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Introduction: Hand-foot syndrome (HFS) is a common cutaneous side effect of capecitabine therapy. Apart from oral cyclooxygenase-2 (COX-2) inhibitor (celecoxib), there are no proven strategies for the prevention of HFS. However, celecoxib is associated with significant cardiotoxicity. To date, no study has evaluated the role of topical COX inhibitor, diclofenac. In this study, we aim to compare topical 1% diclofenac gel with placebo in the prevention of capecitabine-induced HFS.Methods: This is a randomized, placebo-controlled, double-blind, parallel-group superiority trial: the Diclofenac Topical in Reducing Capecitabine induced HFS (D-TORCH) study. A total of 264 patients with breast and gastrointestinal malignancies will be randomly allocated (stratified by sex and type of therapy [monotherapy or combination regimen with capecitabine]) to receive either 1% topical diclofenac or placebo that will be applied over the palmar and dorsal surface of the hands twice daily whilst taking capecitabine for 12 weeks. The patients will be followed up until the end of four cycles. The primary objective of this study is to compare the effect of topical diclofenac with placebo in preventing HFS (incidence of NCI CTCAEv5.0 grade 2 or higher HFS). The secondary objective is to compare the effect of topical diclofenac with placebo on preventing all grades of HFS (incidence of NCI CTCv5.0 all grade HFS), time to develop HFS (from the start of capecitabine), patient-reported outcomes (PROs) (HF-HRQoL questionnaire), adherence with the application (self-reported), capecitabine dose changes (number of patients with dose modifications due to HFS) and safety profile (NCICTCv5.0 all grade HFS) DISCUSSION: The D-TORCH study aims to determine if 1% topical diclofenac reduces the incidence of grade 2 or higher HFS in patients receiving capecitabine. To date, there have been a lot of trials for hand-foot syndrome prevention using agents like pyridoxine, vitamin E, carvedilol, and various polyherbal formulations, but none has been found successful. If the trial meets the primary end point, 1% topical diclofenac will be the new standard of care for HFS prevention.Trial Registration: Clinical Trials Registry of India  CTRI/2021/01/030592 . Prospectively registered on January 19, 2021. [ABSTRACT FROM AUTHOR]

Background: Agnimantha is a constituent of the bṛhatpañcamūla (the roots drugs of 5 tree species) which in turn is a part of daśamūla used in Ayurvedic pharmaceutical practices. Traditionally, the concept of bṛhatpañcamūla envisages the usage of root/ root bark of these tree species. By and large, use of stem bark came into vogue many decades ago for this sub-group of daśamūla. Going by descriptions in Ayurvedic lexicon of medicinal plants- two species are considered as Agnimantha viz. Clerodendrum phlomidis L.f. (Fam.: Lamiaceae) and Premna integrifolia L. (Syn. Premna serratifolia L) (Fam.: Lamiaceae). Objective: With an objective to address sustainability concerns associated with use of root or stem bark a comprehensive study was carried out on bṛhatpañcamūla group. This study kept the anti-inflammatory profile of candidate extracts in the centre-stage. As a part of this study, comparative assessment of two species used as Agnimantha was also carried out. Study Methodology: Different plant parts (Root bark, Stem bark, Leaves and Young roots) of C. phlomidis and P. integrifolia were collected from different parts of India. Each sample was extracted successively into four solvents. These extracts were evaluated for their anti-inflammatory profile using a battery of in-vitro assays, involving inhibition of regulatory enzymes like 5-lipoxygenase (5-LOX), cyclooxygenase 1&2 (COX-1 & COX-2) and analysis of the expression of pro- and anti-inflammatory cytokines in LPS-stimulated RAW 264.7 cells.Result and Conclusions: Both the species were observed to exhibit anti-inflammatory activity of varied degrees in this study. However, the sample of 12 months old roots of P. integrifolia was found to possess profound effect on all markers of inflammation. This sample was followed by 36 months old roots of C. phlomidis in terms of anti-inflammatory profile. Basing on these observations, the study suggests the use of 12 months roots of P. integrifolia (often referred to as Bṛhat-agnimantha) as part of daśamūla. Since the harvesting cycle is of 12 months, it is possible to produce the roots using High-Density Short-Term plantation protocols to address the sustainability concerns associated with use of root or stem bark. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to characterize the expression of cyclooxygenase-2 (COX-2) and prostaglandin-E2 (PGE2) genes in spontaneously aborted tissues from women infected with Chlamydia trachomatis.Methods: A total of 135 spontaneous aborters (Group I) and 45 induced aborters (controls; Group II) attending Obstetrics and Gynaecology Department at Safdarjung hospital (New Delhi, India), were enrolled. Polymerase chain reaction (PCR) assay was performed to detect C. trachomatis DNA in endometrial curettage tissue (ECT). Differential expression of COX-2 and PGE2 receptors at mRNA level was analysed in ECT using reverse transcription PCR and real-time PCR.Results: In total, 14.8% patients were diagnosed as C. trachomatis-positive in Group I whereas all control patients were C. trachomatis-negative. Qualitative expression of COX-2 (p < 0.05) and PGE2 (p < 0.0001) receptors was found increased in C. trachomatis-positive patients (Group I) in comparison to controls. Quantitative real-time PCR analysis also showed upregulation in transcript levels of both COX-2 (p < 0.002) and PGE2 (p < 0.0001) receptors in infected patients (Group I) versus Group II. COX-2 and PGE2 expression was higher (p < 0.002) in recurrent spontaneous aborters in comparison to sporadic spontaneous aborters.Conclusions: Results suggest that chlamydial infection leads to upregulation of COX-2 in C. trachomatis-positive recurrent spontaneous aborters, which probably mediates increased prostaglandin synthesis. [ABSTRACT FROM AUTHOR]

Downy mildew disease in cucurbits is a major constraint to sustainable production of cucurbits in India. The pathogen is known to perpetuate as active mycelium, sporangia and oospores. But in India, the oospores were not reported to play an active role in survival of the pathogen. A little is known about the complete life cycle of P. cubensis , thus, in this study an attempt was made to determine whether the pathogen form oospore under Indian conditions. A survey was undertaken in major cucumber growing regions of Indian Punjab and leaf samples showing symptoms of downy mildew infection were collected. The average size of oospore of P. cubensis ranged from 24 to 28 μm in diameter. The oospores were yellow to light brown in colour with smooth thick outerwall. Species specific primers corresponding to Cytochrome oxidase subunit 2 (COX-2) gene were further used for molecular identification and confirmation of the fungus. Ludhiana, MW855102 (Ldh10) and Sangrur, MW855103 (SC6) isolates shared maximum nucleotide identity i.e 98.96 per cent (%) with the P. cubensis isolates from Germany and Malaysia. This is the first morphological and molecular evidence of occurrence of oospores of P. cubensis in India. These evidences suggest that, oospores can survive as overwintering stage under Indian conditions and can thus play an important role in causation of the disease. • The first morphological and molecular evidence of occurrence of oospores of P. cubensis in India. • Species specific primers corresponding to Cytochrome oxidase subunit 2 (COX-2) gene were utilized for molecular identification of pathogen. • Oospores of P. cubensis can survive as overwintering stage under Indian conditions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Regulatory decision for withdrawal of a drug from market in European Union (EU) or other developed countries poses a challenge to authorities in developing countries specially when decision varies from different countries, such as for nimesulide. OBJECTIVES: To compare and evaluate, benefit and risk data for regulatory action, of nimesulide in India and EU. METHODS: Data on Nimesulide from EU available from Report on EMA website and Indian data from published literature (SCOPUS data base), WHO Vigibase and International Medicines Statistics (IMS) was compared. RESULTS: Publications from India on Adverse drug reactions (ADRs) are case reports (10) and case series (14). Drug Utilization Research (DUR) studies (17) are mostly from tertiary centres. Data in the WHO Vigibase is meagre, data from IMS is not easily available and there is regional variation in prescriptions. Thus incidence of ADRs per sale, prescription or defined daily does (DDD) cannot be calculated, as has been done for EU. CONCLUSION: Limited and varying data in post marketing studies on ADRs and drug utilization for nimesulide from India made regulatory decision difficult. India and other similar countries could contribute to post marketing data for local and global regulatory decisions by systematically planned studies and networking within country and across countries in region. [ABSTRACT FROM AUTHOR]

Objective. To demonstrate clinical equivalence between two standardized Ayurveda (India) formulations (SGCG and SGC), glucosamine and celecoxib (NSAID).Methods. Ayurvedic formulations (extracts of Tinospora cordifolia, Zingiber officinale, Emblica officinalis, Boswellia serrata), glucosamine sulphate (2 g daily) and celecoxib (200 mg daily) were evaluated in a randomized, double-blind, parallel-efficacy, four-arm, multicentre equivalence drug trial of 24 weeks duration. A total of 440 eligible patients suffering from symptomatic knee OA were enrolled and monitored as per protocol. Primary efficacy variables were active body weight-bearing pain (visual analogue scale) and modified WOMAC pain and functional difficulty Likert score (for knee and hip); the corresponding a priori equivalence ranges were ±1.5 cm, ±2.5 and ±8.5.Results. Differences between the intervention arms for mean changes in primary efficacy variables were within the equivalence range by intent-to-treat and per protocol analysis. Twenty-six patients showed asymptomatic increased serum glutamic pyruvic transaminase (SGPT) with otherwise normal liver function; seven patients (Ayurvedic intervention) were withdrawn and SGPT normalized after stopping the drug. Other adverse events were mild and did not differ by intervention. Overall, 28% of patients withdrew from the study.Conclusion. In this 6-month controlled study of knee OA, Ayurvedic formulations (especially SGCG) significantly reduced knee pain and improved knee function and were equivalent to glucosamine and celecoxib. The unexpected SGPT rise requires further safety assessment.Trial registration: Clinical Drug Trial Registry - India, www.ctri.nic.in, CTRI/2008/091/000063. [ABSTRACT FROM PUBLISHER]

Abstract: Garcinia indica Choisy Syn Brindonia indica, commonly known as kokum and belonging to Guttiferae family, is a plant native to certain regions of India. The trees yield fruits annually in the summer season during the months of March to May. The fruits are green when raw and red to dark purple when fully ripe. They are used to prepare juice, pickles and as acidulant in curries. In the traditional Indian system of medicine the Ayurveda and in various folk systems of medicine, the fruit rinds and leaves are used to treat various inflammatory ailments, rheumatic pain and bowel complaints. The kokum butter prepared from the seed is of both commercial and medicinal use. Chemical studies have shown that the rind contains protein, tannin, pectin, sugars, fat, organic acids like (−)-hydroxycitric acid, hydroxycitric acid lactone and citric acid; the anthocyanins, cyanidin-3-glucoside and cyanidin-3-sambubioside; and the polyisoprenylated phenolics garcinol and isogarcinol. Preclinical studies have shown that kokum or and some of its phytochemicals possess antibacterial, antifungal, anti-ulcerogenic, cardioprotective, anticancer, chemopreventive, free radical scavenging, antioxidant and anti-obesity effects. The present paper reviews the nutritional value, the phytochemical compounds, traditional uses and validated pharmacological properties of kokum. [Copyright &y& Elsevier]

Background: Cyclooxygenase-2 (COX-2) is an enzyme involved in the synthesis of prostaglandins and thromboxanes, which are regulators of processes that are relevant to cancer development. It is involved in carcinogenesis, immune response suppression, apoptosis inhibition, angiogenesis, and tumor cell invasion and metastasis. The gene for COX-2, designated as prostaglandin-endoperoxide synthase 2 (PTGS-2), carries polymorphisms, such as -765G>C, 1195G>A in the promoter region, and 8473T>C in the 3''-untranslated region (UTR), which have been associated with susceptibility to malignant disease. Methods: We undertook a case-control study of 212 urothelial bladder cancer (UBC) cases and 250 controls to investigate the association between COX-2 polymorphism and bladder cancer susceptibility, using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method and also investigated gene–environment interactions. Results: Cox-2 765G>C, a variant(C) allele carrier, was at an increased risk of UBC (odds ratio [OR] = 1.90; P = .004); however, –1195G>A; –1290A>G; and 3''UTR 8473T>C polymorphisms of COX-2 gene were not significantly associated with UBC. 765G>C also was associated with the invasive stage of a bladder tumor (OR = 2.73; P = .033). High risk for UBC also was observed with respect to COX-2 haplotypes C-765T8473A-1195A-1290 (OR = 3.47; P = .014). In case-only analysis, COX-2 765 variant allele carrier genotypes also showed an increased risk among former and current smokers (OR = 3.06; P = .041 and OR = 4.39; P = .032, respectively). Conclusion: COX-2 -765G>C polymorphism confers UBC susceptibility particularly in smokers and in patients with invasive tumors. 765C allele carrier genotypes also are influenced with a high risk of recurrence in Bacillus Calmette-Guérin-treated patients. Collectively, these findings confirm that the COX-2 -765G>C polymorphism is a risk factor for the development of bladder cancer and can provide a plausible mechanistic explanation. Further validation in large population-based studies is needed. [Copyright &y& Elsevier]

A standardized, combined flavonoid extracts of Scutellaria baicalensis and Acacia catechu, UP446, demonstrates favorable anti-inflammatory properties. In this study, DNA microarray, quantitative polymerase chain reaction (QPCR), and enzyme-linked immunosorbent assay (ELISA) were used to study the effect of UP446 on the lipopolysaccharide (LPS)-induced pro-inflammatory gene regulation of both animal and human immortalized cell lines and also primary human cells. One consistent result from microarray was that the gene expression levels stimulated or suppressed by LPS were returned to normal levels by the UP446 co-treatment. This normalization effect from UP446 was also shown for pro-inflammatory genes cyclooxygenase (COX)-2, tissue necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 using QPCR, and TNF-α using ELISA. The controlling transcriptional factor of these genes, NFκB, was also down-regulated by UP446 in the LPS-induced cell models. Microarray analysis for numerous genes, including cytokines, chemokines, receptors, transcriptional factors, caspase, growth factors, and phosphatases, suggests not only a genomic anti-inflammatory activity for UP446 but also signaling pathways of cell proliferation, cell death, and lipid metabolism demonstrated on different types of cells. [ABSTRACT FROM AUTHOR]

India has rich heritage of traditional systems of medicine which are mostly based on herbal formulations. Turmeric is a medicinal plant extensively used as home remedy for various diseases. The yellow color of turmeric powder is due to curcumin which is chemically diferuloylmethane. The powder has antibacterial, antiamoebic, anti-HIV, anti-tumor, anti-oxidant, and anti-carcinogenic potential. The volatile oil of C. longa shows anti-inflammatory, antibacterial and antifungal activities. It inhibits lipid peroxidation and cyclooxygenase-2 (COX-2) expression and induces glutathione S-transferase (GST) enzymes which are essential for the normal cellular functioning. It has high first-pass metabolism and peak plasma concentration achieved within 1-2 hrs and primarily metabolized through Sulphation and glucuronidation. Various macromolecules/tissue proteins have been identified as the receptor molecules for the curcumin responsible for the multiple pharmacological effects. Different commercial turmeric preparations are available in market for the therapeutic application having satisfactory and promising reports. Many studies demonstrated its use in cancer prevention and can also inhibit cancer metastasis. [ABSTRACT FROM AUTHOR]

• The Anti-inflammatory activity of Leucas vestita was reported for the first time. • HPLC analysis of Leucas vestita was carried out. • The COX-2 was modeled and the docking efficacy of phytochemicals with COX-2 was analyzed. Leucas vestita Wall. ex. Benth., is an endemic species restricted to Western Ghats, India. In this study, the carrageenan-induced anti-inflammatory model was used to evaluate the influence of L. vestita ethanol extract on inflammation. The Ethanol extract was tested for its anti-inflammatory property at a dose of 200mg/kg po. and 400mg/kg po. The paw volume was reduced gradually, three hours after administration of the extract. The extract showed a dosage dependant activity. The compounds present in the ethanol extract were identified by using HPLC and the binding affinity of these compounds against Cyclo-oxygenase-2 (COX-2, the enzyme involved in the perception of pain) was analyzed by using FlexX molecular docking suite. [ABSTRACT FROM AUTHOR]

Cyclooxygenase-2 (COX-2) inhibitors are rapidly becoming the first choice nonsteroidal anti.inflammatory drugs (NSAIDs) for various rheumatological and other painful conditions. However, they might not be as safe or free of side effects as they are considered to be. These COX-2inhibitors may cause a variety of dermatological and systemic side effects of which we should be aware to avoid their indiscriminate use. We hereby report a case of multifocal fixed drug eruption (FDE) with celecoxib which has not yet been reported in Indian settings. [ABSTRACT FROM AUTHOR]

Myxopyrum serratulum A. W. Hill. (Oleaceae) is a traditionally used Indian medicinal plant for the treatment of cough, asthma and many other inflammatory diseases. In this study, the protective effects of M. serratulum on airway inflammation was investigated in ovalbumin (OVA)-induced murine model of allergic asthma and lipopolysaccharide (LPS)-stimulated inflammation in RAW 264.7 murine macrophages, and the possible mechanisms were elucidated. The phytochemicals present in the methanolic leaf extract of M. serratulum (MEMS) were identified by reverse phase high performance liquid chromatography (RP-HPLC) analysis. In vitro anti-inflammatory activity of MEMS were evaluated by estimating the levels of nitric oxide (NO), reactive oxygen species (ROS) and cytokines (IL-1 α , IL-1 β , IL-2, IL-4, IL-6, IL-10, IL-12, IL-17A, IFN- γ , TNF- α , G-CSF and GM-CSF) in LPS-stimulated RAW 264.7 macrophages. In vivo anti-asthmatic activity of MEMS was studied using OVA-induced murine model. Airway hyperresponsiveness (AHR), was measured; total and differential cell counts, eosinophil peroxidase (EPO), prostaglandin E2 (PGE2), NO, ROS, and cytokines (IL-4, IL-5 and IL-13), were estimated in bronchoalveolar lavage fluid (BALF). Serum total IgE level was measured; and the histopathological changes of lung tissues were observed. The expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in lung tissue homogenates were detected by Western blot. The chromatographic analysis of MEMS identified the presence of gallic acid, protocatechuic acid, catechin, ellagic acid, rutin, p -coumaric acid, quercetin, naringenin and apigenin. MEMS (125 and 250 μg/mL) dose-dependently reduced the levels of NO, ROS and pro-inflammatory cytokines in LPS-stimulated RAW 264.7 macrophages. MEMS (200 and 400 mg/kg, p.o.) significantly (p < 0.05) alleviated AHR; number of inflammatory cells, EPO, PGE2, NO, ROS, and cytokines (IL-4, IL-5 and IL-13) in BALF; serum total IgE and the histopathological changes associated with lung inflammation. Western blot studies showed that MEMS substantially suppressed COX-2 and iNOS protein expressions in the lung tissues of OVA-sensitized/challenged mice. The present study corroborates for the first time the ameliorative effects of MEMS on airway inflammation by reducing the levels of oxidative stress, pro-inflammatory cytokines and inhibiting COX-2, iNOS protein expressions, thereby validating the ethnopharmacological uses of M. serratulum. Image 1 [ABSTRACT FROM AUTHOR]

The major food items of Indian cuisine include rice, wheat, diary products, and abundant fruits and vegetables. Beside these, there are several kinds of herbs and spices as important ingredients, containing many phytochemicals with medicinal properties, adding taste to Indian cuisine. An impressive body of data exists in support of the concept that Indian food ingredients can be used in preventive strategies aimed at reducing the incidence and mortality of different types of cancers because of their antioxidative, antimutagenic and anticarcinogenic properties. Vital ingredients used in Indian cooking include turmeric, cloves, ginger, aniseed, mustard, saffron, cardamom and garlic Garlic is an indispensable ingredient of Indian food and this report concerns the chemopreventive efficacy of garlic in an azoxymethane induced rodent colon carcinogenesis model. The effect of garlic was evaluated in terms of aberrant crypt foci, putative preneoplastic lesions in the colon. In addition, cell proliferation and levels of apoptosis were determined and the expression of cyclooxygenase-2 protein was analyzed. Following treatment, significant inhibition of cell proliferation and induction of apoptosis, as well as suppression of cyclooxygenase-2 activity were observed, associated with significant reduction in the incidence of aberrant crypt foci. The study points to combined protective effects of garlic components on colon carcinogenesis.

Background: Prostate cancer (PCa) incidences vary with genetic, geographical and ethnic dietary background of patients while angiogenesis is modulated through exquisite interplay of tumor-stromal interactions of biological macromolecules. We hypothesized that comprehensive analysis of four biomarkers modulating angiogenesis in PCa progression in two diverse populations might explain the variance in the incidence rates., Results: Immunohistochemical analysis of 42 PCa biopsies reveals that though Anx-II expression is lost in both the Indian and American population with Gleason scores (GS) ranging between 6 and 10, up to 25 % of cells in the entire high grade (GS > 8) PD PCa samples from US show intense focal membrane staining for Anx-II unlike similarly graded specimens from India. Consistent with this observation, the prostate cancer cell lines PC-3, DU-145 and MDA PCa 2A, but not LNCaP-R, LNCAP-UR or MDA PCa 2B cell lines, express Anx-II. Transcriptional reactivation of Anx-II gene with Aza-dC could not entirely account for loss of Anx-II protein in primary PCa. Cyclooxygenase-2 (COX-2) was moderately expressed in most of high grade PIN and some MD PCa and surrounding stroma. COX-2 was not expressed in PD PCa (GS approximately 7-10), while adjacent smooth muscles cells stained weakly positive. Decorin expression was observed only in high grade PIN but not in any of the prostate cancers, atrophy or BPH while stromal areas of BPH stained intensively for DCN and decreased with advancing stages of PCa. Versican expression was weak in most of the MD PCa, moderate in all of BPH, moderately focal in PD PC, weak and focal in PIN, atrophy and adjacent stroma., Conclusions: Expression of pro- and anti-angiogenic modulators changes with stage of PCa but correlates with angiogenic status. Focal membrane staining of Anx-II reappears in high grade PCa specimens only from US indicating differential expression of Anx-II. COX-2 stained stronger in American specimens compared to Indian specimens. The sequential expression of DCN and VCN in progressive stages was similar in specimens from India and USA indicating no population-based differences. The mechanistic and regulatory role of Anx-II in PCa progression warrants further investigation.