Library

Notes: Abstract: In basic solutions, pyruvate enolizes and reacts (through its 3-carbon) with the 4-carbon of the nicotinamide ring of NAD+, yielding an NAD-pyruvate adduct in which the nicotinamide ring is in the reduced form. This adduct is a strong inhibitor of lactate dehydrogenase, presumably because it binds simultaneously to the NADH and pyruvate sites. The potency of the inhibition, however, is muted by the adduct's tendency to cyclize to a lactam. We prepared solutions of the pyruvate adduct of NAD+ and of NAD+ analogues in which the —C(O)NH2 of NAD+ was replaced with C(S)NH2, −C(O)CH3, and −C(O)H. Of the four, only the last analogue, 3-[4-(reduced 3-pyridine aldehyde-adenine dinucleotide)]-pyruvate (RAP) cannot cyclize and it was found to be the most potent inhibitor of beef heart and rat brain lactate dehydrogenases. The inhibitor binds very tightly to the NADH site (Ki∼ 1 nM for the A form). Even at high concentrations (20 μM), RAP had little or no effect on rat brain glyceraldehyde-3-phosphate, pyruvate, α-ketoglutarate, isocitrate, soluble and mitochondrial malate, and glutamate dehydrogenases. The glycolytic enzymes, hexokinase and phosphofructokinase, were similarly unaffected. RAP strongly inhibited lactate production from glucose in rat brain extracts but was less effective in inhibiting lactate production from glucose in synaptosomes.

Notes: Koch's triangle contains the compact part of the atrioventricular node and is anatomically delineated by the Eustachian ridge, the membranous septum, and the insertion of the tricuspid valve. In-feriorly, Koch's triangle ends at the site of the OS of the coronary sinus and, in part, is continuous with the sub-Eustachian pouch. Catheter ablation procedures for several types of reentrant tachycardias are based on identifying these anatomical landmarks. Variability in the dimensions of Koch's triangle thus may be clinically relevant. We examined 50 hearts. Anatomical landmarks measured were the Eustachian ridge, the tricuspid valve, the overall length between the membranous septum and the coronary sinus, the width of the coronary sinus, the Eustachian ridge in its roof and the distance to the tricuspid valve, and that of the sub-Eustachian pouch. Individual variations were marked. The mean values (± SD) were: Eustachian ridge 29.4 ± 5.3 mm. tricuspid valve 28.9 ± 4.5 mm, coronary sinus 10.8 ± 2.2 mm, Eustachian ridge 3.7 ± 2.3 mm, space underneath coronary sinus 8.6 ± 3.4 mm, and sub-Eustachian pouch 26.8 ± 3.3 mm. The overall length varied between 15 and 38 mm, with a mean of 26.3 ± 4.5. In conclusion, Koch's triangle shows considerable individual variations in size. Given the fact that the absolute figures for the range in size of the compact atrioventricular node is much less than that of Koch's triangle, these variations have implications for catheter ablation procedures.

Notes: For the theoretical modeling of physical transformations such as boiling, freezing, glassification, or mixing, it is necessary to know how the partition function of a system depends on its density. Many current treatments rely either on low density expansions or they apply to very simple and symmetric molecular shapes, like spheres or rods. Here we develop an exact analytical lattice theory of materials and mixtures that applies to arbitrarily complex molecular shapes over the full range of densities from gas to crystal. The approach is to compute partition functions for small numbers of shapes and to explore the dependence on density by varying the volume of the system. Recently a question has been raised about whether entropies of dissolution are better treated using classical solvation theories or Flory–Huggins theory. We explore this for a range of molecular sizes and shapes, from lattice squares and cubes, to rods, polymers, crosses, and other shapes. Beyond low densities, the entropic component of the chemical potential depends on shape due to the different degrees to which molecules "interfere'' with each other. We find that neither Flory–Huggins nor classical solvation theories is correct for all shapes. Molecules that are "articulated'' are remarkably well treated by Flory–Huggins theory, over all densities, but globular molecules are qualitatively and quantitatively different, and are better treated by the classical chemical potential, consistent with experiments of Shinoda and Hildebrand. These results confirm that the Flory–Huggins theory differs from classical theory not because of molecular size differences per se; it accounts for the coupling between translations and conformational steric interference. © 1995 American Institute of Physics.

Notes: A 67-year-old man presented in April 1983 with three painful ulcers with bluish margins on the right shin and the lower back. The largest lesion was 6 cm in diameter. The lesions had started as painful nodules 8 months previously; these ulcerated within 2 weeks and fluctuated in size. There was no history of arthritis or bowel disease. Full blood count, erythrocyte sedimentation rate, serum electrolytes, urea, and liver enzymes were normal. Antinuclear antibody and rheumatoid factor were negative. The serum IgA level was elevated at 7.35 g/L (normal 0.8–4 g/L). Immunoelec-trophoresis revealed IgA kappa paraproteinemia. Bence Jones protein was not found in the urine. Skeletal survey, bone marrow, sigmoidoscopy, and rectal biopsy were normal. No bacterial pathogens were grown. Histology of the edge of the ulcer showed dermal abscesses, dermal granulation tissue, and chronic inflammatory infiltrate extending to the subcutis.During the next 2 years the patient developed active pyodermatous lesions on the trunk and left arm. Between April 1983 and March 1986, the patient received a combination of prednisolone 15–40 mgand azathioprine 50–100 mg daily, a 12-week course of dapsone 200 mg daily, and repeated courses of oral and topical antibiotics. During this period, although the disease activity was lessened, the lesions never healed completely.In April 1986, the pyoderma gangrenosum was more active; the ulcers enlarged and deyeloped active pustules at the margins. While the patient was still taking prednisolone 15 mg and azathioprine 50 mg, oral cyclosporin A 6 mg/kg daily (250 mg twice daily) was started; after 3 weeks, the dosage was increased to 10 mg/kg daily (400 mg twice daily) and the prednisolone was reduced to 5 mg daily over 2 months. At 3 weeks the ulcers started to heal, and at seven weeks all ulcers healed, leaving papery scars. Over a period of 4 weeks, the dosage of cyclosporin A was gradually reduced and the ulcers remained healed at a maintenance dosage of 250 mg daily. There was no change in the paraproteinemia. Weekly whole blood cyclosporin A levels were measured, and they fluctuated between 800 ng/ml and 910 ng/ml. On two occasions the levels were 〉1500 ng/ml.During the course of the treatment, the patient developed nausea, hypertrichosis, transient thrombocytopenia, and hypertension (blood pressure of 190/110 mmHg); creatinine clearance fell from 87 to 46 ml/min. At a maintenance dosage of 250 mg daily, the blood pressure was 180/100 mmHg and creatinine clearance was 64 ml/min.

Notes: Betahistine is a cerebral vasodilator structurally related to histamine, which stimulates H1 bronchial and vascular receptors. We report the case of a 28-year-old female patient who presented bronchospasm during treatment with betahistine hydrochloride. The prick test was negative. The oral challenge test showed bronchospasm and urticarial lesions. To the best of our knowledge, this is the first case of betahistine-induced bronchospasm reported in the literature. The study carried out failed to reveal the mechanism of the reaction.

Notes: Abstract New insights into atherosclerosis, the most common disease affecting coronary arteries, may change therapeutic strategies from largely symptomatic to causal. Atherosclerotic plaques contain a lipid-related, immune-mediated inflammation, with release of secretory products capable of changing plaque morphology. Plaques prone to complications contain large numbers of inflammatory cells; stable plaques contain little inflammation. Similarly, atherectomy specimens from patients with coronary syndromes revealed more inflammatory cells in unstable than in stable patients. These observations, and the fact that acute coronary syndromes are associated with increased blood levels of inflammatory markers, have renewed interest in the possible relationship between infection and atherogenesis. Of all potential candidate antigens, Chlamydia pneumoniae presently is considered the most likely because a substantial number of patients with unstable syndromes contain C. pneumoniae-reactive T cells, both in blood and within the atherosclerotic plaque, suggesting enhancement of intraplaque inflammation.