Bezafibrate in men with lower extremity arterial disease: randomised controlled trial

ObjectiveTo assess the effect of bezafibrate on the risk of coronary heart disease and stroke in men with lower extremity arterial disease.DesignDouble blind placebo controlled randomised trial.Setting85 general practices and nine hospital vascular clinics.Participants1568 men, mean age 68.2 years (range 35 to 92) at recruitment.InterventionsBezafibrate 400 mg daily (783 men) or placebo (785 men).ResultsBezafibrate did not reduce the incidence of coronary heart disease and stroke. There were 150 and 160 events in the active and placebo groups respectively (relative risk 0.96, 95% confidence interval 0.76 to 1.21). There were 90 and 111 major coronary events in the active and placebo groups respectively (0.81, 0.60 to 1.08), of which 64 and 65 were fatal (0.95, 0.66 to 1.37) and 26 and 46 non-fatal (0.60, 0.36 to 0.99). Beneficial effects on non-fatal events were greatest in men aged <65 years at entry, in whom benefit was also seen for all coronary events (0.38, 0.20 to 0.72). There were no significant effects in older men. There were 60 strokes in those on active treatment and 49 in those on placebo (1.34, 0.80 to 2.01). There were 204 and 195 deaths from all causes in the two groups respectively (1.03, 0.83 to 1.26). Bezafibrate reduced the severity of intermittent claudication for up to three years.ConclusionsBezafibrate has no effect on the incidence of coronary heart disease and of stroke combined but may reduce the incidence of non-fatal coronary events, particularly in those aged <65 years at entry, in whom all coronary events may also be reduced.

What is already known on this topic

The beneficial effects of bezafibrate on blood lipids and fibrinogen concentrations should reduce the incidence of heart attacks and strokesSo far, however, there is only limited evidence on clinical outcomes from randomised controlled trials

What this study adds

Treatment with bezafibrate was not associated with a reduction in the combined incidence of heart attacks and strokes, though there were substantially fewer non-fatal heart attacks in those taking bezafibrateBezafibrate was associated with a reduction in the incidence of all heart attacks, especially non-fatal, in men aged <65 yearsBezafibrate seems to reduce the severity of intermittent claudication for two or three years     

The formation of short fibres from native cellulose by components of Trichoderma koningii cellulase

Cellulolytic enzyme components of culture filtrates of Trichoderma koningii were fractionated on ionic and non-ionic forms of Sephadex and on cellulose powder (Whatman) and examined for their ability to hydrolyse soluble carboxymethyl-cellulose, and to saccharify, solubilize and form short fibres from native undegraded cellulose of the type found in cotton. DEAE-Sephadex provided two CM-cellulase components and a C(1) component; the C(1) component acted weakly and solely on cotton, forming soluble products but not short fibres. The ability to form short fibres was confined almost wholly to one of the CM-cellulase components which completely degraded cotton, minimally to soluble products and extensively to short fibres. The latter action was unaffected by the presence of the other two components. The two CM-cellulase components solubilized cellulose synergistically whereas the short-fibre-forming component and C(1) component were inhibitory.     

Association of Angiotensin-Converting Enzyme gene polymorphism in Pakistani women with the atypical steroidogenesis in Polycystic ovarian syndrome: A case-control study

BackgroundPolymorphism in the angiotensin-converting enzyme gene (ACE) is responsible for elevated ACE concentrations in plasma. High ACE levels induce insulin resistance and hyperandrogenism, which are the main attributes of polycystic ovary syndrome (PCOS). Therefore, it was hypothesized that I/D polymorphism plays a role in the pathogenesis of PCOS.ObjectiveA case-control study was designed to investigate the association of I/D polymorphism of the ACE gene with PCOS in Pakistani women of reproductive age.MethodsACE I/D polymorphism was assessed in 252 women of age group 16–40 years. For genotypic analysis, PCR amplification of genomic DNA was carried out. Statistical analysis was performed to interpret the results using SPSS software.ResultsOur study showed that PCOS women were more likely to have a high body mass index and waist circumferences. Most PCOS patients had menstrual irregularities 99.3%, hirsutism 75.2% and cysts in ovaries 66.6%, along with other hyperandrogenic conditions (P-value = 0.001). The genotypic and allelic frequencies were significantly different between patients and controls. There was a significant association of three genotypes with the ratio of LH: FSH among PCOS patients (P = 0.05). Anthropometric characters, comorbidities, clinical symptoms, and PCOS conditions showed no statistical significance with ACE polymorphism.ConclusionsACE I/D polymorphism was not found associated with clinical conditions of PCOS in women of reproductive age. However, it was associated with atypical steroidogenesis. So, it indicates that ACE I/D polymorphism aggravates the pathogenesis of PCOS.     

The ventral hippocampus CA3 is critical in regulating timing uncertainty in temporal decision-making

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Heavy metals in urban and peri-urban soils of a heavily-populated and industrialized city: Assessment of ecological risks and human health repercussions

Abstract

Increasing levels of heavy metals in soil have become a serious concern for human health because they can be easily transferred into the human body through contaminated food web. It is imperative to evaluate pollution levels, origin and ecological risks of heavy metals. The geoaccumaualtion (Igeo), contamination factor (CF), pollution load index (PLI) and human health risk were estimated to determine the soil pollution in Faisalabad, a heavily-populated and industrialized city of Pakistan. The maximum CF (1.58) and PLI (1.22) values were estimated for Cd and Pb, respectively, and maximum Igeo (?0.19) value was observed for Cd. Correlation analysis and principal component analysis suggested that common industrial sources for Cd and Pb were identified in the study sites. It clearly indicates that the significant levels of heavy metals pollution arise from local industries, busy commercial centers and heavy traffic load in the last few decades in heavily-populated and industrialized city. Further, soil heavy metals concentration were used to evaluate the human health risk such as chronic or non-carcinogenic including hazard indexes HIexP (ingestion, inhalation and dermal and carcinogenic) and cancer risk (CR). The HIexP values of Pb (10.30) and Cd (4.56) were found above the permissible limit (HI = 1) for children. The CR due to carcinogenic metals (Co, Cr and Cd) are within the safe limit (1E-06 to 1E-04). However, CR was comparatively higher in adults as compared to children. The results from the current investigation can help to develop a sustainable strategy in the study region to minimize the entry of heavy metals in food chain through source identification and pollution abatement techniques.     

Effects of yeast extract on the production of phenylpropanoid metabolites in callus culture of purple basil (Ocimum Basilicum L. var purpurascens) and their in-vitro evaluation for antioxidant potential

Ocimum basilicum L. var. purpurascens is an enriched reservoir of pharmaceutically important compounds with plenty of health and therapeutic attributes such as phenolic acids and anthocyanins. However, the inefficient production of aforementioned metabolites in wild has restricted its commercial utilization. Herein, commercially viable phytochemicals have been enhanced through elicitation of in-vitro cultures of O. basilicum using yeast extract.The impact of various concentrations (YE 1 mg/L,YE 10 mg/L, YE 25 mg/L, YE 50 mg/L, YE 100 mg/L, YE 200 mg/L and YE 400 mg/L) of yeast extract on biomass accumulation, phytochemical production, and antioxidant activities were assessed in callus cultures. Moderate concentration of yeast extract (100 mg/L) enhanced biomass accumulation i.e. fresh weight (FW 216.28 g/L) and dry weight (DW 15.49 g/L) up to 1.5 folds as compared to control (FW 167.14 g/L and DW 10.25 g/L). Similarly, yeast extract (100 mg/L) increased total phenolic and flavonoid contents as well as enhanced antioxidant activities such as ABTS (2,2 azinobis 3-ethylbenzthiazoline-6-sulphonic acid), FRAP (ferric reducing antioxidant power) and DPPH (2,2-diphenyl-1-picryhydrazyl). High performance liquid chromatography (HPLC) analysis was elucidated for further phytochemical investigation. HPLC analysis showed an increase of almost 1.9 folds as compared to control in rosmarinic acid (15.19 mg/g DW), chicoric acid (2.13 mg/g DW), peonidin (2.70 mg/g DW) and cyanidin (1.57 mg/g DW). Likewise, 1.8 fold and 2.4 folds increase was observed in eugenol essential oils (0.25 mg/g DW) and chavicol (0.037 mg/g DW), respectively. For cellular antioxidant activity, reactive oxygen specie or reactive nitogen specie (ROS/RNS) was induced in yeast cells and the effect of O. basilicum callus culture was further investigated in stressed yeast cells. A positive correlation exists between the antioxidant activities, TPC and TFC analysis. In short, these results showed that yeast extract could act as an efficient elicitor to enhance pharmacologically important metabolites in callus cultures of Ocimum basilicum.

Graphical abstract

     

Role of TMPRSS6 rs855791 (T > C) polymorphism in reproductive age women with iron deficiency anemia from Lahore,Pakistan

BackgroundIron deficiency anemia (IDA) is the highest nutritional deficiency worldwide. It is a multifactorial disease, with a higher morbidity rate. TMPRSS6 polymorphisms importantly rs855791 is found to play an essential role in iron homeostasis in the human body. The rs855791 (T > C) polymorphism is highly associated with iron levels, and multiple blood parameters, leading to IDA. The role of TMPRSS6 rs855791 polymorphism and the significance of complete blood count (CBC) parameters in the pathogenesis of IDA is not yet studied in the Pakistani population.MethodsWe enrolled 113 cases and 136 controls to conduct a case control study. Complete blood count (CBC) and iron parameters were analyzed for association studies. PCR-RFLP based genotyping was performed.ResultsThe TMPRSS6 rs855791 (T > C) polymorphism is significantly associated with IDA pathogenesis as observed in the codominant model and recessive models (P < 0.05, OR: 1.5 and 95% CI: 0.9, 2.6, P < 0.05, OR: 0.5 and 95% CI: 0.2, 0.9 respectively). Elderly women among cases (30–49 years) were found to be more susceptible to IDA (P < 0.05, AOR: 2.1 and 95% CI: 1.0, 4.2). The most significant parameters associated with IDA were red blood cell count (RBC) and hematocrit (Hct%) (P < 0.05, AOR: 16.5, 95% CI: 7.6, 35.9 and P < 0.05, AOR: 10.1, 95% CI: 2.5, 41.6, respectively).ConclusionTMPRSS6 polymorphism at rs855791 (T > C) is significantly associated with IDA susceptibility in reproductive age women in Pakistan. Age, RBC count and Hct% are found to play an important role in IDA pathogenesis in our study population.     

Interactive role of zinc and iron lysine on Spinacia oleracea L. growth,photosynthesis and antioxidant capacity irrigated with tannery wastewater

AbstractUntreated wastewater contains toxic amounts of heavy metals such as chromium (Cr), which poses a serious threat to the growth and physiology of plants when used in irrigation. Though, Cr is among the most widespread toxic trace elements found in agricultural soils due to various anthropogenic activities. To explore the interactive effects of micronutrients with amino acid chelators [iron-lysine (Fe-lys) and zinc-lysine (Zn-lys)], pot experiments were conducted in a controlled environment, using spinach (Spinacia oleracea L.) plant irrigated with tannery wastewater. S. oleracea was treated without Fe and Zn-lys (0 mg/L Zn-lys and 0 mg/L Fe-lys) and also treated with various combinations of (interactive application) Fe and Zn-lys (10 mg/L Zn-lys and 5 mg/L Fe-lys), when cultivated at different levels [0 (control) 33, 66 and 100%) of tannery wastewater in the soil having a toxic level of Cr in it. According to the results, we have found that, high concentration of Cr in the soil significantly (P < 0.05) reduced plant height, fresh biomass of roots and leaves, dry biomass of roots and leaves, root length, number of leaves, leaf area, total chlorophyll contents, carotenoid contents, transpiration rate (E), stomatal conductance (gs), net photosynthesis (PN), and water use efficiency (WUE) and the contents of Zn and Fe in the plant organs without foliar application of Zn and Fe-lys. Moreover, phytotoxicity of Cr increased malondialdehyde (MDA) contents in the plant organs (roots and leaves), which induced oxidative damage in S. oleracea manifested by the contents of hydrogen peroxide (H₂O₂) and membrane leakage. The negative effects of Cr toxicity could be overturned by Zn and Fe-lys application, which significantly (P < 0.05) increase plant growth, biomass, chlorophyll content, and gaseous exchange attributes by reducing oxidative stress (H₂O₂, MDA, EL) and increasing the activities of various antioxidant enzymes such as superoxide dismutase (SOD), peroxidase (POD) catalase (CAT) and ascorbate peroxidase (APX). Furthermore, the supplementation of Zn and Fe-lys increased the contents of essential nutrients (Fe and Zn) and decreased the content of Cr in all plant parts compared to the plants cultivated in tannery wastewater without application of Fe-lys. Taken together, foliar supplementation of Zn and Fe-lys alleviates Cr toxicity in S. oleracea by increased morpho-physiological attributes of the plants, decreased Cr contents and increased micronutrients uptake by the soil, and can be an effective in heavy metal toxicity remedial approach for other crops.Graphic abstract