An established abdominal wall multidisciplinary team improves patient care and aids surgical decision making with complex ventral hernia patients.

INTRODUCTION: Abdominal wall reconstruction (AWR) is an emerging subspecialty within general surgery. The practice of multidisciplinary team (MDT) meetings to aid decision making and improve patient care has been demonstrated, with widespread acceptance. This study presents our initial experience of over 150 cases of complex hernia patients discussed in a newly established MDT setting. METHODS: From February 2020 to July 2022 (30-month period), abdominal wall MDTs were held bimonthly. Key stakeholders included upper and lower gastrointestinal surgeons, a gastrointestinal specialist radiologist, a plastic surgeon, a high-risk anaesthetist and two junior doctors integrated into the AWR clinical team. Meetings were held online, where patient history, past medical and surgical history, hernia characteristics and up-to-date computed tomography scans were discussed. RESULTS: Some 156 patients were discussed over 18 meetings within the above period. Ninety-five (61%) patients were recommended for surgery, and 61 (39%) patients were recommended for conservative management or referred elsewhere. Seventy-eight (82%) patients were directly waitlisted, whereas seventeen (18%) required preoperative optimisation: three (18%) for smoking cessation, eleven (65%) for weight-loss management and three (18%) for specialist diabetic assessment and management. In total, 92 (59%) patients (including operative and nonoperative management) have been discharged to primary care. DISCUSSION: A multidisciplinary forum for complex abdominal wall patients is a safe process that facilitates decision making, promotes education and improves patient care. As the AWR subspecialty evolves, our view is that the "complex hernia MDT" will become commonplace. We present our experience and share advice for others planning to establish an AWR centre.

Development, implementation and evaluation of the digital transformation of renal services in Wales: the journey from local to national.

BACKGROUND: Treatment for people with kidney disease is often associated with complicated combinations of medicines. Logistical challenges with traditiona paper-based prescribing means that these patients are particularly susceptible to medication-relation errors and harm. AIM: To improve the quality of care that people with kidney disease receive across Wales through a Value-Based digital transformation programme. SETTING: Renal units within the National Welsh Renal Clinical Network (WRCN). DEVELOPMENT: A novel Electronic Prescribing & Medicines Administration (EPMA) system, integrated into a patient care record and linked to a patient portal was developed in South West Wales (SWW) region of the WRCN, enabled by the Welsh Government (WG) Efficiency Through Technology Fund. National upscale was enabled through the WG Transformation Fund. IMPLEMENTATION: EPMA was designed and rolled out initially in SWW region of the WRCN (2018). A dedicated delivery team used the blueprint to finalise and implement a strategy for successful national roll-out eventually across all Wales (completed 2021). EVALUATION: A multi-factorial approach was employed, as both the technology itself and the healthcare system within which it would be introduced, were complex. Continuous cycles of action research involving informal and formal qualitative interviews with service-users ensured that EPMA was accessible and optimally engaging to all target stakeholders (patients and staff). Results confirmed that EPMA was successful in improving the quality of care that people with kidney disease receive across Wales, contributed to Value-Based outcomes, and put people who deliver and access care at the heart of transformation. CONCLUSION: Key findings of this study align directly with the national design principles to drive change and transformation, put forward by the WG in their plan for Health and Social Care: prevention and early intervention; safety; independence; voice; seamless care.

How reconfiguration of a minor injuries unit has affected service delivery during the COVID-19 pandemic: a retrospective analysis.

INTRODUCTION: Redeployment of orthopaedic consultants to a minor injuries unit (MIU) during the COVID-19 pandemic provided a unique opportunity to assess the impact of early senior specialist input on patient management. METHODS: Patient demographics, diagnosis, location of injury and disposal method were compared between three 7-day periods: during the April 2020 COVID-19 lockdown (period A), one month prior to period A (period B) and one year prior to period A (period C). Orthopaedic consultants staffed the MIU during period A, and emergency nurse practitioners staffed the MIU during periods B and C. RESULTS: Period A witnessed higher injury severity either due to modified activities or altered healthcare-seeking behaviour during lockdown. For fractures, compared with periods B and C, period A saw a lower rate of referral to fracture clinic (41% vs 100% vs 86%, p<0.001) and higher rate of discharge (38% vs 0% vs 9%, p<0.001). The median time to fracture clinic was also longer (15 days vs 6 days vs 10 days, p<0.001), indicating earlier institution of definitive care. There were no other significant differences between periods with radiology alerts and complaints received remaining largely unchanged. CONCLUSION: Early senior orthopaedic input in the patient journey from MIU had clear benefits, this being most true for fracture diagnoses. Earlier definitive management planning was observed as lower rates of fracture clinic referral, higher rates of discharge and deferred first fracture clinic reviews. This study highlights the benefits of greater partnership between MIU and orthopaedics. As the pandemic subsides and redeployed staff return to normal duties, a modification of this model could be utilised to ensure this partnership is sustainable.

Pattern of ß-Diversity and Plant Species Richness along Vertical Gradient in Northwest Himalaya, India.

The structure and distribution patterns of Himalayan vegetation are poorly explored, and research on species composition along the elevation gradient in these mountain ranges is still deficient. The current study was undertaken to analyze the variation and pattern of plant species composition along a vertical gradient in northwestern Himalaya, India. A total of 18 sites were selected along an elevation gradient ranging from 2200 to 3900 m asl positioned at an interval of 100 m. The Renyi diversity profile, non-metric multidimensional scaling based on the Bray-Curtis dissimilarity metric and beta diversity components among the elevation belts were calculated. Furthermore, to study the influence of altitude on species richness and diversity, a generalized additive model was created. Two hundred and ten plant species representing 66 families and 147 genera were recorded. The Renyi diversity profiles show that the lower and mid-altitudes had rich species diversity. The results of the non-metric multidimensional scaling analysis show a considerable variation in the total plant species composition among the studied elevation belts. The observed multiple-site Sorensen dissimilarity index across the studied elevation belts was very high. The contribution of species replacement or the turnover component to the observed dissimilarity was much higher than the nestedness component. Furthermore, the herbaceous and tree richness showed a significant decrease with increase in elevation; however, the richness of shrubs showed a bimodal pattern. The present study increases our understanding of the trends and patterns of species richness along the vertical gradient in the Himalayan region.

Patterns of floristic and functional diversity in two treeline ecotone sites of Kashmir Himalaya.

Globally, the treelines at higher elevations in mountains are reported to be advancing up-slope in response to recent climate warming. However, little is known about the treeline advancement in the Himalaya due to paucity of baseline vegetation data with which to compare, thus making their assessment and monitoring challenging. To fill this knowledge gap, the present study documented floristic and functional diversity of two treeline ecotone sites in Kashmir Himalaya. At each site, we conducted field sampling by laying five 20-m2 plots, with one at the highest limit (T0 plot), two plots below and two above the treeline and two nested subplots of 5-m2 for shrubs and five 1-m2 for herbs in each plot. We recorded 97 plant species belonging to 33 families from the two sites. We observed a considerable difference in species composition and distribution along the treeline ecotone. Majority of the species reported were perennial herbs. We observed a significant association of growth forms with the particular plots along the treeline ecotone. At both the sites, we recorded highest species richness at the T0 plot which was correlated well with the functional traits, thus indicating convergence of floristic and functional diversity at this transition zone. Interestingly, the T0 plot at both the sites showed maximum overlap of species with the plots above and below the treeline. In an era of climate warming, our study provides crucial baseline data that will facilitate assessment and monitoring of the Himalayan treelines.

Conjugated polymer nanoparticles and their nanohybrids as smart photoluminescent and photoresponsive material for biosensing, imaging, and theranostics.

The emergence of conjugated polymers (CPs) has provided a pathway to attain smart multifunctional conjugated polymer nanoparticles (CPNs) with enhanced properties and diverse applications. CPNs based on π-extended CPs exhibit high fluorescence brightness, low cytotoxicity, excellent photostability, reactive oxygen species (ROS) generation ability, high photothermal conversion efficiency (PCE), etc. which endorse them as an excellent theranostic tool. Furthermore, the unique light-harvesting and energy transfer properties of CPNs enables their transformation into smart functional nanohybrids with augmented performance. Owing to such numerous features, simple preparation method and an easy separation process, the CPNs and their hybrids have been constantly rising as a frontrunner in the domain of medicine and much work has been done in the respective research area. This review summarizes the recent progress that has been made in the field of CPNs for biological and biomedical applications with special emphasis on biosensing, imaging, and theranostics. Following an introduction into the field, a first large section provides overview of the conventional as well as recently established synthetic methods for various types of CPNs. Then, the CPNs-based fluorometric assays for biomolecules based on different detection strategies have been described. Later on, examples of CPNs-based probes for imaging, both in vitro and in vivo using cancer cells and animal models have been explored. The next section highlighted the vital theranostic applications of CPNs and corresponding nanohybrids, mainly via imaging-guided photodynamic therapy (PDT), photothermal therapy (PTT) and drug delivery. The last section summarizes the current challenges and gives an outlook on the potential future trends on CPNs as advanced healthcare material.

The Potential of Strategic Environmental Assessment to Improve Urban Planning in Sierra Leone.

Strategic Environmental Assessment (SEA) is a proactive and collaborative method for environmental management designed to integrate environmental considerations into decision-making; and it is good for Sierra Leone. To understand whether SEA would be useful in the context of Sierra Leone, the authors interviewed 64 out of 78 experts face to face from March to July 2019. In addition, government policies and regulatory documents on environmental management and sustainable development, published articles served as secondary sources of data. Data were analyzed using descriptive statistics. These Sierra Leonean experts agreed that SEA would be useful for integration and achievement of improved sustainable urban planning strategies. However, the barriers identified to integrating SEA include: not addressing environmental issues during the preparation of policies and programs, insufficient political will, the absence of clear objectives, targets, principles and approaches, overlapping mandates among environmental institutions, and inadequate institutional coordination and non-integrated development framework as barriers to integrating SEA into their work. The study shows that SEA has the potential to have a positive impact on environmental concerns in decision-making, but it would need to be supported by stronger political will, legal frameworks, and improved technical guidance from the policy perspective. Moreover, we propose a conceptual framework for the inclusion of SEA into the urban planning process in Sierra Leone.

Substantial shifts in flowering phenology of Sternbergia vernalis in the Himalaya: Supplementing decadal field records with historical and experimental evidences.

In an age of anthropocene, shifting plant phenology is one of the most striking biological indicators of global environmental change. Majority of the studies reporting shifts in plant phenology are available from the North America and Europe and largely scarce from the developing world, including the Himalaya; and studies integrating multiple methodological approaches to investigate the climate-driven phenological shifts are too rare. Here, we report the shifts in spring flowering phenology of model plant species, Sternbergia vernalis in response to the changing climate in Kashmir Himalaya, by integrating decadal field observational records with long-term herbarium and dated-photograph data, and supported with experimental evidences. Our results revealed a significant increasing trend of 0.038, 0.016 and 0.023 °C/year in the annual mean maximum temperature (Tmax), mean minimum temperature (Tmin) and diurnal temperature range (DTR) respectively; but an insignificant decreasing trend in annual precipitation of -1.24 mm/year over the last four decades (1980-2019) in this Himalayan region. The flowering phenology of S. vernalis has significantly advanced by 11.8 days/°C and 27.8 days/°C increase in Tmax and Tmin respectively, indicating that the climate warming has led to substantial shifts in flowering phenology of the model plant species. We also observed a strong association of seasonal Tmax (December-February) and DTR on the early onset of spring flowering, however precipitation had no significant effect on the timing of flowering. The greenhouse experiment results further supported a significant effect of temperature in triggering the phenological shifts, wherein the model plant grown under different temperature treatments flowered 9-20 days earlier compared to the control. Our study showcases the integrated use of multiple methodological approaches for unravelling the long-term phenological shifts in response to climate change, and contributes in filling the knowledge gaps in the phenological research from the developing world in general and the Himalaya in particular.

Medicinal importance of Papra (Podophyllum hexandrum Royle) in Unani System of Medicine.

Podophyllum hexandrum Royle [=Sinopodophyllum hexandrum (Royle) T.S. Ying] is an important, endemic medicinal plant species of Himalaya. It is used in Unani System of Medicine under the name of 'Papra'. The drug was not mentioned in previous literatures, but the first time it introduced in Unani Medicine by a great scholar Hakim Najmul Ghani. He has mentioned its uses and benefits in his classical book Khazainul Advia. In Unani Medicine the plant species has been used to treat various ailments like constipation, fever, jaundice, liver disorders, syphilis, diseases of lymph glands etc. In Kashmir Himalaya it is used to treat various diseases by local medicinemen, but now it is listed in rare drugs. Various pharmacological studies have been done such as antioxidant, antimicrobial, anti-inflammatory, antifungal, radio-protective etc., recently it has also been reported that podophyllotoxin or podophyllin can be used to treat some forms of cancers also.

System-Pharmacology Dissection of Traditional Chinese herbs SINI Decoction for Treatment of Cardiovascular Diseases.

Abstract: Cardiovascular diseases (CVDs) are leading causes of death in the world, owing to noticeable incidence and mortality. Traditional Chinese Medicine (TCM) SINI Decoction (SND) is used to prevent and treat CVDs, which has attracted extensive attention for its moderate and little side effects. However, the involved molecular mechanisms are exceedingly complicated and remain unclear. Systems pharmacology, as a novel approach that integrates systems biology and pharmacology plays a significant role in investigating the molecular mechanism of TCM. In systems pharmacology approach, we use to systematically uncover the mechanisms of action in Chinese medicinal formula SND as an effective treatment for CVDs, which mainly includes:1) molecular database building; 2) ADME evaluation; 3) target-fishing 4) network construction and analysis. The results show that 78 underlying valid ingredients and their corresponding 71 direct targets of SND were obtained. And SND take part in cardiomyocyte protection, blood pressure regulation, and lipid regulation module in treatment of CVDs by cooperative way. Systems pharmacology as an emerging field that investigates the molecular mechanisms of TCM through pharmacokinetic evaluation target prediction, and pathway analysis, which will facilitate the development of traditional Chinese herbs in modern medicine.

Attitudes of Primary Care Health Workers Towards Mental Health Patients: A Cross-Sectional Study in Osun State, Nigeria.

World Health Organization (WHO) recommends integration of mental health services into primary health services; however attitude of primary health care workers is one barrier to this. A cross sectional survey using the Community Attitudes towards Mental Illness (CAMI) was done. One hundred and twenty primary care workers were randomly selected from three local government areas. Descriptive and inferential statistics were used in analyses. The results showed that most primary health care workers hold a benevolent (mean = 2.47, SD = 0.52) attitude towards the mentally ill. Workers with 10 years or more experience tend to have less authoritarian (t = 3.19, p = 0.01) and less social restrictive (t = 3.90, p = 0.01) attitudes towards the mentally ill. There were no significant differences in attitude by gender, marital status, or designation of health care workers. The study showed that primary care workers have attitudes similar to that seen in the general population.

An anionic conjugated polymer as a multi-action sensor for the sensitive detection of Cu(2+) and PPi, real-time ALP assaying and cell imaging.

A Cu(2+) ensemble polyfluorene derivative, poly[5,5'-(((9H-fluorene-9,9-diyl)bis(hexane-6,1-diyl))bis(oxy))diisophthalate] sodium salt (PFT), displays unprecedented selectivity for PPi (LOD = 2.26 ppb) in aqueous solution as well as in random urine samples at physiological pH vis-a-vis monitoring ALP activity. Furthermore, intracellular imaging of Cu(2+) and PPi in mouse macrophage (J774A.1) and human breast cancer cells (MDA-MB231) was achieved to confirm the viability of PFT in biological systems.

Transcriptome analysis reveals a classical interferon signature induced by IFNλ4 in human primary cells.

The IFNL4 gene is negatively associated with spontaneous and treatment-induced clearance of hepatitis C virus infection. The activity of IFNλ4 has an important causal role in the pathogenesis, but the molecular details are not fully understood. One possible reason for the detrimental effect of IFNλ4 could be a tissue-specific regulation of an unknown subset of genes. To address both tissue and subtype specificity in the interferon response, we treated primary human hepatocytes and airway epithelial cells with IFNα, IFNλ3 or IFNλ4 and assessed interferon mediated gene regulation using transcriptome sequencing. Our data show a surprisingly similar response to all three subtypes of interferon. We also addressed the tissue specificity of the response, and identified a subset of tissue-specific genes. However, the interferon response is robust in both tissues with the majority of the identified genes being regulated in hepatocytes as well as airway epithelial cells. Thus we provide an in-depth analysis of the liver interferon response seen over an array of interferon subtypes and compare it to the response in the lung epithelium.

Body mass index, waist circumference, hip circumference, waist-hip-ratio and waist-height-ratio: which is the better discriminator of prevalent screen-detected diabetes in a Cameroonian population?

BACKGROUND: The link between measures of adiposity and prevalent screen-detected diabetes (SDM) in Africa has been less well investigated. We assessed and compared the strength of association and discriminatory capability of measures of adiposity including body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-hip-ratio (WHR) and waist-height-ratio (WHtR) for prevalent SDM risk in a sub-Saharan African population. METHODS: Participants were 8663 adults free of diagnosed type 2 diabetes, who took part in the nationally representative Cameroon Burden of Diabetes (CAMBoD) 2006 survey. Logistic regression models were used to compute the odd ratio (OR) and 95% confidence interval (95%CI) for a standard deviation (SD) higher level of BMI (7.3), WC (12.5), HC (11.7), WHR (0.19) and WHtR (0.08) with prevalent SDM risk. Assessment and comparison of discrimination used C-statistic and relative integrated discrimination improvement (RIDI, %). RESULTS: The adjusted OR and 95%CI for prevalent SDM with each SD higher adipometric variable were: 1.05 (0.98-1.13) for BMI, 1.30 (1.16-1.46) for WC, 1.18 (1.05-1.34) for HC, 1.05 (1.00-1.16) for WHR and 1.26 (1.11-1.39) for WHtR. C-statistic comparisons and RIDI analyses showed a trend toward a significant superiority of WC over other adipometric variables in multivariable models. Combining adiposity variables did not improve discrimination beyond multivariable models with WC alone. CONCLUSION: WC was the best predictors and to some extent WHtR of prevalent SDM in this population, while BMI and WHR were less effective.

Highly precise detection, discrimination, and removal of anionic surfactants over the full pH range via cationic conjugated polymer: an efficient strategy to facilitate illicit-drug analysis.

A water-soluble cationic conjugated polyelectrolyte (CPE), poly(1,4-bis(6-(1-methylimidazolium)-hexyloxy)-benzene bromide) (PMI) displays extraordinary stability over the full pH range of 1-14 as well as in seawater, brine, urine, and other solutions and carries out efficient detection, discrimination, and removal of moderately dissimilar anionic surfactants (viz., sodium dodecyl benzenesulfonate (SDBS) and sodium dodecyl sulfate (SDS)) at very low levels (31.7 and 17.3 parts per billion (ppb), respectively). PMI formed stable hydrogels in the presence of SDS that remained unaffected by strong acids/bases, heating, ultrasonication, or exposure to light, whereas SDBS formed precipitate with PMI as a result of its different interpolymer cofacial arrangement via Columbic attraction. The complex-forming ability of PMI with SDS and SDBS facilitated their elimination from water or drug-doped urine samples without the use of any organic solvent, chromatographic technique, or solid support. This protocol, the first of its kind for the removal of anionic surfactants at very low concentrations from any type of solution and competitive environments, demonstrates an original application using a CPE. The surfactant-free sample solutions could be precisely analyzed for the presence of illicit drugs by any standard methods. Using PMI, a newly developed CPE, a rapid and practical method for the efficient detection, discrimination, and removal of SDS and SDBS at ppb levels from water and urine, under harsh conditions, and in natural chemical environments is demonstrated.

Periodontitis in coronary heart disease patients: strong association between bleeding on probing and systemic biomarkers.

AIM: Few studies have examined the relationship of individual periodontal parameters with individual systemic biomarkers. This study assessed the possible association between specific clinical parameters of periodontitis and systemic biomarkers of coronary heart disease risk in coronary heart disease patients with periodontitis. MATERIALS AND METHODS: Angiographically proven coronary heart disease patients with periodontitis (n = 317), aged >30 years and without other systemic illness were examined. Periodontal clinical parameters of bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL) and systemic levels of high-sensitivity C-reactive protein (CRP), fibrinogen (FIB) and white blood cells (WBC) were noted and analyzed to identify associations through linear and stepwise multiple regression analyses. RESULTS: Unadjusted linear regression showed significant associations between periodontal and systemic parameters; the strongest association (r = 0.629; p < 0.001) was found between BOP and CRP levels, the periodontal and systemic inflammation marker, respectively. Stepwise regression analysis models revealed that BOP was a predictor of systemic CRP levels (p < 0.0001). BOP was the only periodontal parameter significantly associated with each systemic parameter (CRP, FIB, and WBC). CONCLUSION: In coronary heart disease patients with periodontitis, BOP is strongly associated with systemic CRP levels; this association possibly reflects the potential significance of the local periodontal inflammatory burden for systemic inflammation.

Phytochemical screening, physicochemical properties, acute toxicity testing and screening of hypoglycaemic activity of extracts of Eremurus himalaicus baker in normoglycaemic Wistar strain albino rats.

In the present study EtOAc, MeOH, and aqueous extracts of Eremurus himalaicus were evaluated for hypoglycaemic effect in normal rats using both oral glucose tolerance test and 14-day oral administration study. Phytochemical and physicochemical screening was also done. In oral glucose tolerance test the aqueous and MeOH extracts of Eremurus himalaicus at a dose level of 500 mg/kg body weight prior to glucose load resulted in a significant fall in blood glucose level within 150 min. of glucose administration. The aqueous extract at a dose level of 250 mg/kg body weight and 500 mg/kg body weight also showed good hypoglycaemic response (P < 0.001); this was followed by MeOH extract at a dose level of 500 mg/kg body weight (P < 0.05), while MeOH extract at dose level of 250 mg/kg body weight and ethyl acetate extract at dose level of 250 mg/kg body weight and 500 mg/kg body weight exhibited insignificant effect. Phytochemical screening of extracts revealed the presence of alkaloids, terpenoids, phenolics, tannins, saponins, cardiac glycosides, and flavonoids. The results indicate that aqueous extract possess significant hypoglycaemic activity in normoglycaemic rats which may be attributed to the above-mentioned chemical constituents.

Scientific Validation of Gentiana kurroo Royle for Anti-Inflammatory and Immunomodulatory Potential.

Gentiana kurroo Royle is a critically endangered medicinal plant species endemic to the northwestern Himalayas. This plant was studied for the immunomodulatory and anti-inflammatory potential. Carrageenan paw edema model was used to study the potential of the drug in inflammation in Wistar rats. SRBC specific haemagglutination titre and DTH assays were carried out in Balb/C mice for observing the effect of test drugs on immune system. The plant extracts were found to be active against inflammation. The methanolic fraction was observed to be the most effective in inhibition of paw edema with the inhibitory potential of 47.62%. In immunomodulation studies the plant extracts showed the immunosuppressant activity. Methanolic fraction was observed to have maximum potential for the suppression of both humoral (57.57% and 54.05%) and cell mediated immunity (65.27% and 75%). From these studies, it can be concluded that the extracts of plant are having anti-inflammatory and immunosuppressant activity. Since in chronic inflammation like arthritis there is the involvement of immune system, this plant may serve as an alternative for the treatment of autoimmune diseases like arthritis.

Evaluation of Artemisia amygdalina D. for Anti-Inflammatory and Immunomodulatory Potential.

Artemisia amygdalina D. is a critically endangered endemic medicinal plant of Kashmir Himalayas. In the current study anti-inflammatory and immunomodulatory activity of the plant was carried out. Carrageenan paw edema model was used to study the potential of the drug in inflammation in Wistar rats. SRBC-specific haemagglutination titre and DTH assays were carried out in Balb/C mice for observing the effect of test drugs on immune system. The plant extracts used as test drugs showed to have anti-inflammatory potential. The methanolic fraction was observed to have the maximum effect on the inhibition of paw edema formation with the inhibitory potential of 42.26%, while in the immunomodulation studies the test drugs were found to have the immunosuppressant activity with methanolic fraction again showing the maximum potential for the suppression of both humoral (55.89% and 47.91%) and cell-mediated immunity (62.27% and 57.21%). The plant in total seems to have the anti-inflammatory potential. The suppression of immune system suggests some mechanistic way by which the inhibition of inflammation takes place. Since, in chronic inflammation like arthritis, there is the involvement of immune system, the plant in that way may serve as an alternative for the treatment of such autoimmune diseases.

Atropa acuminata Royle Ex Lindl. blunts production of pro-inflammatory mediators eicosanoids., leukotrienes, cytokines in vitro and in vivo models of acute inflammatory responses.

ETHNOPHARMACOLOGICAL RELEVANCE: Atropa acuminata Royle Ex Lindl. has been widely used in folk medicine for several inflammatory disorders such as arthritis, asthma, conjunctivitis, encephalitis, pancreatitis, peritonitis, acute infections and neuroinflammatory disorders. AIM OF THE STUDY: Our aim was to evaluate Atropa acuminata for its anti-inflammatory properties and to delineate its possible mechanism of action on the modulation of the inflammatory mediators. MATERIALS AND METHODS: We investigated the inhibitory action of ethanolic extract of Atropa acuminata (AAEE) on production of NO, TNF-α and IL-1ß in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and also assayed it for COX 1/2 and 5-LOX inhibitory activities. Next AAEE was tested in acute inflammatory animal models., carragenean induced rat paw edema, carragenean induce pleurisy in rats and vascular permeability in mice and the effects on NO, PGE2 and LTB4 production in the pleural fluid and paw exudates were evaluated. In addition the effects on leukocyte migration and exudation and vascular permeability were also observed. RESULTS: Our findings summarized novel anti-inflammatory mechanisms for Atropa acuminata based on dual in vitro cyclooxygenase 1/2/ and 5-Lipoxygenase inhibitory activities and also significant downregulation of nitric oxide (NO) and pro-inflammatory cytokin (TNF-α and Il-1 ß) release in LPS-stimulated RAW 246.7 macrophage cell line. In acute inflammatory models in vivo (carragenean induced edema, carragenean induced pleurisy in rats and vascular permeability in mice), AAEE exhibited an extensive diverse mechanism for anti-inflammatory properties. This was indicated on the basis of dose dependent suppression of multi targeted inflammatory mediators., NO, TNF-α and IL-1ß, eicosanoids., PGE2 and leukotrienes., LTB4 along with significantly decreased leucocyte migration, exudation and decreased vascular permeability. These effects were more potent and prolonged than traditional NSAIDS, thereby indicating fewer side effects. AAEE was found to be safe for long term administration, as confirmed by the results of acute toxicity studies and MTT assay. The complex mode of action of the herbs was attributed possibly due to the high polyphenolic, flavanol and flavonoid content present in the extracts as observed by means of quantitative screening for phytochemicals. CONCLUSION: Our study provides scientific evidence to support the traditional anti-inflammatory uses of Atropa acuminata and is probably due to inhibitory effects on multiple inflammatory mediators which indicates a promising potential for the development of a strong anti-inflammatory agent from this plant.