Studies on two polyherbal formulations (ZPTO and ZTO) for comparison of their antidyslipidemic, antihypertensive and endothelial modulating activities

Background Cardiovascular disorders (CVDs) are the leading cause of disease burden worldwide. Apart from available synthetic drugs used in CVDs, there are many herbal formulations including POL-10 (containing 10 herbs), which have been shown to be effective in animal studies but POL-10 was found to cause tachycardia in rodents as its side effect. This study was designed to modify the composition of POL-10 for better efficacy and/or safety profile in CVDs. Methods To assess the antidyslipidemic, antihypertensive and endothelial modulatory properties of two herbal formulations, (ZPTO and ZTO) containing Z: Zingiber officinalis, P: Piper nigrum, T: Terminalia belerica and O: Orchis mascula, different animal models including, tyloxapol and high fat diet-induced dyslipidemia and spontaneously hypertensive rats (SHR) were used. Effect on endothelial function was studied using isolated tissue bath set up coupled with PowerLab data acquisition system. The antioxidant activity was carried out using DPPH radical-scavenging assay. Results Based on preliminary screening of the ingredients of POL-10 in tyloxapol-induced hyperlipidemic rats, ZPTO and ZTO containing four active ingredients namely; Z, P, T and O were identified for further studies and comparison. In tyloxapol-induced hyperlipidemic rats, both ZPTO and ZTO caused significant reduction in serum triglyceride (TG) and total cholesterol (TC). In high fat diet-fed rats, ZPTO decreased TC, low-density lipoproteins cholesterol (LDL-C) and atherogenic index (AI). ZTO also showed similar effects to those of ZPTO with additional merits being more effective in reducing AI, body weight and more importantly raising high-density lipoproteins. In SHR, both formulations markedly reduced systolic blood pressure, AI and TG levels, ZTO being more potent in reversing endothelial dysfunction while was devoid of cardiac stimulatory effect. In addition, ZTO also reduced LDL-C and improved glucose levels in SHR. In DPPH radical-scavenging activity test, ZTO was also more potent than ZPTO. Conclusion The modified formulation, ZTO was not only found more effective in correcting cardiovascular abnormalities than ZPTO or POL-10 but also it was free from tachycardiac side-effect, which might be observed because of the presence of Piper nigrum in ZPTO

Is Gly16Arg β₂ Receptor Polymorphism Related to Impulse Oscillometry in a Real-Life Asthma Clinic Setting?

PURPOSE: We evaluated whether Gly16Arg beta2-receptor genotype relates to impulse oscillometry (IOS) in a real-life clinic setting. METHODS: Patients with persistent asthma taking inhaled corticosteroid ± long-acting beta-agonist (ICS ± LABA) were evaluated. We compared genotype groups comprising either no Arg copies (i.e. GlyGly) versus one or two Arg copies (i.e. ArgArg or ArgGly). IOS outcomes included total airway resistance at 5 Hz (R5), central airway resistance at 20 Hz (R20), peripheral airway resistance (R5–R20), reactance at 5 Hz, area under reactance curve (AX) and resonant frequency (RF). In addition, we recorded ACQ-5 and salbutamol use. RESULTS: One hundred and twelve ICS-treated asthmatic patients (mean ICS dose 1238 µg/day), mean age 43 years, ACQ 2.34, FEV1 82 %, R5 177 % were identified—89 were also taking LABA. 61 patients were GlyGly, while 14 were ArgArg and 37 were ArgGly. There were no significant differences in IOS outcomes, ACQ or salbutamol use between the genotypes. The allelic risk (as odds ratio) for less well-controlled asthma (as ACQ > 1.5) was 1.1 (95 % CI 0.72–1.68) in relation to each Arg copy with a corresponding odds ratio for abnormal R5–R20 > 0.07kPA/l.s being 0.91 (95 % CI 0.57–1.44). 71 % of patients had an ACQ > 1.5 in the GlyGly group, versus 67 % in GlyArg/ArgArg group, with corresponding figures for abnormal R5–R20 > 0.07 kPa/l.s being 69 versus 73 %. CONCLUSION: In a real-life clinic setting for patients with poorly controlled persistent asthma taking ICS ± LABA, we found no evidence of any relationship of Gly16Arg to IOS, ACQ or salbutamol use

Recurrent Chromosomal Copy Number Alterations in Sporadic Chordomas

The molecular events in chordoma pathogenesis have not been fully delineated, particularly with respect to copy number changes. Understanding copy number alterations in chordoma may reveal critical disease mechanisms that could be exploited for tumor classification and therapy. We report the copy number analysis of 21 sporadic chordomas using array comparative genomic hybridization (CGH). Recurrent copy changes were further evaluated with immunohistochemistry, methylation specific PCR, and quantitative real-time PCR. Similar to previous findings, large copy number losses, involving chromosomes 1p, 3, 4, 9, 10, 13, 14, and 18, were more common than copy number gains. Loss of CDKN2A with or without loss of CDKN2B on 9p21.3 was observed in 16/20 (80%) unique cases of which six (30%) showed homozygous deletions ranging from 76 kilobases to 4.7 megabases. One copy loss of the 10q23.31 region which encodes PTEN was found in 16/20 (80%) cases. Loss of CDKN2A and PTEN expression in the majority of cases was not attributed to promoter methylation. Our sporadic chordoma cases did not show hotspot point mutations in some common cancer gene targets. Moreover, most of these sporadic tumors are not associated with T (brachyury) duplication or amplification. Deficiency of CDKN2A and PTEN expression, although shared across many other different types of tumors, likely represents a key aspect of chordoma pathogenesis. Sporadic chordomas may rely on mechanisms other than copy number gain if they indeed exploit T/ brachyury for proliferation

Antihypertensive, antidyslipidemic and endothelial modulating activities of Orchis mascula

The objective of this study was to investigate the possible mode(s) of action for the medicinal use of Orchis mascula (OM) (family Orchidaceae) in hypertension and dyslipidemia. In spontaneously hypertensive rats (SHRs), OM significantly (

The cross on rings performed by an Olympic champion

The cross is a key skill in Male Artistic Gymnastics rings routines. However, few researches were found about this skill. There is knowledge about the forces needed to perform the cross, or about muscles activation, separately. The aim of this paper was to accomplish a comprehensive research about the biomechanics of cross on rings, in order to obtain a descriptive model about this skill. Therefore, the currently Olympic champion on rings event volunteered in this research. He performed three crosses with the usual apparatus in his training gym. The measurement methods were combined: One digital video camera, one strain gauge in each cable and surface electromyography of nine right shoulder muscles were used. Statistical analyses were performed by parametric and non parametric tests and descriptive statistics. Symmetry values were calculated for shoulder angles and cables of right and left side. Coefficient of variation of muscle activation and co contraction were verified. Within gymnast variability was calculated using biological coefficient of variation (BCV), discretely for kinematic measures. Low variability values of shoulder angles and cable forces were verified and low values of asymmetry as well. Muscle activation varied according to muscle function, while co-contraction values were different among trials. These results pointed out the characteristics of the cross performed by an elite gymnast. Knowledge about the characteristics of cross can inform coaches, practitioners and clinicians how a successful skill should be presented

Antifungal, anti-inflammatory and cytotoxicity activities of three varieties of Labisia pumila benth : from microwave obtained extracts.

Background: Labisia pumila, locally known as Kacip Fatimah, is a forest-floor plant that has tremendous potential in the herbal industry. It is one of the five herbal plants identified by the government as one of the national key economic areas to be developed for commercial purposes. There are three varieties of L. pumila namely, L. pumila var. pumila, L. pumila var. alata and L. pumila var. lanceolata and each has its own use.Methods: The leaves and roots of the three varieties of L. pumila Benth. were extracted using microwave assisted extraction (MAE). Antifungal activity of all plant extracts were characterized against Fusarium sp., Candida sp. and Mucor using the agar diffusion disc. Anti-inflammatory assays were performed using NO production by macrophage RAW 264.7 cell lines induced by LPS/IFN-g and cytotoxic activity was determined using several cancer cell lines and one normal cell line.Results: The overall result demonstrated that leaf and root extracts of all three varieties of L. pumila exhibited moderate to appreciable antifungal activity against Fusarium sp., Candida sp. and Mucor compared to streptomycin used as positive control. Leaf and root extracts of all varieties significantly decreased NO release. However, the root extracts showed higher activity compared to the leaf extracts. Cytotoxic activity against MCF-7, MDA-MB-231 and Chang cell lines were observed with all extracts.Conclusions: These findings suggest the potential use of L. pumila Benth. as a natural medicine and indicated the possible application of this medicinal plant such anti inflammatory activity and cytotoxic agents

Elucidation of the Mode of Action of a New Antibacterial Compound Active against Staphylococcus aureus and Pseudomonas aeruginosa.

Nosocomial and community-acquired infections caused by multidrug resistant bacteria represent a major human health problem. Thus, there is an urgent need for the development of antibiotics with new modes of action. In this study, we investigated the antibacterial characteristics and mode of action of a new antimicrobial compound, SPI031 (N-alkylated 3, 6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol), which was previously identified in our group. This compound exhibits broad-spectrum antibacterial activity, including activity against the human pathogens Staphylococcus aureus and Pseudomonas aeruginosa. We found that SPI031 has rapid bactericidal activity (7-log reduction within 30 min at 4x MIC) and that the frequency of resistance development against SPI031 is low. To elucidate the mode of action of SPI031, we performed a macromolecular synthesis assay, which showed that SPI031 causes non-specific inhibition of macromolecular biosynthesis pathways. Liposome leakage and membrane permeability studies revealed that SPI031 rapidly exerts membrane damage, which is likely the primary cause of its antibacterial activity. These findings were supported by a mutational analysis of SPI031-resistant mutants, a transcriptome analysis and the identification of transposon mutants with altered sensitivity to the compound. In conclusion, our results show that SPI031 exerts its antimicrobial activity by causing membrane damage, making it an interesting starting point for the development of new antibacterial therapies

Aquaporins: important but elusive drug targets.

The aquaporins (AQPs) are a family of small, integral membrane proteins that facilitate water transport across the plasma membranes of cells in response to osmotic gradients. Data from knockout mice support the involvement of AQPs in epithelial fluid secretion, cell migration, brain oedema and adipocyte metabolism, which suggests that modulation of AQP function or expression could have therapeutic potential in oedema, cancer, obesity, brain injury, glaucoma and several other conditions. Moreover, loss-of-function mutations in human AQPs cause congenital cataracts (AQP0) and nephrogenic diabetes insipidus (AQP2), and autoantibodies against AQP4 cause the autoimmune demyelinating disease neuromyelitis optica. Although some potential AQP modulators have been identified, challenges associated with the development of better modulators include the druggability of the target and the suitability of the assay methods used to identify modulators

The relationships between workaholism and symptoms of psychiatric disorders: a large-scale cross-sectional study

Despite the many number of studies examining workaholism, large-scale studies have been lacking. The present study utilized an open web-based cross-sectional survey assessing symptoms of psychiatric disorders and workaholism among 16,426 workers (Mage = 37.3 years, SD = 11.4, range = 16–75 years). Participants were administered the Adult ADHD Self-Report Scale, the Obsession-Compulsive Inventory-Revised, the Hospital Anxiety and Depression Scale, and the Bergen Work Addiction Scale, along with additional questions examining demographic and work-related variables. Correlations between workaholism and all psychiatric disorder symptoms were positive and significant. Workaholism comprised the dependent variable in a three-step linear multiple hierarchical regression analysis. Basic demographics (age, gender, relationship status, and education) explained 1.2% of the variance in workaholism, whereas work demographics (work status, position, sector, and annual income) explained an additional 5.4% of the variance. Age (inversely) and managerial positions (positively) were of most importance. The psychiatric symptoms (ADHD, OCD, anxiety, and depression) explained 17.0% of the variance. ADHD and anxiety contributed considerably. The prevalence rate of workaholism status was 7.8% of the present sample. In an adjusted logistic regression analysis, all psychiatric symptoms were positively associated with being a workaholic. The independent variables explained between 6.1% and 14.4% in total of the variance in workaholism cases. Although most effect sizes were relatively small, the study’s findings expand our understanding of possible psychiatric predictors of workaholism, and particularly shed new insight into the reality of adult ADHD in work life. The study’s implications, strengths, and shortcomings are also discussed