Primovist® (Gadotrexate disodium) magnetic resonance use in benign and malignant kidney diagnosis. / Uso de la resonancia magnetica con Primovist® (Gadotrexate disodio) para diagnostico de lesiones renales benignas y malignas.

OBJECTIVE: To evaluate the quality of the contrast images obtained with a Primovist® (gadoxetate disodium) Magnetic Resonance Image in order to diagnose benign, malignant and malformations in the urinary tract. MATERIAL AND METHODS: A retrospective image and diagnosis review of Primovist® MRI studies performed in liver insufficient patients without apparent renal abnormalities was done, in order to evaluate the urinary tract for irregularities. RESULTS: A total of 117 Primovist® MRI studies performed between july 2014 and November 2018 were reviewed, 5 were excluded because they were incomplete. The average age was 59.6 ± 16.6 years old. The following diagnosis were encountered: 36 simple cysts, 6 perirenal fibrosis after pyelonephritis, 1 renal cancer, 1 renal atrophy, 1 proximal uretheric flexure, 1 bilateral hydronephrosis due to lower urinary obstruction because of benign prostatic hyperplasia and 1 complex cyst. No MRI study was indicated with suspicions of renal abnormalities. Relevant images are included that demonstrate the capability of Primovist® MRI to diagnose renal abnormalities. CONCLUSION: Even though none of the Primovist® MRI studies was done with suspicious of renal abnormalities it was possible to diagnose incidental benign, malignant and malformations of the urinary tract. This study shows how Primovist® MRI can be useful contrast study for urinary tract irregularities.

OBJETIVO: Evaluar la calidad de las imágenes contrastadas del tracto urinario que permitan diagnosticar patologías benignas, malignas y malformaciones con el uso de una resonancia magnética contrastada con Primovist® (gadoxetato disodio). MATERIAL Y METODOS: Se realizó una revisión de las imágenes y diagnósticos del servicio de radiología de manera retrospectiva de pacientes con una resonancia magnética contrastada con Primovist® por padecer insuficiencia hepática sin aparente patología urinaria, con el objeto de buscar diagnósticos incidentales en el tracto urinario superior e inferior. RESULTADOS: Se revisaron durante el periodo de julio del 2014 a noviembre del 2018, 117 estudios, se excluyeron 5 por no contar con el estudio completo para su revaloración. La edad promedio fue de 59,6±16,6 años. Se encontraron 48 anormalidades urinarias sin previa sospecha diagnóstica por lo que fueron considerados como incidentales. A continuación se enumeran los hallazgos renales diagnosticados: 36 quistes simples, 6 cambios perirenales compatibles con secuelas de pielonefritis, 1 cáncer renal, 1 hipotrofia renal, 1 angulación funcional del uréter proximal sin cruce vascular con pelvis extrarenal contralateral, 1 hidronefrosis bilateral secundaria a obstrucción vesical por hiperplasia prostática y 1 quiste complejo. Ningún estudio se indicó por sospecha de anormalidades del tracto urinario. CONCLUSIONES: Aun cuando no era la indicación del estudio de resonancia, fue posible encontrar algunas patologías renales como hallazgos que incluyeron patología benigna, maligna y malformaciones, demostrando que la resonancia magnética con Primovist® se podría realizar como estudio contrastado para patologías renales.

Determine safety of outpatient chemotherapy and autotransplants using refrigerated, non-frozen grafts in persons with multiple sclerosis.

BACKGROUND: Persons with multiple sclerosis are increasingly treated with intermediate- or high-dose chemotherapy and a hematopoietic cell autotransplant. This is often done in an inpatient setting using frozen blood cell grafts. OBJECTIVE: Determine if chemotherapy and a hematopoietic cell autotransplant can be safely done in an outpatient setting using refrigerated, non-frozen grafts. METHODS: We developed an autotransplant protocol actionable in an outpatient setting using a refrigerated, non-frozen blood graft collected after giving cyclophosphamide, 50 mg/kg/d × 2 days and filgrastim, 10 µg/kg/d. A second identical course was given 9 days later followed by infusion of blood cells stored at 4°C for 1-4 days. The co-primary outcomes were rates of granulocyte and platelet recovery and therapy-related mortality. RESULTS: We treated 426 consecutive subjects. Median age was 47 years (range, 21-68 years). A total of 145 (34%) were male. Median graft refrigeration time was 1 day (range, 1-4 days). Median interval to granulocytes >0.5 × 10E + 9/L was 8 days (range, 2-12) and to platelets >20 × 10E + 9/L, 8 days (range, 1-12). Only 15 subjects (4%) were hospitalized, predominately for iatrogenic pneumothorax (N = 5) and neutropenic fever (N = 4). There was only 1 early death from infection. CONCLUSION: Intermediate-dose chemotherapy and a hematopoietic cell autotransplant can be safely done in an outpatient setting using, refrigerated, non-frozen grafts.

Metabolic Changes in Children that Received Chemotherapy.

Cancer treatments are associated with short and long-effects. Epidemiological reports have revealed clinical features of metabolic syndrome (MS), obesity or overweight in young cancer survivors. The aim of the study was to examine the prevalence of unhealthy weight status and risk factors associated with MS related to chemotherapy. We study 52 pediatric cancer patients and analyze cholesterol, triglycerides, glycosylated hemoglobin, body mass index, waist circumference (WC), FINDRISC test. All the parameters were analyzed according to the percentile corresponding to sex and age of each child. The data show an important modification in weight, body mass index, and WC as in triglycerides, and cholesterol that could be associated with the development of MS. The variance analysis showed that the WC, triglycerides, and cholesterol are statistically correlated in our population. A follow-up for MS in children cancer survivor should be considered necessary.

P-glycoprotein Activity Correlates With Treatment Response in 2 Leukemia Child Patients.

Acute lymphoblastic leukemia is the most important childhood cancer. Multidrug resistance is an important factor of poor prognosis. We present the P-glycoprotein (P-gp) activity in 2 patients with different outcomes. Both patients had B-cell acute lymphoblastic leukemia; they were responding properly to the treatment, but one of them had an increment in the P-gp activity that correlates with an increment in the disease manifestation, the patient had to be hospitalized and developed sepsis and subsequently died. P-gp levels were correlated with disease progression. P-gp activity needs to be evaluated during treatment to assess and prevent disease relapse or the patient´s death.

Development of Metabolic Syndrome Associated to Cancer Therapy: Review.

Long-term childhood cancer survivors are at great risk of developing late adverse effects after treatment, such as, reduced growth, obesity, decreased fertility, high blood pressure, cardiovascular diseases, impaired glucose, another form of cancer, among others organ dysfunctions, some of them are part of the metabolic syndrome. Metabolic syndrome and cancer connection is still not entirely understood, but there are some notions about it. Metabolic alterations produced during childhood cancer are more likely determined by treatments like radiotherapy, chemotherapy, glucocorticoids therapy, and surgery. Cancer treatment is associated to vascular alterations, hormone deficiencies, changes in insulin sensitivity, lipid metabolism, and inflammatory mediators. Obesity has been considered a crucial component in metabolic syndrome; obesity risk factors during childhood cancer include cranial radiation, female gender, and exposure to glucocorticoids such as dexamethasone. In addition, local radiotherapy or surgery may cause endocrine deficiencies, depends on the directly damage of endocrine organs. Patients who received some types of cancer treatment should be evaluated periodically to early diagnostic metabolic disorders associated to antineoplastic therapy.

Hematoma paravesical espontáneo posterior a dosis única profiláctica de enoxaparina en cirugía ortopédica. Presentación de un caso / Spontaneous paravesical hematoma at a single prophylactic doses of enoxaparin in Orthopedic surgery. Case report

El hematoma paravesical espontáneo es una complicación infrecuente, con pocos casos reportados en la literatura. Aproximadamente el 2 % de los pacientes que se traten con enoxaparina profiláctica tendrán complicaciones hemorrágicas, de las cuales el 20 % son hematomas retroperitoneales o intracraneales, en dependencia de los factores de riesgo. Por tales razones se presenta el caso de un paciente de 35 años de edad, previamente sano, que fue sometido a una sutura de tendón de Aquiles después de sufrir un trauma, al que se le administró profilácticamente una sola dosis de enoxaparina en el posoperatorio inmediato y 24 horas después comenzó a quejarse de dolor en fosa iliaca derecha y disuria. El ultrasonido abdominal demostró un hematoma paravesical, que fue confirmado por topografía. Se manejó conservadoramente con sonda intravesical por diez días. Se realizó seguimiento del paciente, sin que se encontraran secuelas. Los autores infieren que el sangrado fue secundario a una sobredistensión vesical secundaria a la anestesia que provocó el sangrado de la pared de la vejiga. Este reporte demuestra que la enoxaparina profiláctica puede causar hematomas paravesicales espontáneos asociados a la sobredistención vesical. Sin embargo son necesarios otros reportes similares para confirmar lo anteriormente planteado.

Spontaneous paravesical hematoma is an infrequent complication, with a few reported cases in literature. Approximately 2 % of the patients treated with prophylactic enoxoparin will have hemorrhagic complications, from which 2 0% are retroperitoneal or intracranial hematomas depending on the risk factors. For such reasons it is presented a 35 year old patient, previously healthy, who was performed to a suture of the Achilles tendon after suffering a trauma. He was administered prophylactically a single doses of enoxoparin in the immediate post surgery and 24 hours later he started to complain of pain in the right lower quadrant and dysuria. Abdominal ultrasound showed a paravesical hematoma secondary to anesthesia which caused bleeding of the vesicle walls. This report shows prophylactic exoparin may produce spontaneous paravesical hematomas associated to vesical overdistention. However it is necessary other similar reports to confirm the previous statement.

Outcome of Recipients of Hematopoietic Stem Cell Transplants Who Require Intensive Care Unit Support: A Single Institution Experience.

Admission to the intensive care unit (ICU) of a patient who has been grafted with hematopoietic stem cells is a serious event, but the role of the ICU in this setting remains controversial. Data were analyzed from patients who underwent autologous or allogeneic bone marrow transplantation at the Centro de Hematología y Medicina Interna de Puebla, México, between May 1993 and October 2014. In total, 339 patients were grafted: 150 autografts and 189 allografts; 68 of the grafted patients (20%) were admitted to the ICU after transplantation: 27% of the allografted and 11% of the autografted patients (p = 0.2). Two of 17 autografted patients (12%) and 5 of 51 allografted patients (10%) survived. All patients who required insertion of an endotracheal tube died, whereas 7 of 11 patients without invasive mechanical ventilation survived (p = 0.001). Only 10% of the grafted patients survived their stay in the ICU; this figure is lower than those reported from other centers and may reflect several facts, varying from the quality of the ICU support to ICU admission criteria to the initial management of all the grafts in an outpatient setting, which could somehow delay the arrival of patients to the hospital.

Relación del consumo de productos para bajar de peso con el sobrepeso y la obesidad en profesores universitarios de Puebla, México / The relation between overweight and obesity with the use of weight loss products in university professors of Puebla, Mexico

Antecedentes. Las tendencias de obesidad y sobrepeso en México muestran un significativo incremento en las últimas encuestas nacionales. Esto se ve reflejado en el incremento de las enfermedades crónicas no transmisibles, además de un mayor consumo de agentes para pérdida de peso. Objetivo. Encontrar la relación entre el consumo de productos adelgazantes, el sobrepeso y la obesidad en profesores de una universidad privada de Puebla, México. Materiales y métodos. Se realizó un diseño no experimental, transversal descriptivo, utilizando un muestreo probabilístico aleatorio simple, en el que participaron 100 profesionistas; 27 hombres y 73 mujeres. Se aplicó un cuestionario para conocer los hábitos, el consumo de agentes para pérdida de peso, además de mostrárseles modelos anatómicos que determinaron la percepción de la persona con su cuerpo. Finalmente se realizó la medición antropométrica y se obtuvo el cálculo de su índice de masa corporal (IMC). Resultados. El 45% de las personas involucradas presentan sobrepeso y obesidad.38% consumen productos para bajar de peso; de estos, 84,2% eran mujeres. Entre mayor índice de masa corporal (IMC) mayor consumo de productos para bajar de peso (p<0.05). Se observa una relación inversa entre mayor obesidad y menor número de comidas al día, a la par con un menor número de horas de ejercicio. Finalmente, la mayoría de las personas con sobrepeso se perciben con un IMC mayor. Conclusión. El consumo de agentes para pérdida de peso se relaciona con el incremento del sobrepeso y la obesidad en los profesionistas.

Background. Current tendencies in obesity and overweight in México shows a significant increase in the last National Nutrition and Health Surveys, which is reflected in the rise of chronic non-transmissible diseases and an increase of anti-obesity drugs. Objective. Find the relationship between the consumption of anti-obesity drugs, overweight and obesity in teachers at a private university of Puebla city, in Mexico. Materials and methods. This is a non-experimental, cross-sectional descriptive design, where a simple random probability sampling was used. 100 professional workers at a private university of Puebla city participated, 27 men and 73 women. It was applied a test to each one of them, in order to identify their habits and consume of anti-obesity drugs. Anatomical models were presented to the participants to determinate their self-perception of body image. Finally anthropometric measures were done and body mass index was calculated. Results. 45% of participants presented overweight and obesity; 38% consume anti-obesity drugs, of these, 84.2% are women. It was observed that higher body mass index (BMI) gives a higher consume of anti-obesity drugs (p<0.05). It was determined an inversed relationship between a higher obesity degree and a lower number of meals a day, correlated also with a lower number of exercise hours. Finally people with a healthy BMI, have adequate self-perception of body image and the majority of people with overweight, perceived themselves with a higher BMI. Conclusions. The consumption of anti-obesity drugs is related to the increase of overweight and obesity in professional workers.

A comprehensive review of urologic complications in patients with diabetes.

Diabetes Mellitus (DM) is a chronic disease characterized by hyperglycemia, as a result of abnormal insulin production, insulin function, or both. DM is associated with systemic complications, such as infections, neuropathy and angiopathy, which involve the genitourinary tract. The three most significant urologic complications include: bladder cystopathy, sexual dysfunction and urinary tract infections. Almost half of the patients with DM have bladder dysfunction or cystopathy, which can be manifested in women as hypersensitivity (in 39-61% of the diabetic women) or neurogenic bladder. In males it can be experienced as lower urinary tract symptoms (in 25% of diabetic males with a nearly twofold increased risk when seen by age groups). Additionally, an increased prostate volume affects their micturition as well as their urinary tract. Involving sexual dysfunction in women, it includes reduced libido, decreased arousal, clitoral erectile dysfunction and painful or non-sensitive intercourse; and in diabetic males it varies from low libido, ejaculatory abnormalities and erectile dysfunction. Globally, sexual disorders have a prevalence of 18-42%. Erectile dysfunction is ranked as the third most important complication of DM. Urinary tract infections are observed frequently in diabetic patients, and vary from emphysematous infections, Fournier gangrene, staghorn infected lithiasis to repetitive bacterial cystitis. The most frequent finding in diabetic women has been lower urinary tract infections. Because of the high incidence of obesity worldwide and its association with diabetes, it is very important to keep in mind the urologic complication associated with DM in patients, in order to better diagnose and treat this population.

Sertoli-Leydig cell tumor in a 12-year-old girl: a review article and case report.

BACKGROUND: The Sertoli and Leydig cell tumor is an unusual neoplasm that belongs to the sex cord-stromal tumors. Generally these tumors are associated with good prognosis. These tumors usually present virilizing symptoms such as oligomenorrhea or amenorrhea, hirsutism, voice raucity, laryngeal protuberance and clitoromegaly. CASE PRESENTATION: A 12 year old girl referred acute abdominal pain with no other clinical manifestations. An abdominal ultrasound showed a semisolid mass suggestive of ovarian tumor. The diagnosis was confirmed by a computed tomography. A unilateral salpingo oophorectomy was performed and the pathologist reported a Sertoli-Leydig tumor with intermediate differentiation. The outcome was excellent. CONCLUSIONS: These tumors represent a rare condition in children. However, they can occur at any age, therefore it is important to acknowledge the clinical manifestations, diagnostic approach and therapeutic options. In this case the patient presented unusual symptoms which makes it more interesting.

Focal dermal hypoplasia with uterus bicornis and renal ectopia: case report and review of the literature.

Focal dermal hypoplasia (FDH) is a rare inherited genodermatosis with an X-linked dominant trait. FDH is associated with skin defects and other abnormalities of bone, nails, hair, limbs, teeth and eyes. We present the case of a 26-year-old female in the 27th pregnancy week and a previous history of miscarriage. After careful physical examination and dermal biopsy, histopathology revealed that the patient was a carrier of FDH. This is the first report in the literature describing that FDH is associated with uterus bicornis and renal ectopia. Our association could be attributable to early embryonic abnormalities related with FDH because both the uterus bicornis and the renal ectopia originate around the 3th-6th week of embryonic development. We are unable to confirm that the miscarriages were caused by inherited FDH or that uterus bicornis was the cause. We conducted a literature review using the following terms: FDH, Goltz syndrome, uterus bicornis, and renal ectopia.

Modulación de la respuesta inmunológica durante el embarazo / Immunologic response modulation during pregnancy

El sistema inmunológico está capacitado para reconocer lo propio y lo no propio, por el cual, la pregunta ¿por qué el feto no es rechazado?, ha causado curiosidad. Actualmente se sabe que durante el embarazo existen modificaciones fisiológicas tanto en la inmunidad innata como en la adaptativa que le permiten al feto desarrollarse sin ser agredido por la respuesta inmune de la madre y al mismo tiempo le permiten a la madre continuar protegida contra los invasores del medio. Estos cambios que se manifiestan en el sistema inmune son consecuencia de las variaciones hormonales asociadas a la gestación, como consecuencia las células del sistema inmune y la liberación de citocinas es diferente en cada trimestre del embarazo, además también ahora se sabe que la participación de estas citocinas son esenciales en la implantación del feto, así como en los procesos patológicos asociados al embarazo como preeclampsia y abortos espontáneos.

Immunologic system is able to recognize the own and the non-own, therefore the curious question: Why the fetus is not rejected? Nowadays, it is known that during pregnancy there are physiological modifications about the innate immunity as in the adaptive one allowing fetus to develop without any aggression by the immune response of the mother against the environment aggressors. These changes manifesting in the immunologic system are consequences of hormonal variations associated with pregnancy due to the immunologic system cells and the release of cytokines is different in each trimester of pregnancy, now it is possible to know that the involvement of these cytokines is essential in the implantation of fetus, as well as in pathological processes associated with pregnancy including the pre-eclampsia and the spontaneous abortions.

P-glycoprotein activity in renal clear cell carcinoma.

BACKGROUND: The mechanism by which renal cancer patients show poor response to chemotherapy has not been well understood. The aim of this study was to evaluate the functional activity of P-glycoprotein (P-gp) in renal clear cell carcinoma (RCCC) and its possible role in chemotherapy resistance. METHODS: We studied 11 patients who underwent radical nephrectomy due to RCCC; from each patient we obtained a sample from the cancer tissue, and another from normal renal tissue. These biopsies were mechanically disaggregated to allow individual cells analysis. Cells were incubated with daunorubicin (a fluorescent drug extruded by P-gp) at 37 degrees C and 4 degrees C for 30 min. P-gp activity was analyzed using flow cytometry. Results were expressed as the percentage of cells with P-gp activity (i.e., low fluorescence). RESULTS: The analysis of renal cells showed that there was no significant difference in size between normal and cancer cells; however there were clusters of cells with different granularities. We divided the cells according to their granularity. The proportion of cells capable of extruding daunorubicin was significantly higher on tumor cells than in normal renal cells independently of the cell granularity. Our results are congruent with those obtained when mRNA or immunohistochemical test were used. This is the first report quantifying the P-gp activity from fresh samples obtained from kidney cancer in humans. CONCLUSIONS: Percentage of cells extruding daunorubicin in RCCC is elevated, indicating that P-gp activity may contribute to multidrug resistance in RCCC.

Association between polymorphisms of the androgen and vitamin D receptor genes with prostate cancer risk in a Mexican population.

INTRODUCTION: Prostate cancer (PCa) is a worldwide health issue, because of its high incidence and mortality. Its etiology is complex and includes certain risk factors such as age, hormonal status, ethnic origin and family history of PCa. Genetic predisposition is proposed as a major risk factor and there are several controversial reports on the association of PCa and gene polymorphism such as the receptors of the androgen receptor (AR) and the vitamin D (VDR). Objective. To evaluate the CAG triplet repeats in the first exon of the AR and polymorphisms in the restriction site Taql in the VDR in Mexicans with PCa. MATERIAL AND METHODS: A total of 68 Mexicans with histopathological diagnosis of PCa and 48 healthy Mexican with normal prostate-specific antigen and rectal exam where included. 10ml of peripheral blood were extracted to isolate DNA and the polymorphisms were evaluated with specific primers for the AR and VDR. RESULTS: The allelic and genetic distributions of the AR and VDR polymorphisms were consistent with the Hardy-Weinberg equilibrium, and there were no statistical differences between the PCa patients and controls (p > 0.05). However, there was a statistical difference between the number of CAG repeats in younger patients with PCa compared to controls (p = 0.045) but when the young patient group was compared versus the elder group there was not stadistically difference (p = 0.085), but the results showed a tendency towards less repetitions of CAG in elder patients. Concerning the VDR, when we analyzed the patients with PCa and a bad pathological prognosis they had a less frequent genotype of TT (p = 0.03). CONCLUSIONS: Our results suggest an association between the VDR and AR gene polymorphisms, and the histopathological score and age at diagnosis in Mexican patients with PCa, respectively. However, it is important to confirm these results in a larger scale study.

Association between polymorphisms of the androgen and vitamin D receptor genes with prostate cancer risk in a Mexican population / Asociación entre polimorfismo de andrógenos y receptores de vitamina D con riesgo de cáncer prostático en una población mexicana

Introduction. Prostate cancer (PCa) is a worldwide health issue, because of its high incidence and mortality. Its etiology is complex and includes certain risk factors such as age, hormonal status, ethnic origin and family history of PCa. Genetic predisposition is proposed as a major risk factor and there are several controversial reports on the association of PCa and gene polymorphism such as the receptors of the androgen receptor (AR) and the vitamin D (VDR). Objective. To evaluate the CAG triplets repetitions in the first exon of the AR and polymorphisms in the restriction site Taql in the VDR in Mexicans with PCa. Material and methods. A total of 68 Mexicans with histopathological diagnosis of PCa and 48 healthy Mexican with normal prostate specific antigen and rectal exam where included. 10ml of peripheral blood were extracted to isolate DNA and the polymorphisms were evaluated with specific primers for the AR and VDR. Results. The allelic and genetic distributions of the AR and VDR polymorphisms were consistent with the Hardy-Weinberg equilibrium, and there were no statistical differences between the PCa patients and controls (p > 0.05). However, there was a statistical difference between the number of CAG repeats in younger patients with PCa compared to controls (p = 0.045) but when the young patient group was compared versus the elder group there was not stadistically difference (p = 0.085), but the results showed a tendency towards less repetitions of CAG in elder patients. Concerning the VDR, when we analyzed the patients with PCa and a bad pathological prognosis they had a less frequent genotype of TT (p = 0.03). Conclusions. Our results suggest an association between the VDR and AR gene polymorphisms, and the hystopathological score and age at diagnosis in Mexican patients with PCa, respectively. However, it is important to confirm these results in a larger scale study.

Introducción. El cáncer de próstata (PCa) es un problema de salud mundial, tanto por su elevada incidencia como mortalidad. Su etiología es compleja e incluye factores de riesgo reconocidos como la edad, estado hormonal, origen étnico y antecedentes familiares de PCa. El fondo genético es un factor de riesgo y existen reportes controversiales de la asociación de PCa y polimorfismos en los genes como son los receptores de vitamina D (VDR) y el de andrógenos (AR). Objetivo. Evaluar las repeticiones de tripletes de CAG en el primer exon del AR y polimorfismos en el sitio de restricción Taql en el VDR en mexicanos con PCa. Material y métodos. Se incluyeron 68 mexicanos con diagnóstico histopatológico de PCa y 48 mexicanos con niveles normales de antígeno prostático y tacto rectal normal. Se les extrajo 10 mL de sangre periférica para aislar DNA y mediante olígos específicos se evaluaron los polimorfismos mencionados. Resultados. La distribución alélica y genotípica de los polimorfismos en el AR y VDR fueron consistentes con el equilibrio de Hardy-Weinberg, y no mostraron diferencias significativas entre los casos y controles (p > 0.05). Sin embargo, el número de repeticiones de CAG en el AR fueron estadísticamente diferentes en pacientes jóvenes con PCa comparados con los controles (p = 0.045), cuando se comparó el grupo de pacientes de jóvenes contra aquellos mayores de 60 años no se encontró diferencia estadísticamente significativa (p - 0.085); sin embargo, se observó una tendencia de un número menor de repetidos CAG en pacientes mayores con PCa. Por otra parte, al comparar VDR en los pacientes con PCa de mal pronóstico por el patrón histológico tenían menor frecuencia de genotipos TT (p - 0.03). Conclusiones. Nuestros resultados sugieren una asociación entre los polimorfismos de los genes del VDR y AR, y el patrón histológico y la edad al diagnóstico en pacientes mexicanos con PCa, respectivamente. Sin embargo, es necesario confirmar estos resultados en un estudio con mayor número de pacientes.

Human leukocyte antigen class I, class II, and tumor necrosis factor-alpha polymorphisms in a healthy elder Mexican Mestizo population.

BACKGROUND: There is strong evidence that an individual's genetic background is an important predisposing factor to longevity. In the present study we analysed the frequency of HLA class I, class II, as well as the TNF-alpha -308 polymorphism that may be related to an increased life span in Mexican Mestizo healthy elders. RESULTS: HLA typing was performed by polymerase chain reaction sequence specific oligonucleotide (PCR SSO) reverse dot blot. The TNF-alpha -308 polymorphism was assessed by PCR restriction fragment length polymorphism. A significant increased frequency of HLA-DRB1*11 was found in elderly women whereas this allele was not present in elderly males. The TNF2 allele was also increased in the elder group when compared to young controls. The frequencies of the remaining alleles tested were not statistically different among groups. CONCLUSION: These data suggest an ethnicity independent tendency of HLA-DRB1*11 in elder females to increase life span and a possible role of the TNF2 allele with the successful remodelling of senescent immune system.

Melatonin stimulates calmodulin phosphorylation by protein kinase C.

Calmodulin (CaM)-dependent processes can be modulated by the availability of Ca(+2), the subcellular distribution of both CaM and its target proteins, CaM antagonism, and post-translational modifications such as CaM phosphorylation. Melatonin, the pineal secretory product synthesized during the dark phase of the photoperiod is an endogenous CaM antagonist. This indolamine causes CaM subcellular redistribution in epithelial MDCK and MCF-7 cells, and selectively activates protein kinase C alpha (PKC alpha) in neuronal N1E-115 cells. In the present work we have characterized the phosphorylation of CaM mediated by PKC alpha and its stimulation by melatonin in an in vitro reconstituted enzyme system. Additionally, the participation of MAPK and ERKs, downstream kinases of the PKC signaling pathway, was explored utilizing MDCK cell extracts as source of these kinases. Phosphorylation of CaM was characterized in the whole cells by MDCK cell metabolic labeling with [(32)P]-orthoposhospate, and CaM separation by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, as well as by immunocolocalization of phosphorylated threonine/serine residues and CaM in cultured cells incubated with melatonin. Our results show that melatonin increased CaM phosphorylation by PKC alpha with an EC(50) of 10(-8) m in the presence of the phorbol ester, phorbol-12-myristate-13-acetate (PMA) in the in vitro reconstituted enzyme system. An increase in phosphorylated CaM was also observed in cells cultured with melatonin, or PMA for 2 hr, while, PKC, MAPK, or ERK inhibitors abolished CaM phosphorylation elicited by melatonin in MDCK cell extracts. Our data show that melatonin can stimulate phosphorylation of CaM by PKC alpha in the in vitro reconstituted system and suggest that in MDCK cells this phosphorylation is accomplished by PKC. Modification of CaM by melatonin can be another route to inhibit CaM interaction with its target enzymes.

P-glycoprotein in autoimmune diseases.

Multidrug resistance-1 (MDR-1) is characterized by overfunction of P-glycoprotein (P-gp), a pump molecule that decreases intracellular drug concentration by effluxing them from the intracellular space. Broad ranges of structurally unrelated compounds are transported by P-gp, including antineoplastic agents, HIV protease inhibitors, prednisone, gold salts, methotrexate, colchicine as well as several antibiotics. In contrast, many other compounds such as calcium channel blockers (verapamil) and immunosupressors (cyclosporine-A) are able to inhibit P-gp function. The P-gp role in therapeutic failures has been extensively studied in cancer; however, there is little information regarding MDR-1 phenotype in autoimmune disorders. It has been reported that an increased number of lymphocytes are able to extrude P-gp substrates in rheumatoid arthritis, immune thrombocytopenic purpura and systemic lupus erythematosus, the patients with poor response to treatment being the ones that exhibit the highest values. This may be due, at least in part, to a simultaneous long-term usage of several drugs that induce P-gp function. Since abnormally activated cell compartments characterize autoimmune diseases, it is possible that those cells are the ones that exhibit drug resistance. The study of drug resistance mechanisms in autoimmunity may be helpful for the optimization of the current therapeutic schemes through their combination with low doses of P-gp inhibitors.