and in nonpregnant controls. The effect of pregnancy on the glycemic response to exogenous alanine administration during starvation was also investigated. In the nonpregnant group fasting resulted in a 2- to 3-fold increase in the levels of plasma valine, leucine, isoleucine, and alpha-aminobutyrate, while the concentration of alanine and glycine fell. In the pregnant group, the levels of most amino acids were significantly reduced in the postabsorptive state. With starvation, the plasma concentration of alanine fell more rapidly in the pregnant group and was significantly below that of the nonpregnant subjects for the first 60 hr of the fast. In contrast, a significant elevation in plasma glycine, serine, and threonine was observed in the pregnant group after 84 hr of fasting, whereas similar increments were not demonstrable until after 10 days of fasting in previously studied nonpregnant obese subjects. Paralleling the changes in maternal plasma, amniotic fluid levels of valine, leucine, and isoleucine increased while that of alanine fell during the fast. Although the plasma glucose concentration was lower in the pregnant group at termination of the fast, intravenous alanine administration (0.15 g/kg), resulted in a prompt, comparable increase (20-25 mg/100 ml) in plasma glucose in both groups of subjects. It is concluded that (a) pregnancy accelerates and exaggerates the hypoalaninemic and hyperglycinemic effects of starvation; (b) lack of key endogenous substrate rather than altered intrahepatic processes may limit hepatic gluconeogenesis in pregnancy and contribute to gestational hypoglycemia; (c) maternal caloric deprivation profoundly alters the levels of amino acids in amniotic fluid.

Adolescent↗
PubMed1970

Starvation in human pregnancy: hypoglycemia, hypoinsulinemia, and hyperketonemia.

In women fasted during the second trimester of pregnancy, concentrations of glucose and insulin in the plasma fell to a greater extent and ketone acid concentrations in the blood rose more rapidly than in nonpregnant controls. Nitrogen excretion in the urine, particularly ammonia, was increased in the pregnant group. Continuous glucose utilization by the conceptus may exaggerate and accelerate the metabolic consequences of starvation.

Blood Glucose↗
PubMedDate not supplied

Thoracoscopic management of primary spontaneous pneumothorax.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) is the preferred option for the surgical management of primary spontaneous pneumothorax (PSP). AIMS: To evaluate the role of thoracoscopic blebectomy with and without chemical pleurodesis. METHODS: A retrospective study was performed on 113 consecutive cases carried out in one unit. RESULTS; One hundred and thirteen VATS procedures were performed on 108 patients. The mean age was 23 years (range 14-45). The male to female ratio was 82:26. Recurrent pneumothorax was the indication for surgery in 80%. Conversion to an open procedure was required in 10 cases (9%), most commonly due to severe adhesions. Successful endoscopic blebectomy was performed in 98 cases (87%), 48 of which had an additional chemical pleurodesis. Follow-up is currently to a mean of 28 months. Recurrence has occurred in eight cases, including only three in the group managed with additional chemical pleurodesis (6.25%). CONCLUSION: VATS with blebectomy and chemical pleurodesis is a safe and effective procedure in the management of PSP.

Adolescent↗
PubMedDate not supplied

Evaluation of the methadone-alcohol interaction. I. Alterations of plasma concentration kinetics.

Clinical anecdotal reports have indicated a probably additive and/or synergistic response to the co-ingestion of ethyl alcohol and methadone. This study investigated the possible explanations for this observations, which may be associated with alterations of the plasma concentration dynamics of methadone and alcohol in the rat. Plasma concentrations of ethanol, methadone or both were followed over an eight hour period following substance administration. GC/FID and GC/MS were employed to quantify ethanol and methadone, respectively. The results of this study indicated that ethyl alcohol significantly increased peak methadone concentrations. Further, methadone significantly depressed late alcohol elimination.

Animals↗