Development and evaluation of a novel herbal formula for tobacco cessation in nicotine addicted rat model

381-388Tobacco addiction is a major cause of disabilities and premature death. Numerous therapies for de-addiction are available; however, nicotine dependence and withdrawal symptoms pose problems for addicts. Here, we developed novel herbal formulations using natural plant parts and evaluated for de-addiction of nicotine. Parts of Withania somnifera (L.) Dunal, Avena sativa L., Cinnamomum cassia Blume, Acacia catechu (L.f.)Willd., Ocimum tenuiflorum L. and Glycyrrhiza glabra L. were formulated in three formulations containing alcohol extracts (AELF), aqueous extracts (WELF) and powdered herbs (PHLF). Swiss albino Wistar rats were addicted with nicotine 10 mg/kg/day for first five days and 20 mg/kg/day for next 10 days subcutaneously. Control rats were administered with 0.9% NaCl (Group VII) and addicted animals were treated with bupropion, 40 mg/kg, p.o. (Group I), rid-tobak, 200 mg/kg, p.o. (Group II), AELF, 200 mg/kg, p.o. (Group III), WELF, 200 mg/kg, p.o. (Group IV), PHLF, 200 mg/kg, p.o. (Group V), 0.5% sodium carboxymethyl cellulose, p.o. (Group VI) for 15 days. The animals were subjected to Y-maze test, swimming endurance test, behavioural studies on Day 0, 1, 6, 11 and on Day 16 after withdrawal of nicotine. On Day16, brain dopamine and serum cortisol levels were measured. Rats treated with AELF and PHLF showed significant improvement in behavioural parameters, increased brain dopamine level and decreased serum cortisol levels thus being a promising choice for tobacco cessation

Efecto del extracto de metanol de Achyranthes aspera linn. sobre la hepatotoxicidad inducida por rifampicina en ratas

Methanol extract of aerial parts of Achyranthes aspera Linn. (Family: Amaranthaceae) was tested for its effect onrifampicin-induced hepatotoxicity in albino rats at five dose levels. Rifampicin intoxication in rats significantly (p < 0.001)elevated the levels of SGPT, SGOT, ALKP, and total bilirubin, which indicated acute hepatocellular, damage and biliaryobstruction. Methanol extract showed dose dependent decrease in the levels of SGPT, SGOT, ALKP and total bilirubin.Minimum effective dose of extract was found to be 100 mg/kg body weight. Results obtained from histopathological studiesalso supported hepatoprotective activity of drug against rifampicin induced hepatotoxicity. Thus study demonstrates thatA. aspera possess anti-hepatotoxic effect against rifampicin.Se analizó el extracto de metanol de las partes aéreas de Achyranthes aspera Linn. (Familia: Amaranthaceae) paracomprobar su efecto sobre la hepatotoxicidad inducida por rifampicina en ratas albinas en cinco niveles de dosis.La intoxicación por rifampicina en ratas elevó de forma significativa (p > 0,001) los niveles de SGPT-ALT, SGOTAST,FA y bilirrubina total, hecho que fue indicativo de obstrucción biliar y daño hepatocelular agudo. El extractode metanol mostró un descenso dosis-dependiente de los niveles de SGPT-ALT, SGOT-AST, FA y bilirrubina total.La dosis mínima eficaz de extracto fue 100 mg/kg de peso corporal. Los resultados obtenidos de los estudioshistopatológicos también confirmaron la actividad hepatoprotectora del fármaco frente a la hepatotoxicidad inducidapor rifampicina. Por tanto, el estudio demostró que A. aspera posee un efecto antihepatotóxico frente a la rifampicina

Practical computational toolkits for dendrimers and dendrons structure design

Dendrimers and dendrons offer an excellent platform for developing novel drug delivery systems and medicines. The rational design and further development of these repetitively branched systems are restricted by difficulties in scalable synthesis and structural determination, which can be overcome by judicious use of molecular modelling and molecular simulations. A major difficulty to utilise in silico studies to design dendrimers lies in the laborious generation of their structures. Current modelling tools utilise automated assembly of simpler dendrimers or the inefficient manual assembly of monomer precursors to generate more complicated dendrimer structures. Herein we describe two novel graphical user interface (GUI) toolkits written in Python that provide an improved degree of automation for rapid assembly of dendrimers and generation of their 2D and 3D structures. Our first toolkit uses the RDkit library, SMILES nomenclature of monomers and SMARTS reaction nomenclature to generate SMILES and mol files of dendrimers without 3D coordinates. These files are used for simple graphical representations and storing their structures in databases. The second toolkit assembles complex topology dendrimers from monomers to construct 3D dendrimer structures to be used as starting points for simulation using existing and widely available software and force fields. Both tools were validated for ease-of-use to prototype dendrimer structure and the second toolkit was especially relevant for dendrimers of high complexity and size.Peer reviewe

Advances in ophthalmic drug delivery

Various strategies for ocular drug delivery are considered; from basic formulation techniques for improving availability of drugs; viscosity enhancers and mucoadhesives aid drug retention and penetration enhancers promote drug transport into the eye. The use of drug loaded contact lenses and ocular inserts allows drugs to be better placed where they are needed for more direct delivery. Developments in ocular implants gives a means to overcome the physical barriers that traditionally prevented effective treatment. Implant technologies are under development allowing long term drug delivery from a single procedure, these devices allow posterior chamber diseases to be effectively treated. Future developments could bring artificial corneas to eliminate the need for donor tissue and one-off implantable drug depots lasting the patient’s lifetime

Investigating the association between obesity and asthma in 6- to 8-year-old Saudi children:a matched case-control study

Background: Previous studies have demonstrated an association between obesity and asthma, but there remains considerable uncertainty about whether this reflects an underlying causal relationship. Aims: To investigate the association between obesity and asthma in pre-pubertal children and to investigate the roles of airway obstruction and atopy as possible causal mechanisms. Methods: We conducted an age- and sex-matched case–control study of 1,264 6- to 8-year-old schoolchildren with and without asthma recruited from 37 randomly selected schools in Madinah, Saudi Arabia. The body mass index (BMI), waist circumference and skin fold thickness of the 632 children with asthma were compared with those of the 632 control children without asthma. Associations between obesity and asthma, adjusted for other potential risk factors, were assessed separately in boys and girls using conditional logistic regression analysis. The possible mediating roles of atopy and airway obstruction were studied by investigating the impact of incorporating data on sensitisation to common aeroallergens and measurements of lung function. Results: BMI was associated with asthma in boys (odds ratio (OR)=1.14, 95% confidence interval (CI), 1.08–1.20; adjusted OR=1.11, 95% CI, 1.03–1.19) and girls (OR=1.37, 95% CI, 1.26–1.50; adjusted OR=1.38, 95% CI, 1.23–1.56). Adjusting for forced expiratory volume in 1 s had a negligible impact on these associations, but these were attenuated following adjustment for allergic sensitisation, particularly in girls (girls: OR=1.25; 95% CI, 0.96–1.60; boys: OR=1.09, 95% CI, 0.99–1.19). Conclusions: BMI is associated with asthma in pre-pubertal Saudi boys and girls; this effect does not appear to be mediated through respiratory obstruction, but in girls this may at least partially be mediated through increased risk of allergic sensitisation

HGF Mediates the Anti-inflammatory Effects of PRP on Injured Tendons

Platelet-rich plasma (PRP) containing hepatocyte growth factor (HGF) and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP) however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2. © 2013 Zhang et al

Chromomagnetic Catalysis of Color Superconductivity in a (2+1)-dimensional NJL Model

The influence of a constant uniform external chromomagnetic field $H$ on the formation of color superconductivity has been investigated. The consideration was performed in the framework of a (2+1)-dimensional Nambu--Jona-Lasinio model with two different four-fermionic structures responsible for $$and diquark$$ condensates. In particular, it was shown that there exists a critical value $H_c$ of the external chromomagnetic field such that at $H>H_c$ a nonvanishing diquark condensate is dynamically created (the so-called chromomagnetic catalysis effect of color superconductivity). Moreover, external chromomagnetic fields may in some cases enhance the diquark condensate of color superconductivity.Comment: 32 pages, 2 figures, revte

Prevalence and risk factors for HIV-1 infection in rural Kilimanjaro region of Tanzania: Implications for prevention and treatment

BACKGROUND: Variability in stages of the HIV-1 epidemic and hence HIV-1 prevalence exists in different areas in sub-Saharan Africa. The purpose of this study was to investigate the magnitude of HIV-1 infection and identify HIV-1 risk factors that may help to develop preventive strategies in rural Kilimanjaro, Tanzania. METHODS: A cross-sectional study was conducted between March and May of 2005 involving all individuals aged between 15–44 years having an address in Oria Village. All eligible individuals were registered and invited to participate. Participants were interviewed regarding their demographic characteristics, sexual behaviors, and medical history. Following a pre-test counseling, participants were offered an HIV test. RESULTS: Of the 2 093 eligible individuals, 1 528 (73.0%) participated. The overall age and sex adjusted HIV-1 prevalence was 5.6%. Women had 2.5 times higher prevalence (8.0% vs. 3.2%) as compared to men. The age group 25–44 years, marriage, separation and low education were associated with higher risk of HIV-1 infection for both sexes. HIV-1 infection was significantly associated with >2 sexual partners in the past 12 months (women: Adjusted odds ratio [AOR], 2.5 (95%CI: 1.3–4.7), and past 5 years, [(men: AOR, 2.2 (95%CI:1.2–5.6); women: AOR, 2.5 (95%CI: 1.4–4.0)], unprotected casual sex (men: AOR,1.8 95%CI: 1.2–5.8), bottled alcohol (Men: AOR, 5.9 (95%CI:1.7–20.1) and local brew (men: AOR, 3.7 (95%CI: 1.5–9.2). Other factors included treatment for genital ulcers and genital discharge in the past 1 month. Health-related complaints were more common among HIV-1 seropositive as compared to seronegative participants and predicted the presence of HIV-1 infection. CONCLUSION: HIV-1 infection was highly prevalent in this population. As compared to our previous findings, a shift of the epidemic from a younger to an older age group and from educated to uneducated individuals was observed. Women and married or separated individuals remained at higher risk of infection. To prevent further escalation of the HIV epidemic, efforts to scale up HIV prevention programmes addressing females, people with low education, lower age at marriage, alcohol consumption, condom use and multiple sexual partners for all age groups remains a top priority. Care and treatment are urgently needed for those infected in rural areas