Oral D-Aspartate Treatment Improves Sperm Fertility in Both Young and Adult B6N Mice

D-Aspartate (D-Asp) treatment improved the fertility of young male C57BL/6N mice in vivo revealing a direct role on capacitation, acrosome reaction, and fertility in vitro in young males only. We investigated whether the positive effect of D-Asp on fertility could be extended to adult males and evaluated the efficacy of a 2- or 4-week-treatment in vivo. Therefore, 20 mM sodium D-Asp was supplied in drinking water to males of different ages so that they were 9 or 16 weeks old at the end of the experiments. After sperm freezing, the in vitro fertilization (IVF) rate, the birth rate, hormone levels (luteinizing hormone (LH), epitestosterone, and testosterone), the sperm quality (morphology, abnormalities, motility, and velocity), the capacitation rate, and the acrosome reaction were investigated. Oral D-Asp treatment improves the fertilizing capability in mice regardless of the age of the animals. Importantly, a short D-Asp treatment of 2 weeks in young males elevates sperm parameters to the levels of untreated adult animals. In vivo, D-Asp treatment highly improves sperm quality but not sperm concentration. Therefore, D-Asp plays a beneficial role in mouse male fertility and may be highly relevant for cryorepositories to improve mouse sperm biobanking

Lenin on the Agrarian and Peasant Questions

Lenin attached great importance to the processes of agricultural and rural development. This is understandable in view of the fact that tsarist Russia where he prepared a socialist revolution had all the characteristics of an agrarian peasant country. Thus it was in Russia that many theories came into being which were contrary to the Marxist interpretations of historical evolution. Using the example of agriculture and peasantry, their authors tried to prove Marxist analysis wrong. They insisted that the special features of agriculture call for different laws of development (influence of natural factors, work with living matter, land as a special means of production, etc.). Thus defined, the agrarian question raised by bourgeois and revisionist economists did not exist for Lenin. For this sphere too is penetrated by capitalism, which leads to concentration, differentiation and social contrasts. One can only speak of different forms of its emergence in agriculture and industry, while the basic features remain the same. There are numerous works in which Lenin argued with the Populists and other champions of the agrarian question. The second group of questions which Lenin was concerned with derives from attempts to determine the attitude of the proletariat towards the peasants. Like Engels and Kautsky before him, he too was in favour of a firm alliance with small and medium farmers in the preparation for and realization of the revolution and, after its victory, for a gradual inclusion of the peasants in large-scale socialist agriculture on the principle of voluntary agreement and financial interest. The third group of questions studied by Lenin refers to the systems of co- -operation and association. In voluntary large-scale association of small producers Lenin saw the only way for agricultural development in the conditions of pettv ownership. But this involved an indispensable need for the development of industry which would provide agriculture with the necessary means

Impairment of germline transmission after blastocyst injection with murine embryonic stem cells cultured with mouse hepatitis virus and mouse minute virus

The aim of this study was to determine the susceptibility of murine embryonic stem (mESCs) to mouse hepatitis virus (MHV-A59) and mouse minute virus (MMVp) and the effect of these viruses on germline transmission (GLT) and the serological status of recipients and pups. When recipients received 10 blastocysts, each injected with 100 TCID50 MHV-A59, three out of five recipients and four out of 14 pups from three litters became seropositive. When blastocysts were injected with 10−5 TCID50 MMVp, all four recipients and 14 pups from four litters remained seronegative. The mESCs replicated MHV-A59 but not MMVp, MHV-A59 being cytolytic for mESCs. Exposure of mESCs to the viruses over four to five passages but not for 6 h affected GLT. Recipients were seropositive for MHV-A59 but not for MMVp when mESCs were cultured with the virus over four or five passages. The data show that GLT is affected by virus-contaminated mESCs

Medicinal herb use among asthmatic patients attending a specialty care facility in Trinidad

BACKGROUND: There is an increasing prevalence of asthma in the Caribbean and patients remain non-compliant to therapy despite the development of guidelines for management and prevention. Some patients may self-medicate with medicinal herbs for symptomatic relief, as there is a long tradition of use for a variety of ailments. The study assessed the prevalence of use and the factors affecting the decision to use herbs in asthmatic patients attending a public specialty care clinic in Trinidad. METHODS: A descriptive, cross-sectional study was conducted at the Chest Clinic in Trinidad using a de novo, pilot-tested, researcher-administered questionnaire between June and July 2003. RESULTS: Fifty-eight out of 191 patients (30.4%) reported using herbal remedies for symptomatic relief. Gender, age, ethnicity, and asthma severity did not influence the decision to use herbs; however, 62.5% of patients with tertiary level schooling used herbs, p = 0.025. Thirty-four of these 58 patients (58.6%) obtained herbs from their backyards or the supermarket; only 14 patients (24.1%) obtained herbs from an herbalist, herbal shop or pharmacy. Relatives and friends were the sole source of information for most patients (70.7%), and only 10.3% consulted an herbalist. Ginger, garlic, aloes, shandileer, wild onion, pepper and black sage were the most commonly used herbs. CONCLUSIONS: Among patients attending the Chest Clinic in Trinidad the use of herbal remedies in asthma is relatively common on the advice of relatives and friends. It is therefore becoming imperative for healthcare providers to become more knowledgeable on this modality and to keep abreast with the latest developments

Non-homologous end-joining pathway associated with occurrence of myocardial infarction: gene set analysis of genome-wide association study data

<p>Purpose: DNA repair deficiencies have been postulated to play a role in the development and progression of cardiovascular disease (CVD). The hypothesis is that DNA damage accumulating with age may induce cell death, which promotes formation of unstable plaques. Defects in DNA repair mechanisms may therefore increase the risk of CVD events. We examined whether the joints effect of common genetic variants in 5 DNA repair pathways may influence the risk of CVD events.</p> <p>Methods: The PLINK set-based test was used to examine the association to myocardial infarction (MI) of the DNA repair pathway in GWAS data of 866 subjects of the GENetic DEterminants of Restenosis (GENDER) study and 5,244 subjects of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. We included the main DNA repair pathways (base excision repair, nucleotide excision repair, mismatch repair, homologous recombination and non-homologous end-joining (NHEJ)) in the analysis.</p> <p>Results: The NHEJ pathway was associated with the occurrence of MI in both GENDER (P = 0.0083) and PROSPER (P = 0.014). This association was mainly driven by genetic variation in the MRE11A gene (PGENDER = 0.0001 and PPROSPER = 0.002). The homologous recombination pathway was associated with MI in GENDER only (P = 0.011), for the other pathways no associations were observed.</p> <p>Conclusion: This is the first study analyzing the joint effect of common genetic variation in DNA repair pathways and the risk of CVD events, demonstrating an association between the NHEJ pathway and MI in 2 different cohorts.</p&gt

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

The effects of moderate alcohol supplementation on estrone sulfate and DHEAS in postmenopausal women in a controlled feeding study

BACKGROUND: We have demonstrated that moderate alcohol consumption (15 g/d, 30 g/d) for 8 weeks resulted in significantly increased levels of serum estrone sulfate and DHEAS in 51 postmenopausal women in a randomized, placebo-controlled trial. We now report on the relationships between serum estrone sulfate and dehydroepiandrosterone sulfate (DHEAS) levels after 4 weeks of moderate alcohol supplementation, and compare the results to the 8 weeks data to elucidate time-to-effect differences. METHODS: Postmenopausal women (n = 51) consumed 0 (placebo), 15 (1 drink), and 30 (2 drinks) g alcohol (ethanol)/ day for 8 weeks as part of a controlled diet in a randomized crossover design. Blood samples were drawn at baseline, at 4 weeks and at 8 weeks. Changes in estrone sulfate and DHEAS levels from placebo to 15 g and 30 g alcohol per day were estimated using linear mixed models. RESULTS AND DISCUSSION: At week 4, compared to the placebo, estrone sulfate increased an average 6.9% (P = 0.24) when the women consumed 15 g of alcohol per day, and 22.2% (P = 0.0006) when they consumed 30 g alcohol per day. DHEAS concentrations also increased significantly by an average of 8.0% (P < 0.0001) on 15 g of alcohol per day and 9.2% (P < 0.0001) when 30 g alcohol was consumed per day. Trend tests across doses for both estrone sulfate (P = 0.0006) and DHEAS (P < 0.0001) were significant. We found no significant differences between the absolute levels of serum estrone sulfate at week 4 versus week 8 (P = 0.32) across all doses. However, absolute DHEAS levels increased from week 4 to week 8 (P < 0.0001) at all three dose levels. CONCLUSIONS: These data indicate that the hormonal effects due to moderate alcohol consumption are seen early, within 4 weeks of initiation of ingestion

Procjena cito-/genotoksičnosti irinotekana u V79-stanicama primjenom komet-testa, mikronukleus-testa i testa kromosomskih aberacija

Irinotecan is a topoisomerase I interactive agent, widely used in the treatment of metastatic colorectal cancer. The genotoxic effects of the maximum single dose (18 μg mL-1), recommended monotherapy dose (9 μg mL-1), and recommended combined therapy dose (4.5 μg mL-1) of irinotecan were studied on V79 cells using the comet assay, chromosome aberration assay, and micronucleus test. The cells were treated with irinotecan for 2 h or 24 h. The statistical signifi cance of the results was determined using the one-way ANOVA test and a nonparametric Mann Whitney U test. The comet assay did not show dose-dependent or time-dependent effects. The chromosome aberration analysis showed large DNA rearrangements, i.e., chromosome exchanges. Although the exposed cultures showed a signifi cant increase in micronucleated cells in respect to control, no dose-dependent relation was established among the treated cultures. Timedependent effect was also not observed.Irinotekan je citotoksični lijek koji inhibira enzim DNA-topoizomerazu I. U širokoj je primjeni u terapiji metastatskog karcinoma kolona i rektuma. U uvjetima in vitro primjenom komet-testa, analize kromosomskih aberacija i mikronukleus-testa na V79-stanicama istražili smo genotoksični učinak maksimalne pojedinačne doze (18 μg mL-1), preporučene monoterapijske doze (9 μg mL-1) i preporučene doze irinotekana za kombiniranu terapiju (4,5 μg mL-1). Kulture stanica bile su tretirane irinotekanom 2 h i 24 h. Statistička značajnost određivana je jednosmjernim ANOVA-testom i neparametrijskim Mann Whitneyevim U-testom. Komet-testom nije utvrđen učinak koncentracije i/ili vremena izloženosti. Analiza kromosomskih aberacija pokazala je prisutnost izmjena kromatida, tj. porast broja triradijusa i tetraradijusa. Iako je u kulturama stanica izloženi irinotekanu opažen značajan porast broja mikronukleusa u odnosu na kontrolu, nije uočena ovisnost o dozi lijeka ni o vremenu izloženosti u opisanim eksperimentalnim uvjetima. Dobiveni rezultati upućuju na genotoksičnost irinotekana za V79-stanice. Nijednom od primijenjenih metoda nije utvrđena ovisnost učinka irinotekana o vremenu ili dozi

Effect of a weight loss intervention on anthropometric measures and metabolic risk factors in pre- versus postmenopausal women

<p>Abstract</p> <p>Background</p> <p>The present study examines changes in body weight, fat mass, metabolic and hormonal parameters in overweight and obese pre- and postmenopausal women who participated in a weight loss intervention.</p> <p>Methods</p> <p>Seventy-two subjects were included in the analysis of this single arm study (premenopausal: 22 women, age 43.7 ± 6.4 years, BMI 31.0 ± 2.4 kg/m²; postmenopausal: 50 women, age 58.2 ± 5.1 years, BMI 32.9 ± 3.7 kg/m²). Weight reduction was achieved by the use of a meal replacement and fat-reduced diet. In addition, from week 6 to 24 participants attended a guided exercise program. Body composition was analyzed with the Bod Pod^®. Blood pressures were taken at every visit and blood was collected at baseline and closeout of the study to evaluate lipids, insulin, cortisol and leptin levels.</p> <p>Results</p> <p>BMI, fat mass, waist circumference, systolic blood pressure, triglycerides, glucose, leptin and cortisol were higher in the postmenopausal women at baseline.</p> <p>Both groups achieved a substantial and comparable weight loss (pre- vs. postmenopausal: 6.7 ± 4.9 vs 6.7 ± 4.4 kg; n.s.). However, in contrast to premenopausal women, weight loss in postmenopausal women was exclusively due to a reduction of fat mass (-5.3 ± 5.1 vs -6.6 ± 4.1 kg; p < 0.01). In premenopausal women 21% of weight loss was attributed to a reduction in lean body mass.</p> <p>Blood pressure, triglycerides, HDL-cholesterol, and glucose improved significantly only in postmenopausal women whereas total cholesterol and LDL-cholesterol were lowered significantly in both groups.</p> <p>Conclusion</p> <p>Both groups showed comparable weight loss and in postmenopausal women weight loss was associated with a pronounced improvement in metabolic risk factors thereby reducing the prevalence of metabolic syndrome.</p