Pitfalls in acid/base experiments with conscious dogs

Arterial pH and blood gases were measured at intervals in conscious dogs after their first human contact of the day. Blood was sampled through an indwelling catheter in the aorta without disturbing the animals. It appeared that in the first 90 min arterial PO₂, oxygen saturation and haemoglobin concentration significantly declined. PCO₂ and pH changed less consistently when the acid/base status of the dogs was normal, but when a non-respiratory acidosis was present there was a significant decrease in pH and a significant increase in PCO₂. Arterial pH and blood gases were also measured before and after feeding the animals. It appeared that an appreciable metabolic alkalosis developed within 2 h after a meal. The alkaline tide was accompanied by a trend to higher values for PCO₂. It is concluded that, after a period of seclusion, renewed human contact causes behavioural changes in a dog, which may result in appreciable transitory changes in arterial pH and blood gas values. Blood sampling from conscious dogs should therefore take place after a proper period of habituation; preferably, a few samples should be taken at intervals to check that a steady state has been reached. If possible, blood should be collected before feeding; in any case the relationship in time of blood sampling to feeding should be constant throughout.     

Age-dependence of malonate-induced striatal toxicity

Malonate is an inhibitor of cellular metabolism, which, following intrastriatal injection, induces a striatal pathology similar to that seen in Huntington's disease. In two parallel studies, we have investigated the suggested relationship between the neuronal vulnerability to metabolic toxicity and the decline in metabolic function with increasing age. The first experiment investigated malonate-induced neuronal loss in animals aged from 6 weeks up to 27 months, and the second assessed the activities of two mitochondrial enzymes, succinate dehydrogenase and cytochrome oxidase (CYTOX) in animals aged 6 weeks, 3, 8 and 18 months. In the first study, male Lister-Hooded rats received intrastriatal stereotaxic injections of malonate (0.5 or 1.0 M). Animals were killed 10 days after surgery, and the brains were stained with cresyl violet and processed for NADPH-diaphorase activity and glial fibrillary-acidic-protein (GFAP) immunohistochemistry. Animals aged 6 months and older exhibited over 60% striatal neuronal loss. However, the degree of neuronal loss did not show any age-related increase in rats between 6 and 27 months of age, indicating that the extent of malonate-induced toxicity does not increase with age in animals older than 6 months. Infusion of 0.5 M malonate produced smaller lesions, which also demonstrated a consistent extent of neuronal loss from 6 months onwards. Metabolic enzyme activities were decreased in the striatum with increasing age, although this effect was only significant for CYTOX activity. Thus, the pattern of malonate-induced neuronal loss in aged animals partially reflects the changes in metabolic activity during ageing.     

Diagnostische Bedeutung von Muskelbiopsien bei metabolischen Myopathien

Summary In the diagnosis of metabolic myopathies the use of biochemical methods, in addition to morphological examination of muscle biopsies, is often necessary in order to identify a specific metabolic defect. In order to narrow down the spectrum of biochemical methods, extensive clinical investigation and morphological examination, including histology, enzyme histochemistry and electromicroscopy if necessary have to be done beforehand. Patients are classified in the following groups: 1) progressive muscular weakness and/or muscle wasting with storage of a) glycogen, b) lipid or c) mitochondrial alterations; 2) recurrent rhabdomyolysis induced by fasting or exercise a) with glycogen storage or b) without any specific morphological alterations. The spectrum of metabolic defects comprises disorders of glycogen and glucose metabolism (deficiency of acid maltase, debranching and branching enzyme, phosphorylase, phosphofructokinase and other glycolytic enzymes), lipid metabolism (carnitine deficiency, carnitine palmitoyl transferase deficiency), mitochondria (respiratory chain disorders, pyruvate dehydrogenase deficiency) and others such as adenylate deaminase deficiency. In some of these e.g. infantile acid maltase deficiency and mitochondriopathies, it is clinically more important when organs other than muscle are affected; however, muscle biopsy is a useful substrate for diagnosis of these metabolic disorders.

Mit Unterstützung durch die DFG und die Friedrich Baur Stiftung, München     

The detection of chemical impurities by high pressure liquid chromatography and the genetic activity of medical grades of pyrvinium pamoate inSaccharomyces cerevisiae andSalmonella typhimurium

The genetic activity of several medical grades of the anthelmintic drug pyrvinium pamoate, which is a dipyrvinium salt, was studied in a diploid mitotic recombination and gene conversion assay (strain D5 ofSaccharomyces cerevisiae), and in several haploid yeast reversion assays (strains XV185-14C, XY718-1A, and 7854-1A). All of the samples were recombinogenic in strain D5 and mutagenic in the haploid strains, however, the degree of genetic activity varied considerably among the medical grades of pyrvinium pamoate that were tested. Similarly, these samples varied in degree of mutagenicity when they were tested in strains TA97, TA98, TA100, and TA102 ofSalmonella typhimurium, but some of the medical grades of pyrvinium pamoate were mutagenic both in the presence and in the absence of the metabolic transformation system, whereas other medical grades of the drug required such activation to be mutagenic. In addition, the medical grades and dosage forms of several brands of pyrvinium pamoate were examined for purity by fluorescence high pressure liquid chromatography (HPLC) using a methanol:water (9010) solvent system. The HPLC data indicate that monopyrvinium salts are the major contaminants in these pharmaceuticals. In general, there is a correlation between the degree of genetic activity and toxicity, and the number and relative quantity of impurities found in each sample.     

Metabolic syndrome screening using visceral adipose tissue (VAT) from opportunistic MRI locations in a multi-ethnic population

ObjectiveTo determine if visceral adipose tissue (VAT) area measured through MRI can be used opportunistically to assess the presence of cardiometabolic risk factors and compare its performance to simpler adiposity measures.MethodsA cross-sectional analysis was carried out on a subset of 1683 participants (856 women) from the Adiposity Phenotype Study (mean age = 69.2y; range 59.9–77.4). The association of total VAT area (sum of four cross sections, L1–L2, L2–L3, L3–L4, L4–L5) and each location, as well as BMI and body fat % (per SD) with the metabolic syndrome (MetSx) or its components was evaluated through logistic regression analysis.ResultsTotal VAT can be accurately predicted using all sites evaluated (R² range = 0.82?0.96). In men, VAT did not show a superior association to MetSx compared to BMI in men. However, in women, VAT was consistently superior to BMI and body fat % in its association to MetSx, independent of ethnicity [odds ratio for BMI, body fat %and total VAT area = 2.25 (95% CI: 1.93–2.62); 1.66 (95% CI: 1.36–2.03); 6.20 (95% CI: 4.69–8.21) respectively in all women]. Ethnic-specific odds ratios to MetSx in women ranged from 5.38 to 8.63 for total VAT area and 2.12–4.08 for BMI.ConclusionTotal VAT area can be accurately predicted from individual VAT regions in men and women and offers superior association to BMI for MetSx in women but not in men for five ethnicities. Therefore, opportunistic screening for elevated VAT area in women may be warranted across multiple ethnic groups.     

Serum vitamin D status and metabolic syndrome: a systematic review and dose-response meta-analysis

BACKGROUD/OBJECTIVESEvidence has suggested an association between serum vitamin D and metabolic syndrome (MetS), but prospective studies are very limited. The objective was to assess the dose-response association between serum vitamin D concentration and MetS risk using a systematic review and meta-analysis of updated observational studies.MATERIALS/METHODSUsing MEDLINE, PubMed, and Embase, a systematic literature search was conducted through February 2020 and the references of relevant articles were reviewed. A random-effects model was used to estimate the summary odds ratio/relative risk and 95% confidence interval (CI). Heterogeneity among studies was evaluated with I² statistic. In total, 23 observational studies (19 cross-sectional studies, and four cohort studies) were included in the meta-analysis.RESULTSThe pooled estimates (95% CI) for MetS per 25-nmol/L increment in serum vitamin D concentration were 0.80 (95% CI, 0.76–0.84; I² = 53.5) in cross-sectional studies, and 0.85 (95% CI, 0.72–0.98; I² = 85.8) in cohort studies. Similar results were observed, irrespectively of age of study population, study location, MetS criteria, and adjustment factors. There was no publication bias for the dose-response meta-analysis of serum vitamin D concentrations and MetS.CONCLUSIONSDose-response meta-analysis demonstrated that a 25-nmol/L increment in the serum vitamin D concentration was associated with 20% and 15% lower risks of MetS in cross-sectional studies and cohort studies, respectively.     

5种肥胖指标对不同性别及年龄组高血压的预测效果比较

目的 比较不同肥胖指标对不同性别、年龄人群高血压风险的预测价值。方法 基于深圳市龙华区2018年社区居民健康调查数据,对体质指数（BMI）、腰围（WC）、腰围身高比（WHtR）、腰臀比（WHR）和人体肥胖指数（BAI）共5种肥胖指标进行标准化转换,根据Logistic回归分析所得OR值,比较各肥胖指标与高血压的相关性;根据受试者工作特征曲线（ROC）下面积（AUC）,判断各肥胖指标对高血压的预测价值,进而综合评价各肥胖指标对高血压的预测能力。结果 在调整混杂因素后,WC和WHtR与男性和女性高血压的相关性强于其他肥胖指标。WHtR对于男性和女性高血压的预测能力均强于其他肥胖指标,其AUC及95%CI分别为0.694（0.659~0.728）和0.763（0.732~0.794）,其截断值分别为0.51和0.50;女性中各肥胖指标预测高血压的AUC均大于男性,各肥胖指标对女性高血压有更高的预测价值。对男女进行年龄分层后,在男性中除WHR外各肥胖指标对于青年组（18~44岁）高血压的预测价值优于中年组（45~59岁）和老年组（60~80岁）;在女性中各肥胖指标对于高血压的预测价值随着年龄的增长而降低,依次为青年组>中年组>老年组。结论 在综合考虑性别和年龄后,中心型肥胖指标中的WHtR对高血压的预测能力优于WC、BMI、WHR和BAI。     

Specific Dietary Protein Sources Are Associated with Cardiometabolic Risk Factors in the Boston Puerto Rican Health Study

BackgroundPuerto Rican adults residing in the US mainland experience a high prevalence of metabolic syndrome (MetS). A diet containing healthy protein-rich sources may help control risk factors for MetS.ObjectiveThis study aimed to evaluate 2-year longitudinal associations between intake of various protein-rich foods and changes in the six MetS components.DesignThis is a secondary analysis of a longitudinal cohort study using data from the baseline (2004–2007) and 2-year follow-up visits (2006–2011) in the Boston Puerto Rican Health Study.Participants/settingParticipants were self-identified Puerto Ricans, aged 45 to 75 years, residing in Boston, Massachusetts, or the surrounding area (n = 1,126).Main outcome measuresMetS components were fasting glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, systolic and diastolic blood pressures, and waist circumference.Statistical analysisBaseline intake of foods reported in a semiquantitative food frequency questionnaire were expressed as servings/day, and protein-rich foods were categorized as unprocessed white meat, unprocessed red meat, processed meat, milk and yogurt, cheese, fish and seafood, beans, nuts, and eggs. Associations between each continuous protein food group and continuous 2-year change in MetS components were assessed using linear mixed models adjusted for socioeconomic and behavioral factors, and other dietary sources.ResultsThe top contributors to total protein intake were unprocessed red meat (13.3%) and unprocessed poultry (13.0%), and the lowest were eggs (2.92%) and nuts (0.91%). Higher intake of processed meats was associated with an increase in waist circumference over 2 years (β = 1.28; standard error [SE] = 0.63), whereas higher intake of fish and seafood was associated with a decrease in waist circumference (β = ?3.47; SE = 1.39). Intake of unprocessed poultry was associated with a decrease in triglycerides (β = ?24.5; SE = 9.13). No other significant associations were observed between protein sources and 2-year changes in MetS components.ConclusionsConsuming less processed meat and more fish and seafood and unprocessed poultry was associated with decreases in waist circumference and triglycerides among US mainland Puerto Ricans. Other dietary protein sources were not related to cardiometabolic health.     

阻塞性呼吸睡眠暂停综合征与中枢呼吸驱动

目的阐明不同浓度的CO     

上海市华阳社区糖尿病、高血压、血脂紊乱及代谢综合征基线调查

目的 调查上海市区40岁以上自然人群代谢综合征及有关疾病的患病情况。方法 采用多级分层随机抽样的流行病学调查方法进行问卷调查,并进行75g葡萄糖耐量试验、空腹血脂谱、BMI、血压及心电图测定。结果 上海华阳社区40岁以上中老年人中糖尿病、糖耐量减退/空腹血糖减损、高血压、血脂紊乱、超重/肥胖及代谢综合征患病率分别为13.06%、12.91%、47.04%、84.29%、38.67%、及13.06%。结论 上海城市社区40岁以上中老年人中代谢综合征及相关疾病的患病率很高。