Short-term effects of angiotensin II receptor blockade in patients with primary glomerulonephritis: pilot study.

OBJECTIVE: There is evidence that angiotensin II, the main effector of renin-angiotensin system, plays a crucial role in the pathogenesis of chronic renal injury. Angiotensin II type 1 (AT-1) receptor blockers reduce renin-angiotensin system activity by blocking the receptor, the activation of which is responsible for the majority of deleterious angiotensin II effects. The aim of the present study was to investigate renal and metabolic effects of specific AT-1 receptor blocker-losartan in patients with primary glomerulonephritis. DESIGN: Pilot clinical study. SETTING: Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdańsk, Poland. PARTICIPANTS: Fifteen patients aged 43.3 +/- 11.3 years with primary glomerulonephritis confirmed by renal biopsy were studied. INTERVENTION: Creatinine clearance, urinary excretion of protein and uric acid, urinary activity of N-acetyl-beta-D-glucosaminidase, and serum concentrations of lipids, protein, and uric acid were evaluated before and after 3 months of losartan (Cozaar; Merck Sharp & Dohme, Harlow, Essex, United Kingdom) treatment at a dose of 25 mg daily. RESULTS: We found a significant reduction of urinary excretion of protein (P <.008; average, 32%). Results also revealed a decrease of serum uric acid level (P <.01), probably as a consequence of elevated uric acid urinary excretion (P <.09). No significant changes in creatinine clearance, N-acetyl-beta-D-glucosaminidase activity, protein, or lipid levels were observed. CONCLUSION: We concluded that losartan treatment at a small dose of 25 mg daily produces antiproteinuric effect without adverse effects, notably with no decrease of glomerular filtration, and simultaneously induces beneficial changes in purine metabolism.     

Addition of oxiranes to the acids of phosphorus. Direction of ring opening

The proportion of the α- and β-ring opening in the addition of unsymmetrically substituted oxiranes to P? OH acids namely diethyl phosphoric acid, phosphorous acid, and phosphoric acid, was established. Ring opening of propylene oxide does not depend on the number of the P? OH groups in the acid and, for di- and trifunctional acids, does not depend on the degree of substitution. After this first reaction of addition the formed hydroxyl groups add the oxirane molecules and the phosphorus-containing polyethers are formed. All of the propylene oxide additions exhibit a ratio of α/β-ring openings of 1:1. For the higher substituted oxiranes the proportion of the attack on the least substituted carbon atom increases, reaching for 1,1-dimethyloxirane up to 90% of α-addition (almost exclusive formation of the tertiary alcohol).     

Perceived intensity and pleasantness of sucrose taste in male alcoholics

AIMS: The aim of the present study was to evaluate a possible relationship between taste responses to sweet solutions and alcoholic status. METHODS: The rated intensity and pleasantness of sucrose taste was compared in male alcoholics (n = 45) and non-alcoholic controls (n = 33). RESULTS: The rated intensity, but not pleasantness, of water taste (0% sucrose) was higher in the alcoholics. The two groups did not differ with respect to the rated intensity or pleasantness of sucrose solutions (1-30%). The proportion of sweet-likers, i.e. subjects rating 30% sucrose as most pleasant, was similar in both groups (the controls: 57.6%, the alcoholics: 62.2%). A subgroup of alcoholics with a paternal history of alcoholism (n = 22) rated the highest sucrose concentration as more pleasant compared to alcoholics without alcoholic fathers. The proportion of sweet-likers among the alcoholics with a paternal history of alcoholism (77.3%) was significantly higher than that found in the alcoholics without a familial history of alcoholism (47.8%). CONCLUSIONS: The present results suggest the following: (i) alcohol dependence is not associated with any major alterations in taste responses to sucrose solutions, (ii) sweet liking is a phenotypic marker of male alcoholics with a paternal history of alcoholism.     

Biological and Pro-Angiogenic Properties of Genetically Modified Human Primary Myoblasts Overexpressing Placental Growth Factor in In Vitro and In Vivo Studies

Cardiovascular diseases are a growing problem in developing countries; therefore, there is an ongoing intensive search for new approaches to treat these disorders. Currently, cellular therapies are focused on healing the damaged heart by implanting stem cells modified with pro-angiogenic factors. This approach ensures that the introduced cells are capable of fulfilling the complex requirements of the environment, including the replacement of the post-infarction scar with cells that are able to contract and promote the formation of new blood vessels that can supply the ischaemic region with nutrients and oxygen. This study focused on the genetic modification of human skeletal muscle cells (SkMCs). We chose myoblast cells due to their close biological resemblance to cardiomyocytes and the placental growth factor (PlGF) gene due to its pro-angiogenic potential. In our in vitro studies, we transfected SkMCs with the PlGF gene using electroporation, which has previously been proven to be efficient and generate robust overexpression of the PlGF gene and elevate PlGF protein secretion. Moreover, the functionality of the secreted pro-angiogenic proteins was confirmed using an in vitro capillary development assay. We have also examined the influence of PlGF overexpression on VEGF-A and VEGF-B, which are well-known factors described in the literature as the most potent activators of blood vessel formation. We were able to confirm the overexpression of VEGF-A in myoblasts transfected with the PlGF gene. The results obtained in this study were further verified in an animal model. These data were able to confirm the potential therapeutic effects of the applied treatments.

     

Comorbid alcohol and nicotine dependence: from the biomolecular basis to clinical consequences

This article represents the proceedings of a symposium presented at the 12th Congress of the International Society for Biomedical Research on Alcoholism held in Heidelberg/Mannheim, Germany, on October 1, 2004. The organizers and cochairs were Nassima Ait‐Daoud, MD, and Gerhard A. Wiesbeck, MD. The presentations included the following: (1) The Role of Nicotinic Acetylcholine Receptors in Alcohol‐Seeking Behavior, by Przemyslaw Bienkowski, MD, PhD; (2) Utilization of Linkage Analysis Combined with Microarray Technology to Identify Genes and Mechanisms Underlying Nicotine and Alcohol Use and Abuse in Humans and Rodents, by Ming D. Li, PhD; (3) Smoking and Alcoholic Chronic Pancreatitis: The Underestimated Risk?, by Roland H. Pfützer, MD; (4) Anticraving Medication in Alcohol and Nicotine Dependence, by Otto M. Lesch, MD, PhD; and (5) Pharmacotherapy for Promotion of Abstinence from Nicotine Among Alcohol‐Dependent Individuals, by Bankole A. Johnson, DSc, MD, PhD.     

Neuronal sirtuin1 mediates retinal vascular regeneration in oxygen-induced ischemic retinopathy

Regeneration of blood vessels in ischemic neuronal tissue is critical to reduce tissue damage in diseases. In proliferative retinopathy, initial vessel loss leads to retinal ischemia, which can induce either regrowth of vessels to restore normal metabolism and minimize damage, or progress to hypoxia-induced sight-threatening pathologic vaso-proliferation. It is not well understood how retinal neurons mediate regeneration of vascular growth in response to ischemic insults. In this study we aim to investigate the potential role of Sirtuin 1 (Sirt1), a metabolically-regulated protein deacetylase, in mediating the response of ischemic neurons to regulate vascular regrowth in a mouse model of oxygen-induced ischemic retinopathy (OIR). We found that Sirt1 is highly induced in the avascular ischemic retina in OIR. Conditional depletion of neuronal Sirt1 leads to significantly decreased retinal vascular regeneration into the avascular zone and increased hypoxia-induced pathologic vascular growth. This effect is likely independent of PGC-1α, a known Sirt1 target, as absence of PGC-1α in knockout mice does not impact vascular growth in retinopathy. We found that neuronal Sirt1 controls vascular regrowth in part through modulating deacetylation and stability of hypoxia-induced factor 1α and 2α, and thereby modulating expression of angiogenic factors. These results indicate that ischemic neurons induce Sirt1 to promote revascularization into ischemic neuronal areas, suggesting a novel role of neuronal Sirt1 in mediating vascular regeneration in ischemic conditions, with potential implications beyond retinopathy.     

Microbiologically Pure Cotton Fabrics Treated with Tetrabutylammonium OXONE as Mild Disinfection Agent

The microbiological purity of textiles plays a pivotal role in the use of textiles, especially in hospitals and other medical facilities. Microbiological purity of cotton fabric was achieved by a new disinfection method using tetrabutyloammonium OXONE (TBA-OXONE) before washing. As a result of the disinfection, the cotton fabric became microbiologically pure, despite the markedly decreased washing time with respect to the widely used standard procedure. Shortening of the washing time allowed for significant energy savings. In addition, the effect of the number of disinfection and washing cycles on the tensile properties and tearing force of the fabric was examined. After 120 disinfection and washing cycles the mechanical properties of cotton fabric were only slightly worsened.     

The Beneficial Effect of Cinnamon and Red Capsicum Intake on Postprandial Changes in Plasma Metabolites Evoked by a High-Carbohydrate Meal in Men with Overweight/Obesity

The relationship of high-carbohydrate (HC) meal intake to metabolic syndrome is still not fully explained. Metabolomics has the potential to indicate metabolic pathways altered by HC meals, which may improve our knowledge regarding the mechanisms by which HC meals may contribute to metabolic syndrome development. The fasting and postprandial metabolic response to HC or normo-carbohydrate (NC) meals with/without cinnamon + capsicum intake was evaluated using untargeted metabolomics and compared between normal-weight (NW) and overweight/obese (OW/OB) healthy men. Healthy male participants (age-matched) were divided into two groups (12 subjects per group). One was composed of men with normal weight (NW) and the other of men with overweight/obesity (OW/OB). On separate visits (with 2–3 week intervals), the participants received standardized HC or NC meals (89% or 45% carbohydrates, respectively). Fasting (0 min) and postprandial (30, 60, 120, 180 min) blood were collected for untargeted plasma metabolomics. Based on each metabolic feature’s intensity change in time, the area under the curve (AUC) was calculated. Obtained AUCs were analyzed using multivariate statistics. Several metabolic pathways were found dysregulated after an HC meal in people from the OW/OB group but not the NW group. The consumption of HC meals by people with overweight/obesity led to a substantial increase in AUC, mainly for metabolites belonging to phospholipids and fatty acid amides. The opposite was observed for selected sphingolipids. The intake of cinnamon and capsicum normalized the concentration of selected altered metabolites induced by the intake of HC meals. A HC meal may induce an unfavourable postprandial metabolic response in individuals with overweight/obesity, and such persons should avoid HC meals.     

Ueber die Laryngofissur auf Grundlage eigener Erfahrung

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