Endoscopic Treatment for Vesicoureteral Reflux in Recurrent Urinary Tract Infections in Kidney Transplant: Experience of One Center.

Vesicoureteral reflux (VUR) after renal transplantation in adult patients has been reported. In renal transplant recipients, symptomatic urinary tract infection can cause high morbidity despite improved immunosuppressive and antibiotic treatment. In our country there have been few reported cases about use of copolymer of dextranomer and hyaluronic acid (DX-HA) injection in a renal transplant. We present 3 cases of recurrent or complicated infections with evidence of high-grade VUR, which were treated with DX-HA. Only 1 case had a partial remission; however, there were no episodes of urinary tract infection in 12 months of follow-up. Suburethral injection is an endoscopic treatment modality with low morbidity in our country.

The chimerical genome of Isla del Coco feral pigs (Costa Rica), an isolated population since 1793 but with remarkable levels of diversity.

The history of domestic species and of their wild ancestors is not a simple one, and feral processes can clarify key aspects of this history, including the adaptive processes triggered by new environments. Here, we provide a comprehensive genomic study of Isla del Coco (Costa Rica) feral pigs, a unique population that was allegedly founded by two individuals and has remained isolated since 1793. Using SNP arrays and genome sequencing, we show that Cocos pigs are hybrids between Asian and European pigs, as are modern international pig breeds. This conclusively shows that, as early as the 18th century, British vessels were loading crossbred pigs in Great Britain and transporting them overseas. We find that the Y chromosome has Asian origin, which has not been reported in any international pig breed. Chinese haplotypes seem to have been transmitted independently between Cocos and other pig breeds, suggesting independent introgression events and a complex pattern of admixing. Although data are compatible with a founder population of N = 2, variability levels are as high in Cocos pigs as in international pig breeds (~1.9 SNPs/kb) and higher than in European wild boars or local breeds (~1.7 SNPs/kb). Nevertheless, we also report a 10-Mb region with a marked decrease in variability across all samples that contains four genes (CPE, H3F3C, SC4MOL and KHL2) previously identified as highly differentiated between wild and domestic pigs. This work therefore illustrates how feral population genomic studies can help to resolve the history of domestic species and associated admixture events.

Porcine colonization of the Americas: a 60k SNP story.

The pig, Sus scrofa, is a foreign species to the American continent. Although pigs originally introduced in the Americas should be related to those from the Iberian Peninsula and Canary islands, the phylogeny of current creole pigs that now populate the continent is likely to be very complex. Because of the extreme climates that America harbors, these populations also provide a unique example of a fast evolutionary phenomenon of adaptation. Here, we provide a genome wide study of these issues by genotyping, with a 60k SNP chip, 206 village pigs sampled across 14 countries and 183 pigs from outgroup breeds that are potential founders of the American populations, including wild boar, Iberian, international and Chinese breeds. Results show that American village pigs are primarily of European ancestry, although the observed genetic landscape is that of a complex conglomerate. There was no correlation between genetic and geographical distances, neither continent wide nor when analyzing specific areas. Most populations showed a clear admixed structure where the Iberian pig was not necessarily the main component, illustrating how international breeds, but also Chinese pigs, have contributed to extant genetic composition of American village pigs. We also observe that many genes related to the cardiovascular system show an increased differentiation between altiplano and genetically related pigs living near sea level.

Integrating Y-chromosome, mitochondrial, and autosomal data to analyze the origin of pig breeds.

We have investigated the origin of swine breeds through the joint analysis of mitochondrial, microsatellite, and Y-chromosome polymorphisms in a sample of pigs and wild boars with a worldwide distribution. Genetic differentiation between pigs and wild boars was remarkably weak, likely as a consequence of a sustained gene flow between both populations. The analysis of nuclear markers evidenced the existence of a close genetic relationship between Near Eastern and European wild boars making it difficult to infer their relative contributions to the gene pool of modern European breeds. Moreover, we have shown that European and Far Eastern pig populations have contributed maternal and paternal lineages to the foundation of African and South American breeds. Although West African pigs from Nigeria and Benin exclusively harbored European alleles, Far Eastern and European genetic signatures of similar intensity were detected in swine breeds from Eastern Africa. This region seems to have been a major point of entry of livestock species in the African continent as a result of the Indian Ocean trade. Finally, South American creole breeds had essentially a European ancestry although Asian Y-chromosome and mitochondrial haplotypes were found in a few Nicaraguan pigs. The existence of Spanish and Portuguese commercial routes linking Asia with America might have favored the introduction of Far Eastern breeds into this continent.

[Management of bleeding esophageal varices in public and private institutions in Chile]. / Diagnóstico y tratamiento de las várices esófago gástricas en Chile: Realidad nacional.

BACKGROUND: The better treatment modalities for bleeding esophageal varices have improved the prognosis of cirrhosis. AIM: To inquire about diagnostic and treatment modalities for esophageal bleeding in Chile. MATERIAL AND METHODS: An enquiry about diagnosis and treatment of esophageal bleeding was designed and electronically sent to public and private health institutions that could admit patients and were located in cities with more than 100,000 inhabitants. RESULTS: The enquiry was answered by 31 of 35 public and 17 of 19 private health institutions that were consulted. Emergency endoscopy was available in 6 of 27 public and in the 16 private institutions that had an emergency room. Rubber band was available in 16 public (52%) and in all private institutions. Cyanoacrylate injections were done in 10 public (32%) and 11 (65%) private institutions. No public institution installed transjugular intrahepatic portosystemic shunts, but 8 had occasional access to this technique. This procedure was done in 7 (41%) private institutions and all had access to it. Surgical treatment was feasible in 20 public (65%) and all private institutions. Primary prophylaxis was done in 18 public (58%) and 14 private (82%) institutions. Secondary prophylaxis was carried out in 26 public (84%) and 16 private (94%) institutions. CONCLUSIONS: Public health institutions have poor access to adequate diagnostic and treatment methods for esophageal bleeding. The primary and secondary prophylaxis of esophageal varices must be improved in both types of institutions.

Diagnóstico y tratamiento de las várices esófago gástricas en Chile: realidad nacional / Management of bleeding esophageal varices in public and private institutions in Chile

Background: The better treatment modalities for bleeding esophageal varices have improved the prognosis of cirrhosis. Aim: To inquire about diagnostic and treatment modalities for esophageal bleeding in Chile. Material and methods: An enquiry about diagnosis and treatment of esophageal bleeding was designed and electronically sent to public and private health institutions that could admit patients and were located in cides with more than 100,000 inhabitants. Results: The enquiry was answered by 31 of 35 public and 17 of 19 private health institutionis that were consulted. Emergency endoscopy was available in 6 of 27 public and in the 16 private institutionis that had an emergency room. Rubber band ligation was available in 16 public (52 percent) and in all private institutions. Cyanoacrylate injections were done in 10 public (32 percent) and 11 (65 percent) private institutions. No public institution installed transjugular intrahepatic portosystemic shunts, but 8 had occasional access to this technique. This procedure was done in 7 (41 percent) private institutions and all had access to it. Surgical treatment was feasible in 20 public (65 percent) and all private institutions. Primary prophylaxis was done in 18 public (58 percent) and 14 private (82 percent) institutions. Secondary prophylaxis was carried out in 26 public (84 percent) and 16 private (94 percent) institutions. Conclusions: Public health institutions have poor access to adequate diagnostic and treatment methods for esophageal bleeding. The primary and secondary prophylaxis of esophageal varices must be improved in both types of institutions.

Gene array analysis comparison between rat collagen-induced arthritis and human rheumatoid arthritis.

Collagen-induced arthritis (CIA) is an experimental arthritis model used to study the inflammatory processes in this disease and test potential therapeutics. In order to better characterize this model, we conducted the first comprehensive gene expression analysis of rat CIA. To evaluate how closely the rat model reflects human rheumatoid arthritis (RA), we also analysed gene expression in human RA, using genome-wide Affymetrix gene arrays. By applying multiple strategies, including comparison of the highest induced genes, expression of immunological-associated genes as well as Ingenuity Pathway Analysis (IPA), we were able to compare the two expression profiles. Among the highest induced genes in RA were several B-cell-associated genes, including immunoglobulins, B-cell markers such as CD20, and cytokines and chemokines that act on B cells such as TNFSF13b/BLyS and CXCL13, none of which was upregulated in CIA. The latter was instead characterized by the upregulation of genes expressed primarily in macrophages and dendritic cells. Of the 22 pathways identified as significant in both diseases by IPA, only three (IL6, chemokine signalling and antigen presentation) were present in both settings. We conclude that there are significant differences in the inflammatory mechanisms between human RA and rat CIA, and that genome-wide comparative gene expression analyses are useful tools to evaluate the relevance of animal models to human disease.

Selection in the making: a worldwide survey of haplotypic diversity around a causative mutation in porcine IGF2.

Domestic species allow us to study dramatic evolutionary changes at an accelerated rate due to the effectiveness of modern breeding techniques and the availability of breeds that have undergone distinct selection pressures. We present a worldwide survey of haplotype variability around a known causative mutation in porcine gene IGF2, which increases lean content. We genotyped 34 SNPs spanning 27 kb in 237 domestic pigs and 162 wild boars. Although the selective process had wiped out variability for at least 27 kb in the haplotypes carrying the mutation, there was no indication of an overall reduction in genetic variability of international vs. European local breeds; there was also no evidence of a reduction in variability caused by domestication. The haplotype structure and a plot of Tajima's D against the frequency of the causative mutation across breeds suggested a temporal pattern, where each breed corresponded to a different selective stage. This was observed comparing the haplotype neighbor-joining (NJ) trees of breeds that have undergone increasing selection pressures for leanness, e.g., European local breeds vs. Pietrain. These results anticipate that comparing current domestic breeds will decisively help to recover the genetic history of domestication and contemporary selective processes.

Water catalysis of a radical-molecule gas-phase reaction.

There has been considerable speculation about the role of water and water complexes in chemical gas-phase reactions, including the conjecture that water may act as a molecular catalyst through its ability to form hydrogen bonds. Here, we present kinetic studies in which the effect of water on the rate of the reaction between hydroxyl radicals and acetaldehyde has been measured directly in Laval nozzle expansions at low temperatures. An increasing enhancement of the reaction rate by added water was found with decreasing temperatures between 300 and 60 kelvin. Quantum chemical calculations and statistical rate theory support our conclusions that this observation is due to the reduction of an intrinsic reaction barrier caused by specific water aggregation. The results suggest that even single water molecules can act as catalysts in radical-molecule reactions.

Estudio Multicéntrico Centroamericano de Prevalencia de VIH/ITS y Comportamientos en Mujeres trabajadoras Comerciales del Sexo en Nicaragua (EMC) / I study Central American multicéntrico of Prevalencia of VIH/ITS and Behaviors in Commercial hard-working Women of the Sex in Nicaragua (EMC)

Presenta Estudio Multicentrico Centroamericano de Prevalencia de VIH/ITS y Comportamientos en Mujeres trabajadoras Comerciales del Sexo en Nicaragua (EMC. Se realizó en Managua, en los Centros de Salud de los Distrititos V, VI y III (Pedro Altamirano, Altagracia, Francisco Buitrago, Villas Venezuela; en los Puertos Marítimos de Corinto (SILAIS de Chinandega)y Bluefields (zona del Atlántico del país). El propósito del estudio es el fortalecimiento de los procesos de vigilancia epidemiológica, reforzando la capacidad local para obtener información válida, confiable y útil para el uso de los planificadores y tomadores de decisión en la implementación de estrategias eficaces en la prevención y control de las ITS/VIH, para las Mujeres trabajadoras del Sexo.

[Evaluation of the combination of psychosocial and pharmacological treatment in schizophrenic patients]. / Evaluación de la combianación de los tratamientos psicosocial y farmacológico en pacientes con esquizofrenia.

INTRODUCTION: The present treatment of schizophrenia should initially focus on bringing psychotic symptoms under control with the use of antipsychotic medication, but it also should include the psychosocial management of the illness, with the implementation of psychosocial treatment. The purpose of the present study is to describe the results of the comparison of two groups (experimental and control) of schizophrenic out-patients of The National Institute of Psychiatry Ramón de la Fuente in Mexico City. The experimental group received a combination of psychosocial and pharmacological treatment, while the control group received the pharmacological treatment alone. MATERIAL AND METHODS: A quasi-experimental design which included the two groups under study, experimental (n=25) and control group (n=22), was used. Both groups were assessed at the beginning and at the end of a one-year interventions considering variables such as: symptomatology, psychosocial functioning, global functioning, compliance with antipsychotic medication, relapses, rehospitalizations, therapeutic non-compliance, and adherence. RESULTS: Experimental patients, in comparison with control patients, improved their symptomatology, psychosocial functioning and global functioning considerably. They also presented the following: lower relapse frequency - 12% versus 31,8% of the controls as well as low rehospitalizacion rate - 0% versus 13.6% of the control patients, higher antipsychotic medication compliance (90%) when compared with patients under the control condition (80%), a reduced rate of therapeutic non-compliace (19.3%) and a higher degree of adherence (80.7%). On the other hand, control patients remained stabilized in their symptomatology, but did not improved in any of the psychosocial variables. CONCLUSIONS: The results show that the combination of psychosocial and pharmacological therapy is a more effective form of treatment in comparison with the other approach of pharmacotherapy alone. It may be concluded that there is sound evidence that indicates that combined psychosocial and pharmacological therapy combined report beneficial effects for the patients; therefore, it should be considered as an important therapeutic alternative in the treatment of schizophrenic patients.

Involvement of chemokine receptors in breast cancer metastasis.

Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1alpha and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells.

Increased apoptosis in acute puromycin aminonucleoside nephrosis.

Acute puromycin aminonucleoside nephrosis (PAN) in rats is characterized by heavy proteinuria associated with renal hypercellularity. The role of apoptosis in the resolution of renal hypercellularity was investigated in PAN. To study the participation of apoptosis in PAN, renal tissues were collected from nephrotic and control rats on weeks 1, 2 and 7 after a single puromycin aminonucleoside injection. Apoptosis was evaluated by light and electron microscopy. Apoptotic DNA fragmentation was detected by TUNEL staining. Renal tissues were also evaluated by the presence of leukocyte common antigen (LCA), ED1 (macrophages) and proliferating cell nuclear antigen (PCNA) with corresponding monoclonal antibodies. An increased number of apoptotic (TUNEL+) cells was observed in the glomerulus at week 1. Electron microscopy analysis showed glomerular apoptosis mainly in endothelial cells. In the interstitium and tubules, increased apoptosis was observed at weeks 1 and 2. Increased apoptosis was accompanied with increased LCA+, ED1+ and PCNA+ cells in the interstitium and with increased PCNA+ cells in tubules. There was a high significant correlation between the number of apoptotic cells and the number of interstitial LCA+, ED1+ and PCNA+ cells. Tubular PCNA expression was correlated with tubular apoptosis. We also observed significant correlation between glomerular, interstitial and tubular apoptosis with proteinuria during the nephrosis. Double staining analysis showed that about 13% of interstitial or tubular apoptotic cells were positive for PCNA. All these values returned to normal by week 7. These results indicate that apoptosis is involved in the repairing process of this disease model.

Identification of a novel chemokine (CCL28), which binds CCR10 (GPR2).

We report the identification and characterization of a novel CC chemokine designated CCL28 and its receptor CCR10, known previously as orphan G-protein-coupled receptor GPR2. Human and mouse CCL28 share 83% identity at the amino acid and 76% at the nucleic acid levels. We also identified the mouse homologues of CCL28 and of CCR10, which map to mouse chromosomes 13 and 11, respectively. CCL28 is expressed in a variety of human and mouse tissues, and it appears to be predominantly produced by epithelial cells. Both human and mouse CCL28 induce calcium mobilization in human and mouse CCR10-expressing transfectants. CCL28 desensitized the calcium mobilization induced in CCR10 transfectants by CCL27, indicating that these chemokines share this new chemokine receptor. In vitro, recombinant human CCL28 displays chemotactic activity for resting CD4 or CD8 T cells.

Cutting edge: the orphan chemokine receptor G protein-coupled receptor-2 (GPR-2, CCR10) binds the skin-associated chemokine CCL27 (CTACK/ALP/ILC).

We recently reported the identification of a chemokine (CTACK), which has been renamed CCL27 according to a new systematic chemokine nomenclature. We report that CCL27 binds the previously orphan chemokine receptor GPR-2, as detected by calcium flux and chemotactic responses of GPR-2 transfectants. We renamed this receptor CCR10. Because of the skin-associated expression pattern of CCL27, we focused on the expression of CCL27 and CCR10 in normal skin compared with inflammatory and autoimmune skin diseases. CCL27 is constitutively produced by keratinocytes but can also be induced upon stimulation with TNF-alpha and IL-1beta. CCR10 is not expressed by keratinocytes and is instead expressed by melanocytes, dermal fibroblasts, and dermal microvascular endothelial cells. CCR10 was also detected in T cells as well as in skin-derived Langerhans cells. Taken together, these observations suggest a role for this novel ligand/receptor pair in both skin homeostasis as well as a potential role in inflammatory responses.

The reduced expression of 6Ckine in the plt mouse results from the deletion of one of two 6Ckine genes.

6Ckine is an unusual chemokine capable of attracting naive T lymphocytes in vitro. It has been recently reported that lack of 6Ckine expression in lymphoid organs is a prominent characteristic of mice homozygous for the paucity of lymph node T cell (plt) mutation. These mice show reduced numbers of T cells in lymph nodes, Peyer's patches, and the white pulp of the spleen. The genetic reason for the lack of 6Ckine expression in the plt mouse, however, has remained unknown. Here we demonstrate that mouse 6Ckine is encoded by two genes, one of which is expressed in lymphoid organs and is deleted in plt mice. A second 6Ckine gene is intact and expressed in the plt mouse.

Depletion of eosinophils in mice through the use of antibodies specific for C-C chemokine receptor 3 (CCR3).

We have generated rat monoclonal antibodies specific for the mouse eotaxin receptor, C-C chemokine receptor 3 (CCR3). Several anti-CCR3 mAbs proved to be useful for in vivo depletion of CCR3-expressing cells and immunofluorescent staining. In vivo CCR3 mAbs of the IgG2b isotype substantially depleted blood eosinophil levels in Nippostrongyus brasiliensis-infected mice. Repeated anti-CCR3 mAb treatment in these mice significantly reduced tissue eosinophilia in the lung tissue and bronchoalveolar lavage fluid. Flow cytometry revealed that mCCR3 was expressed on eosinophils but not on stem cells, dendritic cells, or cells from the thymus, lymph node, or spleen of normal mice. Unlike human Th2 cells, mouse Th2 cells did not express detectable levels of CCR3 nor did they give a measurable response to eotaxin. None of the mAbs were antagonists or agonists of CCR3 calcium mobilization. To our knowledge, the antibodies described here are the first mAbs reported to be specific for mouse eosinophils and to be readily applicable for the detection, isolation, and in vivo depletion of eosinophils.

Regulation of human lung fibroblast C1q-receptors by transforming growth factor-beta and tumor necrosis factor-alpha.

Transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) are two polypeptide mediators which are believed to play a role in the evolution of idiopathic pulmonary fibrosis (IPF). We have evaluated the effect of these two substances on the expression of receptors for collagen (cC1q-R) and globular (gC1q-R) domains of C1q and on type I collagen in human lung fibroblasts. Two fibroblast subpopulations differing in C1q receptor expression were obtained by culturing human lung explants in medium containing fresh human serum and heated plasma-derived serum and separating them based on C1q binding [Narayanan, Lurton and Raghu: Am J Resp Cell Mol Biol. 1998; 17:84]. The cells, referred to as HH and NL cells, respectively, were exposed to TGF-beta and TNF-alpha in serum-free conditions. The levels of mRNA were assessed by in situ hybridization and Northern analysis, and protein levels compared after SDS-polyacrylamide gel electrophoresis and Western blotting. NL cells exposed to TGF-beta and TNF-alpha contained 1.4 and 1.6 times as much cC1q-R mRNA, respectively, whereas in HH cells cC1q-R mRNA increased 2.0- and 2.4-fold. The gC1q-R mRNA levels increased to a lesser extent in both cells. These increases were not reflected in protein levels of CC1q-R and gC1q-R, which were similar to or less than controls. Both TGF-beta and TNF-alpha also increased procollagen [I] mRNA levels in both cells. Overall, TNF-alpha caused a greater increase and the degree of response by HH fibroblasts to both TGF-beta and TNF-alpha was higher than NL cells. These results indicated that TGF-beta and TNF-alpha upregulate the mRNA levels for cC1q-R and collagen and that they do not affect gC1q-R mRNA levels significantly. They also indicated different subsets of human lung fibroblasts respond differently to inflammatory mediators.