Sclareol exerts anti-osteoarthritic activities in interleukin-1β-induced rabbit chondrocytes and a rabbit osteoarthritis model

Sclareol is a natural product initially isolated form Salvia sclarea which possesses immune-regulation and anti-inflammatory activities. However, the anti-osteoarthritic properties of sclareol have not been investigated. The present study is aimed at evaluating the potential effects of sclareol in interleukin-1β (IL-1β)-induced rabbit chondrocytes as well as an experimental rabbit knee osteoarthritis model induced by anterior cruciate ligament transection (ACLT). Cultured rabbit chondrocytes were pretreated with 1, 5 and 10 μg/mL sclareol for 1 h and followed by stimulation of IL-1β (10 ng/mL) for 24 h. Gene expression of matrix metalloproteinase-1 (MMP-1), MMP-3, MMP-13, tissue inhibitors of metalloproteinase-1 (TIMP-1), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). MMP-3, TIMP-1, iNOS and COX-2 proteins were measured by Western blotting. Enzyme-linked immunosorbent assay (ELISA) was applied for nitric oxide (NO) and prostaglandin E2 (PGE2) assessment. For the in vivo study, rabbits received six weekly 0.3 mL sclareol (10 μg/mL) intra-articular injections in the knees four weeks after ACLT surgery. Cartilage was harvested for measurement of MMP-1, MMP-3, MMP-13, TIMP-1, iNOS and COX-2 by qRT-PCR, while femoral condyles were used for histological evaluation. The in vitro results we obtained showed that sclareol inhibited the MMPs, iNOS and COX-2 expression on mRNA and protein levels, while increased the TIMP-1 expression. And over-production of NO and PGE2 was also suppressed. For the in vivo study, both qRT-PCR results and histological evaluation confirmed that sclareol ameliorated cartilage degradation. Hence, we speculated that sclareol may be an ideal approach for treating osteoarthritis.     

Association of the platelet glycoprotein Ia C807T gene polymorphism with nonfatal myocardial infarction in younger patients

Recently, we have shown that two alleles of the glycoprotein (GP) Ia gene, designated C807 and T807, are associated with low or high platelet GPIa-IIa density and consequently with slower or faster rate of platelet adhesion to type I collagen, respectively. This polymorphism could therefore present a genetic predisposition for the development of thrombotic disease and hemostasis. We investigated the relationship of the GPIa C807T dimorphism to the risk of coronary artery disease (CAD) and myocardial infarction (MI). An allele-specific polymerase chain reaction (PCR) was developed for genotyping of C807T polymorphism. DNA samples from 2237 male patients who underwent coronary angiography on account of coronary heart disease as verified illness or presumptive diagnosis were genotyped. The odds ratio was calculated as an estimate of the relative risk by multiple logistic regression. We found a strong association between the T allele and nonfatal MI among individuals younger than the mean age of 62 years (n = 1,057; odds ratio, 1.57; P =.004). The odds ratio of MI increased for T807 carriers with decreasing age. The highest odds ratio was detected within the youngest 10% of the study sample (<49 years; n = 223; odds ratio, 2. 61; P =.009). In contrast, no evidence of an association between C807T dimorphism with CAD was found. Our findings suggest that inherited platelet GP variations might have an important impact on acute thrombotic disease.     

Diarrhoea episodes and treatment-seeking behaviour in a slum area of North Jakarta, Indonesia

Visits to household during a census in an impoverished area of north Jakarta were used for exploring the four-week prevalence of diarrhoea, factors associated with episodes of diarrhoea, and the patterns of healthcare use. For 160,261 urban slum-dwellers, information was collected on the socioeconomic status of the household and on diarrhoea episodes of individual household residents in the preceding four weeks. In households with a reported case of diarrhoea, the household head was asked which form of healthcare was used first. In total, 8,074 individuals (5%)--13% of children aged less than five years and 4% of adults--had a diarrhoea episode in the preceding four weeks. The two strongest factors associated with a history of diarrhoea were a diarrhoea episode in another household member in the four weeks preceding the interview (adjusted odds ratio [OR] 11.1; 95% confidence interval [CI] 10.4-11.8) and age less than five years (adjusted OR 3.4; 95% CI 3.2-3.5). Of the 8,074 diarrhoea cases, 1,969 (25%) treated themselves, 1,822 (23%) visited a public-health centre (PHC), 1,462 (18%) visited a private practitioner or a private clinic, 1,318 (16%) presented at a hospital, 753 (9%) bought drugs from a drug vendor, and 750 (9%) used other healthcare providers, such as belian (traditional healers). Children with diarrhoea were most often brought to a PHC, a private clinic, or a hospital for treatment. Compared to children, adults with diarrhoea were more likely to treat themselves. Individuals from households in the lowest-income group were significantly more likely to attend a PHC for treatment of diarrhoea compared to individuals from households in the middle- and higher-income groups.     

Flow cytometric analysis of lymph node metastases in advanced ovarian cancer: Clinical and biologic significance

OBJECTIVE: This study was undertaken to evaluate the deoxyribonucleic acid content and S-phase fraction in advanced epithelial ovarian carcinomas to determine whether lymph node metastases are biologically distinct from peritoneal sites of metastases.STUDY DESIGN: Thirty-five patients with stage III or IV epithelial ovarian cancer who had undergone complete pelvic and paraaortic lymphadenectomy had representative samples from the primary ovarian tumor, peritoneal metastases, and lymph node metastases analyzed by flow cytometry for deoxyribonucleic acid nuclear content and S-phase fraction.RESULTS: Diploid cell lines are found in metastatic lymph nodes (52%) significantly more frequently than in peritoneal metastases (25%, p < 0.02) or in primary ovarian tumors (26%, p < 0.001). The ploidy category frequency distribution of peritoneal metastases mirrors that found in the primary tumor, and both are significantly different from the ploidy category frequency distribution found in metastatic lymph nodes. Heterogeneity among sites is common, being identified in 54% of patients. Peritoneal metastases are more likely to be concordant with the primary tumor (69%) than are lymph node metastases (39%, p < 0.001). Mean S-phase fraction did not differ overall by site but was significantly different between diploid and aneuploid samples by site. Diploid lymph node metastases were found to have the lowest mean S-phase fraction (7.2% ± 3.3%), and aneuploid lymph node metastases had the highest mean S-phase fraction (22.3% ± 10.2%). Diploidy of the primary tumor is a positive predictor of long-term survival. Tumoral heterogeneity and lymph node metastases are not related to survival in this group of patients who underwent therapeutic pelvic and aortic lymphadenectomy.CONCLUSIONS: A high proportion of tumor deposits found in metastatic lymph nodes are diploid with a low S-phase fraction. Therapeutic pelvic and aortic lymph node dissection removes disease that, on the basis of flow cytometric characteristics, may be predicted to be resistant to chemotherapy and radiation therapy. (Am J Obstet Gynecol 1997;176:1319-27.)     

Chronobiology and the case for sleep health interventions in the community

Our sleep-wake cycle is determined by the interaction between our homeostatic sleep drive and circadian rhythm. Each of us has a personalised biological rhythm or chronotype that determines the optimal time to fall asleep and wake up. Chronic sleep deprivation has been linked to the development of several physical and mental health disorders, as well as accidents and occupational errors. Around the world, growing recognition of the importance of sleep has led to the adoption of practices that promote sleep health. Given that Singaporeans were consistently found to be one of the most sleep-deprived populations in the world, we believe that there is an urgent need to pursue the introduction of community-based sleep health interventions here. This includes sleep education and promotion of sleep hygiene, adopting practices to reduce social jetlag and improve sleep health, and enhancing screening and treatment of sleep disorders.     

Genomic RFLP typing of human platelet alloantigens Zw(PlA), Ko,Bak and Br (HPA-1, 2, 3, 5)

Summary. The diallelic human platelet alloantigen systems 1–5 have been found to result from single base pair substitutions in the encoding genes of platelet membrane glycoproteins IIIa, Ib, IIb and Ia. This is the basis of DNA methods for determination of platelet alloantigens. In this study, 98 blood donors were typed in the HPA-1, 2, 3 systems and, for the first time, in the HPA-5 system. Serologically obtained data (MAIPA and platelet agglutination) were compared with results from analysis of restriction fragment length polymorphisms (RFLP). Discordances were found in the HPA-2 and 3 systems and can be ascribed to false typing results in both the serological and genomic methods. In the HPA-1, 2 and 5 systems, all samples were typed correctly with RFLP analysis. Serologically, two donors were falsely typed positive with anti-HPA-2b in platelet agglutination and one donor with anti-HPA-3a in MAIPA assay. In the HPA-3 system, another four donors were misinterpreted to be HPA-3 a negative in RFLP analysis. Possible technical problems in PCR-RFLP-typing are discussed and another strategy of HPA-1 typing using the restriction enzyme Scr FI is evaluated.