Killer-Cell Immunoglobulin-like Receptor Diversity in an Admixed South American Population.

Natural Killer (NK) cells are innate immune cells that mediate antiviral and antitumor responses. NK cell activation and induction of effector functions are tightly regulated by the integration of activating and inhibitory receptors such as killer immunoglobulin-like receptors (KIR). KIR genes are characterized by a high degree of diversity due to presence or absence, gene copy number and allelic polymorphism. The aim of this study was to establish the distribution of KIR genes and genotypes, to infer the most common haplotypes in an admixed Colombian population and to compare these KIR gene frequencies with some Central and South American populations and worldwide. A total of 161 individuals from Medellin, Colombia were included in the study. Genomic DNA was used for KIR and HLA genotyping. We analyzed only KIR gene-content (presence or absence) based on PCR-SSO. The KIR genotype, most common haplotypes and combinations of KIR and HLA ligands frequencies were estimated according to the presence or absence of KIR and HLA genes. Dendrograms, principal component (PC) analysis and Heatmap analysis based on genetic distance were constructed to compare KIR gene frequencies among Central and South American, worldwide and Amerindian populations. The 16 KIR genes analyzed were distributed in 37 different genotypes and the 7 most frequent KIR inferred haplotypes. Importantly, we found three new genotypes not previously reported in any other ethnic group. Our genetic distance, PC and Heatmap analysis revealed marked differences in the distribution of KIR gene frequencies in the Medellin population compared to worldwide populations. These differences occurred mainly in the activating KIR isoforms, which are more frequent in our population, particularly KIR3DS1. Finally, we observed unique structural patterns of genotypes, which evidences the potential diversity and variability of this gene family in our population, and the need for exhaustive genetic studies to expand our understanding of the KIR gene complex in Colombian populations.

High dose melphalan is an adequate preparative regimen for autologous hematopoietic stem cell transplantation in relapsed/refractory lymphoma.

INTRODUCTION: High-dose melphalan (HD-Mel) has been successfully employed in autografting patients with multiple myeloma. An advantage of this regimen is that the total dose of Mel can be delivered in a single day, being particularly useful when non-frozen hematopoietic stem cells are employed in the autograft. MATERIAL AND METHODS: All consecutive patients with R/R lymphomas, both HL and NHL studied and treated at two different centers were prospectively included in a study of ASCT employing a single dose of HD-Mel (200 mg/m2). A group of R/R HL or NHL autografted employing BEAM-like preparative regimens was constructed matched by diagnosis and age. The primary endpoint of the study was overall survival (OS), the secondary endpoint was event-free survival (EFS). RESULTS: Twenty-five R/R HL/NHL patients were prospectively accrued in the study. There were 8 (32%) females, 13 (52%) patients had at least 1 adverse effect: 7 (28%) developed mucositis, 5 (20%) neutropenic fever, and 6 (24%) grade IV nausea. In the HD-Mel group, median overall survival (OS) was not achieved and OS at 36 months was 71%, the transplant-related mortality being 0%. In the control group, median OS was not achieved and the 36-month OS was 76%, results not statistically significant (p 0.5). The EFS was also similar in both groups (p 0.5). CONCLUSION: HD-Mel alone is non-inferior to a BEAM-like regimen as a preparative regimen for autografting patients with R/R HL and NHL. The regimen is adequate to graft persons with non-frozen stem cells.

Antioxidant and toxicological evaluation of a Tamarindus indica L. leaf fluid extract.

In the scientific community, there is a growing interest in Tamarindus indica L. leaves, both as a valuable nutrient and as a functional food. This paper focuses on exploring its safety and antioxidant properties. A tamarind leaf fluid extract (TFE) wholly characterised was evaluated for its anti-DPPH activity (IC50 = 44.36 µg/mL) and its reducing power activity (IC50 = 60.87 µg/mL). TFE also exhibited a high ferrous ion-chelating capacity, with an estimated binding constant of 1.085 mol L(-1) while its influence over nitric oxide production in human leucocytes was irregular. At low concentrations, TFE stimulated NO output, but it significantly inhibited it when there was an increase in concentration. TFE was also classified as a non-toxic substance in two toxicity tests: the acute oral toxicity test and the oral mucous irritability test. Further toxicological assays are needed, although results so far suggest that TFE might become a functional dietary supplement.

Effect of Tamarindus indica L. leaves' fluid extract on human blood cells.

Tamarind leaves are edible; however, their saponin content could be toxic to human blood cells. In this article, the effect of tamarind leaf fluid extract (TFE) on human blood cells was evaluated by using several tests. Results revealed that TFE did not cause significant haemolysis on human red blood cells even at the lowest evaluated concentration (20 mg/mL). Blood protein denaturalisation ratio was consistently lower than in control at TFE concentrations greater than 40 mg/mL. Erythrocyte membrane damage caused by the action of oxidative H2O2 displayed a steady reduction with increasing TFE concentrations. In the reactive oxygen species (ROS) measurement by using flow cytometry assay, leucocyte viability was over 95% at tested concentrations, and a high ROS inhibition was also recorded. Protective behaviour found in TFE should be attributed to its polyphenol content. Thus, tamarind leaves can be regarded as a potential source of interesting phytochemicals.

Fludarabine, melphalan, thiotepa and anti-thymocyte globulin conditioning for unrelated cord blood transplant.

Unrelated cord blood transplant (CBT) is an alternative treatment option for patients who lack a matched donor. However, the optimal type and intensity of the preparative regimen remains unclear. We evaluated the toxicity and outcomes of a conditioning regimen consisting of melphalan 140 mg/m(2) (day - 8), thiotepa 10 mg/kg (day - 7), fludarabine 160 mg/m(2) over 4 days (days - 6 to - 3) and rabbit antithymocyte globulin (ATG) 1.25 mg/kg (day - 4) and 1.75 mg/kg (day - 3) (FMT). Forty-seven patients with advanced hematologic malignancies with a median age of 23 years (30 adults and 17 children) were treated. Sixty percent of patients were in remission at transplant. Ninety-one percent of the patients engrafted neutrophils after a median of 22 days, and all but one of the patients achieving donor engraftment had hematopoietic recovery with 100% cord blood-derived cells. Grade 3 gastrointestinal toxicity was the major non-hematopoietic toxicity, occurring in 32% of patients. Cumulative incidence of day-100 grade II-IV acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) was 53% and 34%, respectively, and non-relapse mortality at day 100 and 2 years was 11% and 40%. Two-year disease-free and overall survival rates were 31% and 44%, respectively. These results suggest that FMT is a feasible conditioning regimen for patients undergoing CBT.

Effects of ACE inhibition and beta-blockade on female genital structures in spontaneously hypertensive rats.

INTRODUCTION AND AIM: This study evaluated the possible differences between an angiotensin converting enzyme (ACE) inhibitor and a beta-blocker concerning their potential protective role on female external genitalia in spontaneously hypertensive rats (SHR). MAIN OUTCOME MEASURES: Morphological changes in the clitoris after antihypertensive treatments. METHODS: For 6 months, SHR received no treatment; SHR + ramipril (RAM), SHR + atenolol (AT), and control Wistar Kyoto (WKY) rats received no treatment. Clitorises were processed for immunohistochemistry using anti-alpha-smooth muscle actin (alpha-SMA), anti-collagen I and III, anti-transforming growth factor beta(1) (TGFbeta(1)), and anti-endothelial nitric oxide synthase (eNOS) antibodies. RESULTS: SHR + RAM and SHR + AT presented significantly lower blood pressure in both groups vs. untreated SHR. Compared with WKY, alpha-SMA was increased in the arteries and in the cavernous spaces of the clitoris together with a marked increase in wall/lumen ratio in clitoral vessels in untreated SHR. All these alterations were diminished in SHR + AT (P < 0.01). SHR + RAM presented differences with respect to SHR + AT in the reduction of these variables. TGFbeta(1) expression in the vessel wall from the clitoris and collagen I and III deposition in the interstitium from the clitoris in untreated SHR were significantly more (P < 0.01) than in WKY. While SHR + AT showed a mild decrease in these variables, SHR + RAM presented a significant reduction (P < 0.01) in TGFbeta(1) expression interstitial fibrosis and in both types of collagens. Positive immunostaining of eNOS in the sinusoidal endothelium from the clitoris was less (P < 0.01) in untreated SHR (3.4 +/- 1.3%) and SHR + AT (5.1 +/- 1.2%) than in SHR + RAM (17.2 +/- 1.6%) and WKY (15.9 +/- 1.7%). Untreated SHR and SHR + AT presented more surrounding connective tissue at the perineurium in the clitoris (P < 0.01) than SHR + RAM. CONCLUSION: ACE inhibition provided a considerable protective role on the female external genitalia structures in SHR by a mechanism that may be, at least in part, independent of the degree of blood pressure lowering.

Policitemia secundaria a nefrocalcitosis y acidosis tubular renal / Secondary Polycithemia and nephrocalcynosis and renal tubular acidosis

Las principales causas de policitemia secundaria son las enfermedades pulmonares y cardíacas productoras de hipoxia tisular. Sin embargo, en muy raras ocasiones, es el riñon el causante de la eritrocitosis. Las patologías renales que se asocian con mayor frecuencia a este fenómeno son los riñones poliquísticos, los quistes simples, el hipernefroma, la hidronefrosis, el cistadenoma y la estenosis de la arteria renal (2). No obstante, hay informados en la literatura en inglés cerca de 12 casos en los que la causa fue una nefrocalcinosis. A continuación presentamos un caso visto en el Hospital San Vicente de Paúl de Medellín con esta muy rara asociación.

Impaired vascular smooth muscle nitric oxide-dependent relaxation in human coronary arteries from "transplanted heart vasculopathy".

The long-term prognosis after heart transplant is mainly determined by the development of transplant vasculopathy. The pathogenic mechanism of transplant vasculopathy remain uncertain, although endothelial dysfunction has been postulated. The objective of this work is to evaluate the smooth muscle and endothelium nitric oxide relaxing mechanisms in coronary arteries from patients with transplant vasculopathy. We studied human coronary arteries obtained from heart transplant surgery specimens of patients with heart transplant vasculopathy, ischaemic cardiopathy or dilated cardiomyopathy. Rings from the coronary arteries were mounted on stainless steel hooks in 40 ml organ bath. The tissues were contracted with phenylephrine (approx. ED 80-90) and concentration-response curves were performed with glyceryltrinitrate and acetylcholine. Glyceryltrinitrate relaxed arterial rings from patients with dilated cardiomyopathy and ischaemic cardiopathy. Arterial rings from patients with heart transplant vasculopathy showed a lower response to glyceryltrinitrate. Acetylcholine induced dilatation of coronary arteries from dilated cardiomyopathy but increased the tension in coronary rings from heart transplant vasculopathy and inschaemic cardiopathy. In conclusion, there is a lower response to glyceryltrinitrate and a paradoxical response to acetylcholine in arteries from patients with transplant vasculopathy. The response to glyceryltrinitrate may be a meaningful tool in the early diagnosis of transplant vasculopathy.

[Physiology of erection]. / Fisiología de la erección.

OBJECTIVE: The present study reviews the mechanism involved in the initiation and maintenance of penile erection. METHOD: The study reviews the literature on the basic concepts supporting either "magically" or scientifically the erectile mechanism. An anatomo-physiological update is also included (i.e., the main neurological, muscular, and vasculoendothelial phenomena). RESULTS: Present studies based on the vasoactive action of different drugs have increased the knowledge on the neurological, muscular, and vasculoendothelial phenomena. The cavernous muscular relaxation may start and finish due to the equilibrium between the contractile adrenergic and the relaxing non adrenergic-non cholinergic stimulus through intracellular nitric oxide synthesis. This is an essential phenomenon involved in the entry and "trapping" of blood within the sinus spaces. CONCLUSIONS: Our knowledge on the erectile mechanisms through neuromediators is increasing. The role of the endothelium in intracellular nitric oxide synthesis and its relaxing effect, will improve our understanding of both physiological and therapeutic phenomena.