Human placenta metabolizes fatty acids: implications for fetal fatty acid oxidation disorders and maternal liver diseases

The role of fat metabolism during human pregnancy and in placental growth and function is poorly understood. Mitochondrial fatty acid oxidation disorders in an affected fetus are associated with maternal diseases of pregnancy, including preeclampsia, acute fatty liver of pregnancy, and the hemolysis, elevated liver enzymes, and low platelets syndrome called HELLP. We have investigated the developmental expression and activity of six fatty acid beta-oxidation enzymes at various gestational-age human placentas. Placental specimens exhibited abundant expression of all six enzymes, as assessed by immunohistochemical and immunoblot analyses, with greater staining in syncytiotrophoblasts compared with other placental cell types. beta-Oxidation enzyme activities in placental tissues were higher early in gestation and lower near term. Trophoblast cells in culture oxidized tritium-labeled palmitate and myristate in substantial amounts, indicating that the human placenta utilizes fatty acids as a significant metabolic fuel. Thus human placenta derives energy from fatty acid oxidation, providing a potential explanation for the association of fetal fatty acid oxidation disorders with maternal liver diseases in pregnancy.     

Reversal of slow flow phenomenon during primary stenting by bail-out administration of abciximab

BACKGROUND: Slow flow or no reflow phenomenon is increasingly being recognized as a serious problem during coronary angioplasty and stenting. This phenomenon is seen more often during angioplasty in highly thrombogenic milieux, especially in a setting of acute myocardial infarction. The treatment of this complication is often not satisfactory. In this study the authors assessed the efficacy of abciximab, a potent antiplatelet drug, in treating slow flow or no reflow phenomenon during primary percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction (AMI). METHODS: Twenty-one instances of persistent slow flow phenomenon were encountered in 131 consecutive patients subjected to primary PTCA for AMI (16%). It was more common in patients presenting with AMI complicated by cardiogenic shock (nine of 21, 43%). Of these 21 cases of slow flow, 10 patients were given injection abciximab during the procedure of primary PTCA as a bail-out measure after encountering the complication of slow flow or no reflow. A pre-discharge coronary angiography was carried out in all patients who survived. RESULTS: In seven of 10 patients in the abciximab group flow had improved to TIMI-3. In contrast, in the non-abciximab group TIMI flow improved in only four of 11 patients. Patients with persistent slow flow had significantly higher mortality at the first 30-day follow-up than patients with TIMI-3 flow (33% versus 1.8%, p<0.001). CONCLUSION: In this small nonrandomized study significant improvement in coronary flow was achieved by using intravenous abciximab after observing slow flow or no reflow phenomenon during primary PTCA. More frequent use of this drug in this milieu might help in preventing the development of this complication. Larger studies are warranted to confirm this life-saving beneficial effect of bail-out administration of abciximab during primary angioplasty.     

Transformation of Nicotiana tabacum with a native cry1Ia5 gene confers complete protection against Heliothis armigera

A cry1Ia5 insecticidal toxin coding gene has been cloned from an Indian isolate of Bacillus thuringiensis. Sequence analyses of the cry1Ia5 gene revealed the absence of potential polyadenylation signal sequences thus making it a suitable candidate for expression in plants without extensive modification. This possibility was examined by subcloning the cry1Ia5 gene into a plant expression vector and then transferring it to Nicotiana tabacum through Agrobacterium-mediated transformation. Our results demonstrate that N. tabacum with a stably integrated native cry1Ia5 gene afforded complete protection against predation by Heliothis armigera. Forty three percent of the transgenic plants displayed a high level of protection against insect predation. The protection obtained in transgenic plants with the cry1Ia5 gene was comparable to that obtained with the synthetically modified cry1A(b) or cry1A(c) genes. The results demonstrate that novel insecticidal genes already exist in nature that do not require extensive modifications for efficient expression in plants.     

Methanogenic and perchloroethylene-dechlorinating activity of anaerobic granular sludge

The biodegradation and toxicity of tetrachloroethylene (C₂Cl₄) and trichloroethylene (C₂HCl₃) were studied with different anaerobic enrichment cultures using the following electron donors: acetate, propionate, butyrate, methanol, formate and hydrogen. All of them sustained dechlorination except propionate, for which C₂Cl₄ biodegradation rates were not significant. The best results were obtained with butyrate. Hydrogen appeared to be a relevant electron donor for dechlorination with the present cultures. In the presence of specific inhibitors such as bromoethanesulphonate or molybdate, a slight inhibition of dechlorination was observed. According to dechlorination kinetics, Monod-type behaviour was observed up to 120 μM C₂Cl₄ or 200 μM C₂HCl₃ with K _s values around 7 μM for both compounds. Dechlorination was partially inhibited at higher concentrations. In contrast, methanogens, or at least methane production, were more sensitive to the presence of chlorinated ethylenes and inhibition of methanogenesis was observed to different extents over all the C₂Cl₄/C₂HCl₃ concentration range tested, even at the lowest concentrations. Received: 17 April 1998 / Received revision: 18 June 1998 / Accepted: 19 June 1998     

Evidence that corticosterone is not an obligatory intermediate in aldosterone biosynthesis in the rat adrenal

CGS 16949A is a potent inhibitor of aromatase in vitro with an IC50 of 0.03 microM for the inhibition of LH-stimulated estrogen biosynthesis in hamster ovaries. In vivo, CGS 16949A leads to sequelae of estrogen deprivation (e.g. regression of DMBA-induced mammary tumors) without causing adrenal hypertrophy in adult rats. To complement these in vitro and in vivo findings, the effect of CGS 16949A on adrenal steroid biosynthesis in rats was investigated in vitro and in vivo. The surprising finding in vitro was that CGS 16949A inhibited aldosterone biosynthesis (IC50 = 1 microM) at concentrations 100 times lower than those for inhibition of corticosterone biosynthesis (IC50 = 100 microM). Moreover, deoxycorticosterone (DOC) concentrations were elevated at all concentrations of CGS 16949A which inhibited aldosterone synthesis. The classical biosynthetic pathway for aldosterone is DOC----corticosterone----18-OH-corticosterone----aldosterone. Thus inhibition of aldosterone biosynthesis, reflected in DOC accumulation, without affecting corticosterone concentrations, indicates that corticosterone is not an obligatory intermediate in the conversion of DOC to aldosterone in the rat. In vivo, CGS 16949A showed a suppression of plasma aldosterone in ACTH-stimulated male rats at doses which did not significantly affect plasma corticosterone. In conclusion, aldosterone measured both in vitro and in vivo must be derived primarily from a biosynthetic pathway in which corticosterone is not obligatory intermediate.     

Synthesis,Spectral Characterization,and Pharmacological Importance of New 4H-1,4-Benzothiazines,Their Sulfone Analogues,and Ribofuranosides

The present article describes the synthesis of new 4H-1,4-benzothiazines via condensation and oxidative cyclization of substituted 2-aminobenzenethiols with compounds containing active methylene groups. It is believed that the reaction proceeds via intermediary of the enaminoketone system. The sulfone derivatives were synthesized by oxidation of 4H-1,4-benzothiazines using 30% hydrogen peroxide in glacial acetic acid. Benzothiazines were used as bases to prepare ribofuranosides by treatment with a sugar derivative (β-D-ribofuranosyl-1-acetate-2,3,5-tribenzoate). The pharmacological importance of the synthesized compounds was evaluated by their, antimicrobial properties against various bacterial strains and fungal species. The structures of the compounds have been confirmed by spectral and chemical analysis.