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Gastrointestinal tract conditions are frequently associated with low bone mineral density and increased risk of fractures due to osteoporosis, the latter concerning particularly inflammatory bowel disease (IBD) patients. One of the candidate genes involved in osteoporosis is the transforming growth factor beta-1 (TGFB1) whose polymorphisms may be responsible for the development of this disease. The aim of this study was to analyse the frequency of TGFB1 polymorphic variants and determine the association between the c.29T>C TGFB1 polymorphism, and bone mineral density and fractures in IBD patients. The study subjects included 198 IBD patients [100 suffering from Crohn's disease (CD) and 98 from ulcerative colitis (UC)] and 41 healthy volunteers as a control group. Densitometric bone measurements were obtained using dual energy X-ray absorptiometry. The TGFB1 genotyping was conducted using restriction fragments length polymorphism. We conducted an analysis of genotype distribution's concordance with Hardy-Weinberg equilibrium. We found statistically significant differences in lumbar spine (L2-L4) and femoral neck BMD and T-scores between CD, UC and control subgroups. The distribution of TGFB1 polymorphic variants among CD and UC patients was concordant with Hardy-Weinberg equilibrium. There were no statistically significant differences in densitometric parameters (lumbar spine and femoral neck BMD, T-score, and Z-score) between carriers of different TGFB1 polymorphisms among IBD (CD and UC) patients nor among controls. We have found no statistically significant differences in the prevalence of low-energy fractures between groups of different TGFB1 polymorphic variant carriers. The allele dose effect, recessive effect and dominant effect analysis did not show an association between low-energy fractures and the TGFB1 polymorphisms among CD and UC patients. We have not observed an association between the c.29T>C TGFB1 polymorphic variant and the bone mineral density within the cancellous and cortical bones (L2-L4 and femoral neck, respectively), or the occurrence of fractures among the IBD patients and their family members. [ABSTRACT FROM AUTHOR]

MDM2, a ubiquitin E3-ligase of the RING family, has a key role in regulating p53 abundance. During normal non-stress conditions p53 is targeted for degradation by MDM2. MDM2 can also target itself and MDMX for degradation. MDMX is closely related to MDM2 but the RING domain of MDMX does not possess intrinsic E3-ligase activity. Instead, MDMX regulates p53 abundance by modulating the levels and activity of MDM2. Dimerization, mediated by the conserved C-terminal RING domains of both MDM2 and MDMX, is critical to this activity. Here we report the crystal structure of the MDM2/MDMX RING domain heterodimer and map residues required for functional interaction with the E2 (UbcH5b). In both MDM2 and MDMX residues C-terminal to the RING domain have a key role in dimer formation. In addition we show that these residues are part of an extended surface that is essential for ubiquitylation in trans. This study provides a molecular basis for understanding how heterodimer formation leads to stabilization of MDM2, yet degradation of p53, and suggests novel targets for therapeutic intervention.Cell Death and Differentiation (2008) 15, 841–848; doi:10.1038/sj.cdd.4402309; published online 25 January 2008 [ABSTRACT FROM AUTHOR]

AIM:: Screening and extended assessment of the nutritional status of patients on admission and on discharge from hospital were carried out. DESCRIPTION:: The studies were carried out in four teaching hospitals, four provincial hospitals and four county hospitals in Poland. SUBJECTS:: Screening examinations were carried out for 3310 randomly selected patients (every 10th patient admitted to hospital, including 1916 female cases aged from 16 to 92?y and 1394 male patients aged from 16 to 100?y). Extended examinations were carried out on 210 patients aged from 16 to 87?y (including 122 female and 88 male). MAIN ASSESSMENT PARAMETERS:: Anthropometric (height, weight, body mass index (BMI), waist-to-hip ratio (WHR), arm circumference) and biochemical indices (erythrocyte count, haemoglobin concentration, white blood cell count, blood lymphocyte count and serum albumin serum concentration). The extended examinations included determination of antioxidant vitamins (A, C, E), vitamin B12 and folic acid. RESULTS:: On admission to hospital, 10.43%of the patients surveyed had a BMI below 20?kg/m2, in 20.74%of patients serum albumin concentration was below 3.5?g/dl, indicating possible protein energy malnutrition. In addition, 21.02%had lymphocyte count below 1.5×103/mm3. During hospitalisation, deterioration in the nutritional status of the patient population occurred. On discharge from hospital, the percentage of patients with BMI<20?kg/m2 increased to 11.21%and the percentage with low blood albumin (<3.5?g/dl) increased to 28.57%. On admission, vitamin C deficiency was present in 51.8%of patients, folic acid deficiency in 32%, vitamin E deficiency in 10%, vitamin B12 deficiency in 6.8%and vitamin A deficiency in 1.4%. Vitamin deficiencies were present equally in malnourished, overweight and obese patients. CONCLUSIONS:: In patients admitted to hospitals in Poland, malnutrition risk demonstrated by BMI was observed in 10.43%of patients. On the basis of biochemical indices, increased nutritional risk was demonstrated in 21%of patients. Vitamin malnutrition was seen in the majority of patients. A significant correlation between weight, BMI, arm circumference, blood lymphocyte count and the number of days spent in hospital was observed. SPONSORSHIP:: The Committee of Scientific Research and the Ministry of Health-PBZ 012-14.European Journal of Clinical Nutrition (2005) 59, 552-560. doi:10.1038/sj.ejcn.1602117 Published online 16 February 2005 [ABSTRACT FROM AUTHOR]