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We describe an ancestry-informative autosomal SNP multiplex designed to be a small-scale, flexible panel that can complement uniparental markers in assessing the American variability (i.e. pre-Colombian) found in contemporary indigenous American populations. This study centered on choosing SNPs with the specific characteristics of: 1) extreme allele frequency differences between indigenous Americans and the African, European and East Asian population groups that contribute to present-day population variation in the Americas; 2) high informativeness-for-assignment In values; and 3) well-spaced genomic distribution and chromosomal separation from existing small-scale forensic ancestry marker sets. The resulting capillary electrophoresis SNaPshot single base extension test was named: PIMA (Population Informative Multiplex for the Americas), comprising 26 autosomal SNPs, a single X-chromosome SNP plus the amelogenin sex marker adapted for SNaPshot. PIMA complements the established 34plex forensic ancestry panel to provide a powerful and simple tool for the analysis of American populations, including those with admixed histories, commonly encountered in America. Comparing the results obtained with the combined marker panels of PIMA and 34plex to SNP data from a much larger ancestry panel allowed us to gauge their relative efficiency. PIMA+34plex gives equivalent power to the 314-SNP 'LACE' genomic ancestry control panel, while requiring a much smaller genotyping effort. The ancestry profiles and genetic structure of 22 populations spread across the American continent were estimated using PIMA+34plex data, and those estimates were contrasted with information provided by uniparental markers (mtDNA and Y-chromosome loci) for a small set of admixed individuals from Venezuela. Our results indicate that an American genetic component is efficiently detected in contemporary American populations using a small set of ancestry informative SNPs, and these co-ancestry estimates are consistent with the known history and demography of the Americas. The small scale and high population differentiation power of PIMA, particularly when combined with 34plex, provides a practical and powerful tool for genetic studies of American populations as well as forensic DNA analyses.
Assuntos
Etnicidade/genética , Genética Populacional , Polimorfismo de Nucleotídeo Único , Grupos Raciais/genética , Amelogenina/genética , América , Cromossomos Humanos Y , DNA Mitocondrial , Eletroforese Capilar , Frequência do Gene , Marcadores Genéticos , Genótipo , Humanos , Reação em Cadeia da Polimerase MultiplexRESUMO
Dynamical control of entanglement and its connection with the classical concept of instability is an intriguing matter which deserves accurate investigation for its important role in information processing, cryptography and quantum computing. Here we consider a tripartite quantum system made of three coupled quantum parametric oscillators in equilibrium with a common heat bath. The introduced parametrization consists of a pulse train with adjustable amplitude and duty cycle representing a more general case for the perturbation. From the experimental observation of the instability in the classical system we are able to predict the parameter values for which the entangled states exist. A different amount of entanglement and different onset times emerge when comparing two and three quantum oscillators. The system and the parametrization considered here open new perspectives for manipulating quantum features at high temperatures.
RESUMO
The control of quantum entanglement in systems in contact with environment plays an important role in information processing, cryptography and quantum computing. However, interactions with the environment, even when very weak, entail decoherence in the system with consequent loss of entanglement. Here we consider a system of two coupled oscillators in contact with a common heat bath and with a time dependent oscillation frequency. The possibility to control the entanglement of the oscillators by means of an external sinusoidal perturbation applied to the oscillation frequency has been theoretically explored. We demonstrate that the oscillators become entangled exactly in the region where the classical counterpart is unstable, otherwise when the classical system is stable, entanglement is not possible. Therefore, we can control the entanglement swapping from stable to unstable regions by adjusting amplitude and phase of our external controller. We also show that the entanglement rate is approximately proportional to the real part of the Floquet coefficient of the classical counterpart of the oscillators. Our results have the intriguing peculiarity of manipulating quantum information operating on a classical system.
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Incidence and risk factors for cytomegalovirus (CMV) disease in a Colombian cohort of kidney transplant recipients. CMV infection and disease are important causes of morbidity and mortality in kidney transplant recipients, and its prevalence varies with economic, geographic, and ethnic factors. Among 1620 records from a Colombian reference center, CMV immunoglobulin (Ig)G seroprevalence was found to be 90.9% among recipients and 90.2% among donors. In 86% (n = 264) of the cases, CMV disease occurred during the first 6 months after the transplantation, and the most frequent clinical presentation was CMV syndrome, followed by gastrointestinal disease. The following parameters were independent predictors of CMV disease: serological status of D+/R+ (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.03-2.63) and D+/R- (HR, 2.72; 95% CI, 1.49-4.93), age of the recipient (HR, 1.02; 95% CI, 1.01-1.03), and receiving more than 30 mg of prednisolone by the end of the first month after transplantation (HR, 1.59; 95% CI, 1.22-2.07). Acyclovir prophylaxis or other antiviral agents significantly decreased the risk of disease (HR, 0.41; 95% CI, 0.29-0.58 and HR, 0.34; 95% CI, 0.20-0.58, respectively). In conclusion, we found a high prevalence of CMV infection in a cohort of Latin American transplant recipients. In accord with findings from other regions, serological status is the main risk factor, prophylaxis with acyclovir is effective, and induction with alemtuzumab does not increase the risk of CMV disease.
Assuntos
Infecções por Citomegalovirus/terapia , Transplante de Rim/efeitos adversos , Insuficiência Renal/cirurgia , Aciclovir/uso terapêutico , Adolescente , Adulto , Alemtuzumab , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , Estudos de Coortes , Colômbia , Citomegalovirus , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/epidemiologia , Feminino , Humanos , Imunoglobulina G/sangue , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Insuficiência Renal/complicações , Insuficiência Renal/epidemiologia , Fatores de Risco , Estudos Soroepidemiológicos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Elderly patients are the fastest growing population requiring renal replacement therapy. It has been stated that renal transplantation may be the best treatment option for these patients. However, it has been observed that older patients have a higher mortality rate than those who are younger. Yet the factors that determine post-transplantation outcomes in this population remain poorly defined. The aims of this study were to evaluate the graft and patient survival in kidney transplant recipients who are older than 60 years of age to identify relevant predictive factors. METHODS: In this population-based retrospective cohort study of 201 kidney transplantations performed in elderly patients from January 2002 throughout June 2009, we estimated the 1-,3-,and 5-year patients and graft survival rates. We also evaluated the complications and the predictors of poor outcomes. Survival times were analyzed using the Kaplan-Meier method and survival differences assessed with Mantel-Cox log rank-test. We performed a Cox proportional hazards regression models to evaluate the impact of baseline and treatment characteristics on patient and graft survival. RESULTS: Graft and patient survival rates at 1, 3, and 5 years were 76.4%, 71.3%, and 54.3%, and 78.2%, 73.8%, and 56.4%, respectively. Graft survival rates censored for patient death with a functioning graft were 93.1, 92.1, and 89%. Patient survival rates differed between diabetic and nondiabetic subjects at 1, 3 and 5 years (69.5% versus 83.6%; 59.8% versus 72.3%; 43.6% versus 65.7%; P = .008). On multivariate analysis, the factors associated with patients survival were diabetes mellitus (hazard ratio [HR] 2.058, 95% confidence interval [CI] 1.173-3.611, P = .012) and the 1-month serum creatinine value was > 1.6 mg/dL (HR 2.108 for each point increase, 95% CI 1.521-2.921, P = .000). Furthermore, there was an insignificant trend forward an association between active or past smoker and lower patient survival (HR 1.689, 95% CI 0.937-3.043, P = .08). The main causes of graft loss were patient death (79.5%). acute rejection (6.8%), and chronic allograft nephropathy (5.5%). CONCLUSION: Renal transplantation can be performed safely and with acceptable outcomes in elderly patients after appropriate clinical evaluation. The grafts show excellent survival albeit that deaths with a functional graft continue to be an important issue.
Assuntos
Transplante de Rim , Taxa de Sobrevida , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
A set of autosomal single nucleotide polymorphism (SNP) loci was analyzed using the 52-plex assay previously described by Sanchez et al. [J.J. Sanchez, C. Phillips, C. Borsting, K. Balogh, M. Bogus, M. Fondevila, C.D. Harrison, E. Musgrave-Brown, A. Salas, D. Syndercombe-Court, P.M. Schneider, A. Carracedo, N. Morling, A multiplex assay with 52 single nucleotide polymorphisms for human identification, Electrophoresis 27 (2006) 1713-1724] in 140 samples of unrelated individuals born in the Colombian regions of, Risaralda, Caldas, Quindio, Antioquia, Tolima and Valle, and 164 samples of unrelated individuals with declared Native American ancestry from Colombia. Allele frequencies and statistical parameters of forensic interest are presented for the 52 SNPs. All loci were in agreement with Hardy-Weinberg equilibrium while comparisons with population samples of Argentina, Portugal, Spain, Mozambique, and Taiwan revealed significant differences in allele frequency distributions.
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Genética Populacional , Polimorfismo de Nucleotídeo Único , Colômbia , Impressões Digitais de DNA , Genótipo , Humanos , Reação em Cadeia da PolimeraseRESUMO
Los injertos de piel cultivados in vitro han sido utilizados tanto en la regeneración de tejidos de áreas cruentas de la piel (úlceras crónicas y quemaduras de diversos grados), como para el tratamiento de genodermatosis. En nuestro medio existe un alto índice de pacientes con úlceras crónicas y un total de 2319 pacientes quemados, en un período de 10 años. El tratamiento convencional de estos pacientes genera estadías de hospitalización prolongadas y costos hospitalarios muy elevados. En este trabajo se establecieron las condiciones para el cultivo y expansión de queratinocitos y fibroblastos humanos, con el propósito de generar un equivalente cutáneo. A su vez, se evaluaron sus características histológicas con el objeto de ofrecer otras opciones de tratamiento. Las células se obtuvieron a partir de piel proveniente de donantes de órganos y de sobrantes de procedimientos quirúrgicos. Se logró un mayor éxito en la obtención de cultivos primarios, con muestras provenientes de donantes menores de 40 años (65%), comparado con los obtenidos de mayores (33%). En el equivalente cutáneo producido con estas células se demostró que los queratinocitos y los fibroblastos, presentan características funcionales, estructurales y morfológicas semejantes a la piel intacta. El equivalente cutáneo además de conservar las características funcionales y estructurales de la piel intacta, presenta otras ventajas en términos de costos, manipulación y estabilidad frente a otros productos similares importados.
In vitro skin culture have been used in the regeneration of skin wound (chronic ulcers and burns), and for genodermatosis treatment. In our country there is a high patient number with chronic ulcers and 2319 burned in a period of 10 years. Conventional treatment generates long hospitalization stays and high costs. We established culture conditions of keratinocytes and fibroblasts expansion, to generate a cutaneous substitute in order to offer other treatment options. Skin cells were obtained from organs donors and surgical surpluses procedures. Major success was achieved in primary cultures obtained from 40-year-old younger donors samples (65%), compared with older donors (33%). In one cutaneous substitute produced with these cells, was demonstrated that keratinocytes and fibroblasts, presented functional, structural and morphologic characteristics similar to normal skin. Cutaneous substitute besides preserve normal skin functional and structural characteristic, compared with other similar imported products, our cutaneous substitute, showed many advantages in terms of costs, manipulation and stability.
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Fifteen autosomal short tandem repeat (STR) loci were analyzed using the AmpFISTR Identifiler PCR Amplification Kit in 1944 samples of healthy unrelated individuals, born in the regions of Caldas, Quindio and Risaralda, Colombia. Allele frequencies and statistical parameters of forensic interest are presented for all markers (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, THO1, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA). All loci of the pooled data were in agreement with Hardy-Weinberg equilibrium, after Bonferroni correction. Comparisons with neighboring Latin American populations and Andalucia (Spain) revealed significant differences in allele distributions. Genetic data presented in this study can be used for routine forensic applications in the region.
Assuntos
Repetições de Microssatélites/genética , Polimorfismo Genético , Alelos , Colômbia , DNA/genética , DNA/isolamento & purificação , Impressões Digitais de DNA/métodos , Ciências Forenses/estatística & dados numéricos , Frequência do Gene , Marcadores Genéticos , Genética Populacional , Geografia , Humanos , Controle de Qualidade , SoftwareRESUMO
Hepatitis C virus (HCV) infection is highly prevalent in renal transplant candidates; however, its effect on the transplant outcome is still controversial. The aim of the present study was to determine the effect of HCV infection in the outcome of kidney transplantation in a single transplant center. The study population 144 HCV- randomized selected patients and 64 HCV+ patients transplanted from 1973 to 2000, followed for up to 60 months post-transplantation. This retrospective study included the following variables: type of dialysis, time on renal replacement therapy, number of transfusions before and after transplantation, number of transplants, type of donor, immunosuppression, and rejection episodes. The Kaplan-Meier method was used to estimate graft and patient survival. Log-rank test was used to assess the difference in survival between HCV+ and HCV-. A multivariate Cox proportional hazards model was used to analyze the relation between graft and patient survival. HCV+ and HCV- patients had similar demographic and clinical characteristics; however, a higher number of HCV+ patients received blood transfusions after transplantation. Patient survival was not significantly different in 39 HCV+ and 96 HCV- patients transplanted with living-related donors (71% and 77% at five yr, respectively). Similarly, there was not significant difference in 25 HCV+ and 48 HCV- patients transplanted with kidneys from deceased donors, although there was a tendency to better outcome in HCV- patients (55% and 72% at five yr respectively). Regarding graft survival, there was also no differences in HCV+ and HCV- recipients of living-related grafts (61% and 66% at five yr post-transplant, respectively) and recipients of kidneys from deceased donors (44% and 41%, respectively). The results show that HCV+ patients can be transplanted with the same success than HCV- patients.
Assuntos
Sobrevivência de Enxerto , Hepatite C/epidemiologia , Nefropatias/epidemiologia , Transplante de Rim/imunologia , Adolescente , Adulto , Anti-Inflamatórios/administração & dosagem , Transfusão de Sangue/estatística & dados numéricos , Criança , Pré-Escolar , Comorbidade , Ciclosporina/administração & dosagem , Feminino , Humanos , Imunossupressores/administração & dosagem , Nefropatias/cirurgia , Cirrose Hepática/epidemiologia , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do TratamentoRESUMO
We described a case of allograft kidney dysfunction associated with renal parenchymal infection with amastigotes of Trypanosoma cruzi. The patient was diagnosed as being chronically infected prior to transplantation. The infection was probably acquired by blood transfusion. He could not complete antiparasitic treatment due to drug toxicity. He was transplanted from a cadaver who showed a negative test for Chagas' disease. One year after transplantation the serum creatinine progressively increased. Histological examination of renal biopsy revealed intracytoplasmic amastigotes of T cruzi. No evidence of other specific alterations in the graft was detected. It was unknown whether graft dysfunction was only due to parasitic infection. The present case confirmed that T cruzi can infect kidney grafts and that immunosuppression in kidney transplantation is potentially a cause of dissemination of Chagas' disease.
Assuntos
Doença de Chagas/patologia , Transplante de Rim/patologia , Rim/parasitologia , Trypanosoma cruzi/isolamento & purificação , Adulto , Animais , Humanos , Falência Renal Crônica/cirurgia , Nefrite Lúpica/cirurgia , Masculino , Resultado do TratamentoRESUMO
Different polymorphisms of the ADRB2 gene encoding the beta-adrenergic receptor (ADRB2) are associated with changes in a variety of responses of the sympathetic nervous system (SNS). In this study, we have investigated the distribution of frequencies of ADRB2-related allelic variants (Arg16Gly, Gln27Glu, Thr164Ile) in the Colombian population, as well as the influence of the Gln27Glu polymorphism as a risk factor for the development of dyslipidemia following propranolol administration. Genotyping was performed in unrelated Colombian volunteers, using PCR-RFLP methods. To examine the association between the Gln27Glu polymorphism of the ADRB2 gene and dyslipidemia induced by propranolol, we recruited 19 healthy individuals who were homozygous for either the Gln27 (wild-type, N = 11) or the Glu27 (homozygous mutant, N = 8) genotype. Electrocardiography (ECG), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), serum lipid levels (T-CHO, HDL-CHO, TG), and fibrinogen were determined before and after propranolol administration. The distribution of genotypes was as follows: Arg16Arg 46%, Arg16Gly 47.4%, Gly16Gly 6.6%, Gln27Gln 44.7%, Gln27Glu 48.2%, and Glu27Glu 7.1%, with allelic frequencies of 69.7% for Arg16, 30.3% for Gly16, 68.8% for Gln27, and 31.2% for Glu27. The Thr164Ile polymorphism was found only in one subject, who was heterozygous for the isoleucine variant. Significant changes in physiological parameters (HR, SBP, DBP) have been found in association with ADRB2 variants in both native and mutant subgroups after propranolol intake. HDL-CHO levels diminished (p = 0.005) in native homozygous individuals (Gln27Gln), whereas TG levels were found increased (p = 0.012) in the mutant homozygous individuals (Glu27Glu). T-CHO levels and serum fibrinogen levels remained unaltered in both subgroups. The evidence that subjects homozygous for Gln27 in the ADRB2 gene show a significant reduction of HDL-CHO levels, as well as the increased TG levels in subjects homozygous for Glu27 after propranolol administration, suggest that the Gln27Glu polymorphism represents a risk factor for dyslipidemia induced by propranolol. These results may contribute to a better understanding of the mechanisms underlying dyslipidemia induced by ADRB2 antagonists.
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Antagonistas Adrenérgicos beta/farmacologia , Hiperlipidemias/genética , Propranolol/farmacologia , Receptores Adrenérgicos beta 2/genética , Adolescente , Antagonistas Adrenérgicos beta/sangue , Adulto , Pressão Sanguínea/efeitos dos fármacos , HDL-Colesterol/efeitos dos fármacos , HDL-Colesterol/metabolismo , Colômbia/epidemiologia , Feminino , Frequência do Gene , Genótipo , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/fisiopatologia , Masculino , Fenótipo , Polimorfismo Genético , Propranolol/sangue , Triglicerídeos/metabolismoRESUMO
Thiopurine methyltransferase (TPMT) catalyzes the inactivation of thiopurine drugs (mercaptopurine, thioguanine and azathioprine) used to treat acute lymphoblastic leukemia, autoimmune diseases and recipients of transplanted organs. No endogenous substrates for this enzyme are known. The TPMT polymorphism is a major determinant of individual differences in the toxicity or therapeutic efficacy of these drugs. The molecular basis of this polymorphism has been established in Caucasians, Africans, African-Americans and Asians, but not yet in the heterogeneous Latin American groups, including the Colombian population. The frequency of the four allelic variants of the TPMT gene, TPMT*2 (G238C), TPMT*3A (G460A and A719G), TPMT*3B (G460A) and TPMT*3C (A719G), were determined in 140 Colombian volunteers of Mestizo origin, using allele-specific PCR and PCR-RFLP assays. The *3A allele was found in 10 samples and the *2 allele in one, all heterozygotes; neither homozygous mutant genotypes nor the *3B and *3C alleles were detected. In agreement with these results, 92.1% and 7.9% of the Colombian population correspond to the phenotypes high and intermediate methylators, respectively. These results show that the frequency of mutations and the allelic distribution of the TPMT gene in the Colombian population are similar to the genetic profile found among US and European Caucasian populations, where the *3A allele is prevalent and the *2 allele is currently present.
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Metiltransferases/genética , Adulto , Alelos , Colômbia , Eletroforese em Gel de Ágar , Éxons , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de RestriçãoRESUMO
Cytochrome P450 2D6 monooxygenase metabolizes several commonly used drugs, particularly psychotropics and cardiovascular agents. The gene that encodes this isoenzyme is highly polymorphic, with 1-10% of the population carrying mutations that produce an inactive enzyme, and 1-29% of individuals who possess additional copies of functional CYP2D6 genes. The genotypic features of the CYP2D6 gene have already been studied in many ethnic groups; however, the genetic characteristics of this enzyme are unknown in the Colombian population. The allelic variants and mutations of this polymorphic isoenzyme are the main cause of interindividual and interethnic differences in the therapeutic efficacy and adverse effects at standard doses of drugs metabolized by the products of the CYP2D6 gene. In the present study we have isolated, sequenced and genotyped the CYP2D6 gene in the Colombian population. The distribution of allelic frequencies of 10 alleles associated with normal, diminished or increased CYP2D6 activity has been studied in 121 healthy volunteers. The commonest alleles detected in the Colombian people were the functional alleles *1 (38.8%) and *2 (37%). Among the seven nonfunctional alleles studied in our sample, we found frequencies of 19.4%, 1.6%, 1.2% and 0.8%, for the *4, *17, *3 and *5 alleles, respectively. The alleles *6, *7 and *8 could not be identified in any of the subjects studied. The frequency of the duplicate allele was 1.2%. In this Colombian sample, 91.7% of the individuals were normal metabolizers (EM), 6.6% were poor metabolizers (PM), and 1.7% were ultrarapid metabolizers (UM). These results show that the allelic distribution of the CYP2D6 gene in the Colombian population of mestizo-prevalent subjects is compatible with the genomic assembly of the constitutive tri-ethnic origin of this Latin American country.
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Citocromo P-450 CYP2D6/genética , Preparações Farmacêuticas/metabolismo , Adolescente , Adulto , Alelos , Colômbia/epidemiologia , DNA/genética , DNA/isolamento & purificação , Primers do DNA , Eletroforese em Gel de Ágar , Feminino , Deleção de Genes , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , FenótipoRESUMO
Dematiaceous fungi are being increasingly recognized as pathogens in organ transplant recipients. This investigation reports five cases of subcutaneous phaeohyphomycosis that occurred in five kidney transplant recipients in the Renal Unit at the San Vicente de Paul Hospital, Medellin, Colombia. Fungi of the genus Exophiala were isolated in three cases, but the agent was not identified in two cases. Physicians are likely to develop increased awareness of the clinical manifestation of infection with the dematiaceous fungi as the population of immunocompromised hosts continues to grow.