Chronic Exposure to E-Cigarettes Elevates CYP2A5 Activity, Protein Expression, and Cotinine-Induced Production of Reactive Oxygen Species in Mice.

Coumarin 7'-hydroxylase activity, a specific marker of CYP2A5 activity, and the protein level were measured in liver microsomes of male mice after chronic exposure to e-cigarettes (e-cigs) (2.4% nicotine). After exposure for 240 minutes per day for 5 days, the activity and the protein level in preproenkephalin (ppENK)-heterozygous [ppENK (+/-)] mice were significantly elevated (P <0.05) compared with the untreated control. This elevation was not due to deletion of the ppENK gene because the activity did not differ among untreated ppENK (+/-), ppENK (-/-), and wild-type ppENK (+/+) controls. Hence, the elevation can reasonably be attributed to nicotine exposure. The production of reactive oxygen species (ROS) upon incubation of the hepatic microsomes of these mice with cotinine was higher in microsomes from the e-cig-treated mice compared with the untreated controls (P < 0.01). Liquid chromatography mass spectrometry assay showed three oxidation products of cotinine, viz trans 3'-hydroxycotinine (3'-HC), 5'-hydroxycotinine (5'-HC), and cotinine N-oxide (CNO) in the plasma of these mice. The result identifies these three oxidation reactions as the source of the observed ROS and also shows that, in nicotine-treated mice, the appropriate "nicotine metabolite ratio" is (3'-HC + 5'-HC + CNO)/cotinine. The results suggest intriguing possibilities that 1) this metabolite ratio may correlate with plasma nicotine clearance and hence impact nicotine's psychoactive effects and 2) chronic e-cig treatment causes ROS-induced oxidative stress, which may play a major role in the regulation of CYP2A5 expression. Our present results clearly show that both the activity and the protein level of CYP2A5 are elevated by repeated exposure to nicotine. SIGNIFICANCE STATEMENT: Nicotine, the psychoactive ingredient of tobacco, is eliminated as the oxidation products of cotinine in reactions catalyzed by the enzymes CYP2A5 in mice and CYP2A6 in humans. This study shows that repeated exposure to e-cigarettes elevates the level of CYP2A5 and the formation of reactive oxygen species. The results suggest an intriguing possibility that CYP2A5 may be upregulated by chronic nicotine exposure due to oxidative stress caused by the oxidation of cotinine in this preclinical model of human smokers.

Genomic analysis of wolves from Pakistan clarifies boundaries among three divergent wolf lineages.

Among the three main divergent lineages of gray wolf (Canis lupus), the Holarctic lineage is the most widespread and best-studied, particularly in North America and Europe. Less is known about Tibetan (also called Himalayan) and Indian wolf lineages in southern Asia, especially in areas surrounding Pakistan where all three lineages are thought to meet. Given the endangered status of the Indian wolf in neighboring India and unclear southwestern boundary of the Tibetan wolf range, we conducted mitochondrial and genome-wide sequencing of wolves from Pakistan and Kyrgyzstan. Sequences of the mitochondrial D-loop region of 81 wolves from Pakistan indicated contact zones between Holarctic and Indian lineages across the northern and western mountains of Pakistan. Reduced-representation genome sequencing of 8 wolves indicated an east-to-west cline of Indian to Holarctic ancestry, consistent with a contact zone between these two lineages in Pakistan. The western boundary of the Tibetan lineage corresponded to the Ladakh region of India's Himalayas with a narrow zone of admixture spanning this boundary from the Karakoram Mountains of northern Pakistan into Ladakh, India. Our results highlight the conservation significance of Pakistan's wolf populations, especially the remaining populations in Sindh and Southern Punjab that represent the highly endangered Indian lineage.

Identification of 5-Hydroxycotinine in the Plasma of Nicotine-Treated Mice: Implications for Cotinine Metabolism and Disposition in Vivo.

Two oxidation products of cotinine, 5-hydroxycotinine (5-HC) and cotinine N-oxide (CNO), were identified for the first time in vivo in the plasma of C57BL/6 mice after injection of nicotine (1 mg/kg) or exposure to an e-cigarette (e-cig) containing 2.4% nicotine. Liquid chromatography-mass spectrometry was used to separate 3-hydroxycotinine (3-HC), 5-HC, and CNO and to quantify each by the sensitive direct detection of their parent ion with m/z of 193.097. In nicotine-injected mice, 5-HC was as abundant as 3-HC 15 minutes postinjection, and CNO was readily detectable. In e-cig-exposed mice with plasma nicotine levels resembling that of human smokers, plasma 5-HC and CNO, as well as 3-HC, were readily quantifiable at the end of the 4-hour exposure time. In nicotine-injected mice, the combined concentration of 3-HC plus 5-HC plus CNO, all formed from cotinine by CYP2A5, was higher (P < 0.01) in females than in males, although the male-female difference in cotinine plasma level did not reach statistical significance. The result highlights the importance of considering these three oxidation products of cotinine in examining cotinine metabolism and disposition. Coumarin 7-hydroxylase activity, a specific marker of CYP2A5, measured in the hepatic microsomes of untreated mice showed that females have higher activity (P < 0.001) than males (N = 8 per sex). The abundance of plasma 5-hydroxycotinine in nicotine-treated mice raises intriguing questions about the site of its origin (hepatic or possibly kidney CYP2A5) and the routes of its disposition because urinary excretion of 5-HC has not been detected by liquid chromatography with tandem mass spectrometry in mice and is controversial in human smokers. SIGNIFICANCE STATEMENT: Nicotine is the active ingredient of tobacco, but its elimination route through its biomarker cotinine is not fully understood. By liquid chromatography-mass spectrometry, this study has identified and quantified for the first time 5-hydroxycotinine and cotinine N-oxide, which are oxidation products of cotinine, in the plasma of mice treated with nicotine or exposed to e-cigarettes. The results raise intriguing questions about nicotine disposition in vivo in this well established preclinical model of human smokers.

Improving cardiovascular health with the patient-centered, integrated primary care HEARTS model in Trinidad and Tobago.

This article describes the introduction of the Pan American Health Organization's HEARTS in the Americas program in Trinidad and Tobago and the successful experiences and challenges encountered in introducing and scaling it up as a strategy for strengthening the health system's response to cardiovascular diseases. Evidence about implementation of the HEARTS program in the World Health Organization's Region of the Americas was reviewed to identify the progress made, barriers, success factors and lessons learned. In 2019, the Ministry of Health commenced implementation of the program in 5 (4.9%) of the 102 primary health care centers, and by the end of 2021, it had been scaled up to 46 (45.0%) centers. The HEARTS program ensures that patients' cardiovascular health is managed in a comprehensive way through providing counseling about a healthy lifestyle, using evidence-based treatment protocols, ensuring access to essential medicines and technologies, and using a risk-based team approach, a monitoring and evaluation system and also a team-based approach to care delivery. The barriers encountered during implementation included the fragmentation of the existing health care system, the paternalistic role assumed by health care professionals, the resistance of some health care workers to change and a lack of team-based approaches to providing care. Successful implementation of the program was enabled through ensuring high-level political commitment, establishing the national HEARTS Oversight Committee, ensuring stakeholder involvement throughout all phases and implementing standardized approaches to care. When implemented in the context of existing primary health care settings, the HEARTS program provides an exceptionally well integrated and comprehensive model of care that embodies the principles of universal health care while ensuring the health of both populations and individuals. Thus, it enables and promotes a strengthened primary health care system and services that are responsive and resilient.

En este artículo se describe la introducción del programa HEARTS en las Américas de la Organización Panamericana de la Salud en Trinidad y Tabago y las experiencias satisfactorias y los desafíos encontrados con su ejecución y ampliación como estrategia para fortalecer la respuesta del sistema de salud a las enfermedades cardiovasculares. Se reunieron datos sobre la ejecución del programa HEARTS en la Región de las Américas de la Organización Mundial de la Salud con el fin de determinar cuáles han sido los avances, los obstáculos, los factores de éxito y las enseñanzas extraídas. En el año 2019, el Ministerio de Salud inició la ejecución del programa en cinco (4,9%) de los 102 centros de atención primaria de salud, y para fines del 2021, se había ampliado a 46 (45,0%). El programa HEARTS garantiza el manejo integral de la salud cardiovascular de los pacientes mediante la prestación de asesoramiento sobre hábitos saludables, la aplicación de protocolos de tratamiento basados en la evidencia, la garantía de acceso a medicamentos y tecnologías esenciales, así como el uso de un enfoque de trabajo en equipo basado en el riesgo, un sistema de monitoreo y evaluación, y un enfoque basado en el equipo para abordar la prestación de la atención. Entre los obstáculos para su ejecución se encontraron la fragmentación del sistema de atención médica, el papel paternalista asumido por los profesionales de la salud, la resistencia al cambio de algunos trabajadores de salud y la falta de enfoques de trabajo en equipo para la prestación de la atención. La ejecución satisfactoria del programa fue posible gracias a un compromiso político de alto nivel, la creación de un comité nacional de supervisión de HEARTS, la participación de las partes interesadas en todas las fases del programa y la aplicación de enfoques estandarizados para la atención. En su ejecución en el contexto de los entornos de atención primaria de salud existentes, el programa HEARTS proporciona un modelo de atención excepcionalmente bien integrado y exhaustivo que encarna los principios de acceso universal a la atención de salud al tiempo que garantiza la salud individual y poblacional. De este modo, este modelo fomenta un sistema de atención primaria de salud fortalecido y unos servicios receptivos y resilientes.

Este artigo descreve a introdução do programa HEARTS nas Américas da Organização Pan-Americana da Saúde em Trinidad e Tobago e as experiências bem-sucedidas e os desafios encontrados durante a introdução e expansão do programa como estratégia para fortalecer a resposta do sistema de saúde às doenças cardiovasculares. Analisaram-se evidências sobre a implementação do programa HEARTS na Região das Américas da Organização Mundial da Saúde para identificar os avanços obtidos, os obstáculos, os fatores de sucesso e as lições aprendidas. Em 2019, o Ministério da Saúde iniciou a implementação do programa em 5 (4,9%) dos 102 centros de atenção primária à saúde; no final de 2021, o programa havia sido ampliado para 46 (45,0%) centros. O programa HEARTS assegura que a saúde cardiovascular dos pacientes seja manejada de uma forma abrangente por meio de aconselhamento sobre estilo de vida saudável, uso de protocolos de tratamento baseados em evidências, garantia de acesso a medicamentos e tecnologias essenciais e utilização de uma estratégia de equipe baseada no risco, de um sistema de monitoramento e avaliação e de uma abordagem de atendimento baseado em equipe. Os obstáculos encontrados durante a implementação incluíam a fragmentação do sistema de saúde existente, o papel paternalista assumido pelos profissionais de saúde, a resistência de alguns profissionais de saúde a mudanças e a falta de abordagens baseadas em equipe na prestação do atendimento. Para permitir que a implementação do programa fosse bem-sucedida, obteve-se compromisso político de alto nível, criou-se o Comitê de Supervisão do HEARTS nacional, assegurou-se o envolvimento de interessados diretos em todas as fases e implementaram-se abordagens padronizadas de atendimento. Quando implementado no contexto dos ambientes existentes de atenção primária à saúde, o programa HEARTS oferece um modelo de atenção excepcionalmente bem integrado e abrangente que incorpora os princípios de atenção universal à saúde, ao mesmo tempo em que garante a saúde das populações e dos indivíduos. Dessa forma, viabiliza e promove um sistema de atenção primária à saúde fortalecido e serviços responsivos e resilientes.

Soybean herbage yield, nutritional value and profitability under integrated manures management.

Organic manures are more preferred and environmentally friendly than chemical fertilizers for minimally contaminating soil, water and environmental resources, but the determination of right source of organic manures continues to remain an unexplored aspect. Considering the important issue, a multi-year field trial was carried out to determine the response of forage soybean to four sources of nutrients such as chemical fertilizers (IF), poultry litter (PL), bovine's farm yard slurry (BFYS) and sewage sludge (SS) and their seven binary combinations (PL+BFYS, PL+SS, PL+IF, BFYS+SS, BFYS+IF, SS+IF and PL+BFYS+SS). Supplementation of organic manures with mineral fertilizers remained superior to their sole application, particularly BFYS + IF was found significantly (p≤0.05) superior for yielding the highest fresh biomass (23.9, 26.4 and 25.7 t ha-1) with improved nutritional quality. The same combination of integrated fertilizer management also recorded higher sustainability as per sustainable forage yield index along with the highest net income and the benefit-cost ratio. PL and SS applied in conjunction with IF performed better than sole or binary application of organic manures. Therefore, BFYS + IF may be recommended for adoption to produce comparable forage yield and nutritional quality of soybean along with reducing dependency on chemical fertilizers.

The role of pituitary adenylyl cyclase activating polypeptide in affective signs of nicotine withdrawal.

Recent evidence implicates endogenous pituitary adenylyl cyclase activating polypeptide (PACAP) in the aversive effect of nicotine. In the present study, we assessed if nicotine-induced conditioned place preference (CPP) or affective signs of nicotine withdrawal would be altered in the absence of PACAP and if there were any sex-related differences in these responses. Male and female mice lacking PACAP and their wild-type controls were tested for baseline place preference on day 1, received conditioning with saline or nicotine (1 mg/kg) on alternate days for 6 days and were then tested for CPP the next day. Mice were then exposed to four additional conditioning and were tested again for nicotine-induced CPP 24 hr later. Controls were conditioned with saline in both chambers and tested similarly. All mice were then, 96 hr later, challenged with mecamylamine (3 mg/kg), and tested for anxiety-like behaviors 30 min later. Mice were then, 2 hr later, forced to swim for 15 min and then tested for depression-like behaviors 24 hr later. Our results showed that male but not female mice lacking PACAP expressed a significant CPP that was comparable to their wild-type controls. In contrast, male but not female mice lacking PACAP exhibited reduced anxiety- and depression-like behaviors compared to their wild-type controls following the mecamylamine challenge. These results suggest that endogenous PACAP is involved in affective signs of nicotine withdrawal, but there is a sex-related difference in this response.

Seroprevalence of Hepatitis B Infection Among a Population of Blood Donors in the Kpandai District of Northern Ghana: A Five-Year Retrospective Study from 2014 to 2018.

Hepatitis B virus (HBV) infection is an infectious disease that is specific to the liver, causing both acute and chronic hepatitis. This study determined the trend of HBV infection among blood donors in the Kpandai District Hospital from January 2014 to December 2018. Retrospective analysis of donor profiles for a period of 5 years was used to assess the distribution of seropositive cases in relation to age, sex, and trend. The data was collected using pre-designed questionnaire and managed using Microsoft Excel spread sheet 2013. The overall sero-prevalence of HBV was 8.2% (230/2802). The year to year analysis depicted significant trends in reduction of HBV infection among the study population at a rate of 13 percentage points above the mean from 2014 to 2015, and 4.3 percentage points below the mean from 2016 to 2018 across the period. The prevalence in males was 8.4% (225/2687) and that of the females was 4.4% (5/115) and the highest rate of infection was among those below 30 years 9.8% (163/1666). Although the general prevalence of HBV infection was high (8.2%), there was a significant trend reduction in rate of infection across the study period. This suggests that the public health interventional strategies put in place to manage the HBV infection in Kpandai District seem to be working.

A Novel and Selective Nociceptin Receptor (NOP) Agonist (1-(1-((cis)-4-isopropylcyclohexyl)piperidin-4-yl)-1H-indol-2-yl)methanol (AT-312) Decreases Acquisition of Ethanol-Induced Conditioned Place Preference in Mice.

BACKGROUND: Nociceptin/orphanin FQ, the endogenous peptide agonist for the opioid receptor-like receptor (also known as NOP or the nociceptin receptor), has been shown to block the acquisition and expression of ethanol (EtOH)-induced conditioned place preference (CPP). Here, we report the characterization of a novel small-molecule NOP ligand AT-312 (1-(1-((cis)-4-isopropylcyclohexyl)piperidin-4-yl)-1H-indol-2-yl)methanol) in receptor binding and GTPγS functional assays in vitro. We then investigated the effect of AT-312 on the rewarding action of EtOH in mice using the CPP paradigm. Further, using mice lacking the NOP receptor and their wild-type controls, we also examined the involvement of NOP in the effect of AT-312. Motivational effects of AT-312 alone were also assessed in the CPP paradigm. METHODS: Female mice lacking NOP and/or their wild-type controls received conditioning in the presence or absence of the NOP agonist [AT-312 (1, 3, and 10 mg/kg) or the control NOP agonist SCH221510 (10 mg/kg)] followed by saline/EtOH for 3 consecutive days (twice daily) and tested for CPP in a drug-free state on the next day. RESULTS: Our in vitro data showed that AT-312 is a high-affinity, selective NOP full agonist with 17-fold selectivity over the mu opioid receptor and >200-fold selectivity over the kappa opioid receptor. The results of our in vivo studies showed that AT-312 reduced EtOH CPP at the lowest dose (1 mg/kg) tested but completely abolished EtOH CPP at higher doses (3 or 10 mg/kg) compared to their vehicle-treated control group. AT-312 (3 mg/kg) did not alter EtOH-induced CPP in mice lacking NOP, confirming that AT-312 reduced EtOH CPP through its action at the NOP receptor. AT-312 (3 mg/kg) did not induce reward or aversion when administered alone, showing that the novel small-molecule NOP agonist shows efficacy in blocking EtOH-induced CPP via the NOP receptor. CONCLUSIONS: Together, these data suggest that small-molecule NOP agonists have the potential to reduce alcohol reward and may be promising as medications to treat alcohol addiction.

Donor-specific HLA antibody-mediated complement activation is a significant indicator of antibody-mediated rejection and poor long-term graft outcome during lung transplantation: a single center cohort study.

Complement-mediated allograft injury, elicited by donor-specific HLA antibodies (DSA), is a defining pathophysiological characteristic of allograft damage. We aimed to study DSA-induced complement activation as a diagnostic marker of antibody-mediated rejection (AMR) and a risk stratification tool for graft loss in the context of lung transplantation (LT). We identified 38 DSA-positive patients whose serum samples were submitted for C3d deposition testing via the C3d assay. Among these 38 patients, 15 had AMR (DSAPos AMRPos ). Results were reported for each patient as the C3d ratio for each DSA, the immunodominant DSA, and the C3d ratio for all DSA present in a sample (C3d ratioSUM ). DSAPos AMRPos patients had higher C3d ratioSUM values (58.66 (-1.32 to 118.6) vs. 1.52 (0.30 to 2.74), P = 0.0016) and increased immunodominant C3d ratios (41.87 (1.72 to 82.02) vs. 0.69 (0.21 to 1.19), P = 0.001) when compared with DSAPos AMRNeg patients. Specificity and calculated positive predictive value of the immunodominant C3d ratio and BCMsum tests for AMR diagnosis were both 100% (CI = 17.4-100) in this cohort. Worst graft survival was associated with both immunodominant C3d ratio ≥4 or C3d ratioSUM ≥10 or BCMsum >7000, suggesting that the antibody composition and/or strength are the principal determinants of an HLA DSA's capacity to activate complement.

Antipyretic potential of herbal coded formulation (Pyrexol).

The antipyretic effect of the aqueous extract of herbal coded formulation containing equal amount of Salix alba, Emblica officinalis, Glycyrrhiza glabra, Adhatoda vasica, Viola odorata, Thea sinensis, Veleriana officinalis, Foeniculum vulgare, Sisymbrium irrio and Achillea millefolium was investigated using the yeast induced pyrexia model in rabbits. Paracetamol was used as a control group. Rectal temperatures of all rabbits were recorded immediately before the administration of the extract or paracetamol and again at 1 hour, after this, temperature was noted at 1 hrs interval for 5 hrs using digital thermometer. At 240mg/kg dose the extract showed significant reduction in yeast-induced elevated temperature as compared with that of standard drug paracetamol (150mg/kg). It is concluded that herbal coded medicine at a dose of 240mg/kg has marked antipyretic activity in animal models and this strongly supports the ethno pharmacological uses of medicinal plants of this formulation.

Rural-urban comparisons of dengue seroprevalence in Malaysia.

BACKGROUND: Each year an estimated 390 million dengue infections occur worldwide. In Malaysia, dengue is a growing public health concern but estimate of its disease burden remains uncertain. We compared the urban-rural difference of dengue seroprevalence and determined age-specific dengue seroprevalence in Malaysia. METHODS: We undertook analysis on 11,821 subjects from six seroprevalence surveys conducted in Malaysia between 2001 and 2013, which composed of five urban and two rural series. RESULTS: Prevalence of dengue increased with age in both urban and rural locations in Malaysia, which exceeded 90 % among those aged 70 years or beyond. The age-specific rates of the 5 urban surveys overlapped without clear separation among them, while prevalence was lower in younger subjects in rural series than in urban series, the trend reversed in older subjects. There were no differences in the seroprevalence by gender, ethnicity or region. Poisson regression model confirmed the prevalence have not changed in urban areas since 2001 but in rural areas, there was a significant positive time trend such that by year 2008, rural prevalence was as high as in urban areas. CONCLUSION: Dengue seroprevalence has stabilized but persisted at a high level in urban areas since 2001, and is fast stabilizing in rural areas at the same high urban levels by 2008. The cumulative seroprevalence of dengue exceeds 90 % by the age of 70 years, which translates into 16.5 million people or 55 % of the total population in Malaysia, being infected by dengue by 2013.

Review: Comprehensive review on treatment of HIV.

HIV or AIDS is a major threat for humanity in the world especially in developing countries. The causative factor of the syndrome is HIV, which infects and destroys one of the cellular components of the immune system, the T cells, causing deficiency in the immunological surveillance and ultimately leading to AIDS. According to WHO, around 35 million people were living with HIV in 2013 and since the start of epidemic 39 million people have died due to AIDS. Center for disease control and prevention estimated in 2014 that 1,201,100 people aged 13 and above were suffering from HIV infection Worldwide. The most effective approach is the highly active antiretroviral therapy (HAART) containing the combined use of drugs having different mechanisms of action. However, complete eradication of HIV from the body does not occur by HAART, but it lead to long term toxicity occurs and emerges as drug resistant. Despite the recent development of various new antiretroviral compounds, there is still a need to develop need to search for new alternatives which are equally efficient and less expensive as compared to the contemporary treatment available. This review provides an overview and a summary of herbal medicines for HIV infection and summarized the efficacy and medicinal use of different plants used in the treatment of HIV infection. The objective of this review is to enlighten the recent advances in the exploration of medicinal plants used for treatment of HIV/AIDS.

High Emergency Lung Transplantation: dramatic decrease of waiting list death rate without relevant higher post-transplant mortality.

Many candidates for lung transplantation (LT) die on the waiting list, raising the question of graft availability and strategy for organ allocation. We report the experience of the new organ allocation program, "High Emergency Lung Transplantation" (HELT), since its implementation in our center in 2007. Retrospective analysis of 201 lung transplant patients, of whom 37 received HELT from 1st July 2007 to 31th May 2012. HELT candidates had a higher impairment grade on respiratory status and higher Lung Allocation Score (LAS). HELT patients had increased incidence of perioperative complications (e.g., perioperative bleeding) and extracorporeal circulatory assistance (75% vs. 36.6%, P = 0.0005). No significant difference was observed between HELT and non-HELT patients in mechanical ventilation duration (15.5 days vs. 11 days, P = 0.27), intensive care unit length of stay (15 days vs. 10 days, P = 0.22) or survival rate at 12 (81% vs. 80%), and 24 months post-LT (72.9% vs. 75.0%). Lastly, mortality on the waiting list was spectacularly reduced from 19% to 2% when compared to the non-HELT 2004-2007 group. Despite a more severe clinical status of patients on the waiting list, HELT provided similar results to conventional LT. These results were associated with a dramatic reduction in the mortality rate of patients on the waiting list.

Waist circumference and not body mass index as the outcome of a group weight intervention for patients with severe mental illness.

OBJECTIVE: Most weight interventions among patients with severe mental illness (SMI) used body mass index (BMI) as outcome measure but excluded waist circumference (WC) although the latter is a stronger predictor of obesity complications. This study aimed to assess a weight-management program consisting of education, exercise and behavioural techniques for patients with SMI using weight parameters including WC as the outcome measures. METHODS: A group intervention was carried out as part of psychiatric outpatient community service. It used structured modules on diet, exercise and related topics comprising of education and exercises sessions with a total of 12-week duration. The participants were outpatients with SMI recruited through referrals to the program by the treating doctor. The participants' body weight, BMI and WC were measured at the baseline, fortnightly and at the end of the program. RESULTS: A total of 27 patients participated in the program which was carried out in 6 cycles. The pre- and post-intervention comparisons analysis of the weight parameters found a significant reduction in the WC (mean=3.878 cm+5.165, p=0.001) while no significant changes were recorded in body weight and BMI. CONCLUSION: Small but significant loss in WC and possibly weight maintenance were achieved using this non-pharmacological intervention. Modest loss in WC may have an impact on reducing the risk of obesity-related health risks.

In vitro xanthine oxidase inhibitory and in vivo hypouricemic activity of herbal coded formulation (Gouticin).

Currently, natural products have been used in treating gouty arthritis and are recognized as xanthine oxidase inhibitors. Current study was designed to evaluate in vitro xanthine oxidase inhibitory potential of Gouticin and its ingredients extracts and in vivo hypouricemic activity of gouticin tablet 500 mg twice daily. Ethanol extracts of Gouticin and its ingredients were evaluated in vitro, at 200, 100, 50, 25 µ g/ml concentrations for xanthine oxidase inhibitory activity. IC(50) values of Gouticin and its ingredients were estimated. Further, in vivo therapeutic effect of Gouticin was investigated in comparison with allopathic medicine (Allopurinol) to treat gout. Total patients were 200 that were divided into test and control group. Herbal coded medicine (Gouticin) was given to test group and allopathic medicine allopurinol was administered to control group. In vitro, Gouticin has the highest percent inhibition at 96% followed by Allopurinol with 93% inhibition. In vivo study, mean serum uric acid level of patients was 4.62 mg/dl and 5.21mg/dl by use of Gouticin and Allopurinol at end of therapy. The study showed that herbal coded formulation gouticin and its ingredients are potential sources of natural xanthine oxidase inhibitors. Gouticin 500 mg twice daily is more effective than the allopurinol 300mg once daily in the management of gout.

Comprehensive review on therapeutic strategies of gouty arthritis.

Traditional medicines are practiced worldwide for treatment of gouty arthritis since ancient times. Herbs and plants always have been used in the treatment of different diseases such as gout. The present article deals with the therapeutic strategies and options for the cure of gouty arthritis. Bibliographic investigation was carried out by analyzing classical textbooks and peer reviewed papers, consulting worldwide accepted scientific databases. In this article a detailed introduction, classification, epidemiology, risk factors, symptoms, diagnosis and treatment of gout with reference to modern and Unani system of medicines have been discussed. It is also tried to provide a list of plants used in the treatment of gout along with their formulations used in Unani system of medicine. The herbs and formulations have been used in different systems of medicine particularly Unani system of medicines exhibit their powerful role in the management and cure of gout and arthritis. Most of herbs and plants have been chemically evaluated and some of them are in clinical trials. Their results are magnificent and considerable. However their mechanisms of actions are still on the way.

Bioprosthetic mitral valve thrombosis: the role of cardiac CT in diagnosis and guiding the management.

A patient in his 60s with a bioprosthetic aortic and mitral valve replacement presented with dyspnoea, tiredness and dizziness 2 years postoperatively. Transthoracic echocardiography showed mitral valve stenosis and increased pulmonary artery pressure suggesting bioprosthetic valve failure. Cardiac CT confirmed the diagnosis of bioprosthetic mitral valve thrombosis. Treatment with anticoagulation resulted in a remarkable improvement of the valve area and gradient and complete resolution of the thrombus. Herein, we report a case of rare bioprosthetic mitral valve thrombosis.

Small molecule NOP agonists reverse locomotor sensitization induced by cocaine in male C57BL/6 mice.

Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand of the nociceptin opioid receptor (NOP) has been shown to block cocaine-induced locomotor sensitization in mice and rats, and also reverses this phenomenon when injected intracerebroventricularly in animals with an established sensitized response. In the present study, we determined whether small-molecule NOP agonists would recapitulate this effect after systemic administration. Male C57BL/6 mice treated with cocaine (15 mg/kg) on days 1-3 and showed locomotor sensitization to the same dose of cocaine on day 8 were injected with vehicle or one of the two NOP agonists (AT-202 and AT-524) (but not cocaine) on days 9-11. On day 15, locomotor sensitization was assessed after a cocaine challenge (15 mg/kg). Subchronic administration of the two NOP agonists to sensitized mice significantly decreased the sensitized response on day 15. In a separate experiment conducted in male and female mice lacking NOP and their wildtype littermates, AT-524 reversed sensitization in male wildtype but not in mice lacking NOP. Further, co-administration of the NOP agonist with cocaine for three days on days 16-18 prevented the development of locomotor sensitization from this cocaine treatment in wild-type but not in NOP knockout mice. However, none of these effects of the NOP agonist was observed in female mice. Together, these results suggest that subchronic repeated administration of small-molecule NOP agonists may reverse adaptive behavioral changes associated with repeated intermittent cocaine treatment in male but not female mice.

Biomass as an alternative feedstock to oleochemicals.

The huge demands for petrochemicals have led to a rapid increase in the production of these fossil-based derivatives. Biomass represents a promising feedstock for addressing the challenges related to petrochemicals in terms of the necessity to apply renewable sources and the need to decrease carbon emissions. Among the natural biomass products, most studies have attempted to upgrade natural oils owing to their promising advantages of worldwide availability, low-cost processing, and built-in functionality. This paper discusses the upgradation of natural oils to the most beneficial oleochemicals, including fatty acids, fatty alcohols, and fatty acid methyl esters. This review also covers the utility, physico-chemical properties, and the production processes for such materials. The interconnected reaction routes to produce oleochemicals and the affecting parameters (catalyst design, temperature, and pressure) are also elucidated. Furthermore, this article discusses the future perspective of oleochemicals based on their development in recent years.

Stroke incidence in the South West District of the Penang Island, Malaysia: PEARLs: Penang Acute Stroke Research Longitudinal Study.

OBJECTIVES: This community based incidence study aims to report the stroke incidence in the south-west region of the Penang Island. METHODS: All strokes occurring in the population of residents in the southwest region of the Penang Island, Malaysia during a period of 12 months, from April 2010 to March 2011 were screened and assessed. Standard definitions for stroke were used. All stroke cases were ascertained using multiple overlapping sources. Incidence rate was based on first ever in a lifetime stroke cases. All recurrent strokes were excluded from the incidence count. RESULTS: The overall stroke incidence rate in the study region during the study period was 67 per 100,000 after age adjustment to 2010 Malaysian population. CONCLUSION: This study provides the first stroke incidence data in Malaysia and is vital for effective health system planning.