Sports and Leisure Time Physical Activity During Pregnancy in Nulliparous Women

To describe patterns of leisure time physical activity during pregnancy in relation to pre-pregnancy leisure time physical activity, socio-demographic characteristics, fertility history, and lifestyle factors. 4,718 nulliparous with singleton pregnancy and intended spontaneous vaginal delivery were included in the study at gestational week 33 from May 2004 to July 2005. Information was provided by self-administered questionnaires. Leisure time physical activity was categorised into four categories: competitive sport, moderate-to-heavy, light or sedentary. In this population of nulliparous women, 4% participated in competitive sport, 25% in moderate-to-heavy activities, 66% in light activities, and 5% in sedentary activities in the year prior to pregnancy. Physical activity before pregnancy was statistically significantly associated with age, pre-pregnancy BMI, chronic diseases, number of years at school, and smoking habits. The proportion of women who took part in competitive sports, and moderate-to-heavy activities decreased over the three trimesters of pregnancy. The proportion of women with light physical activity was stable during pregnancy while the proportion of women with sedentary activity increased from 6% to 29%. During the third trimester women performing competitive sports or moderate-to-heavy activities before pregnancy continued to have a higher level of physical activity than women with light activities or sedentary activities before pregnancy. In general the intensity and time spent on exercise decreased during pregnancy. Women with the highest level of exercise prior to pregnancy continued to be the most active during pregnancy. Among women with sedentary activities before pregnancy one-fourth changed to light activity during pregnancy.     

Langerhans cell markers CD1a and CD207 are the most rapidly responding genes in lesional psoriatic skin following adalimumab treatment

TNFα‐, IL‐23‐ and IL‐17‐targeting drugs are highly effective in the treatment of psoriasis. However, the precise molecular mechanism remains unknown. In psoriatic skin, the presence of Langerhans cells (LCs) is reduced, but the role of LC is poorly understood. The purpose of this study was to investigate the impact of TNFα and IL‐23/IL‐17 on the presence of LC in the skin during treatment. Therefore, psoriatic skin was investigated before and after 4 days of adalimumab or ustekinumab treatment. Furthermore, TNFα and IL‐17A stimulation was investigated in an ex vivo model of epidermis and dermis from healthy normal skin kept in cultures at an air‐liquid interphase for 4 days. In a gene array analysis, we found that the two LC markers, CD1a and CD207, were among the most up‐ or downregulated genes in psoriatic skin after anti‐TNFα therapy. Validation showed that both mRNA expression and protein level followed the same pattern and became significantly upregulated after 4 days of treatment. No changes were seen after ustekinumab treatment. In the ex vivo skin model, a decrease in the CD1a level was seen after TNFα stimulation and it was caused by LC migration from epidermis. No response in LC migration was seen after IL‐17A stimulation. Taken together, we demonstrated that changes in the LC level in epidermis precede the histological and clinical changes during adalimumab treatment in psoriatic skin. Furthermore, TNFα plays a prominent role in orchestrating LC migration in the skin. This seems not to be the true for the IL‐23/IL‐17A pathway.     

Tumor progression in waiting time for radiotherapy in head and neck cancer.

INTRODUCTION: Waiting-time prior to radiotherapy is a well-known problem. This study aims to determine the impact of time on tumor growth in a patient population with squamous-cell carcinoma of the head and neck (SCCHN). MATERIAL AND METHODS: In a consecutive cohort, all patients with both a diagnostic scan and a treatment-planning scan were identified. In total 648 patients were seen, and 414 treated with primary radiotherapy. Ninety-five had two scans and 61 sets were eligible for comparison. Endpoints were change in tumor volume, tumor volume doubling time (TVD) and disease progression measured by TNM-classification and RECIST criteria. RESULTS: Median interval between eligible scans was 28 (5-95) days. Thirty-eight (62%) had measurable increase in tumor volume, median 46% (6-495%). For all patients TVD was median 99 days, but for the half of patients with fastest growing tumors TVD was 30 days (15-41). Tumor volume increase was significantly correlated to time and histological differentiation. Twelve (20%) developed new lymph-node metastasis and 10 (16%) progressed in TNM-classification. Evaluated by RECIST criteria 18 (30%) patients had progressive disease. INTERPRETATION: This study shows a negative impact of waiting time in patients with SCCHN. Within an average time of 4 weeks the majority of the patients developed significant signs of tumor progression. It was not possible to define a threshold for acceptable time intervals in order to avoid volume changes, or to define a subgroup that has no negative impact of delay.     

Using biorelevant dissolution to obtain IVIVC of solid dosage forms containing a poorly-soluble model compound

The usefulness of selected biorelevant dissolution media (BDM) to predict in vivo drug absorption was studied. Dissolution profiles of solid formulations of a poorly soluble model compound were compared in BDM simulating fasted and two levels of fed state. A non-physiologically relevant medium containing the cationic surfactant, cetrimide, was also investigated. All the media studied were capable of differentiating between the formulations employed, with formulation A consistently ranking high and formulations C and D ranking low. An in vivo dog study was carried out and an attempt was made to obtain a level A correlation between the plasma absorption curves and in vitro dissolution curves, using non-linear regression software. The in vitro-in vivo correlation (IVIVC) models developed indicated that fed state media (BDM 3) containing high levels of both bile salts (BS) and lipolysis products (LP) were best able to predict in vivo pharmacokinetic parameters (Cmax and AUC) with prediction errors lower than 10%. Overall, design and use of appropriate media for in vitro dissolution is extremely important. This study demonstrates the potential of physiologically relevant media containing both BS and LP for use in formulation and early drug development.     

Immunotoxicity of nucleic acid reduced BioProtein--a bacterial derived single cell protein--in Wistar rats

BioProtein is a single cell protein produced by a mixed methanotrophic and heterotrophic bacteria culture using natural gas as energy source, which has been approved for animal feed. BioProtein contains a large amount of nucleic acids making the product less suitable for human consumption, therefore, a nucleic acid reduced variant (NABP) has been developed by the manufacturer. The purpose of the present study was to establish the safety of NABP in a subchronic toxicity rat study. Groups of 10 male and 10 female Wistar rats were fed diets containing 0, 6, 12 or 24% NABP for 13 weeks. Feeding NABP induced a humoral immune response and proliferation of phagocytic cell lines, mainly macrophages. The humoral response involved induction of NABP specific IgM and IgG. The proliferation of phagocytic cells involved increase of the white blood cell count of all dosed female groups. Males showed the same tendency, although, not statistically significant (P=0.09). The subsets of cells identified as neutrophils and eosinophils were increased and lymphocytes decreased. The histopathological examination revealed histiocytosis and accumulation of foamy macrophages in the mesenteric lymph nodes, hyperplasia of Kupffer cells in the liver, increased granulopoiesis in spleen and bone marrow, and infiltration of lamina propria of the large intestine with eosinophilic granulocytes. The most consistent and pronounced changes were observed in the highest dose group, but even at the lowest dose level some of the changes were present. Accordingly, a no-observed-effect level could not be established based on this study.     

Studies of curcumin and curcuminoids. XXVII. Cyclodextrin complexation: solubility,chemical and photochemical stability

Cyclodextrin complexes of the natural compound curcumin were prepared in order to improve the water solubility and the hydrolytic and photochemical stability of the compound. Complex formation resulted in an increase in water solubility at pH 5 by a factor of at least 10(4). The hydrolytic stability of curcumin under alkaline conditions was strongly improved by complex formation, while the photodecomposition rate was increased compared to a curcumin solution in organic solvents. The cavity size and the charge and bulkiness of the cyclodextrin side-chains influenced the stability constant for complexation and the degradation rate of the curcumin molecule.     

An observational study of slimming behavior in Denmark in 1992 and 1998

OBJECTIVE: To elucidate how frequent weight-loss attempts are made, the methods used to achieve weight loss, and the extent to which the outcome is positive. RESEARCH METHODS AND PROCEDURES: Two independent interviews were conducted in 1992 and in 1998, each with 1200 randomly selected adult subjects. Each survey was designed to ensure an equal distribution of age, gender, and geographical regions in Denmark. RESULTS: The proportion of subjects having attempted weight loss did not change from 1992 to 1998, although the prevalence of overweight and obesity increased from 1992 (overweight, 30%; obesity, 6%) to 1998 (overweight, 35%; obesity, 8%). Almost twice as many women (61%) than men (32%) had attempted weight loss (p < 0.0001). Slimming occurred more often in subjects <50 years (51%) than >50 years (39%) (p < 0.0001), although overweight and obesity were more frequent in the elderly. Over-the-counter diet pills or meal replacements were associated with a negative outcome of slimming treatment (p < 0.0001). DISCUSSION: Approximately half of all adult Danes have attempted weight loss, particularly women and individuals <50 years. This finding is inconsistent with the fact that overweight and obesity are more prevalent in men and in individuals >50 years. Changes in habitual diet and increased physical activity are the most prevalent modes of slimming, whereas the use of over-the-counter diet pills or meal replacements has decreased from 1992 to 1998. This development may have a positive impact on future body- weight-management strategies.     

Population-based study of acute respiratory infections in children,Greenland

Acute respiratory infections (ARI) are frequent in Inuit children, in terms of incidence and severity. A cohort of 294 children <2 years of age was formed in Sisimiut, a community on the west coast of Greenland, and followed from 1996 to 1998. Data on ARI were collected during weekly visits at home and child-care centers; visits to the community health center were also recorded. The cohort had respiratory symptoms on 41.6% and fever on 4.9% of surveyed days. The incidence of upper and lower respiratory tract infections was 1.6 episodes and 0.9 episodes per 100 days at risk, respectively. Up to 65% of the episodes of ARI caused activity restriction; 40% led to contact with the health center. Compared with studies from other parts of the world, the incidence of ARI appears to be high in Inuit children.     

Nizatidine and omeprazole enhance the effect of metronidazole on Helicobacter pylori in vitro

Treatment failures are common in patients infected with metronidazole-resistant Helicobacter pylori in the gastric mucosa when triple therapy including metronidazole is used. In patients with treatment failure and metronidazole-resistant H. pylori, a higher eradication rate for H. pylori was found after secondary treatment with bismuth/ranitidine in combination with antibiotics including metronidazole, compared with the same antibiotics combined with a standard dose of omeprazole. This agrees with our previous finding that bismuth was able to reduce the susceptibility of H. pylori to metronidazole. In this study, we have found that nizatidine, an H(2)-receptor antagonist, is also able to reduce the susceptibility of H. pylori to metronidazole in vitro, despite having no direct inhibitory effect on the growth of H. pylori. This agrees with earlier findings that compounds having the ability to reverse antibiotic resistance do not necessarily have an antibiotic or chemotherapeutic effect in the sense of growth inhibition. Therefore, it was decided to investigate the effect of nizatidine and omeprazole on the oxidative respiratory chain, as it is known that metronidazole is able to inhibit the activity of fumarate reductase of H. pylori. This enzyme is a key enzyme in the alternative respiratory chain under anaerobic conditions. Nizatidine was, in these preliminary experiments, found to inhibit fumarate reductase in a dose-dependent way, like metronidazole, whereas omeprazole had almost no effect on fumarate reductase. No other significant effects on the enzymes of the respiratory chain were found. The synergistic effect of nizatidine on metronidazole resistant H. pylori strains could be explained by the effect on fumarate reductase, whereas the effect of omeprazole is different and could be an inhibition of a proton pump in H. pylori. Reversal of antimicrobial resistance with the help of different non-antibiotics seems to be possible by using quite different compounds, and is therefore to be explained by different molecular mechanisms.