Charge effect on the photoinactivation of Gram-negative and Gram-positive bacteria by cationic meso-substituted porphyrins

Background  

In recent times photodynamic antimicrobial therapy has been used to efficiently destroy Gram (+) and Gram (-) bacteria using cationic porphyrins as photosensitizers. There is an increasing interest in this approach, namely in the search of photosensitizers with adequate structural features for an efficient photoinactivation process. In this study we propose to compare the efficiency of seven cationic porphyrins differing in meso-substituent groups, charge number and charge distribution, on the photodynamic inactivation of a Gram (+) bacterium (Enterococcus faecalis) and of a Gram (-) bacterium (Escherichia coli). The present study complements our previous work on the search for photosensitizers that might be considered good candidates for the photoinactivation of a large spectrum of environmental microorganisms.     

Hippocampal Membranes Contain a Neurotrophic Activity That Stimulates Cholinergic Properties of Fetal Rat Septal Neurons Cultured Under Serum-Free Conditions

Primary cultures of fetal rat septal neurons were used to identify a membrane-associated cholinergic neurotrophic activity. Under serum-free culture conditions, approximately 98% of the septal cells are neurons, and approximately 6% of the neurons are cholinergic as determined immunocytochemically. Crude membranes prepared from rat hippocampal homogenates stimulate choline acetyltransferase (ChAT) activity in treated septal neurons. The membrane-associated trophic activity is apparent at lower protein concentrations than activity present in the soluble fraction and is unevenly distributed in various brain regions; it is highest in hippocampus and striatum and negligible in cerebellum. Membrane trophic activity is developmentally regulated, is heat and trypsin sensitive, and increases the rate of expression of ChAT in septal neurons. Upon gel filtration chromatography of a high-salt membrane extract, trophic activity elutes as a broad peak in the 500 kilodalton (kD) molecular mass range. Stimulation of septal neuronal ChAT activity by either crude membranes or partially purified preparations is not inhibited by antibodies against nerve growth factor (NGF), and its maximal activity is additive to maximally active doses of NGF. The results indicate that hippocampal membranes contain cholinergic neurotrophic activity which may be important for the development of septal cholinergic neurons.     

Obesity‐related hypertension: Pathogenesis,cardiovascular risk,and treatment—A position paper of the The Obesity Society and the American Society of Hypertension

In light of the worldwide epidemic of obesity, and in recognition of hypertension as a major factor in the cardiovascular morbidity and mortality associated with obesity, The Obesity Society and The American Society of Hypertension agreed to jointly sponsor a position paper on obesity‐related hypertension to be published jointly in the journals of each society. The purpose is to inform the members of both societies, as well as practicing clinicians, with a timely review of the association between obesity and high blood pressure, the risk that this association entails, and the options for rational, evidenced‐based treatment. The position paper is divided into six sections plus a summary as follows: pathophysiology, epidemiology and cardiovascular risk, the metabolic syndrome, lifestyle management in prevention and treatment, pharmacologic treatment of hypertension in the obese, and the medical and surgical treatment of obesity in obese hypertensive patients. Obesity (2012)     

Differentiation of pre- and postsynaptic high affinity serotonin receptor binding sites using physico-chemical parameters and modifying agents

The two³H-labeled agonists [³H]8-hydroxy-2-(di-n-propylamino) tetralin ([³H]8-OH-DPAT) and [³H]serotonin ([³H]5-HT) have been used to examine the effects of physico-chemical parameters and modulatory agents on the high affinity 5-HT receptor binding sites in various regions of the rat central nervous system. Sites labeled by [³H]8-OH-DPAT and [³H]5-HT were differentially sensitive to changes in incubation demperature and pH, such that the optimal interaction of [³H]8-OH-DPAT with specific sites in the striatum was at 30°C and pH 7.4, whereas [³H]5-HT sites in the same region were most easily labeled at 2–23°C and pH 8.2. Micromolar concentrations of Mn²⁺ enhanced [³H]5-HT binding but inhibited markedly [³H]8-OH-DPAT binding to striatal membranes. In contrast, both [³H]5-HT and [³H]8-OH-DPAT binding were incerased by the cation in hippocampal membranes. Conversely, GTP reduced the binding of either ligand in the hippocampus but affected only [³H]5-HT binding in the striatum. Furthermore, N-ethylmaleimide inhibited equally [³H]5-HT and [³H]8-OH-DPAT binding to hippocampal membranes, but was markedly less potent against [³H]8-OH-DPAT binding to striatal     

Characterization of the minimum domain required for targeting budding yeast myosin II to the site of cell division

Background  

All eukaryotes with the exception of plants use an actomyosin ring to generate a constriction force at the site of cell division (cleavage furrow) during mitosis and meiosis. The structure and filament forming abilities located in the C-terminal or tail region of one of the main components, myosin II, are important for localising the molecule to the contractile ring (CR) during cytokinesis. However, it remains poorly understood how myosin II is recruited to the site of cell division and how this recruitment relates to myosin filament assembly. Significant conservation between species of the components involved in cytokinesis, including those of the CR, allows the use of easily genetically manipulated organisms, such as budding yeast (Saccharomyces cerevisiae), in the study of cytokinesis. Budding yeast has a single myosin II protein, named Myo1. Unlike most other class II myosins, the tail of Myo1 has an irregular coiled coil. In this report we use molecular genetics, biochemistry and live cell imaging to characterize the minimum localisation domain (MLD) of budding yeast Myo1.     

The delivery of genetic counseling services in Europe

Summary Oranizational forms and the current status of genetic counseling within the health care system of 15 European countries were evaluated by questionnaire and at a symposium, with individuals present from Austria, Belgium, Czechoslovakia, Denmark, the Federal Republic of Germany, the German Democratic Republic, Finland, France, Hungary, Italy, the Netherlands, Norway, Switzerland, the United Kingdom, and the Soviet Union. In spite of wide differences between these countries, certain similarities with respect to the delivery of genetic counseling services could be observed: (i) most genetic counseling is done within university institutions or closely linked to it; (ii) governmental support of genetic counseling is developing slowly, and genetic counseling is usually not yet fully integrated into the health care system; (iii) there is lack of qualified personnel; (iv) no guide lines for formal education have been developed, but a postgraduate training period of no less than four years is considered a minimum; (v) without appropriate support, genetic counseling is a burden for research in human genetics; yet, a strict separation of genetic counseling and research activities is not recommended; (vi) on the average, a team providing genetic counseling for about 1–2 million people should consist of 3–4 physicians, 5–10 technicians, 2–3 secretaries, and other supportive personnel.This study was supported in part by the Deutsche Forschungsgeneinschaft     

Familial Mediterranian fever: clastogenic plasma factors correlated with increased O2 –– production by neutrophils

Familial Mediterranean fever (FMF) is an autosomal recessive disease predominantly affecting Armenians and non-Ashkenazi Jews. The disease begins in childhood with paroxysmal attacks of pain and fever accompanied by peritonitis, pleuritis, and synovitis. During the acute phase, there is a massive influx of polymorphonuclear leukocytes into the serosal membranes, connected with degranulation of the neutrophils and with secretion of lysosomal enzymes and pyrogenic substances. An increase in the lipoxygenase product, leukotriene B₄, a chemotactic agent, and a decrease in the activity of the inhibitor of chemotaxis, C5a, in serosal fluids have been considered responsible. Previous work from our laboratories had shown that the chromosomal instability observed in blood cultures of patients with FMF is secondary to circulating clastogenic factors (CFs), and that the antioxidant enzyme superoxide dismutase, as well as lipoxygenase inhibitors, reduce the chromosome damaging effects. CFs are observed in chronic inflammatory diseases and in various other pathological conditions accompanied by oxidative stress. Similar clastogenic materials were found in supernatants of neutrophils and monocytes after a respiratory burst and were shown to contain lipid peroxidation products and cytokines. In the present study we compared the clastogenic effects exerted by plasma ultrafiltrates from 20 adult patients with FMF to the unstimulated O₂ ^– production of their neutrophils. In comparison to 20 age- and sex-matched controls, which were studied simultaneously, the O₂ ^– production by patient’s neutrophils was routinely higher than that of controls. The clastogenic effects of patient’s plasma, expressed as the number of chromosomal aberrations induced in test cultures of healthy donors, were correlated with the importance of O₂ ^– production by their neutrophils (r = 0.5235). Even if the relative contribution of disturbance in arachidonic acid metabolism, neutrophil activation, and CF formation in the disease process remains unclear, the demonstration of oxidative stress in this genetic disorder suggests the use of antioxidants and free radical scavengers, in particular during acute attacks, when the classical colchicine treatment is without effect. Received: 15 June 1997 / Accepted: 18 July 1997