Novel pharmacological therapies for management of chronic constipation.

Chronic constipation is a common health problem that significantly affects the quality of life of patients and impacts in terms of costs; current treatments based on fiber and laxatives cause dissatisfaction to doctors and patients in more than half of the cases. New drugs are now available or in very advanced stages of research, with different and innovative mechanisms of action as prucalopride, lubiprostone, and linaclotide. Prucalopride an enterokinetic, is a selective high-affinity 5-hydroxytryptamine (5-HT)4 receptor agonist of serotonin that increases the peristaltic reflex and the colonic contractions; lubiprostone, a type 2 chlorine channel activator, or linaclotide, a guanylate cyclase-C agonist of enterocytes, both prosecretory agents, stimulate the secretion of fluid within the intestinal lumen. In general, these promising drugs have proven efficacy and safety as a specific therapeutic option in patients with chronic constipation. Yet the solution might not be sufficient for everybody and still without the ideal drug that might be useful in all cases, the pharmacological revolution for colonic motility disorders has arrived.

Hepatotoxicity associated with dietary energy supplements: use and abuse by young athletes.

 In recent years there has been a significant increase in the consumption of dietary energy supplements (DES) associated with the parallel advertising against obesity and favoring high physical performance. We present the case and outcome of a young patient who developed acute mixed liver injury (hepatocellular and cholestatic) after ingestion of various "over the counter" products to increase muscle mass and physical performance (NO Xplode®, creatine, L-carnitine, and Growth Factor ATN®). The diagnosis was based on the exclusion of other diseases and liver biopsy findings. The dietary supplement and herbal multivitamins industry is one with the highest growth rates in the market, with annual revenues amounting to billions and constantly lacking scientific or reproducible evidence about the efficacy and/or safety of the offered products. Furthermore, and contrary to popular belief, different forms of injury associated with these natural substances have been documented particularly in the liver, supporting the need of a more strict regulation.

Anatomical cardiac alterations in liver cirrhosis: an autopsy study.

BACKGROUND: It has been suggested that liver cirrhosis (LC), regardless of etiology, may be associated with anatomical cardiac alterations. OBJECTIVE: To describe the frequency and type of macroscopical anatomic cardiac abnormalities present in alcoholic and non-alcoholic cirrhotic patients in an autopsy series. MATERIAL AND METHODS: The autopsy records performed at our institution during a 12-year period (1990-2002) were reviewed. All cases with final diagnosis of LC were included, their demographic characteristics as well as cirrhosis etiology and macroscopic anatomical cardiac abnormalities (MACA) analyzed. Patients with any known history of heart disease prior to diagnosis of cirrhosis were excluded. RESULTS: A total of 1,176 autopsies were performed, of which 135 cases (11.5%) were patients with LC. Two patients with cardiac cirrhosis were excluded. Chronic alcohol abuse (29%) and chronic hepatitis due to hepatitis C virus (HCV) infection (20%) were the most common causes of cirrhosis. The etiology was not identified in 35% of the cases, even after exhaustive clinical, serological and/or radiological assessment. In the postmortem analysis, 43% of the cases were informed to have MACA (47% in the group of patients with alcoholic cirrhosis and 41% in other types of cirrhosis); this rate increased to 62% in patients with ascites. The most frequent alterations were cardiomegaly and left ventricular hypertrophy (LVH). CONCLUSION: The results confirm the high frequency of cardiac abnormalities in patients with cirrhosis, regardless of cirrhosis etiology.

Hepatotoxicity from ingestion of wild mushrooms of the genus Amanita section Phalloideae collected in Mexico City: two case reports.

We present two cases of acute liver injury resulting from consumption of wild mushrooms. The first case was a male who developed acute hepatitis after ingestion of diverse mushrooms including Amanita species. His clinical course was favorable with complete recovery of liver function. The second case was a male who developed acute liver failure (ALF) after ingestion of Amanita bisporigera. He required MARS therapy as a bridge to liver transplantation but transplantation was not performed because he succumbed to multiorgan failure. There are few trials demonstrating the efficacy of the different treatments for mushroom poisoning. These cases demonstrate that the consumption of wild mushrooms without proper knowledge of toxic species represents a serious and under recognized health problem.

Pneumocystosis in a patient with Crohn's disease treated with combination therapy with adalimumab.

Pneumocystis jirovecii pneumonia (PCP) is a potential complication of immunosuppression. Crohn's disease (CD) is an immune granulomatous disorder characterized by transmural inflammation that can affect any part of the gastrointestinal tract. Its treatment is based on steroids and immunosuppressants but in non-responders, biologic compounds such as anti-tumor necrosis factor alpha (TNF) antibodies have been used. Neutralization of TNF causes a decrease in the inflammatory response but increases susceptibility to opportunistic infections such as fungal infections. We report a young male with chronic diarrhea, fever and weight loss who was diagnosed with CD and began conventional treatment with immunosuppressants, but due to lack of response after several weeks, biologic therapy with adalimumab was initiated. Seven weeks later he developed persistent fever and upper respiratory symptoms. After chest CT, bronchoscopy and bronchial lavage, P. jirovecii was identified by silver staining and confirmed by immunofluorescence. To our knowledge this is the second case of pneumocystosis associated with the use of adalimumab in CD and the first reported Mexican case confirmed by microbiological and immunological studies in this setting.

Prucaloprida: enterocinético selectivo como una nueva alternativa en el tratamiento del estreñimiento crónico / Prucalopride: selective enterokinetic as a new alternative in the treatment of chronic constipation

El estreñimiento crónico es un problema de salud frecuente que afecta a todos los grupos de edad, genera pobre calidad de vida en quienes lo padecen, e impacta de manera negativa en los sistemas de salud de países desarrollados como en aquellos en vías de desarrollo. La definición de estreñimiento se basa en la objetividad de la frecuencia de las deposiciones como también en lo subjetivo de los síntomas asociados a este trastorno como son pujo, sensación de evacuación incompleta o heces duras. El tratamiento incluye modificaciones en el estilo de vida, ejercicio aeróbico, mayor ingesta de agua y fibra, laxantes y el uso de estimulantes de la motilidad o procinéticos. Una novedosa alternativa es prucaloprida, un enterocinético selectivo agonista de los receptores 5HT4 de serotonina, que incrementa el reflejo peristáltico y desencadena las contracciones musculares de alta amplitud sobre el intestino grueso promoviendo la deposición. La prucaloprida, ha demostrado ser eficaz y seguro en pacientes adultos y adultos mayores con estreñimiento crónico.

Chronic constipation is a common health problem that affects all ages, generates poor quality of life, and impacts negatively on the health systems of developed and developing countries. The definition of constipation is based on the objectivity of stool frequency as well as in the subjective symptoms associated with this disorder like straining, sensation of incomplete evacuation or hard stools. The treatment includes changes in lifestyle, aerobic exercise, increased intake of water and fiber, laxatives and the use of motility stimulants or prokinetics. A novel alternative is the enterokinetic prucalopride, a selective 5HT4 serotonin agonist, which increases the peristaltic reflex and triggers high amplitude muscle contractions of the colon promoting intestinal deposition. Prucalopride has proven efficacy and safety in adults including elderly patients with chronic constipation.