Pharmacokinetics and pharmacodynamics of pentoxifylline and metabolites

Pentoxifylline is a haemorheologic drug with complex pharmacokinetics and pharmacodynamics due to both reversible metabolism and the formation of active metabolites. In humans, pentoxifylline is metabolised to at least seven phase 1 metabolites (M1-M7). The reversible metabolism of pentoxifylline to the enantiomers of M1 has only been partly studied. This thesis investigates the pharmacokinetics of pentoxifylline and metabolites and their contributions to the haemorheological effects. When pentoxifylline is administered either orally or intravenously to healthy humans the plasma concentrations of M5 and S-M1 are higher than the pentoxifylline concentrations, whereas the ones for M4 are lower and R-M1 much lower. In-vitro studies showed that this can be mainly explained by a 15 times faster formation of S-M1 than R-M1 from pentoxifylline. Had the enantiomers been present at equal concentrations the reversible metabolism would have been 4 times faster from S-M1 than from R-M1. Pentoxifylline, R-M1, and M5 increases retinal blood flow after administration of pentoxifylline to healthy humans. In the following potency order R-M1, rac-M1, S-M1, pentoxifylline and M4 significantly inhibit platelet aggregation in a concentration-dependent manner in whole blood from healthy humans. The thesis also includes a phase two, double-blind, placebo-controlled randomised clinical trial investigating pentoxifylline and vitamin E treatment for prevention of radiation-induced side effects in 83 women with breast cancer. The study showed that the combination of pentoxifylline and vitamin E was well tolerated and may be used for prevention of some radiation-induced side effects, e.g. increased arm volume and pain described as stiffness in the skin

Övervikt hos romerska kvinnor - synen på övervikt i antik och modern medicin

This essay is written because I would like to find out what the doctors in ancient Rome thought about overweight women. The reason why it is written is due to the fact that modern medicine associates many diseases with overweight, and because I myself happen to be overweight. I will do a comparison between modern medicine and the ancient medical writers to see if they did associate overweight with a number of health problems as we do today. The ancient medical writers I have chosen are the Hippocratic corpus, Soranos, Celsus and Galenos. The questions for this essay are: What medical conditions, in women, did the ancient doctors consider that overweight could cause? What medical conditions in women does modern medicine consider overweight to be a cause of? Does overweight in women, from a medical point of view, always mean something negative? First I will see what the ancient medical texts and modern medicine says about overweight, separately, and then in the discussion I will see if the ancient doctors did associate overweight with the same diseases as we do today, and where the ancient doctors had their focus when it came to women who were overweight. As I have seen the ancient doctors did not focus a lot on overweight and neither did they focus a lot on women as the main patients in their writings were male. Although when it comes to the matter of fertility they give more attention to women and also, but still not all that much, overweight. But in some cases they think the same as we do today, for example that overweight can make a woman less fertile

Health-Related Quality of Life in Children and Adolescents with Celiac Disease: From the Perspectives of Children and Parents

Aim. To examine how celiac children and adolescents on gluten-free diet valued their health-related quality of life, and if age and severity of the disease at onset affected the children's self-valuation later in life. We also assessed the parents' valuation of their child's quality of life. Methods. The DISABKIDS Chronic generic measure, short versions for both children and parents, was used on 160 families with celiac disease. A paediatric gastroenterologist classified manifestations of the disease at onset retrospectively. Results. Age or sex did not influence the outcome. Children diagnosed before the age of five scored higher than children diagnosed later. Children diagnosed more than eight years ago scored higher than more recently diagnosed children, and children who had the classical symptoms of the disease at onset scored higher than those who had atypical symptoms or were asymptomatic. The parents valuated their children's quality of life as lower than the children did. Conclusion. Health-related quality of life in treated celiac children and adolescents was influenced by age at diagnosis, disease severity at onset, and years on gluten-free diet. The disagreement between child-parent valuations highlights the importance of letting the children themselves be heard about their perceived quality of life

Роль кафедры акушерства и гинекологии ФПК и ПК в подготовке врачей-интернов

ИНТЕРНАТУРА И РЕЗИДЕНТУРААКУШЕРСТВОГИНЕКОЛОГИЯМЕДИЦИНСКОЙ ПРАКТИКИ МЕНЕДЖМЕНТОБРАЗОВАНИЕ МЕДИЦИНСКО

Mitigating the carbon footprint and improving productivity of ruminant livestock agriculture using a red seaweed

Ruminants are responsible for a large proportion of agricultural greenhouse gas emissions in the form of methane. This can be managed. It is a global initiative to increase productivity of the livestock sector to meet a growing population, but with emphasis on decreasing enteric methane to achieve emissions targets. We investigated the marine red macroalga (seaweed) Asparagopsis taxiformis as a feed ingredient to fundamentally eliminate enteric methane in beef cattle fed a high grain diet and provide evidence of improved livestock production performance. Asparagopsis was included in the feed of Brahman-Angus cross steers at 0.00%, 0.05%, 0.10%, and 0.20% of feed organic matter. Emissions were monitored in respiration chambers fortnightly over 90 d of treatment, steers were weighed weekly prior to feeding, feed intake monitored daily, rumen fluid samples collected in conjunction with respiration chambers for assessment of rumen function, feces were collected for bromoform residue analysis, and meat, organ, and fat were collected post slaughter for residue analysis and sensory evaluation. Steers receiving 0.10% and 0.20% Asparagopsis demonstrated decreased methane up to 40% and 98%, and demonstrated weight gain improvements of 53% and 42%, respectively. There was no negative effect on daily feed intake, feed conversion efficiencies, or rumen function, and no residues or changes in meat eating quality were detected. Commercial production of Asparagopsis could create new economies, and with low inclusion rates of this seaweed in ruminant diets the industry has the potential to revolutionize management of greenhouse gas emissions across the ruminant livestock sector with complementary benefits to the environment, and economy of the wider agriculture sector

Long working hours, anthropometry, lung function, blood pressure and blood-based biomarkers : cross-sectional findings from the CONSTANCES study

Background Although long working hours have been shown to be associated with the onset of cardiometabolic diseases, the clinical risk factor profile associated with long working hours remains unclear. We compared the clinical risk profile between people who worked long hours and those who reported being never exposed to long hours. Methods A cross-sectional study in 22 health screening centres in France was based on a random population-based sample of 75 709 participants aged 18-69 at study inception in 2012-2016 (the CONSTANCES study). The data included survey responses on working hours (never, former or current exposure to long working hours), covariates and standardised biomedical examinations including anthropometry, lung function, blood pressure and standard blood-based biomarkers. Results Among men, long working hours were associated with higher anthropometric markers (Body Mass Index, waist circumference and waist:hip ratio), adverse lipid levels, higher glucose, creatinine, white blood cells and higher alanine transaminase (adjusted mean differences in the standardised scale between the exposed and unexposed 0.02-0.12). The largest differences were found for Body Mass Index and waist circumference. A dose-response pattern with increasing years of working long hours was found for anthropometric markers, total cholesterol, glucose and gamma-glutamyltransferase. Among women, long working hours were associated with Body Mass Index and white blood cells. Conclusion In this study, men who worked long hours had slightly worse cardiometabolic and inflammatory profile than those who did not work long hours, especially with regard to anthropometric markers. In women, the corresponding associations were weak or absent.Peer reviewe

Dichloroacetate alleviates development of collagen II-induced arthritis in female DBA/1 mice

Introduction Dichloroacetate (DCA) has been in clinical use for the treatment of lactacidosis and inherited mitochondrial disorders. It has potent anti-tumor effects both in vivo and in vitro, facilitating apoptosis and inhibiting proliferation. The proapoptotic and anti-proliferative properties of DCA prompted us to investigate the effects of this compound in arthritis. Methods In the present study, we used DCA to treat murine collagen type II (CII)-induced arthritis (CIA), an experimental model of rheumatoid arthritis. DBA/1 mice were treated with DCA given in drinking water. Results Mice treated with DCA displayed much slower onset of CIA and significantly lower severity (P less than 0.0001) and much lower frequency (36% in DCA group vs. 86% in control group) of arthritis. Also, cartilage and joint destruction was significantly decreased following DCA treatment (P = 0.005). Moreover, DCA prevented arthritis-induced cortical bone mineral loss. This clinical picture was also reflected by lower levels of anti-CII antibodies in DCA-treated versus control mice, indicating that DCA affected the humoral response. In contrast, DCA had no effect on T cell-or granulocyte-mediated responses. The beneficial effect of DCA was present in female DBA/1 mice only. This was due in part to the effect of estrogen, since ovariectomized mice did not benefit from DCA treatment to the same extent as sham-operated controls (day 30, 38.7% of ovarectomized mice had arthritis vs. only 3.4% in sham-operated group). Conclusion Our results indicate that DCA delays the onset and alleviates the progression of CIA in an estrogen-dependent manner

Work stress, anthropometry, lung function, blood pressure, and blood-based biomarkers : a cross-sectional study of 43,593 French men and women

Work stress is a risk factor for cardio-metabolic diseases, but few large-scale studies have examined the clinical profile of individuals with work stress. To address this limitation, we conducted a cross-sectional study including 43,593 working adults from a French population-based sample aged 18-72 years (the CONSTANCES cohort). According to the Effort-Reward Imbalance model, work stress was defined as an imbalance between perceived high efforts and low rewards at work. A standardized health examination included measures of anthropometry, lung function, blood pressure and standard blood-based biomarkers. Linear regression analyses before and after multivariable adjustment for age, socioeconomic status, depressive symptoms, health-related behaviours, and chronic conditions showed that work stress was associated with higher BMI, waist circumference, waist-hip ratio, alanine transaminase, white blood cell count and lower high-density lipoprotein cholesterol in men, and with higher BMI and white blood cell count in women (differences 0.03-0.06 standard deviations, P <0.05 between individuals with and without work stress). No robust associations were observed with lung function, haemoglobin, creatinine, glucose levels or resting blood pressure measures. This indicates that work stress is associated altered metabolic profile, increased systemic inflammation, and, in men, poorer liver function, which is a marker of high alcohol consumption.Peer reviewe

Benefits and risks of including the bromoform containing seaweed Asparagopsis in feed for the reduction of methane production from ruminants

The agricultural production of ruminants is responsible for 24% of global methane emissions, contributing 39% of emissions of this greenhouse gas from the agricultural sector. Strategies to mitigate ruminant methanogenesis include the use of methanogen inhibitors. For example, the seaweeds Asparagopsis taxiformis and Asparagopsis armata included at low levels in the feed of cattle and sheep inhibit methanogenesis by up to 98%, with evidence of improvements in feed utilisation efficiency. This has resulted in an increasing interest in and demand for these seaweeds globally. In response, research is progressing rapidly to facilitate Asparagopsis cultivation at large scale, and to develop aquaculture production systems to enable a high quality and consistent supply chain. In addition to developing robust strategies for sustainable production, it is important to consider and evaluate the benefits and risks associated with its production and subsequent use as an antimethanogenic feed ingredient for ruminant livestock. This review focuses on the relevant ruminal biochemical pathways, degradation, and toxicological risks associated with bromoform (CHBr3), the major active ingredient for inhibition of methanogenesis in Asparagopsis, and the effects that production of Asparagopsis and its use as a ruminant feed ingredient might have on atmospheric chemistry