Chemical Conversion of Ribonucleoside 5′-S-Methyl Phosphorothiolates into Ribonucleotide Anhydrides Including Adenosine 5′-Triphosphate and Uridine Diphosphate Glucose

Ribonucleotide anhydrides have been prepared from corresponding ribonucleoside 5′-S-methyl phosphorothiolates by demethylthiolation with iodine in dry pyridine at room temperature in the presence of appropriate phosphates such as inorganic orthophosphate, inorganic pyrophosphate or glucose 1-phosphate. Thus synthesis of ribonucleotide anhydrides have been achieved and three ribonucleoside 5′-triphosphates (ATP, CTP and UTP), three ribonucleoside 5′-diphosphates (ADP, CDP and UDP) and a pyrophosphate coenzyme (UDPG) have been synthesized and isolated as lithium salts by charcoal treatment followed by ion exchange chromatography.     

Protective role of magnesium in cardiovascular diseases: A review

A considerable number of experimental, epidemiological and clinical studies are now available which point to an important role of Mg²⁺ in the etiology of cardiovascular pathology. In human subjects, hypomagnesemia is often associated with an imbalance of electrolytes such as Na⁺, K⁺ and Ca²⁺. Abnormal dietary deficiency of Mg²⁺ as well as abnormalities in Mg²⁺ metabolism play important roles in different types of heart diseases such as ischemic heart disease, congestive heart failure, sudden cardiac death, atheroscelerosis, a number of cardiac arrhythmias and ventricular complications in diabetes mellitus. Mg²⁺ deficiency results in progressive vasoconstriction of the coronary vessels leading to a marked reduction in oxygen and nutrient delivery to the cardiac myocytes.Numerous experimental and clinical data have suggested that Mg²⁺ deficiency can induce elevation of intracellular Ca²⁺ concentrations, formation of oxygen radicals, proinflammatory agents and growth factors and changes in membrane permeability and transport processes in cardiac cells. The opposing effects of Mg²⁺ and Ca²⁺ on myocardial contractility may be due to the competition between Mg²⁺ and Ca²⁺ for the same binding sites on key myocardial contractile proteins such as troponin C, myosin and actin.Stimulants, for example, catecholamines can evoke marked Mg²⁺ efflux which appears to be associated with a concomitant increase in the force of contraction of the heart. It has been suggested that Mg²⁺ efflux may be linked to the Ca²⁺ signalling pathway. Depletion of Mg²⁺ by alcohol in cardiac cells causes an increase in intracellular Ca²⁺, leading to coronary artery vasospasm, arrhythmias, ischemic damage and cardiac failure. Hypomagnesemia is commonly associated with hypokalemia and occurs in patients with hypertension or myocardial infarction as well as in chronic alcoholism.The inability of the senescent myocardium to respond to ischemic stress could be due to several reasons. Mg²⁺ supplemented K⁺ cardioplegia modulates Ca²⁺ accumulation and is directly involved in the mechanisms leading to enhanced post ischemic functional recovery in the aged myocardium following ischemia. While many of these mechanisms remain controversial and in some cases speculative, the beneficial effects related to consequences of Mg²⁺ supplementation are apparent. Further research are needed for the incorporation of these findings toward the development of novel myocardial protective role of Mg²⁺ to reduce morbidity and mortality of patients suffering from a variety of cardiac diseases.     

Periodontal health of older men: the MrOS dental study

Objective: The purpose of this study was to evaluate the prevalence and severity of periodontitis in men of 65+ years and identify demographic and lifestyle factors associated with its presence. Methods: Participants were recruited from the Osteoporotic Fractures in Men Study, a longitudinal study of risk factors for fractures in older men. Dental measures included clinical attachment loss (CAL), pocket depth (PD), calculus, plaque and bleeding on a random half‐mouth, plus a questionnaire regarding access to care, symptoms and previous diagnosis. Results: 1210 dentate men completed the dental visit. Average age was 75 years, 39% reported some graduate school education, 32% smoked 20 + pack years and 88% reported their overall health as excellent/good. In terms of periodontal health, 38% had sub‐gingival calculus, 53% gingival bleeding, 82% CAL ≥5 mm and 34% PD ≥6 mm. The prevalence of severe periodontitis was 38%. Significant demographic and lifestyle factors associated with severe periodontitis in multivariate analyses included age ≥75 (OR 1.4, 95% CI 1.1–1.7) non‐white race (OR 1.9, 95% CI 1.3–2.8), less than an annual dental visit (OR 1.5, 95% CI 1.1–2.0), and 20 + pack years (OR 2.1, 95% CI 1.6–2.7). Conclusion: A high proportion of healthy older men have evidence of periodontal destruction which could, given the growing ageing population, have a significant impact on the dental profession’s ability to provide preventive and therapeutic care. The population at highest risk of periodontitis in MrOS is older minority men who smoke and do not have annual dental visits.     

冠心病患者低密度脂蛋白与血小板GMP-140水平相关性研究

目的：探讨冠心病患者低密度脂蛋白与血小板功能活化产物GMP-140的关系。方法：应用酶联免疫分析法对120例研究对象进行了血浆LDL、GMP-140水平的测定,其中包括急性冠脉综合征组40例,稳定性心绞痛组40例,并与40例正常健康人作比较。结果：ACS患者血浆LDL和GMP-140水平均非常显著的高于正常人组（P〈0.01）,ACS组又高于SAP组（P〈0.05）,且血浆LDL与GMP-140水平呈正相关。结论：检测CHD患者血浆LDL和GMP-140水平的变化对CHD的发生和发展以及疗效和预后观察均具有重要的临床意义。     

冠心病患者低密度脂蛋白与血小板GMP-140水平相关性研究

目的:探讨冠心病患者低密度脂蛋白与血小板功能活化产物GMP-140的关系。方法:应用酶联免疫分析法对120例研究对象进行了血浆LDL、GMP-140水平的测定,其中包括急性冠脉综合征组40例,稳定性心绞痛组40例,并与40例正常健康人作比较。结果:ACS患者血浆LDL和GMP-140水平均非常显著的高于正常人组(P<0.01),ACS组又高于SAP组(P<0.05),且血浆LDL与GMP-140水平呈正相关。结论:检测CHD患者血浆LDL和GMP-140水平的变化对CHD的发生和发展以及疗效和预后观察均具有重要的临床意义。     

类风湿关节炎破骨细胞的活化机制及其预测指标

类风湿关节炎(rheumatoid arthritis, RA)是一种系统性、慢性、炎性的自身免疫性疾病。骨破坏在RA的发生和发展中占有重要地位,是RA致残致畸的主要原因。破骨细胞(osteoclast, OC)的异常增生与活化对RA骨侵蚀的发病进展具有重要作用。近年来,RA患者骨破坏的研究逐渐增多。本文结合国内外研究对核因子-κB受体活化因子配体(receptor activation for nuclear factor-κB ligand, RANKL)/核激活因子受体(receptor activator for nuclear factor-κB, RANK)/骨保护素(orthopantomography, OPG)信号通路、Wnt信号通路、抗瓜氨酸蛋白抗体(anti-citrulline protein antibody, ACPA)、基质金属蛋白酶(matrixmetalloproteinases,MMPs)、14-3-3η蛋白、基质细胞衍生因子-1(stromalcellderivedfactor-1,SDF-1)、小泛素样修饰物蛋白(smallubiquitin-likemodifierprotein,SUMO)、分泌型卷曲相关蛋白(secreted frizzled-related protein, SFRP)、骨转换标志物等作一阐述,旨在为RA早期骨破坏诊断提供相关依据。     

The reasons for tooth loss in geriatric patients attending two surgical clinics in Jerusalem,Israel.

Abstract Objectives Numerous studies around the world have been conducted in order to understand the reasons for tooth extractions in various age groups. Most studies have dealt with the general adult population but little attention has been paid to the elderly population. In Israel, as in most of the western countries, the elderly population is growing rapidly and thus demands for its dental needs are also increasing. In order to meet the dental requirements of the geriatric population, data on the main reasons of tooth mortality have been collected. Design Retrospective analysis of reasons for extraction divided into three categories: caries, periodontal disease and “other’’. Subjects The files of 302 consecutive elderly patients aged 65-95 years attending for extraction. The cause for tooth extraction was gathered from the written diagnosis described by the operator as well as from radiographs. Setting Two surgical clinics in Jerusalem serving low income residents. Results Results indicated that 30% of the extractions were due to caries, 65% were due to periodontal disease and only 6.4% related to “other’’ reasons. In both, males and females, periodontal disease was the major cause for tooth loss yet, females exhibited more extractions due to caries than males (35%vs 23% respectively). A relatively high incidence of tooth loss was documented for the 85+ age group. Of the teeth that were extracted, incisors and molars were equally the most frequent (29%) followed by premolars (26%) and canines (17%). Premolars were the teeth most frequently extracted out of the teeth removed due to caries (32%) whereas incisors were the most frequently removed within the group of teeth extracted due to periodontal disease (31%). Conclusions The results of this study point to the importance of prevention and treatment of dental diseases, particularly periodontal disease, in adults aged 0 years and above in order to prevent tooth loss in their later years.     

Metabolic gene polymorphisms and p53 mutations in healthy centenarians and younger controls

To obtain insights into the genetic mechanisms of ageing, we studied the frequency of the simultaneous presence of polymorphisms in phase I and phase II genes and of several p53 germline mutations in a group of 66 nonagenarians and centenarians in good health, selected from a larger sample of a multicentre Italian study in Northern Italy, and in a sample of 150 young healthy volunteers of the same ethnic group. We found a statistically significant difference in the frequency of the GSTT1 deletion and the p53 genotypes: the absence of any p53 polymorphisms and of GSTT1 deletion, and the simultaneous presence of the three p53 polymorphisms and of GSTT1 deletion, were much more frequent in young subjects than in centenarians (41.5% versus 26.9% and 8.8% versus 3.8%, respectively). One hypothesis to explain this difference is that subjects with both GSTT1 deletion and p53 polymorphisms may accumulate carcinogens and may have reduced DNA repair ability, and thus are more at risk for cancer. Another possible explanation is that both metabolic genes and p53 act on pathways related to cell ageing and death, and therefore certain composite genetic patterns could represent a generic mechanism of protection against ageing, not just against the development of chronic diseases. It is likely that longevity is related to a complex genetic trait as well as to certain environmental exposures.     

Metabolic gene polymorphisms and p53 mutations in healthy centenarians and younger controls

To obtain insights into the genetic mechanisms of ageing, we studied the frequency of the simultaneous presence of polymorphisms in phase I and phase II genes and of several p53 germline mutations in a group of 66 nonagenarians and centenarians in good health, selected from a larger sample of a multicentre Italian study in Northern Italy, and in a sample of 150 young healthy volunteers of the same ethnic group. We found a statistically significant difference in the frequency of the GSTT1 deletion and the p53 genotypes: the absence of any p53 polymorphisms and of GSTT1 deletion, and the simultaneous presence of the three p53 polymorphisms and of GSTT1 deletion, were much more frequent in young subjects than in centenarians (41.5% versus 26.9% and 8.8% versus 3.8%, respectively). One hypothesis to explain this difference is that subjects with both GSTT1 deletion and p53 polymorphisms may accumulate carcinogens and may have reduced DNA repair ability, and thus are more at risk for cancer. Another possible explanation is that both metabolic genes and p53 act on pathways related to cell ageing and death, and therefore certain composite genetic patterns could represent a generic mechanism of protection against ageing, not just against the development of chronic diseases. It is likely that longevity is related to a complex genetic trait as well as to certain environmental exposures.     

The scoring of defects of the alveolar process in human crania

Scoring methods for interalveolar and alveolar resorption, furcation involvement, fenestrations and dehiscences in the alveolar process of human skull material are presented.     

Predictors and correlates of edentulism in the healthy old people in Edinburgh (HOPE) study

Objectives: To determine the extent to which correlates of edentulism are explained by an association between tooth loss and cognitive ability. Methods: Participants in the Healthy Old People in Edinburgh (HOPE) study aged 70 or more at baseline were assessed and health, cognitive, socio‐economic and socio‐environmental data collected on four consecutive occasions. It was noted whether the participant had any retained teeth and if not, the age when the last tooth was lost. Prior determinants of edentulism were investigated with binary logistic regression models. At the 9‐year follow‐up, associations with edentulism were examined using general linear models with edentulism as an independent factor. Results: 201 participants were adequately tested, of whom 104 (51.7%) were edentulous. A logistic regression model that considered age, sex, education, social class, deprivation index of residence, objective distance from dentist, participant’s estimate of distance from dentist and NART‐estimated IQ (NARTIQ) found age (p = 0.032), occupational class (p = 0.019) and NARTIQ (p = 0.027) as significant predictors of edentulism. Cox’s proportional hazards modelling found only NARTIQ (p = 0.050) to be correlated. Being edentulous was associated with poorer respiratory function but not hand grip strength (p = 0.23). Edentulous participants had lower self esteem scores (p = 0.020) and poorer dietary assessment scores (p = 0.028). Being edentulous was also associated with significantly lower mean scores on all cognitive testing, although these associations became non‐significant after adjustment for NARTIQ and age. Conclusions: In healthy older people, edentulism is associated with relative impairment of cognitive ability, although this association is explained by the fact that lower original intelligence predisposes to edentulism and poorer performance on cognitive tests in old age. Once original intelligence is adjusted for, tooth loss is not related to cognitive ability. Tooth loss is, however, associated with poorer status across a wide range of health measures: physical health, nutrition, disability and self‐esteem. Establishing the degree to which these health outcomes are causally related to edentulism could usefully be factored into cost–benefit analyses of programmes designed to prevent tooth loss.