Risk factors for metabolic bone disease in Crohn's disease patients

Background: The aim was to evaluate the presence of metabolic bone disease (MBD) in patients with Crohn’s disease (CD) and to identify potential etiologic factors. Methods: The case–control study included 99 patients with CD and 56 controls with a similar age and gender distribution. Both groups had dual-energy x-ray absorptionmetry and a nutritional evaluation. Single nucleotide polymorphisms at the IL1, TNF-a, LTa, and IL-6 genes were analyzed in patients only. Statistical analysis was performed using SPSS software. Results: The prevalence of MBD was significantly higher in patients (P ¼ 0.006). CD patients with osteoporosis were older (P < 0.005), small bowel involvement and surgical resections were more frequent (P < 0.005), they more often exhibited a penetrating or stricturing phenotype (P < 0.05), duration of disease over 15 years (P < 0.005), and body mass index (BMI) under 18.5 kg/m2 (P < 0.01) were more often found. No association was found with steroid use. Patients with a Z-score < 2.0 more frequently had chronic active disease (P < 0.05). With regard to diet, low vitamin K intake was more frequent (P ¼ 0.03) and intake of total, monounsaturated, and polyunsaturated fat was higher in patients with Z-score < 2.0 (P < 0.05). With respect to genetics, carriage of the polymorphic allele for LTa252 A/G was associated with a higher risk of osteoporosis (P ¼ 0.02). Regression analysis showed that age over 40 years, chronic active disease, and previous colonic resections were independently associated with the risk of developing MBD. Conclusions: The prevalence of MBD was significantly higher in CD patients. Besides the usual risk factors, we observed that factors related to chronic active and long-lasting disease increased the risk of MBD.

Familial amyloid polyneuropathy (FAP): clinical features, pathophysiology and treatment

In the literature, concepts of “polyneuropathy”, “peripheral neuropathy” and “neuropathy” are often mistakenly used as synonyms. Polyneuropathy is a specific term that refers to a relatively homogenous process that affects multiple peripheral nerves. Most of these tend to present as symmetric polyneuropathies that first manifest in the distal portions of the affected nerves. Many of these distal symmetric polyneuropathies are due to toxic-metabolic causes such as alcohol abuse and diabetes mellitus. Other distal symmetric polyneuropathies may result from an overproduction of substances that result in nerve pathology such as is observed in anti-MAG neuropathy and monoclonal gammopathy of undetermined significance. Other “overproduction” disorders are hereditary such as noted in the Portuguese type of familial amyloid polyneuropathy (FAP). FAP is a manifestation of a group of hereditary amyloidoses; an autosomal dominant, multisystemic disorder wherein the mutant amyloid precursor, transthyretin, is produced in excess primarily by the liver. The liver accounts for approximately 98% of all transthyretin production. FAP is confirmed by detecting a transthyretin variant with a methionine for valine substitution at position 30 [TTR (Met30)]. Familial Amyloidotic Polyneuropathy (FAP) – Portuguese type was first described by a Portuguese neurologist, Corino de Andrade in 1939 and published in 1951. Most persons with this disorder are descended from Portuguese sailors who sired offspring in various locations, primarily in Sweden, Japan and Mallorca. Their descendants emigrated worldwide such that this disorder has been reported in other countries as well. More than 2000 symptomatic cases have been reported in Portugal. FAP progresses rapidly with an average time course from symptom onset to multi-organ involvement and death between ten and twenty years. Treatments directed at removing this aberrant protein such as plasmapheresis and immunoadsorption proved to be unsuccessful. Liver transplantation has been the only effective solution as evidenced by almost 2000 liver transplants performed worldwide. A therapy for FAP with a novel agent, “Tafamidis” has shown some promise in ongoing phase III clinical trials. It is well recognized that regular physical activity of moderate intensity has a positive effect on physical fitness as gauged by body composition, aerobic capacity, muscular strength and endurance and flexibility. Physical fitness has been reported to result in the reduction of symptoms and lesser impairment when performing activities of daily living. Exercise has been advocated as part of a comprehensive approach to the treatment of chronic diseases. Therefore, this chapter concludes with a discussion of the role of exercise training on FAP.

Development of TNBS-induced colitis: animal model to test new pharmacological approaches

IBD is a gastro-intestinal disorder marked with chronic inflammation of intestinal epithelium, damaging mucosal tissue and manifests into several intestinal and extra-intestinal symptoms. Currently used medical therapy is able to induce and maintain the patient in remission, however no modifies or reverses the underlying pathogenic mechanism. The research of other medical approaches is crucial to the treatment of IBD and, for this, it´s important to use animal models to mimic the characteristics of disease in real life. The aim of the study is to develop an animal model of TNBS-induced colitis to test new pharmacological approaches. TNBS was instilled intracolonic single dose as described by Morris et al. It was administered 2,5% TNBS in 50% ethanol through a catheter carefully inserted into the colon. Mice were kept in a Tredelenburg position to avoid reflux. On day 4 and 7, the animals were sacrificed by cervical dislocation. The induction was confirmed based on clinical symptoms/signs, ALP determination and histopathological analysis. At day 4, TNBS group presented a decreased body weight and an alteration of intestinal motility characterized by diarrhea, severe edema of the anus and moderate morbidity, while in the two control groups weren’t identified any alteration on the clinical symptoms/signs with an increase of the body weight. TNBS group presented the highest concentrations of ALP comparing with control groups. The histopathology analysis revealed severe necrosis of the mucosa with widespread necrosis of the intestinal glands. Severe hemorrhagic and purulent exsudates were observed in the submucosa, muscular and serosa. TNBS group presented clinical symptoms/signs and histopathological features compatible with a correct induction of UC. The peak of manifestations became maximal at day 4 after induction. This study allows concluding that it’s possible to develop a TNBS induced colitis 4 days after instillation.

Bisphenol A alters transcript levels of biomarker genes for major depressive disorder

Major depressive disorder is a moderately heritable disorder characterized by one or more major depressive episodes. Laboratory tests to suport MDD diagnosis are not available. Diagnosis and treatment are based on various signs and symptoms not always fitting into strict diagnostic categories. Research for biological markers of neuropsychiatric disorders has been a challenge.

A comprehensive high-throughput FTIR spectroscopy-based method for evaluating the transfection event: estimating the transfection efficiency and extracting associated metabolic responses

Reporter genes are routinely used in every laboratory for molecular and cellular biology for studying heterologous gene expression and general cellular biological mechanisms, such as transfection processes. Although well characterized and broadly implemented, reporter genes present serious limitations, either by involving time-consuming procedures or by presenting possible side effects on the expression of the heterologous gene or even in the general cellular metabolism. Fourier transform mid-infrared (FT-MIR) spectroscopy was evaluated to simultaneously analyze in a rapid (minutes) and high-throughput mode (using 96-wells microplates), the transfection efficiency, and the effect of the transfection process on the host cell biochemical composition and metabolism. Semi-adherent HEK and adherent AGS cell lines, transfected with the plasmid pVAX-GFP using Lipofectamine, were used as model systems. Good partial least squares (PLS) models were built to estimate the transfection efficiency, either considering each cell line independently (R 2 ≥ 0.92; RMSECV ≤ 2 %) or simultaneously considering both cell lines (R 2 = 0.90; RMSECV = 2 %). Additionally, the effect of the transfection process on the HEK cell biochemical and metabolic features could be evaluated directly from the FT-IR spectra. Due to the high sensitivity of the technique, it was also possible to discriminate the effect of the transfection process from the transfection reagent on KEK cells, e.g., by the analysis of spectral biomarkers and biochemical and metabolic features. The present results are far beyond what any reporter gene assay or other specific probe can offer for these purposes.