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Biomedical subjects

F H Schmidt

Publications and source records attributed to F H Schmidt.

At least 37 records · Page 2Linked to original sources
PubMed1985

A new inhibitor of the long-chain fatty acid transfer across the mitochondrial membrane: 2-(3-methylcinnamylhydrazono)-propionate (BM 42.304).

Using two different assay systems to distinguish between overt and inner forms of carnitine palmitoyl transferase (CPT, EC 2.3.1.21) of intact guinea-pig liver mitochondria, we have shown that the hypoglycemic agent 2-(3-methylcinnamylhydrazono)-propionate (BM 42.304) inhibits the activity of carnitine-acylcarnitine translocase of liver mitochondria. The results offer an explanation for the inhibitory effect of the compound on ketogenesis with oleate but not with octanoate in the perfused guinea-pig liver, previously reported by us (Biochem. Pharmacol. 32, 3405-3412, 1983).

Acyltransferases↗
PubMed1985

Inhibition of cholesterol biosynthesis by BM 15.766.

BM 15.766 (4-[2-[1-(4-chlorocinnamyl)piperazin-4-yl]ethyl]benzoic acid) showed a dose dependent action on 14C-acetate incorporation in cholesterol and intermediates including squalene by adult rat hepatocytes in primary monolayer culture. The biosynthesis of cholesterol could be reduced by more than 90%. Simultaneously, the 7-dehydrocholesterol level rose in the cells and, to a less marked extent, in the culture medium.

Animals↗
PubMed1984

The pharmacological profile of the thromboxane A2 antagonist BM 13.177. A new anti-platelet and anti-thrombotic drug.

BM 13.177 (4-[2-(benzenesulfonamido)-ethyl]-phenoxyacetic acid) is a representative of a new class of sulfonamidophenylcarboxylic acids which possess platelet-inhibitory and anti-thrombotic activity and inhibits the contraction of rabbit aorta stimulated by PG endoperoxides and TXA2. BM 13.177 5 mg/kg body weight p.o. protected rabbits from arachidonate-induced sudden death and greater than or equal to 10 mg/kg dose-dependently reduced the experimental thrombus formation induced in the rabbit aorta by perivascular administration of silver nitrate. In guinea-pigs, the collagen-induced bronchoconstriction was inhibited in a dose- and time-dependent fashion. The formation of TXA2 and the TXA2-induced platelet aggregation and smooth muscle contraction are probably crucial events in these experimental models. The protective effect of BM 13.177 may, therefore, be due to the TXA2-antagonizing effect of BM 13.177, which has been conclusively demonstrated in human platelets (PATSCHEKE and STEGMEIER, Thrombosis Res., 33, 277-288 (1984). The antagonism of TXA2 is supported by the observation that BM 13.177 also specifically inhibits the contraction of isolated arterial strips from rabbits which were stimulated with the thromboxane A2 mimetic U 46619. Schild-plot with a slope close to unity suggests a competitive type of antagonism. BM 13.177 exhibited neither anti-inflammatory nor ulcer-inducing activity of cyclooxygenase inhibitors. Furthermore it did not block the TXB2 formation in spontaneously clotting blood from rabbits and did not inhibit the release of prostacyclin-like activity from rabbit aortas. The lack of toxicological effects in long-term toxicity studies in rat and dog, together with the absence of objective and subjective side effects in the first human studies have encouraged us to initiate clinical trials in order to evaluate the therapeutic benefit of this new approach in humans.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1984

In vivo and in vitro effects of a new hypoglycemic agent, 2-(3-methylcinnamylhydrazono)-propionate (BM 42.304) on glucose metabolism in guinea pigs.

A new compound, 2-(3- methylcinnamylhydrazono )-propionate (BM 42.304), showed a dose dependent hypoglycemic effect in starved guinea pigs after both oral and intraperitoneal administration. In contrast to biguanides (phenformin and metformin) the new compound produced only a moderate increase in blood lactate concentration and did not alter the content of adenine nucleotides in the freeze-clamped liver in vivo. Gluconeogenesis from a variety of precursors in the perfused guinea-pig liver was also inhibited by BM 42.304. These properties suggest that the compound deserves further investigation in connection with its potential usefulness for the treatment of diabetes.

Animals↗
PubMed1984

Gentamicin diffusion across hydrogel bandage lenses and its kinetic distribution on the eye.

Soft contact lenses have been used as therapeutic bandages to aid epithelial healing following pentrating keratoplasty. Often the hydrogel lenses are used in conjunction with topical medications such as gentamicin. A reported complication is the persistence of infectious ulcers even though the eye is being treated with topical antibiotics. The purpose of this study was to measure the gentamicin diffusion coefficients for some hydrogel bandage lenses and to design a kinetic model to estimate the drug distribution on an eye covered with a hydrogel contact lens. The model includes the hydrogel diffusion coefficients and literature values for tear production, tear exchange per blink around the edge of a lens, fit, etc. From the computer generated data, it can be shown that the permeability of gentamicin sulfate through the Saulfon-80 hydrogel lens on a normal eye was only 0.002% of the amount of the drug under the contact lens after 10 minute intervals of topical drug application. The important drug distribution pathway was around the edge of the lens.

Biological Availability↗
PubMed1983

Studies on the mechanism of action of the hypoglycemic agent, 2-(3-methylcinnamylhydrazono)-propionate (BM 42.304).

A new hypoglycemic agent, 2-(3-methylcinnamylhydrazono)-propionate MCHP (BM 42.304) was shown to be an inhibitor of the transfer of long-chain fatty acids across the mitochondrial inner membrane. The following data support this conclusion: the drug, at already 5 microM, inhibited ketogenesis from oleate but not from octanoate in the perfused guinea-pig liver; likewise, ketogenesis from L-(-)-palmitoylcarnitine and palmitoyl-CoA + L-(-)-carnitine, but not from octanoate, was depressed in isolated guinea-pig liver mitochondria. Oxigraphic measurements of the oxygen uptake by isolated mitochondria showed that the drug impaired oxygen uptake with the long-chain fatty acid derivatives but not with octanoate. Finally, in vivo effects of the drug such as hypoketonemia and an increased concentration of free fatty acids in blood are in agreement with the above formulated mechanism of action. A comment is given on the relationships between fatty acid oxidation and gluconeogenesis in the guinea-pig liver.

Animals↗
PubMed1983

A mathematical model for estimation of infarct size from serum creatine phosphokinase.

A mathematical model for kinetics of creatine phosphokinase (CK) after myocardial infarct is presented. The transport of CK from the infarct to the distribution space is modeled by a gamma variate. CK is released from the distribution space by a first-order process. The model permits simultaneous estimation of the disappearance rate parameter KD, the integrated appearance function, and the baseline from a set of observations of serum CK concentration.

Computers↗
PubMed1982

Phosphorylation and hydrolysis of 7-deazaadenine nucleotides by rat liver and beef heart mitochondria.

Tubercidin nucleotides [tubercidin 5'-mono-phosphate (TuMP), 5'-diphosphate (TuDP), and 5'-triphosphate (TuTP)] were tested as potential substrates for the mitochondrial phosphotransferases from rat liver and beef heart. TuDP is recognized by the mitochondrial translocase and phosphorylated by the respiratory chain enzymes in both mitochondria and submitochondrial particles from rat liver and beef heart; the low transport rate of the analogue into the matrix space of the intact organelles seems to be not a limiting step in the formation of TuTP. The phosphorylation of TuDP is significantly lower in beef heart mitochondria because of a higher specificity for ADP of the heart oxidative phosphorylation system. On the basis of the kinetic parameters of the partially purified liver mitochondrial adenylate kinase, one can conclude that the liver mitochondria are able to phosphorylate in vivo TuMP at a rate practically equal to the rate of AMP phosphorylation. The liver mitochondrial NDP kinase ensures a further fast phosphorylation of TuDP without the direct involvement of respiratory chain enzymes. In the case of heart mitochondria, two factors limit the rate of TuMP phosphorylation to TuTP: the lower acceptor activity of adenylate kinase with TuMP as compared with AMP and the different localization of heart NDP kinase situated on the inner face of the inner mitochondrial membrane. TuDP and TuTP preserve the ability of the natural nucleotides to interact with the "tight" nucleotide binding sites of isolated or membrane-bound F1. The low hydrolytic rate of TuTP with F1 may be related to the unusual flexibility of the glycosyl bond of tubercidin nucleotides in aqueous solution, with a high accessibility to syn conformation.

Adenine Nucleotides↗
PubMed1979

[Fractional distribution of anti-glucagon immunoreactivity (GIR) and amino acid concentration in the plasma in duodenopancreatectomized patients; preliminary report].

Glucagon immunoreactivity (IRG) was measured in plasma of 8 duodenopancreatectomized patients with antiserum 30-K. Arginine infusions failed to raise plasma IRG, whereas in control subjects IRG rose 3-fold. Column chromatography revealed that the basal IRG measured in these plasmas was not due to glucagon (molecular weight 3485) but to other plasma factors, mainly of high molecular weight. This suggests that diabetes mellitus does not require the presence of glucagon to produce the clinical picture, as suggested by other authors. Plasma levels of the amino acids alanine, serine, ornithine, and arginine were significantly (p less than 0.05) elevated, the former two being gluconeogenic substrates and the latter two constituents of the urea cycle. This amino acid abnormality may be a consequence of glucagon deficiency.

Amino Acids↗
PubMed1979

Glucagon immunoreactivities and amino acid profile in plasma of duodenopancreatectomized patients.

Glucogon immunoreactivity (IRG) was measured in plasma of duodenopancreatectomized subjects with a nonspecific (K-4023) and a specific (30-K) glucagon antiserum. After an overnight fast, plasma IRG (K-4023) was significantly (P < 0.05) higher in the subjects without pancreas, averaging 782+/-79 (SEM) pgeq/ml, than in the controls (482+/-80 pgeq/ml). IRG (30-K) of 162+/-68 pg/ml did not change during an infusion of arginine (450 mg/kg per 40 min). Insulin deprivation during 3 d in one patient did not restore the IRG response to arginine as reported in depancreatized dogs.Bio-Gel P-30 column chromatography revealed that virtually all IRG (30-K) measured in whole plasma was of different molecular weight than glucagon, and primarily of a mol wt >/= 40,000. Intravenous arginine did not significantly alter the chromatographic pattern of these plasmas. Thus, as postulated by others, duodeno-pancreatectomized humans have virtually no circulating 3,500-dalton glucagon. Hence, the presence of 3,500-dalton glucagon in plasma is not a condition for the diabetic state. It might, nevertheless, when present in normal or excessive amounts, worsen the metabolic state of diabetic patients. Among 14 amino acids measured in plasma of these patients, the concentrations of alanine, serine, ornithine, and arginine were significantly (P < 0.05) elevated to approximately twice that of normal: alanine and serine are both substrates for gluconeogenesis, whereas ornithine and arginine are involved in the formation of urea, the second product of hepatic gluconeogenesis. As the concentrations of branched chain amino acids were not grossly altered, it is hypothesized that this amino acid pattern is a consequence of glucagon deficiency rather than secondary to the diabetic state of these patients.

Adult↗
PubMed1977

[The enzymatic determination of maltose in blood (author's transl)].

An enzymatic method for the determination of maltose in blood is described. In this method after neutral deproteinization the assay is carried out by the hexokinase technique [6--7] after splitting of the maltose with alpha-glucosidase [8]. This time-saving procedure of high specificity and sensitivity requires only small volumes of blood. The practicability of the method is shown by analysis of blood level during an infusion of maltose.

Alloxan↗
PubMed1977

Contraceptive and sterilization practices and extrauterine pregnancy: a realistic perspective.

Comparative data on the incidence of ectopic pregnancy among accidental pregnancies associated with failure of a contraceptive or sterilization procedure are shown in Table 16. The practical clinical significance of the data in this review is predicated upon a number of related factors. One of the most important of these is the realistic failure rate (or success rate) of each contraceptive or sterilization method. The reported efficacy of various contraceptive methods has such a wide range that we have not attempted to calculate the likelihood that a woman may experience an ectopic pregnancy within a particular time period while using a specific method. The success or failure rate of each method is influenced by such variables as (1) the conscientiousness and ability of the patient to follow instructions, (2) the true failure rate of the method itself, (3) the experience of the clinician prescribing a method or performing a surgical procedure, and (4) other factors less clearly defined. Because of these many variables, the data shown in Table 16 were calculated on the basis of the number of reported accidental pregnancies which occurred coincidentally with, or subsequent to, a specific contraceptive or sterilization modality. (formula: see text). These data do not reflect the actual rate of occurrence of ectopic pregnancy with respect to woman-months of experience. We recognize the significant influence that age, race, gravidity, and socioeconomic factors have upon the incidence of ectopic pregnancy, but were unable to control for these factors in the data presented in this review. These data reprresent only what has occurred under specific circumstances and cannot logically be extrapolated to any specific future case or study series. It is important to emphasize the necessity of constant awareness by the medical and paraprofessional personnel of the potentially increased risk to the patient of an extrauterine pregnancy should one or another of these contraceptive or sterilization procedures fail. Complacency or a false sense of security on the part of responsible medical personnel concerning women who are "protected against conception" can quickly lead to a life-threatening situation in case of an ectopic pregnancy. Prompt diagnosis and definitive treatment of the extrauterine pregnancy is vital for the successful management of this serious complication of conception.

Contraceptive Agents, Female↗