Exocrine pancreas glutamate secretion help to sustain enterocyte nutritional needs under protein restriction.

Glutamine (Gln) is the most concentrated amino acid in blood and considered conditionally essential. Its requirement is increased during physiological stress, such as malnutrition or illness, despite its production by muscle and other organs. In the malnourished state, Gln has been suggested to have a trophic effect on the exocrine pancreas and small intestine. However, the Gln transport capacity, the functional relationship of these two organs, and the potential role of the Gln-glutamate (Glu) cycle are unknown. We observed that pancreatic acinar cells express lower levels of Glu than Gln transporters. Consistent with this expression pattern, the rate of Glu influx into acinar cells was approximately sixfold lower than that of Gln. During protein restriction, acinar cell glutaminase expression was increased and Gln accumulation was maintained. Moreover, Glu secretion by acinar cells into pancreatic juice and thus into the lumen of the small intestine was maintained. In the intestinal lumen, Glu absorption was preserved and Glu dehydrogenase expression was augmented, potentially providing the substrates for increasing energy production via the TCA cycle. Our findings suggest that one mechanism by which Gln exerts a positive effect on exocrine pancreas and small intestine involves the Gln metabolism in acinar cells and the secretion of Glu into the small intestine lumen. The exocrine pancreas acinar cells not only avidly accumulate Gln but metabolize Gln to generate energy and to synthesize Glu for secretion in the pancreatic juice. Secreted Glu is suggested to play an important role during malnourishment in sustaining small intestinal homeostasis. NEW & NOTEWORTHY Glutamine (Gln) has been suggested to have a trophic effect on exocrine pancreas and small intestine in malnourished states, but the mechanism is unknown. In this study, we suggest that this trophic effect derives from an interorgan relationship between exocrine pancreas and small intestine for Gln-glutamate (Glu) utilization involving the uptake and metabolism of Gln in acinar cells and secretion of Glu into the lumen of the small intestine.

Intestinal IMINO transporter SIT1 is not expressed in human newborns.

The expression of amino acid transporters in small intestine epithelia of human newborns has not been studied yet. It is further not known whether the maturation of imino acid (proline) transport is delayed as in the kidney proximal tubule. The possibility to obtain small intestinal tissue from patients undergoing surgery for jejunal or ileal atresia during their first days after birth was used to address these questions. As control, adult terminal ileum tissue was sampled during routine endoscopies. Gene expression of luminal imino and amino acid transporter SIT1 (SLC6A20) was approximately threefold lower in newborns versus adults. mRNA levels of all other luminal and basolateral amino acid transporters and accessory proteins tested were similar in newborn mucosa compared with adults. At the protein level, the major luminal neutral amino acid transporter B0AT1 (SLC6A19) and its accessory protein angiotensin-converting enzyme 2 were shown by immunofluorescence to be expressed similarly in newborns and in adults. SIT1 protein was not detectable in the small intestine of human newborns, in contrast to adults. The morphology of newborn intestinal mucosa proximal and distal to the obstruction was generally normal, but a decreased proliferation rate was visualized distally of the atresia by lower levels of the mitosis marker Ki-67. The mRNA level of the 13 tested amino acid transporters and accessory proteins was nonetheless similar, suggesting that the intestinal obstruction and interruption of amniotic fluid passage through the small intestinal lumen did not affect amino acid transporter expression. NEW & NOTEWORTHY System IMINO transporter SIT1 is not expressed in the small intestine of human newborns. This new finding resembles the situation in the proximal kidney tubule leading to iminoglycinuria. Lack of amniotic fluid passage in small intestinal atresia does not affect amino acid transporter expression distal to intestinal occlusion.

Aminoacidurias: Clinical and molecular aspects.

Inherited aminoacidurias are caused by defective amino-acid transport through renal (reabsorption) and in many cases also small intestinal epithelia (absorption). Recently, many of the genes causing this abnormal transport have been molecularly identified. In this review, we summarize the latest findings in the clinical and molecular aspects concerning the principal aminoacidurias, cystinuria, lysinuric protein intolerance, Hartnup disorder, iminoglycinuria, and dicarboxylic aminoaciduria. Signs, symptoms, diagnosis, treatment, causative or candidate genes, functional characterization of the encoded transporters, and animal models are discussed.

Oral administration of sodium selenite minimizes cisplatin toxicity on proximal tubules of rats.

Cisplatin (c-DDP) is a widely used antineoplastic drug whose main side effect is nephrotoxicity. Selenium, administered intravenously or intraperitoneally, has been shown to provided protection against c-DDP-induced nephrotoxicity in rats. In the present study, the protective effect of orally administered sodium selenite on c-DDP toxicity was further examined. Animals treated with c-DDP alone showed increased urinary volume, decreased creatinine clearance (GFR), and a rise in urinary N-acetyl-(beta-D-glucosaminidase) (NAG) isoenzyme B activity. When sodium selenite was given prior to c-DDP, rats showed less GFR decline, delayed urinary volume increases, and no urinary NAG isoenzyme B activity increment. It is suggested that a single oral dose of sodium selenite given prior to c-DDP administration, although not preventing deterioration of renal function, partially protects rats from early proximal tubular injury.

Lung transplantation for patients older than 65 years: is it a feasible option?

BACKGROUND: Advanced age has been a relative contraindication to lung transplantation. However, the exact age limit for this procedure has not yet been established. The aim of this work is to present our experience with this particular group. METHODS: This retrospective review included medical charts of patients who underwent lung transplantation at our institution from January 2004 to February 2009: namely, 112 cadaveric lung transplants with 12 patients (10.7%) >65 years old. RESULTS: There were 9 male patients and the overall mean age was 68 years (range 66-72). The indications were pulmonary fibrosis in 8 and emphysema in 4 cases. Four patients had mild coronary artery disease and 4 systemic hypertension. All of the procedures were unilateral and only 2 required extracorporeal circulation. Only 5 patients received blood product transfusions intraoperatively; the mean ischemic time was 222 minutes. Four patients developed primary graft dysfunction, the mean requirement for mechanical ventilation was 30 hours, and the mean intensive care unit stay, 11 days. Postoperative complications were respiratory infections (n = 8), catheter-related infection (n = 1), atrial fibrillation (n = 2). The mean hospital stay was 28 days and the 1-year survival was 75%. CONCLUSION: Lung transplantation is a feasible option for well-selected patients with end-stage pulmonary disease who are >65 years old. Our study reinforces the modern trend for unilateral procedures in this situation.

Lung transplantation for lymphangioleiomyomatosis: single-center Brazilian experience with no chylothorax.

BACKGROUND: Lymphangioleiomyomatosis (LAM), a rare cystic disease characterized by proliferation of smooth muscle cells in the lung interstitium, almost exclusively affects females in their reproductive years. Lung transplantation has been established as effective therapy for end-stage pulmonary LAM. METHODS: This retrospective study includes lung transplantation patients with LAM at a single institution between 1989 and 2009. RESULTS: During the study period we performed 300 lung transplantations, and in 10 cases the recipients had LAM. All patients were females with a mean age of 43.8 years. The mean time from the diagnosis to lung transplantation was 5 years. Seven patients had experienced previous pneumothoraces, five of whom were treated with pleurodesis. In all patients we performed a single-lung transplantation (left-sided = 9 and right-sided = 1). In three cases, the pleurodesis was on the same side as the transplantation, with great intraoperative bleeding in one subject (left pleurectomy). There was one early death due to infective endocarditis at posttransplant day 19. The median length of mechanical ventilation was 13 hours, while the mean hospital stay was 16.75 days. There was no case of chylothorax. Late complications included one case of native lung pneumothorax, one diaphragmatic hernia, one posttransplant lymphoproliferative disease, one respiratory sepsis, and one mycobacterial infection. The 1- and 3-year survival rates were 90% and 80%, respectively. CONCLUSION: Lung transplantation is a feasible therapeutic option for patients with LAM, despite previous ipsilateral pleurodesis. The left-sided predilection for our procedures may have been responsible for the absence of chylothorax in this series.

Recommendations for the use of extended criteria donors in lung transplantation.

Selection criteria for lung donation were based on initial experiences with lung transplantation without further studies to improve them, thereby guaranteeing the best use of donated organs. A definition of an extended criteria donor is therefore required to obtain more lungs to meet the demands of patients awaiting transplantation. Studies have been reviewed for the impact on survival and morbidity of age ranges, oxygen fraction, cause of death, smoking habits, x-ray findings, infection, hepatitis serology and non-heart-beating status, seeking to support physicians to make decisions regarding the use of marginal organs.

Multiple synchronous bronchial carcinoid tumors: report of a case.

Peripheral bronchial carcinoids are uncommon. Their presentation as synchronous tumors is rare and limited to anecdotal cases.We report the case of a 62-year-old female with the radiological finding of multiple bilateral nodular lesions. Bilateral sequential thoracotomies were performed and all three nodules were treated by sublobar resections. Pathological examination revealed all specimens to be carcinoid tumors and subsequent investigation confirmed the lung as the primary site. A review of previous cases of multiple carcinoids is presented and the particularities of their management are discussed.

Effect of oral selenium administration on cisplatin-induced nephrotoxicity in rats.

Cis -diamminedichloroplatinum(II) (CP), an important antineoplasic drug, shows remarkable toxicity to the kidney. Methods to reduce CP nephrotoxicity include the use of sodium selenite. The aim of the present study was to investigate the interaction between orally administered selenium and CP in the rat. After observing the effects of CP on body growth rate, urinary volume, serum creatinine, serum selenium levels, creatinine clearance, renal malondialdehyde, and glutathione levels, as well as on renal light microscopically visible lesions, the effects of the sodium selenite administration by gavage of 2 mg per kg of body wt. 24 h and 1 h prior to a single CP intraperitoneal injection of 5 mg per kg of body wt. followed by its daily administration for the 7 subsequent days on these parameters, were examined. CP increased renal malondialdehyde, renal glutathione, and serum creatinine and decreased creatinine clearance. Lipid peroxidation is one of the mechanisms by which CP induces renal damage. Selenium treatment decreased the effect of CP on serum creatinine, and renal malondialdehyde levels, but did not affect the other parameters with the exception of kidney necrosis which was also diminished by this treatment.

Quantitative shedding of two genotypes of Cryptosporidium parvum in California ground squirrels (Spermophilus beecheyi).

Sixteen percent of California ground squirrels (Spermophilus beecheyi) were found to be shedding an average of 53,875 Cryptosporidium parvum oocysts/g of feces. Male squirrels had a higher prevalence and higher intensity of shedding than did female squirrels. The majority of C. parvum isolates matched a bovine-murine genotype, with a few isolates resembling a porcine genotype. Higher intensities of shedding by males may enhance dissemination and genotypic mixing of this protozoa given males' proclivity to disperse to nonnatal colonies.