Glucagon-like peptide 2 enhances maltase-glucoamylase and sucrase-isomaltase gene expression and activity in parenterally fed premature neonatal piglets

Exogenous glucagon-like peptide 2 (GLP-2) mimics the stimulatory effect of enteral nutrition on intestinal mucosal growth in preterm neonatal pigs. Little is known about its effects on small intestinal function. In this study, we investigated whether the trophic actions of GLP-2 and enteral nutrition are paralleled by effects on small intestinal function. Cesarean-delivered piglets (92% of gestation) were given either a parenteral nutrient infusion [total parenteral nutrition (TPN), n = 7], TPN + human GLP-2 (25 nmol/kg/d, n = 8), or enteral nutrition (ENT, n = 6) for 6 d. Gene expression (mRNA) and activities of lactase phlorizin hydrolase (LPH), maltase-glucoamylase (MGA), sucrase-isomaltase (SI), aminopeptidase N (ApN), and A (ApA) and dipeptidyl peptidase IV (DPP IV) were measured. Both GLP-2 and enteral nutrition increased mucosal weight (+30-40%, p < 0.05) relative to TPN. GLP-2 stimulated jejunal MGA and SI mRNA abundance and activity levels but did not change LPH in parenterally fed pigs (p < 0.05). Enteral nutrition decreased jejunal LPH and MGA mRNA abundance and activity and increased ileal ApN, ApA, and DPP IV activities relative to TPN (p < 0.05). We conclude that GLP-2 and enteral nutrition exert different effects on intestinal enzyme function despite similar effects on intestinal growth. In addition, the effects of GLP-2 on intestinal function in these parenterally fed, premature neonatal pigs differed from those previously reported for similarly fed term neonates.     

Effect of prolonged hyperdynamic endotoxemia on jejunal motility in fasted and enterally fed pigs

OBJECTIVE: To determine the effects of hyperdynamic endotoxemia on the motility of the small intestine. SUMMARY BACKGROUND DATA: Motility disorders of the gastrointestinal tract are a common complication of sepsis. It has been suggested that gram-negative endotoxin plays a role in the pathogenesis of the accompanying diarrhea frequently observed. METHODS: Pigs were infused with lipopolysaccharide for a 24-hour period. During this fasting period jejunal motility was measured using ambulatory manometry. One and 4 days after cessation of endotoxin, pigs were enterally fed, and again motility was recorded. RESULTS: Hyperdynamic endotoxemia was achieved in this model. Manometric pressure recordings revealed that endotoxin infusion accelerated the migrating motor complex (MMC) migration along the jejunum. Also, a simultaneous increase in MMC cycling frequency was observed in the endotoxin-treated group. Elevated MMC migration velocity and cycling frequency were maintained the following day after endotoxin during feeding and returned to basal values 4 days after endotoxin. CONCLUSIONS: A small dose of continuously infused endotoxin significantly provokes jejunal motility disturbances that may contribute to diarrhea.     

Endoscopic mitral valve repair: feasible,reproducible, and durable

OBJECTIVE: We sought to document the feasibility, safety, and effectiveness of performing mitral valve repair using a totally endoscopic approach. METHODS: Between February 1997 and October 1, 2001, 187 patients underwent totally endoscopic mitral valve repair at our institution. The mean age was 60.7 +/- 13.1 years, and 62% were male. Median preoperative functional class and degree of mitral regurgitation were II and 4, respectively. Data collection included an institutional protocol assessing procedure-related pain, cosmesis, and functional recovery. Statistical analysis included Kaplan-Meier and Cox regression methods. Mean follow-up was 19 +/- 15.2 months and was 100% complete. RESULTS: Associated atrial procedures were performed in 9.1% (n = 17) of the patients. Two patients required intraoperative conversion to sternotomy. Thoracoscopic re-evaluation for suspected bleeding (n = 19) was part of our aggressive postoperative management. One patient required sternotomy for control of bleeding. Hospital mortality included 1 (0.5%) patient and was not technology related. There were 1 early and 6 late reoperations, 4 of which were due to endocarditis. No risk factors for repair failure could be detected. Freedom from mitral valve reoperation at 4 years was 93.3% +/- 2.6%. The median degree of mitral regurgitation at follow-up was 0. Ninety-three percent of the patients were highly satisfied with either no or mild postoperative pain, and 98.4% believed they had an aesthetically pleasing scar. CONCLUSIONS: Totally endoscopic mitral valve repair can be done safely with excellent results and a high degree of patient satisfaction. It is now our exclusive approach for isolated atrioventricular valve disease.     

Therapeutic options for Huntington's disease

Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder. The genetic defect lies in the expansion of a CAG repeat on chromosome 4 and neuropathologically it is characterized by neuronal loss in the striatum. Clinical signs are chorea, impaired voluntary movement, behavioral changes and dementia. Present therapies are limited to these symptoms without any influence on the course of the disease, whereas current pharmacological developments mainly focus on delaying disease progression. This review discusses the present symptomatic treatments and focuses on recent developments of new therapeutic approaches for HD.     

Mechanisms and treatment of postoperative ileus

OBJECTIVE: To review the pathogenesis and treatment of postoperative ileus. DATA SOURCES: Data collected for this review were identified from a MEDLINE database search of the English-language literature. The exact indexing terms were "postoperative ileus," "treatment," "etiology," and "pathophysiology." Previous review articles and pertinent references from those articles were also used. STUDY SELECTION: All relevant studies were included. Only articles that were case presentations or that mentioned postoperative ileus in passing were excluded. DATA SYNTHESIS: The pathogenesis of postoperative ileus is complex, with multiple factors contributing either simultaneously or at various times during the development of this entity. These factors include inhibitory effects of sympathetic input; release of hormones, neurotransmitters, and other mediators; an inflammatory reaction; and the effects of anesthetics and analgesics. Numerous treatments have been used to alleviate postoperative ileus without much success. CONCLUSIONS: The etiology of postoperative ileus can best be described as multifactorial. A multimodality treatment approach should include limiting the administration of agents known to contribute to postoperative ileus (narcotics), using thoracic epidurals with local anesthetics when possible, and selectively applying nasogastric decompression.     

Psychiatric comorbidity, health, and function in epilepsy

Epilepsy is a chronic condition that has complex effects on social, vocational, and psychological function. Several psychiatric disorders have been shown to have increased prevalence in persons with epilepsy compared to the general population. Depression appears to be the most common psychiatric comorbidity, but anxiety and other diagnoses have not been extensively investigated. Several studies have found that depression or psychological distress may be the strongest predictors of health-related quality of life, even including seizure frequency and severity, employment, or driving status. Despite the high prevalence and adverse effects of comorbid psychiatric disorders in epilepsy, very little is known about optimal treatment strategies, or even the efficacy of standard treatments. Further research is needed to increase understanding of the mechanisms of psychiatric illness in epilepsy, the effects of depression and anxiety on long-term clinical outcomes, and the most effective treatments.     

Disruption of B-cell homeostatic control mediated by the BLV-Tax oncoprotein: association with the upregulation of Bcl-2 and signaling through NF-kappaB

Transactivating proteins associated with complex onco-retroviruses including human T-cell leukemia virus-1 (HTLV-1) and bovine leukemia virus (BLV) mediate transformation using poorly understood mechanisms. To gain insight into the processes that govern tumor onset and progression, we have examined the impact of BLV-Tax expression on ovine B-cells, the targets of BLV in experimentally infected sheep, using B-cell clones that are dependent on CD154 and gammac-common cytokines. Tax was capable of mediating progression of B-cells from cytokine dependence to cytokine independence, indicating that the transactivator can over-ride signaling pathways typically controlled by cytokine receptor activation in B-cells. When examined in the presence of both CD154 and interleukin-4, Tax had a clear supportive role on B-cell growth, with an impact on B-cell proliferation, cell cycle phase distribution, and survival. Apoptotic B-cell death mediated by growth factor withdrawal, physical insult, and NF-kappaB inhibition was dramatically reduced in the presence of Tax. Furthermore, the expression of Tax was associated with higher Bcl-2 protein levels, providing rationale for the rescue signals mediated by the transactivator. Finally, Tax expression in B-cells led to a dramatic increase of nuclear RelB/p50 and p50/p50 NF-kappaB dimers, indicating that cellular signaling through NF-kappaB is a major contributory mechanism in the disruption of B-cell homeostasis. Although Tax is involved in aspects of pathogenesis that are unique to complex retroviruses, the viral strategies associated with this transactivating oncoprotein may have wide-ranging effects that are relevant to other B-cell malignancies.     

Differential involvement of the hMRE11/hRAD50/NBS1 complex,BRCA1 and MLH1 in NF-kappaB activation by camptothecin and X-ray

Camptothecin (CPT) and X-ray (XR) generate double-strand breaks (DSB) that can be processed by homologous or nonhomologous recombination. We studied the participation of proteins involved in recombination pathways and cell cycle control in the signal transduction between DNA damage and NF-kappaB. Cells harbouring mutated NBS, hMRE11, BRCA1 or MLH1 were analysed. NBS- and hMRE11-deficient cells present a classical kinetic of NF-kappaB induction after camptothecin treatment. When DSB are generated by XR, NBS-deficient cells exhibit a delayed and strongly reduced level of NF-kappaB induction, whereas the hMRE11 mutated cells do not induce NF-kappaB at all. This indicates an important role of the hMRE11/hRAD50/NBS complex in the signal transduction initiated by XR. In HCC1937 cells that express a truncated version of BRCA1, XR induces a very rapid and transient NF-kappaB activation, whereas CPT leads to a delayed activation suggesting that BRCA1 modulates the transduction pathways in different manners after these two stresses. Finally, we found that a proficient MMR pathway is essential to the NF-kappaB activation after both CPT and XR. These results indicate that DSB originating from XR or CPT do not induce NF-kappaB in a unique way. MMR participates in both cascades, whereas the hMRE11/hRAD50/NBS trimer is specifically involved in the response elicited by XR.