Barley ß-glucan accelerates wound healing by favoring migration versus proliferation of human dermal fibroblasts.

ß-Glucans are considered candidates for the medication in different human pathologies. In this work, we have purified ß-glucan from a selected barley line and tested their effects in primary human dermal fibroblasts. Unexpectedly, we have observed that this compound promoted a short-transitory proliferation arrest at 24 h after its addition on the medium. We have determined that this transitory arrest was dependent on the cell-cycle regulator protein Retinoblastoma. Moreover, dermal fibroblasts increase their migration capacities at 24 h after barley ß-glucan addition. Also, we have described that barley ß-glucan strongly reduced the ability of fibroblasts to attach and to spread on cell plates. Our data indicates that barley ß-glucan signal induces an early response in HDF cells favoring migration versus proliferation. This feature is consistent with our observation that the topical addition of our barley ß-glucan in vivo accelerates the wound closure in mouse skin.

Pancreas Transplantation at a Single Latin-American Center; Overall Results with Type 1 and Type 2 Diabetes Mellitus.

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) has become the treatment of choice for type 1 diabetes mellitus (T1DM) patients with chronic renal failure. Type 2 diabetes mellitus (T2DM), was once considered to be a contraindication for pancreas transplantation; however, it has been accepted as a new indication, under strict criteria. Although favorable results have increase the indication for T2DM in developed countries, there have been no reports of long-term results for this indication from Latin American centers. METHODS: From April 2008 to March 2016, patients receiving SPK or pancreas transplant alone (PTA) for T2DM were included and compared with T1DM recipients. Variables were compared between groups with the use of χ2 and t tests; Kaplan-Meier with log rank was used for patient and graft survivals; P < .05 was considered to be significant. RESULTS: A total of 45 SPK and 1 PTA were performed, 35 (76.1%) for T1DM and 11 (24.5%) for T2DM. Mean pre-transplantation C-peptide was significantly higher in the T2DM group (P = .01); HbA1c was higher in the T1DM group (P = .03). No differences were found in weight, body mass index, and pre-transplantation glycemia. Patient survivals for T1DM recipients were 88.2% and 84.8% at 1 and 5 years, respetively, versus 100% and 74.1% for T2DM recipients (P = .87). CONCLUSIONS: Our initial prospective experience in a single Latin American center showed that medium- and long-term outcomes for T1DM and T2DM individuals receiving pancreas transplants are similar, under strict selection criteria.

Right Extended Split Liver Transplantation Compared With Whole Liver Transplantation: Lessons Learned at a Single Center in Latin America-Results From a Match Case-Control Study.

BACKGROUND: Despite the progressively increasing gap between patients waiting for liver transplant under the Model for End-stage Liver Disease MELD system and the availability of deceased donor organs, the use of right extended split liver grafts (RESLG) has not been accepted by all centers. In this study, we compared the results obtained using RESLG vs a group of matched whole liver graft (WLG) recipients at a single center in Latin America. METHODS: A single-center retrospective review performed between August 2009 and December 2015. RESULTS: Fifteen RESLGs were implanted to recipients between 13 and 70 years of age; 80% were performed ex situ. The "biological MELD" score for the RESLG group was 17.5 ± 5.6, and it was 12.8 ± 4.5 for the WLG group (P = .01). Cold ischemia times were significantly longer in RESLG recipients compared with WLG recipients (528 minutes vs 420 minutes; P < .01). No significant differences were found in biliary (leak or strictures P = .40) and arterial complications (hepatic artery thrombosis, P = .06). RESLG patients benefited from a considerable reduction on their waiting time in list. The 1-, 3-, and 5-year patient survival rates were 93%, 93%, and 93% respectively, for RESLG recipients vs 100%, 95.7%, and 86.1%, respectively, for WLG recipients. The 1-, 3-, and 5-year graft survival rates were 79.4%, 79.4%, and 79.4% for RESLG recipients and 89.7%, 89.7%, and 89.7% for WLG recipients, respectively. No statistical differences were observed. CONCLUSION: RESLG allows expeditious transplantation for low MELD recipients. Its use should be expanded in Latin America and worldwide as a valid alternative to increase the donor pool as it has been used in other regions.

Case Report: Multivisceral Transplantation for an Extensive Cystic Lymphangioma of the Mesenteric Root.

BACKGROUND: We report the case of a 7-year-old girl with intestinal failure owing to a cystic lymphangioma compromising the root of the mesentery, not amenable to resection, leading to intestinal failure. Oncologic treatment was attempted to reduce tumor size with no response; therefore, she was listed for multivisceral transplantation. PROCEDURE: Resection of the tumor required resection of all abdominal organs with vascular inflow and outflow. A multivisceral graft (liver, stomach, duodenum-pancreas and spleen complex, small bowel, and right colon) was implanted. For vascular reconstruction, donor's superior vena cava was sutured to the recipient's suprahepatic veins in a common patch. For arterial inflow, an arterial conduit was placed directly to the infrarenal aorta, and sutured to an aortic patch of the graft. Cold ischemia time was 8:45 hours; warm ischemia time was 35 minutes. A double-layer gastrogastric anastomosis and piloroplasty was made; and the distal reconstruction was performed with ileocolic side-to-end anastomosis that allowed to perform of a Bishop-Koop ileostomy for endoscopic monitoring. OUTCOME: The patient recovered well after the procedure and was discharged 36 days after transplantation with intestinal sufficiency. To the best of our knowledge, this is the first report describing cystic lymphangioma as an indication for multivisceral transplantation.

Case Report: Spleen-preserving Multivisceral Transplant for Peutz-Jeghers Syndrome.

CASE REPORT: A 24-year-old man diagnosed with Peutz-Jeghers syndrome as a child underwent multiple surgeries owing to intussusception. Pretransplant workup showed >150 polyps along the gastrointestinal (GI) tract, some of them with high-grade dysplasia. Despite having intestinal sufficiency, a modified multivisceral transplantation was offered. PROCEDURE: An 18-year-old donor was procured using University of Wisconsin solution. The recipient's surgery started with a midline incision. Mobilization of the right colon and the root of the mesentery was done to isolate the superior mesenteric artery. The same maneuver was done with the left and sigmoid colon. The common bile duct was then isolated and transected at the cystic duct level. The abdominal portion of the esophagus and the proximal stomach were isolated and divided at the gastroesophageal junction. After that, the pancreas was mobilized, preserving the spleen with the splenic vessels. The distal GI tract was transacted at the level of the proximal rectum. For engraftment, an arterial conduit was placed in the infrarenal aorta and anastomosed to the graft's aortic patch. End-to-side portal reconstruction was made at the level of the portal vein, allowing performing a duct-to-duct biliary reconstruction over a 5-Fr T-tube. A hand-sewn gastrogastric anastomosis and piloroplasty were performed; the distal anastomosis was done with circular staplers. A gastrojejunostomy and a loop ileostomy were the final steps of the procedure. RESULTS: The patient stayed in intensive care for 2 days and enteral feeds were started on day 7. Currently, 23 months after transplant he is alive with an excellent quality of life.

Positive C4d in kidney transplantation biopsy: clinical impact.

BACKGROUND: Deposition of C4d in peritubular capillaries of renal graft is normally associated with the presence of antibody-mediated rejection. The clinical impact of its presence in patients with renal transplant in Colombia is uncertain, as well as the association in acute rejection and the response to the management and survival of the graft. The aim of this study was to determine the risk of having positive C4d in biopsies of patients with episodes of acute cellular rejection. METHODS: We retrospectively reviewed 226 biopsies of kidney transplantation, all of them with acute rejection and histopathological findings classified according to Banff criteria 2009 and performed between January 2005 and December 2012 for graft dysfunction. C4d staining was performed by immunohistochemistry. RESULTS: C4d staining was positive in 25 of 226 biopsies. Rejection time in patients with positive C4d was 15 months in average vs 8 months with negative C4d. CONCLUSIONS: With the use of a multivariate analysis, we found that the unique risk for C4d in our population was the positive panel reactive antibodies and elapsed time between transplant and the rejection (odds ratio: 2.12, P = .034) and that the other variables analyzed are not related to the expression of C4d.

Diverticulosis del yeyuno: complicaciones y manejo; reporte de caso y revisión de la literatura / Diverticulosis of the jejunum: complications and management

Se presenta el caso clínico de un paciente que cursó con una complicación secundaria a la presencia de múltiples divertículos de yeyuno, a la cual se le dio manejo quirúrgico, con un resultado satisfactorio.Los divertículos de yeyuno constituyen una alteración poco frecuente que se presenta, principalmente, en mayores de edad y, normalmente, no se sospecha entre los diagnósticos diferenciales del dolor abdominal, lo cual hace que se retarde el manejo adecuado. Este último es tan variado como las presentaciones clínicas de la enfermedad.Se hizo una revisión de la literatura con énfasis en la presentación, las complicaciones y las diferentes opciones de tratamiento, tanto para los pacientes que presentan sintomatología crónica como en los casos que se presentan de forma aguda. Se listan las herramientas que nos permitan tener un diagnóstico más certero para así ofrecer mejores oportunidades de manejo a nuestros pacientes.

A 74 year old male developed secondary complications due to the presence of multiple diverticula in the jejunum. The patient underwent surgical management with satisfactory outcome.Jejunal diverticula constitute an infrequent pathological condition occurring mainly in elderly patients, which is frequently overlooked in the differential diagnosis in persons presenting with abdominal pain. This results in delayed diagnosis and proper management. Management is as varied as the clinical presentation of this entity.We present a literature review, emphasizing clinical presentation, complications and the different treatment options, both in chronic and acute cases. The article describes the different tools that permit a more accurate diagnosis, thus offering the best opportunities for cure.

Differential regulation of expression of genes encoding uncoupling proteins 2 and 3 in brown adipose tissue during lactation in mice.

Thermogenic activity in brown adipose tissue (BAT) decreases during lactation; the down-regulation of the gene encoding uncoupling protein 1 (UCP1) is involved in this process. Our studies show that UCP2 mRNA expression does not change during the breeding cycle in mice. In contrast, UCP3 mRNA is down-regulated in lactation but it recovers after weaning, in parallel with UCP1 mRNA. This leads to a decrease in the content of UCP3 in BAT mitochondria during lactation. Lowering the energy-sparing necessities of lactating dams by decreasing litter size or feeding with a high-fat diet prevented the down-regulation of UCP1 mRNA and UCP3 mRNA. In most cases this resulted in a less marked decrease in UCP1 and UCP3 protein in BAT mitochondria owing to lactation. Fasting for 24 h caused a different response in UCP1 and UCP3 mRNA expression: it decreased UCP1 mRNA levels but had no effect on UCP3 mRNA abundance in virgin mice; it even increased UCP3 mRNA expression in lactating dams. These changes did not lead to modifications in UCP1 or UCP3 protein abundance. Whereas acute treatment with peroxisome-proliferator-activated receptor (PPAR)alpha and PPARgamma agonists increased UCP1 mRNA levels only in lactating dams, UCP3 mRNA expression was induced by both kinds of PPAR activator in lactating dams and by PPARalpha agonists in virgin mice. It is concluded that modifications of UCP2 mRNA levels are not part of the physiological adaptations taking place in BAT during lactation. In contrast, the down-regulation of UCP3 mRNA expression and mitochondrial UCP3 content is consistent with a role for the gene encoding UCP3 in the decrease in metabolic fuel oxidation and thermogenesis in BAT during lactation.

Peroxisome proliferator-activated receptor alpha activates transcription of the brown fat uncoupling protein-1 gene. A link between regulation of the thermogenic and lipid oxidation pathways in the brown fat cell.

High expression of the peroxisome proliferator-activated receptor alpha (PPARalpha) differentiates brown fat from white, and is related to its high capacity of lipid oxidation. We analyzed the effects of PPARalpha activation on expression of the brown fat-specific uncoupling protein-1 (ucp-1) gene. Activators of PPARalpha increased UCP-1 mRNA levels severalfold both in primary brown adipocytes and in brown fat in vivo. Transient transfection assays indicated that the (-4551)UCP1-CAT construct, containing the 5'-regulatory region of the rat ucp-1 gene, was activated by PPARalpha co-transfection in a dose-dependent manner and this activation was potentiated by Wy 14,643 and retinoid X receptor alpha. The coactivators CBP and PPARgamma-coactivator-1 (PGC-1), which is highly expressed in brown fat, also enhanced the PPARalpha-dependent regulation of the ucp-1 gene. Deletion and point-mutation mapping analysis indicated that the PPARalpha-responsive element was located in the upstream enhancer region of the ucp-1 gene. This -2485/-2458 element bound PPARalpha and PPARgamma from brown fat nuclei. Moreover, this element behaved as a promiscuous responsive site to either PPARalpha or PPARgamma activation, and we propose that it mediates ucp-1 gene up-regulation associated with adipogenic differentiation (via PPARgamma) or in coordination with gene expression for the fatty acid oxidation machinery required for active thermogenesis (via PPARalpha).

The human uncoupling protein-3 gene promoter requires MyoD and is induced by retinoic acid in muscle cells.

The uncoupling protein-3 (UCP-3) gene encodes for a mitochondrial protein expressed preferentially in skeletal muscle. UCP-3 mRNA is expressed in cultured muscle cells (C2C12 or L6E9) only when differentiated, at which stage UCP-3 is highly induced by all-trans retinoic acid (RA). Here we report that human UCP-3 promoter activity is dependent on MyoD and inducible by all trans-RA. The action of all trans-RA is increased by co-transfection with RA receptor (RAR). We have characterized the RA response element that controls the induction by RA in the 5' noncoding region of the UCP-3 gene. Deletion and point-mutation analysis of the hUCP-3 promoter led us to identify a direct-repeat element with one base-pair spacing (DR1) at position -71/-59 responsible for the induction by RA of the activity of the promoter. This DR1 element bound a nuclear protein complex from muscle cells that contain RAR and retinoid X receptor (RXR). In the absence of this element, the promoter became unresponsive to RA, but it was still dependent on MyoD. In conclusion, it has been established that UCP-3 gene promoter activity is dependent on MyoD, and the first regulatory pathway for UCP-3 gene promoter regulation has been recognized by identifying RA as a transcriptional activator of the gene.

Impaired expression of the uncoupling protein-3 gene in skeletal muscle during lactation: fibrates and troglitazone reverse lactation-induced downregulation of the uncoupling protein-3 gene.

The expression of uncoupling protein (UCP)-3 mRNA in skeletal muscle is dramatically reduced during lactation in mice. The reduction in UCP-3 mRNA levels lowers the amount of the UCP-3 protein in skeletal muscle mitochondria during lactation. Spontaneous or abrupt weaning reverses the downregulation of the UCP-3 mRNA but not the reduction in UCP-3 protein levels. In lactating and virgin mice, however, fasting increases UCP-3 mRNA levels. Changes in UCP-3 mRNA occur in parallel with modifications in the levels of free fatty acids, which are reduced in lactation and are upregulated due to weaning or fasting. Modifications in the energy nutritional stress of lactating dams achieved by manipulating litter sizes do not influence UCP-3 mRNA levels in skeletal muscle. Conversely, when mice are fed a high-fat diet after parturition, the downregulation of UCP-3 mRNA and UCP-3 protein levels due to lactation is partially reversed, as is the reduction in serum free fatty acid levels. Treatment of lactating mice with a single injection of bezafibrate, an activator of the peroxisome proliferator-activated receptor (PPAR), raises UCP-3 mRNA in skeletal muscle to levels similar to those in virgin mice. 4-chloro-6-[(2,3-xylidine)-pirimidinylthio] acetic acid (WY-14,643), a specific ligand of the PPAR-alpha subtype, causes the most dramatic increase in UCP-3 mRNA, whereas troglitazone, a specific activator of PPAR-gamma, also significantly increases UCP-3 mRNA abundance in skeletal muscle of lactating mice. However, in virgin mice, bezafibrate and WY-14,643 do not significantly affect UCP-3 mRNA expression, whereas troglitazone is at least as effective as it is in lactating dams. It is proposed that the UCP-3 gene is regulated in skeletal muscle during lactation in response to changes in circulating free fatty acids by mechanisms involving activation of PPARs. The impaired expression of the UCP-3 gene is consistent with the involvement of UCP-3 gene regulation in the reduction of the use of fatty acids as fuel by the skeletal muscle and in impaired adaptative thermogenesis, both of which are major metabolic adaptations that occur during lactation.