Trastornos funcionales y motores digestivos

This article discusses the most interesting studies on functional and motility gastrointestinal disorders presented in Digestive Diseases Week (DDW) in 2013. New data were reported on the clinical importance of functional gastrointestinal disorders (FGID) and on how they can produce numerous disturbances such as inflammatory bowel disease. These disturbances are associated with somatic functional disease and particularly with fatigue. In addition, new data have emerged on the physiopathology of these disorders, with some studies reporting that environmental factors and events in early infancy can favor their development. Data were also presented on how bile acids can increase susceptibility to diarrhea in patients with irritable bowel syndrome (IBS) and on how the type of food intake can favor the development of symptoms. More data are available on the presence of underlying celiac disease in patients with IBS, which should prompt us to investigate this disease in our patients. Likewise, indiscriminate application of a gluten-free diet in patients with IBS has been shown not to produce a clear improvement. Regarding the physiopathology of functional dyspepsia (FD), results have been presented on how psychological factors can modify gastric accommodation and how this is in turn related to visceral hypersensitivity and gastric emptying. Regarding therapy, mirtazapine can improve symptoms and lead to weight gain in patients with severe FD and substantial weight loss. Results were presented on new drugs for IBS such as ibodutant and on old drugs with new applications such as mesalazine and ebastine. The antinociceptive effect of linaclotide is now better understood and a meta-analysis has shown its effectiveness in IBS with constipation as the main symptom. In patients with constipation, pelvic floor dysynergy can be diagnosed by a simple clinical interview and rectal touch. More data are available on the efficacy of prucalopride (which has been shown to accelerate colon transit time) and data were provided on plecanatide, a potential new drug that could be useful in constipation. Finally, results were presented on the use of botulinum toxin injection in patients with spastic motility disorders of the esophagus. Also worthy of mention is a study confirming a higher frequency of esophageal cancer patients with achalasia who receive treatment.     

Dose-dependent antiinflammatory effect of ursodeoxycholic acid in experimental colitis

The denomination of inflammatory bowel disease comprises a group of chronic inflammatory diseases of the digestive tract, ulcerative colitis and Crohn's disease being the most important conditions. Bile acids may play a role both in etiology and pharmacology of this disease. Thus, although deoxycholic acid is regarded as a proinflammatory agent ursodeoxycholic acid, which is currently being used to treat certain types of cholestasis and primary biliary cirrhosis, because of their choleretic, cytoprotective and immunomodulatory effects, it has been reported to exert an anti-inflammatory activity. We aim to confirm and characterize the intestinal antiinflammatory activity of ursodeoxycholic acid. The experimental model trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats has been used. Animal status was characterized by a number of macroscopic and biochemical parameters. Oral administration of ursodeoxycholic acid was able to ameliorate experimental colonic inflammation. This occurred only at a relatively high dose (50 mg/kg day), whereas ursodeoxycholic acid was without significant effect at doses of 10 and 25 mg/kg day. The therapeutic effect was evidenced, among others, by a higher body weight recovery, a diminished affected to total mucosal area and lower alkaline phosphatase activity in treated vs. control (TNBS treated) animals. These results indicate that, at the appropriate dose, ursodeoxycholic acid is a potentially useful drug to reduce intestinal inflammation and could be envisaged to be incorporated in the treatment of inflammatory bowel diseases.     

Comparison of intravenous dexketoprofen and dipyrone in acute renal colic

Objective

The aim of this study was to assess the efficacy and safety of a single intravenous (i.v.) bolus of dexketoprofen trometamol compared with an i.v. infusion of dipyrone in patients with moderate to severe pain due to renal colic.

Methods

A total of 308 patients with renal colic and visual analog scale (VAS) score ≥40 mm participated in a multicenter, randomized, double blind, double-dummy, parallel, and active-controlled study and were randomized to dexketoprofen 25 mg (n?=?101), dexketoprofen 50 mg (n?=?104), and dipyrone 2 g (n?=?103).

Results

Mean [± standard deviation (SD)] total pain relief (TOTPAR) scores were similar in the dexketoprofen 50 mg (15.3?±?8.6) and dipyrone (15.5?±?8.6) and slighly higher than in dexketoprofen 25 mg (13.5?±?8.6), although significant differences were not achieved. In the same way, patients in the dexketoprofen 50 mg and dipyrone groups showed higher scores in the sum of pain intensity differences (SPID) and the sum of analogue pain intensity differences (SAPID) than patients in the dexketoprofen 25 mg group, reaching statistical significance in comparison with dexketoprofen 25 mg and dipyrone for SPID and SAPID (p?p?Conclusions Dexketoprofen 50 mg administered as a single i.v. bolus was effective for the relief of moderate to severe pain in patients with renal colic, with a good safety profile and efficacy similar to i.v. dipyrone 2 g. Dexketoprofen produced analgesia that was faster in onset.     

Reduction in energy efficiency induced by expression of the uncoupling protein, UCP1, in mouse liver mitochondria

Uncoupling Protein 1 (UCP1) is an inner mitochondrial membrane protein, uniquely expressed in brown adipocytes, which uncouples the mitochondrial respiration impairing ATP production and energy efficiency. The aim of the present study was to express UCP1 in liver mitochondria using a non-viral system in order to affect energy utilization. The effect of ectopic protein expression on liver energy metabolism, which was evaluated 42 h after DNA transfer, showed that mitochondria expressing UCP1 presented decreased ATP production, lasted more time in membrane potential state 3, and consumed more molecular oxygen to produce the same amount of ATP than the control group. In summary, the successful functionality of the mitochondrial protein, UCP1, after hydrodynamic delivery is a novel and significant finding. This approach could be useful to ectopically express mitochondrial proteins and, in this particular case, to manage metabolic disorders related to energy efficiency and expenditure, such as obesity.     

Weight gain induced by an isocaloric pair-fed high fat diet: A nutriepigenetic study on FASN and NDUFB6 gene promoters

Experimental studies have demonstrated that dietary macronutrient distribution plays an important role in insulin regulation, a risk factor associated to obesity, diabetes and other metabolic disorders. To assess whether the macronutrient composition of the diet could be related to obesity onset by affecting the epigenetic regulation of gene expression, we investigated in rats the metabolic effects of two pair-fed isocaloric diets: control (rich in carbohydrates) and high fat diet (rich in fat; HFD). Compared to controls, HFD induced higher weight gain and adiposity and impaired glucose tolerance, which was accompanied by a slight increase in adiponectin levels and liver steatosis. Epididymal adipose tissue expression of the fatty acid synthase (FASN) gene and NADH dehydrogenase (ubiquinone) 1β-subcomplex 6 (NDUFB6) were significantly reduced in HFD group. These variations in mRNA levels were accompanied by changes in the methylation patterns of several CpG islands located in the promoter region of these genes. However, no correlations were found between gene expression and the methylation status. These results suggest that high fat intake produces overweighted rats independently of total energy intake. These diets could also induce some epigenetic changes in the promoters of key genes that could influence gene expression and may be behind metabolic alterations.     

Uncertainty in visual processes predicts geometrical optical illusions

It is proposed in this paper that many geometrical optical illusions, as well as illusory patterns due to motion signals in line drawings, are due to the statistics of visual computations. The interpretation of image patterns is preceded by a step where image features such as lines, intersections of lines, or local image movement must be derived. However, there are many sources of noise or uncertainty in the formation and processing of images, and they cause problems in the estimation of these features; in particular, they cause bias. As a result, the locations of features are perceived erroneously and the appearance of the patterns is altered. The bias occurs with any visual processing of line features; under average conditions it is not large enough to be noticeable, but illusory patterns are such that the bias is highly pronounced. Thus, the broader message of this paper is that there is a general uncertainty principle which governs the workings of vision systems, and optical illusions are an artifact of this principle.     

Genetic manipulation in nutrition, metabolism, and obesity research

We summarize the current standard methods for overexpressing, inactivating, or manipulating genes, with special focus on nutritional and obesity research. These molecular biology procedures can be carried out with the maintenance of the genetic information to subsequent generations (transgenic technology) or devised to exclusively transfer the genetic material to a given target animal, which cannot be transmitted to the future progeny (gene therapy). On the other hand, the RNA interference (RNAi) approach allows for the creation of new experimental models by transient ablation of gene expression by degrading specific mRNA, which can be applied to assess different biological functions and mechanisms. The combination of these technologies contributes to the study of the function and regulation of different metabolism- and obesity-related genes as well as the identification of new pharmacologic targets for nutritional and therapeutic approaches.