Aliment Pharmacol Ther 2010; 32: 377–383
Summary
Background Vitamin D has immune‐regulatory functions in experimental colitis, and low vitamin D levels are present in Crohn’s disease.
Aim To assess ...the effectiveness of vitamin D3 treatment in Crohn’s disease with regard to improved disease course.
Methods We performed a randomized double‐blind placebo‐controlled trial to assess the benefits of oral vitamin D3 treatment in Crohn’s disease. We included 108 patients with Crohn’s disease in remission, of which fourteen were excluded later. Patients were randomized to receive either 1200 IU vitamin D3 (n = 46) or placebo (n = 48) once daily during 12 months. The primary endpoint was clinical relapse.
Results Oral vitamin D3 treatment with 1200 IU daily increased serum 25OHD from mean 69 nmol/L standard deviation (s.d.) 31 nmol/L to mean 96 nmol/L (s.d. 27 nmol/L) after 3 months (P < 0.001). The relapse rate was lower among patients treated with vitamin D3 (6/46 or 13%) than among patients treated with placebo (14/48 or 29%), (P = 0.06).
Conclusions Oral supplementation with 1200 IE vitamin D3 significantly increased serum vitamin D levels and insignificantly reduced the risk of relapse from 29% to 13%, (P = 0.06). Given that vitamin D3 treatment might be effective in Crohn’s disease, we suggest larger studies to elucidate this matter further. ClinicalTrial.gov(NCT00122184).
Although common sense suggests that environmental influences increasingly account for individual differences in behavior as experiences accumulate during the course of life, this hypothesis has not ...previously been tested, in part because of the large sample sizes needed for an adequately powered analysis. Here we show for general cognitive ability that, to the contrary, genetic influence increases with age. The heritability of general cognitive ability increases significantly and linearly from 41% in childhood (9 years) to 55% in adolescence (12 years) and to 66% in young adulthood (17 years) in a sample of 11 000 pairs of twins from four countries, a larger sample than all previous studies combined. In addition to its far-reaching implications for neuroscience and molecular genetics, this finding suggests new ways of thinking about the interface between nature and nurture during the school years. Why, despite life's 'slings and arrows of outrageous fortune', do genetically driven differences increasingly account for differences in general cognitive ability? We suggest that the answer lies with genotype-environment correlation: as children grow up, they increasingly select, modify and even create their own experiences in part based on their genetic propensities.
Aliment Pharmacol Ther 2010; 32: 1364–1372
Summary
Background Vitamin D3 has shown immune‐modulating effects in CD4+ T cells from Crohn’s disease patients in vitro.
Aim To investigate the effects ...of in vivo vitamin D3 treatment on T cells in Crohn’s disease patients.
Methods Peripheral blood mononuclear cells (PBMC) were isolated at week 0 and at week 26 from 10 vitamin D3‐ and 10 placebo‐treated Crohn’s disease patients participating in a randomized, placebo‐controlled, clinical trial study. Monocyte‐depleted PBMC were stimulated with anti‐CD3 and anti‐CD28, and cultured for 7, days, to investigate CD4+ T‐cell proliferation and T‐cell cytokine production.
Results In vitamin D3‐treated patients, the median 25‐hydroxyvitamin D3 levels increased 70 nmol/L compared with −5 nmol/L in the placebo group. Vitamin D3 treatment increased interleukin‐6 production (delta = 188 pg/mL, range: −444 to 4071) compared with a decrease in the placebo group (delta = −896 pg/mL, range: −3841 to 1323) (P < 0.02, Wilcoxon rank sum test). Interestingly, vitamin D3 increased the amount of proliferating stimulated CD4+ T cells from median 41% (range: 10–75%) to 56% (range: 26–77%) (P = 0.02, Wilcoxon rank sum test).
Conclusions Vitamin D3 treatment of Crohn’s disease patients increased the IL‐6 levels. Interestingly, vitamin D3 treatment enhanced the CD4+ T cell proliferation.
Summary
Crohn's disease (CD) is a chronic inflammatory disease associated with a dysregulated T cell response towards intestinal microflora. Vitamin D has immune modulatory effects on T cells through ...the nuclear vitamin D receptor (VDR) in vitro. It is unclear how oral vitamin D treatment affects VDR expression. The aim of this study was to establish a flow cytometry protocol, including nuclear and cytoplasmic VDR expression, and to investigate the effects of vitamin D treatment on T cell VDR expression in CD patients. The flow cytometry protocol for VDR staining was developed using the human acute monocytic leukaemia cell line (THP‐1). The protocol was evaluated in anti‐CD3/CD28‐stimulated peripheral blood mononuclear cells (PBMCs) from vitamin D3‐ (n = 9) and placebo‐treated (n = 9) CD patients. Anti‐VDR‐stained PBMCs were examined by flow cytometry, and their cytokine production was determined by cytokine bead array. VDR, CYP27B1 and RXRα mRNA expression levels in CD4+ T cells were measured by quantitative reverse transcriptase polymerase chain reaction. The flow cytometry protocol enabled detection of cytoplasmic and nuclear VDR expression. The results were confirmed by confocal microscopy and supported by correlation with VDR mRNA expression. VDR expression in CD4+ T cells increased following stimulation. This VDR up‐regulation was inhibited with 30% by vitamin D treatment compared to placebo in CD patients (P = 0·027). VDR expression was correlated with in‐vitro interferon‐γ production in stimulated PBMCs (P = 0·01). Flow cytometry is a useful method with which to measure intracellular VDR expression. Vitamin D treatment in CD patients reduces T cell receptor‐mediated VDR up‐regulation.
The study sought to formulate and evaluate suppositories using a locally produced brand of alum (Aw) obtained from bauxite waste generated at Awaso bauxite mine in the Western-North region of Ghana, ...for use in the treatment of hemorrhoids. The suppositories were formulated using shea butter modified, respectively, with amounts of beeswax and theobroma oil. In another development, theobroma oil was modified with different concentrations of beeswax. Drug-base interactions were investigated using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy. The suppositories were prepared using the hot melt and trituration methods. Quality control checks were carried out on the formulations. The evaluated parameters included physical characteristics (texture, presence or absence of entrapped air, and contraction holes), weight uniformity, disintegration time, drug content, and in vitro release profile of the alum from the formulated suppositories. An in vivo analysis was carried out on the most suitable formulation to ascertain its efficacy on inflamed tissues using croton oil-induced rectal inflammation in a rat model. A critical examination of the ATR-FTIR spectra revealed no drug-base interactions. The suppository formulations passed all Pharmacopoeia stated tests. The in vivo study revealed the use of suppositories ameliorated the croton oil-induced hemorrhoid in the rectoanal region of the rats.
The propagation of hard X‐ray synchrotron beams in waveguides with guiding layer diameters in the 9–35 nm thickness range has been studied. The planar waveguide structures consist of an optimized ...two‐component cladding. The presented fabrication method is suitable for short and leak‐proof waveguide slices with lengths (along the optical axis) in the sub‐500 µm range, adapted for optimized transmission at photon energies of 11.5–18 keV. A detailed comparison between finite‐difference simulations of waveguide optics and the experimental results is presented, concerning transmission, divergence of the waveguide exit beam, as well as the angular acceptance. In a second step, two crossed waveguides have been used to create a quasi‐point source for propagation‐based X‐ray imaging at the new nano‐focus endstation of the P10 coherence beamline at Petra III. By inverting the measured Fraunhofer diffraction pattern by an iterative error‐reduction algorithm, a two‐dimensional focus of 10 nm × 10 nm is obtained. Finally, holographic imaging of a lithographic test structure based on this optical system is demonstrated.
To prevent transmission of, and infection with, meticillin-resistant Staphylococcus aureus (MRSA), eradication treatment of colonized individuals is recommended. Throat colonization is a well-known ...risk factor for eradication failure. Staphylococcus aureus throat colonization is associated with colonization of the rhinopharynx, but in the currently recommended Danish MRSA eradication strategies, rhinopharynx colonization is not directly targeted. Rhinopharynx colonization could therefore be an important risk factor for prolonged MRSA throat carriage.
To determine whether irrigation and wash of the rhinopharynx and mouth with dissolved mupirocin is a feasible and potentially efficacious supplementary strategy against treatment-resistant MRSA throat carriage.
The patient study was an open, non-blinded, trial including 20 treatment-resistant MRSA throat carriers. In the study, the patients received a supplementary treatment besides the standard treatment according to the Danish MRSA eradication strategy. The supplementary treatment consisted of rhinopharyngeal irrigation and mouth-gurgling twice a day for 14 days with a mupirocin ointment (22 g 2% ointment per litre of isotonic sterile saline solution) in a 37°C solution.
Eighteen patients (90%) complied with the treatment protocol and none ex-perienced any major adverse events. Out of the 18 patients who finished the study per protocol, 15 (83%) and seven (39%) patients had negative MRSA sampling results one and six months after end of treatment, respectively.
This study demonstrates the feasibility and clinical potential of also targeting the rhinopharynx and oropharynx in non-systemic throat MRSA eradication strategies.
Community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) isolates belonging to clonal complex 80 (CC80) are recognized as the European CA-MRSA. The prevailing European CA-MRSA clone ...carries a type IVc staphylococcal cassette chromosome mec (SCCmec) and expresses Panton-Valentine leukocidin (PVL). Recently, a significant increase of PVL-negative CC80 MRSA has been observed in Denmark. The aim of this study was to examine their genetics and epidemiology, and to compare them to the European CA-MRSA clone in order to understand the emergence of PVL-negative CC80 MRSA.
Phylogenetic analysis of the CC80 S. aureus lineage was conducted from whole-genome sequences of 217 isolates (23 methicillin-susceptible S. aureus and 194 MRSA) from 22 countries. All isolates were further genetically characterized in regard to resistance determinants and PVL carriage, and epidemiologic data were obtained for selected isolates.
Phylogenetic analysis revealed the existence of three distinct clades of the CC80 lineage: (a) an methicillin-susceptible S. aureus clade encompassing Sub-Saharan African isolates (n = 13); (b) a derived clade encompassing the European CA-MRSA SCCmec-IVc clone (n = 185); and (c) a novel and genetically distinct clade encompassing MRSA SCCmec-IVa isolates (n = 19). All isolates in the novel clade were PVL negative, but carried remnant parts (8–12 kb) of the PVL-encoding prophage ΦSa2 and were susceptible to fusidic acid and kanamycin/amikacin. Geospatial mapping could link these isolates to regions in the Middle East, Asia and South Pacific.
This study reports the emergence of a novel CC80 CA-MRSA sublineage, showing that the CC80 lineage is more diverse than previously assumed.
Relative diffusion coefficients were determined in water for the D, H, and Mu isotopes of atomic hydrogen by measuring their diffusion-limited spin-exchange rate constants with Ni2+ as a function of ...temperature. H and D atoms were generated by pulse radiolysis of water and measured by time-resolved pulsed EPR. Mu atoms are detected by muonium spin resonance. To isolate the atomic mass effect from solvent isotope effect, we measured all three spin-exchange rates in 90% D2O. The diffusion depends on the atomic mass, demonstrating breakdown of Stokes–Einstein behavior. The diffusion can be understood using a combination of water “cavity diffusion” and “hopping” mechanisms, as has been proposed in the literature. The H/D isotope effect agrees with previous modeling using ring polymer molecular dynamics. The “quantum swelling” effect on muonium due to its larger de Broglie wavelength does not seem to slow its “hopping” diffusion as much as predicted in previous work. Quantum effects of both the atom mass and the water librations have been modeled using RPMD and a qTIP4P/f quantized flexible water model. These results suggest that the muonium diffusion is very sensitive to the Mu versus water potential used.
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