Efficacy and safety of topical capsaicin in the treatment of osteoarthritis pain: A systematic review and meta-analysis.

Osteoarthritis (OA) affects hundreds of millions of people worldwide. The objective was to critically appraise the efficacy and safety of topical capsaicin in reducing pain in OA. MEDLINE (PubMed) and Embase (Ebsco) were searched from inceptions until February 2023. The eligibility criteria included randomized controlled trials (RCTs), evaluating topical capsaicin in OA patients. Standard Cochrane methods were used to extract data and to appraise eligible studies. Eight double-blind RCTs involving 498 patients were included. Five trials (62.5%) were at an overall low risk of bias, and three (37.5%) were at a high risk of bias. Meta-analysis showed that, in various OA patients, compared with placebo, topical capsaicin (0.0125%-5%) may reduce pain severity measured with visual analog scale (standardized mean difference = -0.84, 95% confidence intervals [CIs] = -1.48 to -0.19, p = 0.01; eight studies). However, topical capsaicin may increase burning sensation at the application site (risk ratio = 5.56, 95% CI = 1.75-17.69, p = 0.004, numbers needed to harm = 3; five studies) when compared with placebo. Limitations include short study durations, small sample sizes, high heterogeneity, and overall low-to-very-low certainty of the evidence. Topical capsaicin may reduce OA pain at follow-ups of up to 3 months. Larger trials, potentially evaluating capsaicin in combination with phytopharmaceuticals having anti-inflammatory effects, with longer follow-ups might be needed to reduce the existing uncertainties. Topical capsaicin might be recommended for short-term management of pain in OA patients intolerant to nonsteroidal anti-inflammatory drugs.

Knowledge, attitude and practice on antimicrobial use and antimicrobial resistance among competent persons in the community pharmacies in Bhutan.

Introduction: Since the discovery, antimicrobials have been used to treat variety of infections both in humans and animals caused by microbes. However, with the increasing use, microbes developed resistance to the antimicrobials and many of the antimicrobials became ineffective against certain microbes. Many factors are reported to contribute to the resistance of microbes to antimicrobials. One contributing factor is the misuse and overuse of antibiotics which mainly occur due to the lack of knowledge, careless attitudes, and incorrect practices about use of antibiotics. Methods: This cross-sectional survey study was conducted among the competent persons (CP) in the community pharmacies in Bhutan, with the aim to assess their knowledge, attitude and practice (KAP) on antimicrobial use (AMU) and antimicrobial resistance (AMR). Results: Results from the survey revealed that the competent persons had good level of knowledge about antimicrobial use and antimicrobial resistance. They also had favourable attitude towards antimicrobial resistance and rational use of antimicrobials. Their knowledge and attitude had led to good practices while dispensing antimicrobials from their pharmacies. However, almost all of them had never had any opportunity to take part in activities related to antimicrobial use and antimicrobial resistance that were organized by the public sector. Many of them did not even hear or know about the existence of the policies on use of antimicrobials or on curbing antimicrobial resistance in the country. Conclusion: Involvement of the community pharmacies through trainings and participations in policy making processes is seen as a vital mechanism that can eventually help achieve the goals in the national drive towards reducing antimicrobial resistance.

Effects of ß-eudesmol and atractylodin on target genes and hormone related to cardiotoxicity, hepatotoxicity, and endocrine disruption in developing zebrafish embryos.

Atractylodes lancea, commonly known as Kod-Kamao in Thai, a traditional medicinal herb, is being developed for clinical use in cholangiocarcinoma. ß-eudesmol and atractylodin are the main active components of this herb which possess most of the pharmacological properties. However, the lack of adequate toxicity data would be a significant hindrance to their further development. The present study investigated the toxic effects of selected concentrations of ß-eudesmol and atractylodin in the heart, liver, and endocrine systems of zebrafish embryos. Study endpoints included changes in the expression of genes related to Na/K-ATPase activity in the heart, fatty acid-binding protein 10a and cytochrome P450 family 1 subfamily A member 1 in the liver, and cortisol levels in the endocrine system. Both compounds produced inhibitory effects on the Na/K-ATPase gene expressions in the heart. Both also triggered the biomarkers of liver toxicity. While ß-eudesmol did not alter the expression of the cytochrome P450 family 1 subfamily A member 1 gene, atractylodin at high concentrations upregulated the gene, suggesting its potential enzyme-inducing activity in this gene. ß-eudesmol, but not atractylodin, showed some stress-reducing properties with suppression of cortisol production.

Anti-angiogenic effects of beta-eudesmol and atractylodin in developing zebrafish embryos.

Angiogenesis is the process of formation of new blood vessels which plays an essential role in the normal physiological development of the organs and systems. Several factors contribute to and regulate this process. Unregulated angiogenesis, however, is harmful and is usually found in tumors and cancerous cells. ß-Eudesmol and atractylodin are sesquiterpenoid contents extracted from the rhizome of Atractylodes lancea (AL). Reports suggest potential anti-angiogenic activities of both compounds. In this study, the anti-angiogenic activities of both compounds were investigated using the well-established zebrafish in vivo model. Zebrafish embryos were treated with a series of concentrations (6.3, 12.5, 25, and 50 µM) of ß-eudesmol and (6.3, 12.5, and 25 µM) of atractylodin up to 72 h post-fertilization. Assessment of the effects on phenotypic blood vessel development (sub-intestinal vessel intersection count) revealed that both the compounds inhibited vessel development, particularly at higher concentrations. At the genetic levels, only ß-eudesmol significantly downregulated the expression of the Vegfaa gene and also its receptor Vegfr2. ß-Eudesmol also affected the expression of Vegfaa protein in a concentration-dependent manner. Results indicate that ß-eudesmol exerts anti-angiogenic property through inhibition of Vegfaa at both the gene and protein levels. However, atractylodin does not possess this property.

Embryotoxicity evaluation of atractylodin and ß-eudesmol using the zebrafish model.

Atractylodin and ß-eudesmol are the major active ingredients of Atractylodes lancea (Thunb) DC. (AL). Both compounds exhibit various pharmacological activities, including anticancer activity against cholangiocarcinoma. Despite the widespread use of this plant in traditional medicine in China, Japan, Korea, and Thailand, studies of their toxicological profiles are limited. The present study aimed to evaluate the embryotoxicity of atractylodin and ß-eudesmol using the zebrafish model. Zebrafish embryos were exposed to a series of concentrations (6.3, 12.5, 25, 50, and 100 µM) of each compound up to 72 h post-fertilization (hpf). The results showed that atractylodin and ß-eudesmol induced mortality of zebrafish embryos with the 50% lethal concentration (LC50) of 36.8 and 53.0 µM, respectively. Both compounds also caused embryonic deformities, including pericardial edema, malformed head, yolk sac edema, and truncated body. Only ß-eudesmol decreased the hatching rates, while atractylodin reduced the heart rates of the zebrafish embryos. Additionally, both compounds increased reactive oxygen species (ROS) production and altered the transcriptional expression levels of superoxide dismutase 1 (sod1), catalase (cat), and glutathione S-transferase pi 2 (gstp2) genes. In conclusion, atractylodin and ß-eudesmol induce mortality, developmental toxicity, and oxidative stress in zebrafish embryos. These findings may imply similar toxicity of both compounds in humans.

CYP2C9, CYP2C19, CYP2D6 and CYP3A5 polymorphisms in South-East and East Asian populations: A systematic review.

WHAT IS KNOWN AND OBJECTIVE: Genetic polymorphism is one of the most important factors responsible for interindividual and interethnic variability in drug response. Studies in major populations, ie, Caucasians, Asians, and Africans, have provided evidence of differences in the genotype frequencies of major drug-metabolizing enzyme cytochrome P450 (CYP). This study aimed to review systematically, all relevant articles related to the genetic polymorphisms in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 in South-East and East Asian (SEEA) populations. METHODS: Articles that report genetic polymorphisms, genotype frequencies and allele frequencies in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 were retrieved from the PubMed database. RESULTS AND DISCUSSIONS: A total of 86 studies that fulfilled the eligibility criteria representing different ethnic populations of SEEA, ie, Burmese, Chinese, Japanese, Karen ethnic minority, Korean, Malaysian, Philippino, Singaporean, Taiwanese, Thai, Indonesian, and Vietnamese, were included in the analysis. In general, the genotype frequencies across SEEA populations are comparable. The CYP2C9*1/*1 (69.3%-99.1%), *1/*3 (2.3%-20.1%) and *3/*3 (0%-2.2%) genotypes are reported in most SEEA populations. Six major CYP2C19 genotypes, ie, *1/*1 (6.25%-88.07%), *1/*2 (21.5%-86.46%), *1/*3 (0.8%-15.8%), *2/*2 (3.4%-14.5%), *2/*3 (0%-7.3%) and *3/*3 (0%-10.2%), are reported in most SEEA populations. Major CYP2D6 genotypes include *10/*10 (0%-69.6%), *1/*1 (0%-61.21%) and *1/*10 (0%-62.0%). Major CYP3A5 genotypes are *3/*3 (2.0%-71.4%), *1/*3 (16.0%-57.1%) and *1/*1 (0%-82.0%). Genotyping of abnormal genotypes of CYP2C9 (*1/*3), CYP2C19 (*1/*2, *1/*3), CYP3A5 (*1/*3) and CYP2D6 (*5/*10) associated with IM (Intermediate metabolizer) status, may be clinically beneficial in SEEA populations. Similarly, with CYP2C19 (*2/*2, *2/*3), CYP2D6 (*5/*5 ) linked to PM (Poor metabolizer), CYP2D6 (*10/*10, *1/*5 and to lesser extent *1/*4, *2/*5, *10/*41, *10/*49, *10/*14) and CYP3A5 (*1/*1) associated with EM (extensive metabolizer). WHAT IS NEW AND CONCLUSION: Sufficient number of studies has provided comparable results in general. This review suggests that comparable genotype frequencies of CYP2C9, CYP2C19, CYP2D6 and CYP3A5 exist among the SEEA populations. It is noted that more research data are reported from East Asians compared with South-East Asians. Concerned efforts are required to establish partnerships among SEEA countries that will ensure sufficient data from South-East Asian countries which will assist in establishing the databases for SEEA populations.

Biomarkers for the Diagnosis of Cholangiocarcinoma: A Systematic Review.

Cholangiocarcinoma (CCA), a malignant tumor of the bile duct, is a major public health problem in many Southeast Asian countries, particularly Thailand. The slow progression makes it difficult for early diagnosis and most patients are detected in advanced stages. This study aimed to review all relevant articles related to the biomarkers for the diagnosis of CCA and point out potential biomarkers. A thorough search was performed in PubMed and ScienceDirect for CCA biomarker articles. Required data were extracted. A total of 46 articles that fulfilled the inclusion and had none of the exclusion criteria were included in the analysis (17, 22, 3, 4, and 1 articles on blood, tissue, bile, both blood and tissue, and urine biomarkers, respectively). Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA), either alone or in combination with other biomarkers, are the most commonly studied biomarkers in the serum. Their sensitivity and specificity ranged from 47.2% to 98.2% and 89.7% to 100%, respectively. However, in the tissue, gene methylations and DNA-related markers were the most studied CCA biomarkers. Their sensitivity and specificity ranged from 58% to 87% and 98% to 100%, respectively. Some articles investigated biomarkers both in blood and tissues, particularly CA19-9 and CEA, with sensitivity and specificity ranging from 33% to 100% and 50% to 97.7%, respectively. Although quite a number of biomarkers with a potential role in the early detection of CCA have been established, it is difficult to single out any particular marker that could be used in the routine clinical settings.

Phylogeny of local sheep breeds in East Asia, focusing on the Bayanbulak sheep in China and the Sipsu sheep in Bhutan.

The phylogenetic positions of the Bayanbulak sheep in China and the Sipsu sheep in Bhutan in the northern Asian sheep group were determined on the basis of allele frequency data for five informative and polymorphic loci of blood protein and nonproteins, such as transferrin (TF), arylesterase (ES), hemoglobin-beta (HB-beta), X-protein (XP), and potassium transport (KE), using different electrophoretic and ion-densitometric techniques. Based on Nei's genetic distance, clustering analysis by the UPGMA method showed that the Bayanbulak sheep is clustered in the northern Asian sheep group. Furthermore, the Bayanbulak sheep belongs to a subgroup containing the Khalkhas and Hu sheep of the Mongolian sheep group, which is distinguished from another subgroup of the small-tailed Han, Tan, Tong, and Wadi sheep. The Bayanbulak sheep was closest to the Hu sheep, despite a morphological difference in the fat deposits. In addition to these findings, the Sipsu sheep was verified to belong to the Baruwal sheep.