Development and validation of RP HPLC method for simultaneous determination of picroside I, picroside II, phyllanthin and boeravinone B in a polyherbal hepatoprotective tablet formulation

Purpose: To develop and validate RP-HPLC method for simultaneous determination of four active ingredients: picroside I (PSI), picroside II (PSII), phyllanthin (PHY) and boeravinone-B (BVB) in a polyherbal hepatoprotective tablet formulation.Methods: The study was carried out using Waters X-Bridge, C18 (250 mm x 4.6 mm, 5 μm) column with mobile phase consisting of 5 mM ammonium acetate in 10 % methanol and acetonitrile, with gradient programme at dual wavelengths of 220 nm and 274 nm and flow speed of 1 mL.min-1. The procedure was validated with respect to specificity, linearity, precision, accuracy, system suitability, limit of detection (LOD) and of quantification (LOQ), and robustness in line with ICH specifications.Results: The method was linear within the concentration range of 25 to 200 %, and the values of correlation coefficients (R2) were > 0.999. Intra-day and inter-day RSDs of PAs and RTs were < 5.0 %, with recovery in the range of 100.0 - 106.0 %.Conclusion: The four active ingredients have with good resolution with regard to the method used. The method is rapid, simple, highly selective, sensitive and cost effective, which make it an efficient method for quality assurance

Simultaneous determination of four active pharmaceuticals in tablet dosage form by reversed-phase high performance liquid chromatography

Purpose: To develop a single, low-cost and rapid analytical method for the simultaneous determination of four active components - chlorpheniramine maleate, paracetamol, phenylephrine hydrochloride and caffeine – in a tablet dosage form. Method: This method was based on reverse-phase high performance liquid chromatography (RPHPLC) and involved the use of a C-18 column (250 × 4.6 mm, 5.0 μm), a mobile phase consisting of buffer solution and methanol at a flow rate of 1.00 mL/min, and gradient determination with UV detection at 220 nm. Results: Retention time was 4.33, 10.36, 13.85, and 17.35 min for phenylephrine hydrochloride, paracetamol, caffeine, and chlorpheniramine maleate, respectively. Specificity data showed no interference from the excipients, and accuracy of the method was close to 100 %. The method was validated as per the guidelines of International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), and all the results met the acceptance criteria for accuracy, precision, linearity, specificity, limit of quantitation, limit of detection, and robustness. Conclusion: This method can successfully perform quantitative assessment of phenylephrine HCl, chlorpheniramine maleate, paracetamol, and caffeine in tablet combination dosage forms faster and more cost-effectively than conventional methods

Functional outcome of mild and moderate residual varus in posterior stabilized total knee arthroplasty in primary osteoarthritis knee: a prospective study

Background: Total knee arthroplasty (TKA) is one of the most commonly done orthopaedic surgical procedures for treating severe arthritis of the knee joint caused by osteoarthritis or inflammatory arthritis. The current clinical investigation, done at the Sanjay Gandhi Institute of Trauma and Orthopaedics in Bengaluru, provided the short-term functional result of mild and moderate residual varus in posterior stabilized TKA. The aim was to evaluate the efficacy of mild and moderate residual varus in total knee replacement for primary OA knee in terms of pain relief, range of motion and stability of the joint. Methods: 30 total knee replacements were performed. All patients were examined pre- and post-operatively using the knee society clinical and functional score. The average pre-op KSS knee score was 38.7, with a functional score of 23.3. The most common reason for TKR was osteoarthritis. The follow-up time ranged from 6 to 12 months.Results: By the knee society clinical, functional score method, 96.6% of our patients received an outstanding assessment after scoring 80 points or higher. The mean post-operative KSS knee score is 86.57, and the knee society functional score is 92. 92% of patients had little/no pain after surgery, and walking ability increased and was unlimited in 80% of patients.Conclusions: After a short term follow up of 1 year in a research population of 30 with pre-operative osteo arthritis of the knee, with post-operative mild to moderate varus alignment showed better clinical results

Managing Process Variants as an Information Resource

Many business solutions provide best practice process templates, both generic as well as for specific industry sectors. However, it is often the variance from template solutions that provide organizations with intellectual capital and competitive differentiation. In this paper, we present a modeling framework that is conducive to constrained variance, by supporting user driven process adaptations. The focus of the paper is on providing a means of utilizing the adaptations effectively for process improvement through effective management of the process variants repository (PVR). In particular, we will provide deliberations towards a facility to provide query functionality for PVR that is specifically targeted for effective search and retrieval of process variants

A prospective comparative study of functional outcome of distal extra articular tibia fracture fixed with intramedullary nail versus locking compression plate

Background: Distal tibia fractures are one of the most common long bone fractures and their management presents with a series of problems due to the soft tissue surroundings and even more at risk due to their proximity to ankle joint. In our paper we showed functional outcome of distal extra articular tibia fracture while comparing its management between intramedullary nailing and locking compression plate.Methods: There were 40 patients from November 2019 to November 2020 with distal extra articular tibia fracture. Patients were divided into 2 groups, first group included 20 patients managed with intramedullary nail and the second group included 20 patients managed with locking compression plate. Patients were followed preoperatively, intraoperatively and postoperatively for functional outcome and assessed clinically using AOFAS score and radiologically using X-ray.Results: Out of the 40 cases treated in this manner, all cases were available for the follow up for a period of 1 year. Overall results by 1 year follow up showed excellent in 7 cases (35%) good in 13 cases (65%) in nailing group and in plating group showed excellent in 4 cases (20%), good in 12 cases (60%), fair in 3 cases (15%) and poor in 1 case (5%).Conclusions: All fractures united well. Complications were encountered in 4 patients, 2 patients had superficial wound infections,1 patient had deep infection and another had persistent ankle pain in plating group and 2 patients had superficial wound infection in nailing group. No cases showed malunion or nonunion in both plating as well as nailing group

DESIGN AND IN VIVO EVALUATION OF METOPROLOL TARTRATE BILAYER FLOATING TABLETS IN HEALTHY HUMAN VOLUNTEERS

The aim of the present investigation was to prepare bilayer floating tablets of metoprolol tartrate using the combination of superdisintigrants, HPMC K grade polymers and natural polymers like xanthan gum and guar gum by direct compression method. Bilayer floating tablets were prepared using optimized immediate release layer and floating layer as sustained release layer. The physico-chemical characteristics of the prepared tablets were evaluated and found to be satisfactory. All the prepared batches showed in vitro buoyancy. It was observed that the tablets remained buoyant for more than 12 h.  Formulation F7 was selected as best formulation based on the in vitro characteristics and used in vivo radiographic studies by adding barium sulphate. These studies revealed that the tablets remained in the stomach for 210±5.4 min (n=3) in fasting human volunteers. Based on the in vivo performance in healthy subjects, the developed bilayer floating tablets showed superior bioavailability than the marketed tablets, the drug release was up to 12 h in controlled manner. The systemic availability of the best formulation was high after administration to obtain immediate action due to the immediate release layer, from sustained release layer the drug was released in controlled manner. It can be concluded that the best formulation F7 by choosing biphasic drug release pattern in a single dosage form could improve patient compliance and ensure better disease management

Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer

Background: ATR-Chk1 signalling network is critical for genomic stability. ATR-Chk1 may be deregulated in breast cancer and have prognostic, predictive and therapeutic significance. Patients and methods: We investigated ATR and phosphorylated CHK1Ser345 protein (pChk1) expression in 1712 breast cancers (Nottingham Tenovus series). ATR and Chk1 mRNA were evaluated in 1950 breast cancers (METABRIC cohort). Pre-clinically, biological consequences of ATR gene knockdown or ATR inhibition by small molecule inhibitor (VE-821) were investigated in MCF-7 and MDA-MB-231 breast cancer cell lines and in non-tumorigenic breast epithelial cells (MCF10A). Results: High ATR and high cytoplasmic pChk1 expression was significantly associated with higher tumour stage, higher mitotic index, pleomorphism and lymphovascular invasion. In univariate analysis, high ATR and high cytoplasmic pChk1 protein expression was associated with shorter breast cancer specific survival (BCSS). In multivariate analysis, high ATR remains an independent predictor of adverse outcome. At the mRNA level, high Chk1 remains associated with aggressive phenotypes including lymph node positivity, high grade, Her-2 overexpression, triple-negative phenotype and molecular classes associated with aggressive behaviour and shorter survival.. Pre-clinically, Chk1 phosphorylation at serine 345 following replication stress (induced by gemcitabine or hydroxyurea treatment) was impaired in ATR knockdown and in VE-821 treated breast cancer cells. Doxycycline inducible knockdown of ATR suppressed growth, which was restored when ATR was re-expressed. Similarly, VE-821 treatment resulted in a dose dependent suppression of cancer cell growth and survival (MCF7 and MDA-MB-231) but had no effect on non-tumorigenic breast epithelial cells (MCF10A). Conclusions: We provides evidence that ATR and Chk1 are promising biomarkers and rational drug target for personalized therapy in breast cancer

Interactions between urban water policy, residential irrigation, and plant & bird diversity in the Fresno-Clovis Metro Area

*Background/Question/Methods:*

Ecological theory has begun to incorporate humans as part of coupled socio-ecological systems. Modern urban development provides an excellent laboratory to examine the interplay among socio-ecological relationships. Urban land and water management decisions result from dynamic interactions between institutional, individual and ecological factors. Landscaping and irrigation at any particular residence, for example, is a product of geography, hydrology, soil, and other local environmental conditions, the homeowners’ cultural preferences, socioeconomic status, identity construction, neighborhood dynamics, as well as zoning laws, market conditions, city policies, and county/state/federal government regulations. Since land and water management are key determinants of habitat for other species, urban biodiversity is strongly driven by the outcome of interactions between these variables. This study addresses the significance of water as a key variable in the Fresno-Clovis Metropolitan Area (FCMA), shaping current patterns of landscape and water use, at a time when the city of Fresno is installing meters as a regulatory tool to conserve water. We combine data from a citizen science bird monitoring project, field surveys of trees, and mail surveys of residents to address interactions among key components of the urban socioecological system.

*Results/Conclusions:*

We present results of multivariate analyses of bird and tree surveys to show that neighborhood income and irrigation levels interact to influence species diversity of both taxa. Data from the Fresno Bird Count found that bird species richness and functional group diversity are both strongly correlated with residential irrigation and neighborhood income levels. Tree species diversity shows a similar pattern. We examine these results to test and develop several theoretical models explaining outdoor water use behaviors, with the aim of assessing the resilience of such behaviors with the introduction of water metering in Fresno, and the resilience of urban plant and bird communities to resulting changes in water use in the landscape. We argue that socioeconomic status results from a complex interplay of cultural, economic, structural, and social-psychological factors, influencing institutional policies regarding the governance of water resources, and in turn impacts biodiversity within the urban landscape through spatial and temporal variations in water usage. This study is part of a long-term research project that examines the impacts of human water usage and water use policies on biodiversity within an urban environment