RESUMO
Chronic kidney disease (CKD) is a progressive disease with a high mortality rate and a worldwide prevalence of 13.4%, triggered by various diseases with high incidence. The aim of the present study was to investigate the anti-inflammatory and antifibrotic effect of pioglitazone on kidney in an adenine-induced Wistar rats and the mechanisms possibly involved. CKD was induced in 40 rats. Rats were divided into two groups, which were split into the following sub-groups: i) Therapeutic (pioglitazone administered after renal damage) divided into intact (healthy), adenine (CKD) and adenine/pioglitazone (treatment) and ii) prophylactic (adenine and pioglitazone administered at the same time) split into intact (healthy), adenine (CKD), endogenous reversion (recovery without treatment), adenine/pioglitazone (treatment) and pioglitazone sub-groups. Reverse transcription-quantitative PCR (collagen I, α-SMA and TGF-ß), and hematoxylin-eosin, Masson's trichrome and Sirius red staining were performed to measure histological markers of kidney damage, also the serum markers (urea, creatinine and uric acid) were performed, for analyze the effects of pioglitazone. In the adenine/pioglitazone rats of the therapeutic group, renal function parameters such as eGFR increased and serum creatinine decreased from those of untreated rats (CKD), however the renal index, serum urea, abnormalities in renal morphology, inflammatory cells and relative gene expression of collagen I, α-SMA and TGF-ß did not change relative to the CKD rats. In adenine/pioglitazone rats, extracellular matrix collagen accumulation was significantly lower than the CKD rats. On the other hand, in adenine/pioglitazone rats of the prophylactic group, the renal index, creatinine, urea, uric acid serum and relative gene expression of collagen I, α-SMA, and TGF-ß were significantly lower, as well as the presence of 2,8-dihydroxyadenine crystals, and extracellular matrix collagen compared with CKD rats. In addition, the eGFR in the treatment group was similar to healthy rats, renal morphology was restored, and inflammatory cells were significantly lower. In conclusion, pioglitazone has a nephroprotective effect when administered in the early stages of kidney damage, reducing inflammatory and fibrotic processes and improving glomerular filtration rate. Furthermore, in the late phase of treatment, a tendency to decrease creatinine and increase eGFR was observed.
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PURPOSE: Breast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC). PATIENTS AND METHODS: The MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery. RESULTS: Overall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor-negative-human epidermal growth factor receptor 2-positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%). CONCLUSION: In LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.
Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Humanos , Neoplasias da Mama/terapia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Feminino , Pessoa de Meia-Idade , América Latina/epidemiologia , Adulto , IdosoRESUMO
Previous computational and experimental studies showed that charges located at the surroundings of hydrogen bonds can exert two opposite effects on them: rupture or strengthening of the hydrogen bond. This work aims to generalize the effect of charges in different hydrogen-bonded systems and to propose a coherent explanation of this effect. For these purposes, 19 systems with intra- and intermolecular hydrogen bonds were studied computationally with DFT. The FT-IR spectra of the systems were simulated, and two energy components of the hydrogen bond were studied separately to determine their variation upon the presence of a charge: charge transfer and molecular overlap. It was determined that either the breaking or strengthening of the hydrogen bond can be favored one over the other, for instance, depending on the heteroatom involved in the hydrogen bond. In addition, it is showed that the strengthening of the hydrogen bond by the presence of a charge is directly related to the decrease in charge transfer between the monomers, which is explained by an increase in molecular overlapping, suggesting a more covalent character of the interaction. The understanding of how hydrogen bonds are affected by charges is important, as it is a key towards a strategy to manipulate hydrogen bonds at convenience.
Assuntos
Elétrons , Hidrogênio , Ligação de Hidrogênio , Espectroscopia de Infravermelho com Transformada de Fourier , Espectrofotometria Infravermelho , Hidrogênio/químicaRESUMO
Oncoplastic techniques in breast cancer treatment allow increasing indications of breast-conserving surgery and improving cosmetic results. Breast tumors located at the superior edge of the upper quadrant or at the upper inner quadrant represent a challenge for conservative surgery due to insufficient breast thickness and risk of skin involvement. We present a modified Burow's triangle advancement flap for breast-conserving surgery in patients with breast tumors at these locations. This retrospective observational study analyzed 8 out of 213 patients submitted to major oncoplastic breast procedures, who underwent breast-conserving surgery with matrix rotation mammaplasty, using a modified Burow's triangle advancement flap. All patients were treated in public and private health systems in Santiago, Chile. The median age at diagnosis was 47 years. The average initial tumor size was 5.9 cm, and the mean excised breast weight was 117 g. Patients required neither symmetrization nor displacement of the nipple-areola complex. Only one patient had a minor complication (wound dehiscence). During follow-up, no local recurrences were reported. We conclude that the modified Burow's triangle advancement flap is a safe and effective technique to manage tumors at this complex location. It provides adequate oncological margins, good cosmetic results, and contralateral symmetry, with complication rates similar to those of standard conservative surgery
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El alineamiento incorrecto de la columna vertebral origina estrés y una tensión innecesaria que afecta el aparato locomotor. El objetivo de este trabajo fue identificar y establecer la prevalencia de hipercifosis e hiperlordosis y su relación con el índice de masa corporal (IMC) e índice cintura-talla (ICT) en estudiantes de 12 años de edad en Arica, Chile. Ochenta estudiantes de sexo masculino (n = 80) de tres tipos de subvención escolar fueron reclutados. Se les evaluó peso (kg), talla (m), IMC e ICT como indicador de riesgo metabólico. Para la evaluación postural de hipercifosis e hiperlordosis se utilizó el test de flechas sagitales. Para los análisis estadísticos fueron ocupadas las pruebas Kruskal-Wallis, ANOVA de una vía y exacta de Fisher y Chi-cuadrado para las variables categóricas. Los resultados muestran una prevalencia total de alteración postural de un 57,5 %, un IMC de sobrepeso/obesidad de un 52,5 % y un 35 % de riesgo metabólico. No se observó una asociación entre IMC, ICT y alteraciones de columna, excepto en ICT e hipercifosis. Las alteraciones más frecuentes fueron hiperlordosis seguida de hipercifosis con un 38,8 % y 25,7 % respectivamente, donde las mayores prevalencias se registraron en el establecimiento municipal. En la muestra estudiada se reportan altas prevalencias de hipercifosis e hiperlordosis que no presentan asociación con los índices de sobrepeso y obesidad. Además, las mayores prevalencias de alteraciones posturales en el plano sagital se reportaron en el establecimiento municipal. La prevención de alteraciones posturales y el control del sobrepeso y obesidad deben realizarse precozmente en todo el sistema educativo.
Incorrect alignment of the spinal column causes stress and unnecessary stress affecting the locomotor system. The objective of this study was to identify and establish the prevalence of hyperkyphosis and hyperlordosis and its relationship with body mass index (BMI) and waist-height ratio (WHR) in 12- year-old students from Arica, Chile. Eighty male students (n = 80) from three types of school: public, private subsidized, and private nonsubsidized schools were recruited. They were assessed weight (kg), height (m), BMI and WHR as an indicator of metabolic risk. The sagittal arrow test was used for postural evaluation of hyperkyphosis and hyperlordosis. Kruskal-Wallis tests, one-way ANOVA and Fisher's exact test and Chi-square test were used for the categorical variables. The results show a total prevalence of postural alteration of 57.5 %, a BMI of overweight / obesity of 52.5 % and a 35 % of metabolic risk. There was no association between BMI, WHR and spinal alterations, except for WHR and hyperkyphosis. The most frequent alterations were hyperlordosis followed by hyperkyphosis with 38.8 % and 25.7 % respectively, where the highest prevalences were recorded in the public school. In the sample studied we report the high prevalence of hyperkyphosis and hyperlordosis that there were not association with the indexes of overweight and obesity. In addition, the higher prevalences of postural alterations in the sagittal plane were reported in the public school. The prevention of postural alterations and the control of overweight and obesity should be carried out early in the whole elementary education system.
Assuntos
Humanos , Masculino , Criança , Cifose/epidemiologia , Lordose/epidemiologia , Postura , Índice de Massa Corporal , Distribuição de Qui-Quadrado , Chile/epidemiologia , Estado Nutricional , Prevalência , Estudos Transversais , Análise de Variância , Ensino Fundamental e Médio , Razão Cintura-EstaturaRESUMO
Corante, Noemí, Cecilia Anza-Ramírez, Rómulo Figueroa-Mujíca, José Luis Macarlupú, Gustavo Vizcardo-Galindo, Grzegorz Bilo, Gianfranco Parati, Jorge L. Gamboa, Fabiola León-Velarde, and Francisco C. Villafuerte. Excessive erythrocytosis and cardiovascular risk in Andean highlanders. High Alt Med Biol. 19:221-231, 2018.-Cardiovascular diseases are the main cause of death worldwide. Life under high-altitude (HA) hypoxic conditions is believed to provide highlanders with a natural protection against cardiovascular and metabolic diseases compared with sea-level inhabitants. However, some HA dwellers become intolerant to chronic hypoxia and develop a progressive incapacitating syndrome known as chronic mountain sickness (CMS), characterized by excessive erythrocytosis (EE; Hb ≥21 g/dL in men, Hb ≥19 g/dL in women). Evidence from HA studies suggests that, in addition to CMS typical signs and symptoms, these highlanders may also suffer from metabolic and cardiovascular disorders. Thus, we hypothesize that this syndrome is also associated to the loss of the cardiometabolic protection observed in healthy highlanders (HH), and therefore to a higher cardiovascular risk (CVR). The aim of the present work was to evaluate the association between EE and CVR calculated using the Framingham General CVR Score and between EE and CVR factors in male highlanders. This cross-sectional study included 342 males from Cerro de Pasco, Peru at 4340 m (HH = 209, CMS = 133). Associations were assessed by multiple logistic regressions adjusted for potential confounders (BMI, pulse oxygen saturation and age). The adjusted models show that the odds of high CVR (>20%) in highlanders with EE was 3.63 times the odds in HH (CI 95%:1.22-10.78; p = 0.020), and that EE is associated to hypertension, elevated fasting serum glucose, insulin resistance, and elevated fasting serum triglycerides. Our results suggest that individuals who suffer from EE are at increased risk of developing cardiovascular events compared with their healthy counterparts.
Assuntos
Altitude , Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Policitemia/epidemiologia , Adolescente , Adulto , Idoso , Glicemia/metabolismo , Doenças Cardiovasculares/fisiopatologia , Estudos Transversais , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Peru/epidemiologia , Policitemia/fisiopatologia , Fatores de Risco , Triglicerídeos/sangue , Adulto JovemRESUMO
RESUMEN: El alineamiento incorrecto de la columna vertebral origina estrés y una tensión innecesaria que afecta el aparato locomotor. El objetivo de este trabajo fue identificar y establecer la prevalencia de hipercifosis e hiperlordosis y su relación con el índice de masa corporal (IMC) e índice cintura-talla (ICT) en estudiantes de 12 años de edad en Arica, Chile. Ochenta estudiantes de sexo masculino (n = 80) de tres tipos de subvención escolar fueron reclutados. Se les evaluó peso (kg), talla (m), IMC e ICT como indicador de riesgo metabólico. Para la evaluación postural de hipercifosis e hiperlordosis se utilizó el test de flechas sagitales. Para los análisis estadísticos fueron ocupadas las pruebas Kruskal-Wallis, ANOVA de una vía y exacta de Fisher y Chi-cuadrado para las variables categóricas. Los resultados muestran una prevalencia total de alteración postural de un 57,5 %, un IMC de sobrepeso/obesidad de un 52,5 % y un 35 % de riesgo metabólico. No se observó una asociación entre IMC, ICT y alteraciones de columna, excepto en ICT e hipercifosis. Las alteraciones más frecuentes fueron hiperlordosis seguida de hipercifosis con un 38,8 % y 25,7 % respectivamente, donde las mayores prevalencias se registraron en el establecimiento municipal. En la muestra estudiada se reportan altas prevalencias de hipercifosis e hiperlordosis que no presentan asociación con los índices de sobrepeso y obesidad. Además, las mayores prevalencias de alteraciones posturales en el plano sagital se reportaron en el establecimiento municipal. La prevención de alteraciones posturales y el control del sobrepeso y obesidad deben realizarse precozmente en todo el sistema educativo.
SUMMARY: Incorrect alignment of the spinal column causes stress and unnecessary stress affecting the locomotor system. The objective of this study was to identify and establish the prevalence of hyperkyphosis and hyperlordosis and its relationship with body mass index (BMI) and waist-height ratio (WHR) in 12- year-old students from Arica, Chile. Eighty male students (n = 80) from three types of school: public, private subsidized, and private nonsubsidized schools were recruited. They were assessed weight (kg), height (m), BMI and WHR as an indicator of metabolic risk. The sagittal arrow test was used for postural evaluation of hyperkyphosis and hyperlordosis. Kruskal-Wallis tests, one-way ANOVA and Fisher's exact test and Chi-square test were used for the categorical variables. The results show a total prevalence of postural alteration of 57.5 %, a BMI of overweight / obesity of 52.5 % and a 35 % of metabolic risk. There was no association between BMI, WHR and spinal alterations, except for WHR and hyperkyphosis. The most frequent alterations were hyperlordosis followed by hyperkyphosis with 38.8 % and 25.7 % respectively, where the highest prevalences were recorded in the public school. In the sample studied we report the high prevalence of hyperkyphosis and hyperlordosis that there were not association with the indexes of overweight and obesity. In addition, the higher prevalences of postural alterations in the sagittal plane were reported in the public school. The prevention of postural alterations and the control of overweight and obesity should be carried out early in the whole elementary education system.
Assuntos
Humanos , Masculino , Criança , Estudantes , Cifose/epidemiologia , Lordose/epidemiologia , Índice de Massa Corporal , Distribuição de Qui-Quadrado , Chile/epidemiologia , Estado Nutricional , Prevalência , Estudos Transversais , Análise de VariânciaRESUMO
BRCA1 has been found to be absent or miss localized in the cytoplasm in a relevant proportion of breast cancer tumors with no germline mutations. BRCA1 main function is in the nucleus, and its interaction with BARD1 is relevant for its nuclear translocation and retention. Our aim was to analyze the sub-cellular localization of BRCA1 and BARD1 in breast cancer tumors, and determine the level of expression of their splice variants BRCA1-Δ11q and BARD1-α and BARD1-ß. BRCA1 and BARD1 expressions were performed by immunohistochemistry and immunofluorescence in 103 breast cancer tumors. Colocalization was determined by confocal microscopy. Transcript variants were determined by qRT-PCR. We found BRCA1 localized in the cytoplasm with BARD1 in 51.4 % of tumors. An exclusive nuclear localization of both proteins was observed in 7/103 tumors (6.8 %). Indeed, these tumors displayed an apparent nucleolar colocalization of BARD1 and BRCA1. In relation to splice variants, there is a tendency to an overexpression of BARD1-α mRNA (30 % of tumors) and a decreased expression of BARD1-ß (41 %). BRCA1 full-length was downregulated in 63 % of tumors, and 37 % showed BRCA1-Δ11q variant overexpressed. Our findings contribute to a better understanding of the expression and sub-cellular localization of BRCA1 in breast cancer tumors. Interaction of BRCA1 and BARD1 seems to be not affected in 58.2 % of tumors, which showed colocalization of both proteins. The absence of BRCA1 in 41 % of tumors reveals a BRCAness phenotype, constituting an excellent marker for therapy sensitivity, to platinum drugs or PARP inhibitors.
Assuntos
Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Processamento Alternativo , Neoplasias da Mama/patologia , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Feminino , Humanos , Ligação Proteica , Isoformas de Proteínas , Transporte ProteicoRESUMO
Objetivo: Determinar la proporción de ojos sanos con degeneraciones predisponentes de roturas retinianas del total de pacientes con desprendimiento de retina regmatógeno en el ojo contralateral hospitalizados en el Hospital Nacional Guillermo Almenara Irigoyen durante Julio 2013 a Junio 2014. Materiales y Métodos: Se llevara a cabo un tipo de estudio Observacional con diseño de investigación prospectivo, trasversal y descriptivo. Se realizara una historia clínica completa a los pacientes hospitalizados con diagnóstico de desprendimiento de retina regmatógeno y posteriormente se recolectaran los datos en una ficha de registro elaborada especialmente para estos fines. Se registrará los datos de las fichas recopiladas a una base de datos en el Excel, tras lo cual se procesaran los datos y se obtendrán gráficas didácticas para mostrar nuestros objetivos de estudio. Resultados: Durante el periodo Julio 2013 a Junio 2014 se obtuvo una muestra de 81 pacientes, de entre los cuales se encontró un 47 por ciento de ojos con degeneración lattice, de los cuales un 12.3 por ciento ya presentaban agujeros atróficos y el lugar donde se encontró con más frecuencia fue el cuadrante temporal inferior. Discusión: Nuestros hallazgos fueron algo superior al de otros investigadores como Gonzales CR o Mastropasqua, quienes en 2004 y 1999 respectivamente hallaron proporciones de 10.8 por ciento y 38 por ciento cada uno pero fue menor de lo encontrado por Gonzales CR en otro estudio del 2004 donde hallo un 60 por ciento. Conclusiones: Puedo concluir entonces por los resultados obtenidos que las degeneraciones predisponentes a roturas retinianas son frecuentes en el ojo contralateral de los pacientes con desprendimiento de retina, siendo la más frecuente la degeneración lattice.
Objective: To determine the proportion of healthy eyes with retinal breaks precursors of all patients with rhegmatogenous retinal detachment in the fellow eye at the Hospital Guillermo Almenara Irigoyen during July 2013 to June 2014. Materials and Methods: Observational study with a prospective, transversal and descriptive design. A complete medical history will be made in patients with rhegmatogenous retinal detachment and then the data will be collected in a registration card made especially for this purpose. Data will be collected in Excel; after that, the data will be processed and graphs. Results: During the period between July 2013 to June 2014, a sample of 81 patients, among which found 47 per cent of eyes with lattice degeneration, of which 12.3 per cent already had atrophic holes and the place where it was found with more frequently obtained was the inferior temporal quadrant Discussion: Our findings were somewhat higher than other researchers as Gonzales CR or Mastropasqua, who in 2004 and 1999 respectively found rates of 10.8 per cent and 38 per cent each other but was lower than found by Gonzales CR in another study in 2004 where he found 60 per cent Conclusions: I can conclude from the results found that the predisposing degeneration to retinal breaks are frequent in the fellow eye of patients with retinal detachment, being the most common one, the lattice degeneration.
Assuntos
Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Descolamento Retiniano , Fatores de Risco , Perfurações Retinianas , Procedimentos Cirúrgicos Oftalmológicos , Estudos Observacionais como Assunto , Estudos Prospectivos , Estudos TransversaisRESUMO
The hypoxic conditions at high altitudes present a challenge for survival, causing pressure for adaptation. Interestingly, many high-altitude denizens (particularly in the Andes) are maladapted, with a condition known as chronic mountain sickness (CMS) or Monge disease. To decode the genetic basis of this disease, we sequenced and compared the whole genomes of 20 Andean subjects (10 with CMS and 10 without). We discovered 11 regions genome-wide with significant differences in haplotype frequencies consistent with selective sweeps. In these regions, two genes (an erythropoiesis regulator, SENP1, and an oncogene, ANP32D) had a higher transcriptional response to hypoxia in individuals with CMS relative to those without. We further found that downregulating the orthologs of these genes in flies dramatically enhanced survival rates under hypoxia, demonstrating that suppression of SENP1 and ANP32D plays an essential role in hypoxia tolerance. Our study provides an unbiased framework to identify and validate the genetic basis of adaptation to high altitudes and identifies potentially targetable mechanisms for CMS treatment.
Assuntos
Doença da Altitude/genética , Genoma Humano/genética , Análise de Sequência de DNA , Adulto , Animais , Doença Crônica , Regulação para Baixo/genética , Drosophila melanogaster/genética , Feminino , Estudos de Associação Genética , Genética Populacional , Genômica , Humanos , Hipóxia/genética , Masculino , Peru , Reprodutibilidade dos Testes , Análise de SobrevidaRESUMO
In tropical and subtropical regions of the world, parasitic diseases are a main cause of losses in livestock productivity. The increased acquired resistence to anthelmintics by gastrointestinal nematodes, requires biological control be considered as a potential feasible and effective alternative. The most effective natural soil enemies of nematodes are nematophagous fungi. In order to collect and identify predator nematophagous fungi (PNF), samples were obtained from 51 farms distributed throughout the seven provinces of Costa Rica. The origin samples included: soil from different crops (potatoes, tomatoes, bananas, ornamental plants, squash and coffee); animal feces (cattle, sheep, goat and horse); soil and fallen leaves from forest; and plants with signs of nematode infection. Each sample was processed using three techniques for the extraction of fungi from soil: sprinkling technique, soil dilution and humidity chamber. Twenty four strains of nematophagous fungi were found in 19 farms; 83.3% of the fungi were isolated by sprinkling technique. The following fungi were identified: Arthrobotrys oligospora (n = 13); Candelabrella musiformis (n = 9); and for the first time there was isolation of A. conoides (n = 1) and A. dactyloides (n = 1) in the country. Moreover, 16 strains from Trichoderma (n=13), Beauveria (n = 1), Clonostachys (n = 1) and Lecanicillium (n = 1) were obtained. In addition, pH of each possible fungal isolation source was measured, and it varied from 5.2 to 9.9, however PNF isolates fell within the range of 5.6 to 7.5. The PNF strains were cultivated in four different media for the production of chhlamydospores: potato dextrose agar (PDA); corn meal agar (CMA); malt extract agar (MEA) and potato carrot agar (PCA). Out of these cultures, 95.8% of the strains formed chlamydospores primarily in the PCA. Of these strains, the profilic spore producers were subjected to ruminant artificial gastrointestinal conditions. A total of 14 fungi were tested, out of which 42.9% survived the digestive analysis. Neither A. conoides nor A. dactyloides were viable following the in vitro gastrointestinal test. The PNF isolated in this study demonstrated an action against ovine and caprine gastrointestinal nematodes and are candidates for use in biological control of these organisms. Among these microorganisms, Candelabrella musiformis appears to be the most promising fungi for use as a biological control agent in Costa Rica.
Assuntos
Fungos/fisiologia , Doenças das Cabras/prevenção & controle , Nematoides/microbiologia , Infecções por Nematoides/veterinária , Controle Biológico de Vetores/métodos , Doenças dos Ovinos/prevenção & controle , Animais , Costa Rica , Fezes/microbiologia , Fungos/isolamento & purificação , Doenças das Cabras/parasitologia , Cabras , Infecções por Nematoides/prevenção & controle , Ovinos , Doenças dos Ovinos/parasitologia , Microbiologia do SoloRESUMO
In tropical and subtropical regions of the world, parasitic diseases are a main cause of losses in livestock productivity. The increased acquired resistence to anthelmintics by gastrointestinal nematodes, requires biological control be considered as a potential feasible and effective alternative. The most effective natural soil enemies of nematodes are nematophagous fungi. In order to collect and identify predator nematophagous fungi (PNF), samples were obtained from 51 farms distributed throughout the seven provinces of Costa Rica. The origin samples included: soil from different crops (potatoes, tomatoes, bananas, ornamental plants, squash and coffee); animal feces (cattle, sheep, goat and horse); soil and fallen leaves from forest; and plants with signs of nematode infection. Each sample was processed using three techniques for the extraction of fungi from soil: sprinkling technique, soil dilution and humidity chamber. Twenty four strains of nematophagous fungi were found in 19 farms; 83.3% of the fungi were isolated by sprinkling technique. The following fungi were idenified: Arthrobotrys oligospora (n=13); Candelabrella musiformis (n=9); and for the first time there was isolation of A. conoides (n=1) and A. dactyloides (n=1) in the country. Moreover, 16 strains from Trichoderma (n=13), Beauveria (n=1), Clonostachys (n=1) and Lecanicillium (n=1) were obtained. In addition, pH of each possible fungal isolation source was measured, and it varied from 5.2 to 9.9, however PNF isolates fell within the range of 5.6 to 7.5. The PNF strains were cultivated in four different media for the production of chhlamydospores: potato dextrose agar (PDA); corn meal agar (CMA); malt extract agar (MEA) and potato carrot agar (PCA). Out of these cultures, 95.8% of the strains formed chlamydospores primarily in the PCA. Of these strains, the profilic spore producers were subjected to ruminant artificial gastrointestinal conditions. A total of 14 fungi were tested, out of which 42.9% survived the digestive analysis. Neither A. conoides nor A. dactyloides were viable following the in vitro gastrointestinal test. The PNF isolated in this study demostrated an action against ovine and caprine gastrointestinal nematodes and are candidates for use in biological control of these organisms. Among these microorganisms, Candelabrella musiformis appears to be the most promising fungi for use as a biological control agent in Costa Rica. Rev. Biol. Trop. 59 (1): 37-52. Epub 2011 March 01.
El control biológico es en la actualidad una alternativa para el control de los nematodos gastrointestinales que desarrollaron resistencia a los principales grupos de antihelmínticos. Para el aislamiento e identificación de hongos nematófagos depredadores, se tomaron muestras de 51 fincas distribuidas entre todas las provincias de Costa Rica. La naturaleza de las muestras incluyó: suelos de diferentes sembradíos (papa, tomate, banano, plantas ornamentales, chayote y café), heces de animales (bovinos, ovinos, caprinos y equinos), suelo y hojarasca de bosques y plantas con signos de enfermedad causada por nematodos. Las muestras se procesaron mediante 3 técnicas diferentes para la extracción de hongos a partir del suelo: espolvoreado en placa, dilución de suelos y cámara húmeda. Veinticuatro cepas de hongos nematófagos fueron aisladas de 19 fincas; el 83.3% de éstos fueron aislados mediante las técnica de espolvoreado en placa. Los hongos fueron identificados como: Arthrobotrys oligospora (n=13), Candelabrella musiformis (n=9) y por primera vez se reporta el aislamiento de A. conoides (n=1) y A. dactyloides (n=1) en el país. Asimismo, se aislaron 16 cepas de hongos de los géneros Trichoderma (n=13), Beauveria (n=1), Clonostachys (n=1) y Lecanicillium (n=1). Adicionalmente se les midió el pH, el cual varió entre 5.2-9.9, ubicándose los HND dentro de un rango entre 5.6-7.5. Las cepas de HND fueron cultivadas en 4 medios diferentes para la producción de clamidosporas: papa dextrosa agar, harina de maíz, extracto de malta y agar papa-zanahoria. El 95.8% de las cepas aisladas produjeron clamidosporas, principalmente en el medio agar papa-zanahoria. De estas cepas, se escogieron las de mayor producción para ser sometidas a la prueba de digestibilidad in vitro. Un total de 14 cepas fueron sometidos a esta prueba, de las cuales el 42.9% resultaron viables; de éstas, las cepas de A. conoides y A. dactyloides no sobrevivieron a la prueba de digestibilidad in vitro. De los microorganismos aislados, Candelabrella musiformis se considera el más promisorio de los hongos como agente biológico en Costa Rica.
Assuntos
Animais , Fungos/fisiologia , Doenças das Cabras/prevenção & controle , Nematoides/microbiologia , Infecções por Nematoides/veterinária , Controle Biológico de Vetores/métodos , Doenças dos Ovinos/prevenção & controle , Costa Rica , Fezes/microbiologia , Fungos/isolamento & purificação , Cabras , Doenças das Cabras/parasitologia , Infecções por Nematoides/prevenção & controle , Ovinos , Microbiologia do Solo , Doenças dos Ovinos/parasitologiaRESUMO
Sloths may serve as host to a wide range of parasites. However, there is little information available on the types of parasites that affect Costa Rica's sloth population. During a 1-yr period, 65 specimens of Costa Rican sloth species (Choloepus hoffmanni; n = 56) and Bradypus variegates; n = 9) from a local zoo were sampled. Fecal samples were evaluated using two different diagnostic techniques, Sheather's flotation and sedimentation. Concurrently, these sloths were examined for ectoparasites. Gastrointestinal parasites were found in 14 sloths (21.5%), from which 13 animals were C. hoffmanni and one was B. variegatus. Gastrointestinal parasites were recognized as Coccidia 71.4% (10/14), Cestoda 21.4% (3/14), and Spiruroidea 7.1% (1/14). Coccidia and cestodes were seen in C. hoffmanni, and spirurids were identified in B. variegatus. Among 27 sloths examined, only six had dermal problems (five C. hoffmanni and two B. variegatus). Ectoparasites recovered were Sarcoptes scabiei (Acari, Sarcoptidae) mites and Amblyomma varium (Acari, Ixodidae) ticks. This is the first time that cestode strobilae and nematode eggs are reported in sloth feces and that Monezia benedeni and L. leptocephalus were found in captive sloths.
Assuntos
Ectoparasitoses/veterinária , Enteropatias Parasitárias/veterinária , Doenças Parasitárias em Animais/epidemiologia , Bichos-Preguiça/parasitologia , Animais , Animais de Zoológico/parasitologia , Costa Rica/epidemiologia , Ectoparasitoses/epidemiologia , Fezes/parasitologia , Feminino , Helmintíase Animal/epidemiologia , Enteropatias Parasitárias/epidemiologia , Masculino , Infecções Protozoárias em Animais/epidemiologiaRESUMO
BACKGROUND: Life at altitude depends on adaptation to ambient hypoxia. In the Andes, susceptibility to chronic mountain sickness (CMS), a clinical condition that occurs to native highlanders or to sea level natives with prolonged residence at high altitude, remains poorly understood. We hypothesized that hypoxia-associated gene expression in children of men with CMS might identify markers that predict the development of CMS in adults. We assessed distinct patterns of gene expression of hypoxia-responsive genes in children of highland Andean men, with and without CMS. METHODS: We compared molecular signatures in children of highland (HA) men with CMS (n = 10), without CMS (n = 10) and in sea level (SL) children (n = 20). Haemoglobin, haematocrit, and oxygen saturation were measured. Gene expression in white cells was assessed at HA and then, in the same subjects, within one hour of arrival at sea level. RESULTS: HA children showed higher expression levels of genes regulated by HIF (hypoxia inducible factor) and lower levels of those involved in glycolysis and in the tricarboxylic acid (TCA) cycle. Pyruvate dehydrogenase kinase 1(PDK1) and HIF prolyl hydroxylase 3 (HPH3) mRNA expressions were lowest in children of CMS fathers at altitude. At sea level the pattern of gene expression in the 3 children's groups was indistinguishable. CONCLUSION: The molecular signatures of children of CMS patients show impaired adaptation to hypoxia. At altitude children of CMS fathers had defective coupling between glycolysis and mitochondria TCA cycle, which may be a key mechanism/biomarker for adult CMS. Early biologic markers of disease susceptibility in Andeans might impact health services and social planning.
Assuntos
Doença da Altitude/fisiopatologia , Altitude , Metabolismo Energético/fisiologia , Hipóxia/fisiopatologia , Adaptação Fisiológica/genética , Adaptação Fisiológica/fisiologia , Adolescente , Adulto , Doença da Altitude/genética , Doença da Altitude/metabolismo , Criança , Pré-Escolar , Doença Crônica , Ciclo do Ácido Cítrico/fisiologia , Estudos Transversais , Dioxigenases/genética , Metabolismo Energético/genética , Expressão Gênica , Glicólise/fisiologia , Hematócrito , Hemoglobina A/análise , Humanos , Prolina Dioxigenases do Fator Induzível por Hipóxia , Masculino , Valor Preditivo dos Testes , Proteínas Serina-Treonina Quinases/genética , Piruvato Desidrogenase Quinase de Transferência de Acetil , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The study of the biology of evolution has been confined to laboratories and model organisms. However, controlled laboratory conditions are unlikely to model variations in environments that influence selection in wild populations. Thus, the study of "fitness" for survival and the genetics that influence this are best carried out in the field and in matching environments. Therefore, we studied highland populations in their native environments, to learn how they cope with ambient hypoxia. The Andeans, African highlanders and Himalayans have adapted differently to their hostile environment. Chronic mountain sickness (CMS), a loss of adaptation to altitude, is common in the Andes, occasionally found in the Himalayas; and absent from the East African altitude plateau. We compared molecular signatures (distinct patterns of gene expression) of hypoxia-related genes, in white blood cells (WBC) from Andeans with (n = 10), without CMS (n = 10) and sea-level controls from Lima (n = 20) with those obtained from CMS (n = 8) and controls (n = 5) Ladakhi subjects from the Tibetan altitude plateau. We further analyzed the expression of a subset of these genes in Ethiopian highlanders (n = 8). In all subjects, we performed the studies at their native altitude and after they were rendered normoxic. We identified a gene that predicted CMS in Andeans and Himalayans (PDP2). After achieving normoxia, WBC gene expression still distinguished Andean and Himalayan CMS subjects. Remarkably, analysis of the small subset of genes (n = 8) studied in all 3 highland populations showed normoxia induced gene expression changes in Andeans, but not in Ethiopians nor Himalayan controls. This is consistent with physiologic studies in which Ethiopians and Himalayans show a lack of responsiveness to hypoxia of the cerebral circulation and of the hypoxic ventilatory drive, and with the absence of CMS on the East African altitude plateau.
Assuntos
Adaptação Fisiológica/genética , Doença da Altitude/genética , Altitude , Hipóxia/genética , Doença da Altitude/fisiopatologia , Estudos de Coortes , Etiópia , Hipóxia/fisiopatologia , Nepal , PeruRESUMO
Hypoxia is implicated in aging and neurodegenerative diseases. We posited that changes in gene expression induced by ambient hypoxia at altitude may be neuroprotective to natives of these regions. We studied 30 men. Twenty natives of Cerro de Pasco (CP), altitude 4,338 m were examined in CP; then transported within 6 h to Lima (150 m-sea level) and examined 1 h after arrival. They were assessed by a Chronic Mountain Sickness-score (CMS-sc) in CP, 10 were normal Andeans and 10 had chronic mountain sickness (CMS), a sudden inexplicable loss of adaptation to their native environment. RNA was extracted from venous blood white cells. The Andeans were compared to 10 normal US men living at 1500 m using RT-PCR. We focused on the cyto-neuro-protective genes, Ataxia telangiectasia mutated (ATM), heme-oxygenase-1 (HMOX 1), heat shock protein-70 (HSP-70), heat shock protein-90 (HSP-90), and the neuroprotective enzyme, nicotinamide mononucleotide adenylyl transferase 1 (Nnmat 1). CMS patients had significantly higher levels of gene expression (HMOX-1, HSP-70, ATM) than Andean controls in CP. HSP-90 and Nmnat 1, however, were higher in Andean controls in all locations. Significant reductions of all gene products, within an hour of arriving in normoxia in Lima, were found. In Andean controls, the gene products in Lima fell to levels approaching US controls. Correlation and regression methods showed men with high expression of all gene products had an average CMS-sc=19.8; those with low expression a normal score (9.4, P=0.02). ATM expression was related to age (P<0.001). The natural experiment that unfolds in the mountainous regions of the world provides opportunities to study neuroprotection in intact humans.
Assuntos
Altitude , Perfilação da Expressão Gênica , Hipóxia/fisiopatologia , Adaptação Fisiológica , Envelhecimento/metabolismo , Doença da Altitude/metabolismo , Doença da Altitude/fisiopatologia , Doença da Altitude/prevenção & controle , Doença Crônica , Humanos , Hipóxia/metabolismo , Hipóxia/prevenção & controle , Masculino , Peru , Valores de Referência , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Autonomic function is altered by altitude in sojourners and natives. We hypothesized that these physiologic responses are modulated by changes in gene expression. We compared gene product levels in 20 natives of Cerro de Pasco (CP), (4338 m), 10 of which had chronic mountain sickness (CMS) established by a CMS-scoring system, with gene products in the same men after 1 h at sea level. We further compared the results with those obtained from 10 US men residing at 1500 m. We measured gene products in white cells by reverse transcription polymerase chain reaction (RT-PCR). We focused on genes important in vascular autonomic physiology, and/or activated by hypoxia; hypoxia inducible factor 1-alpha (HIF 1-alpha), 2 splicing variants of vascular endothelial growth factor (VEGF); VEGF-121, VEGF-165, and phosphoglycerate kinase 1 (PGK 1). Normal CP natives showed high expression of all genes in CP, compared to US controls. Within 1 h of arrival at sea level, they had comparable levels to US residents. In CMS, the gene products were higher in CP. Although gene products decreased in Lima in this group, they never reached US values. VEGF 121 and 165 were correlated (P<0.001). VEGF 165 was higher in CMS in CP (P=0.006), and was positively correlated with CMS-score (R=0.86, P<0.001), and negatively correlated with arterial saturation (R=-0.79, P<0.001). Our findings underscore the changes in gene expression levels in intact humans in response to environmental stress. These changes may support the physiologic alterations induced by the ambient hypoxia at altitude and impact organism survival. They also suggest therapeutic strategies for autonomic and neurodegenerative diseases at sea level.
Assuntos
Doença da Altitude/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Regulação da Expressão Gênica , Hipóxia/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adaptação Fisiológica , Adulto , Altitude , Doença da Altitude/genética , Doença da Altitude/metabolismo , Doença Crônica , Humanos , Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Peru , Fosfoglicerato Quinase/classificação , Fosfoglicerato Quinase/genética , Fosfoglicerato Quinase/metabolismo , Estados Unidos , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Plasma catechols and blood volume were measured in 20 male, native high-altitude residents of Cerro de Pasco, Peru (4338 m), while hypoxic and subsequently while normoxic at sea level. Ten subjects were healthy controls,with hematocrits lower than 61%, and ten had chronic mountain sickness (CMS), a syndrome of maladaptation to altitude, characterized by polycythemia (hematocrit > 61%), profound hypoxemia, and neurologic symptoms. The main aim of the study was to evaluate the chronic effects of hypoxia on plasma catechols and on blood volume, by studying these parameters during hypoxia at high altitude (HA) and shortly after exposure to normoxia at sea level (SL). Subjects were first studied at HA in their habitual hypoxic environment, and measurements were repeated within 4 hours of arrival at SL (Lima, Peru, 150 m). All subjects had higher plasma norepinephrine (NE), dopamine (DA), and dihydroxyphenylglycol (DHPG) levels in HA (NE in controls and CMS: 414+/-47 and 514+/-35 pg/mL; DA: 9+/-1 and 13+/-1 pg/mL, DHPG: 817+/-48 and 972+/-77 pg/mL) than at SL (NE: 164+/-9 and 243+/-28 pg/mL; DA: 4+/-0.5 and 5+/-1 pg/mL DHPG: 502+/-23 and 649+/-39 pg/mL). Group differences were statistically significant only for NE in the CMS group. Plasma volume was higher in HA in both groups (p<0.05); red cell volume was higher in HA only in the CMS group. The results indicate sympathetic nervous stimulation by chronic ambient hypoxia at altitude in Andean natives, independent of maladaptation to their native environment.
Assuntos
Altitude , Volume Sanguíneo , Catecolaminas/sangue , Hipóxia/sangue , Oxigênio/fisiologia , Adaptação Fisiológica , Adulto , Doença da Altitude/sangue , Doença da Altitude/fisiopatologia , Estudos de Casos e Controles , Dopamina/sangue , Epinefrina/sangue , Hematócrito , Humanos , Masculino , Metoxi-Hidroxifenilglicol/análogos & derivados , Metoxi-Hidroxifenilglicol/sangue , Pessoa de Meia-Idade , Norepinefrina/sangue , Peru , Sistema Nervoso Simpático/fisiologia , Fatores de TempoRESUMO
Chronic mountain sickness (CMS), a maladaptation syndrome to chronic hypoxia, occurs in the Andes. Gene expression differences in Andeans could explain adaptation and maladaptation to hypoxia, both of which are relevant to neurology at sea level. Expression of genes responsive to cellular oxygen concentration, hypoxia-inducible factor-1alpha (HIF-1alpha), three splicing variants of vascular endothelial growth factor (VEGF) and von Hippel-Lindau protein (pVHL) was measured by reverse transcription polymerase chain reaction (RT-PCR) in 12 Cerro de Pasco (CP) (altitude 4338 m) natives and 15 CMS patients in CP. Thirteen high altitude natives living in Lima and five Lima natives were sea level controls. A CMS score (CMS-sc) was assigned clinically. Expression was related to the clinical assessment. High expression of HIF-1alpha and VEGF-121 was found in CMS (P<0.001). Samples from CP had higher expression than those from Lima (P<0.001). Expression of HIF-1alpha and VEGF-121 was related to age (P<0.001); adjusting for age did not abolish the group effect. Higher CMS-sc was related to expression independent of age (P<0.001). VEGF-165 and -189 were expressed only in CMS. Birth altitude had no effect on gene expression. pVHL was not quantifiable.HIF-1alpha and VEGF-121 participate in adaptation to hypoxia. The high levels may explain blood vessel proliferation in Andeans and hold lessons for patients at sea level. VEGF-165 expression suggests that it contributes to preservation of neuronal function in human chronic hypoxia. VHL mutations may mark those destined to develop neural crest tumors which are common in the Andes.
Assuntos
Doença da Altitude/metabolismo , Altitude , Regulação da Expressão Gênica/fisiologia , Fatores de Transcrição , Adulto , Doença da Altitude/genética , Doença da Altitude/fisiopatologia , Análise de Variância , Proteínas de Ligação a DNA/biossíntese , Fatores de Crescimento Endotelial/biossíntese , Humanos , Fator 1 Induzível por Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Linfocinas/biossíntese , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/biossíntese , Peru/epidemiologia , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
Polycythemia is one of the key factors involved in the chronic mountain sickness syndrome, a condition frequent in Andean natives but whose causes still remain unclear. In theory, polycythemia may be secondary to abnormalities in ventilation, occurring during day or night (e.g. due to sleep abnormalities) stimulating excessive erythropoietin (Epo) production, or else it may result from either autogenous production, or from co-factors like cobalt. To assess the importance of these points, we studied subjects with or without polycythemia, born and living in Cerro de Pasco (Peru, 4330m asl, CP) and evaluated the relationship between Epo and respiratory variables both in CP and sea level. We also assessed the relationship between sleep abnormalities and the circadian rhythm of Epo. Polycythemic subjects showed higher Epo in all conditions, lower SaO2 and hypoxic ventilatory response, higher physiological dead space and higher CO2, suggesting ventilatory inefficiency. Epo levels could be highly modified by the level of oxygenation, and were related to similar directional changes in SaO2. Cobalt levels were normal in all subjects and correlated poorly with hematologic variables. The diurnal variations in Epo were grossly abnormal in polycythemic subjects, with complete loss of the circadian rhythm. These abnormalities correlated with the levels of hypoxemia during the night, but not with sleep abnormalities, which were only minor even in polycythemic subjects. The increased Epo production is mainly related to a greater ventilatory inefficiency, and not to altered sensitivity to hypoxia, cobalt or sleep abnormalities. Improving oxygenation can represent a possible therapeutic option for this syndrome.