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Enriquez J.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz | Garcia G.,National Autonomous University of Mexico | Herrero B.,INCMNSZ | Larrea F.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz
Endocrine Research | Year: 2017

Background: Clinical studies have shown that gestodene (GDN), a potent third-generation synthetic progestin, affects bone resorption. However, its mode of action in bone cells is not fully understood. The aim of this study was to establish whether GDN affects bone directly or through its bioconversion to other metabolites with different biological activities. Methods: In this study, we investigated the effects of GDN and its A-ring reduced metabolites on proliferation, differentiation, and mineralization of calvarial osteoblasts isolated from neonatal rat and their capacity to displace [3H]-E2 at ER binding sites. Results: In contrast to progesterone, gestodene did exert significant effects on osteoblast activities. The most striking finding was the observation that the A-ring reduced derivatives 3β,5α-tetrahydro-GDN and 3α,5α-tetrahydro-GDN, though to a lesser extent, had greater stimulatory effects on the osteoblast activity than those observed with GDN. The effects on osteoblast proliferation and differentiation induced by GDN-reduced derivatives were abolished by the antiestrogen ICI 182780, consistent with their binding affinities for the estrogen receptor. In addition, the presence of a 5α-reductase inhibitor or inhibitors of aldo-keto hydroxysteroid dehydrogenases abolished the GDN-induced enhancement of osteoblast differentiation. These results indicated that GDN is metabolized to the A-ring reduced metabolites with estrogen-like activities and through this mechanism, GDN may affect the osteoblast activity. Conclusion: Together, the data suggest that synthetic progestins derived from 19-nortestosterone such as GDN, have beneficial effects on bone due to their biotransformation into metabolites with intrinsic estrogenic activity. © 2017 Taylor & Francis

Larrieta-Carrasco E.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz | Leon-Mimila P.,National Autonomous University of Mexico | Villarreal-Molina T.,Laboratorio Of Genomica Of Enfermedades Cardiovasculares | Villamil-Ramirez H.,National Autonomous University of Mexico | And 12 more authors.
Gene | Year: 2013

Background and aims: Non-alcoholic fatty liver disease (NAFLD) and elevated alanine transaminase (ALT) levels are common in obese Hispanic adults and children. Recently, a PNPLA3 gene variant (I148M) was strongly associated with NAFLD and higher ALT levels in obese adults, including Hispanics. The aims of this study were to estimate the frequency of elevated ALT levels, and to address the influence of obesity and PNPLA3/I148M on ALT levels in a general population sample of Mexican school-aged children. Methods: A total of 1037 non-related Mexican children aged 6 to 12. years were genotyped for the I148M variant. Anthropometric, clinical and metabolic parameters were collected from all participants. Results: Elevated ALT levels (>35U/L) were more frequent in obese (26.9%) and overweight (9.3%) than in normal weight children (2.2%). The M148M genotype was significantly associated with elevated ALT levels in this population (OR=3.7, 95% CI 2.3-5.9; P=3.7×10-8), and children carrying the M148M genotype showed significantly lower HDL cholesterol levels and BMI z-core (P=0.036 and 0.015, respectively). On stratifying by BMI percentile, this genotype conferred a much greater risk of elevated ALT levels in normal weight (OR=19.9, 95% CI 2.5-157.7; P=0.005) than overweight and obese children (OR=3.4, 95% CI 1.3-8.9; P=0.014 and OR=3.1, 95% CI 1.7-5.5; P=1.4 x10-4, respectively). Conclusions: The I148M PNPLA3 variant is strongly associated with elevated ALT levels in normal weight and overweight/obese Mexican children. Thus, the M148M genotype may be considered as an important risk factor for liver damage in this population. © 2013 Elsevier B.V.

Leon-Mimila P.,National Autonomous University of Mexico | Vega-Badillo J.,National Autonomous University of Mexico | Gutierrez-Vidal R.,National Autonomous University of Mexico | Villamil-Ramirez H.,National Autonomous University of Mexico | And 11 more authors.
Experimental and Molecular Pathology | Year: 2015

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) near/in PNPLA3, NCAN, LYPLAL1, PPP1R3B, and GCKR genes associated with non-alcoholic fatty liver disease (NAFLD) mainly in individuals of European ancestry. The aim of the study was to test whether these genetic variants and a genetic risk score (GRS) are associated with elevated liver fat content and non-alcoholic steatohepatitis (NASH) in Mexicans with morbid obesity. Methods: 130 morbidly obese Mexican individuals were genotyped for six SNPs in/near PNPLA3, NCAN, LYPLAL1, PPP1R3B, and GCKR genes. Hepatic fat content [triglyceride (HTG) and total cholesterol (HTC)] was quantified directly in liver biopsies and NASH was diagnosed by histology. A GRS was tested for association with liver fat content and NASH using logistic regression models. In addition, 95 ancestry-informative markers were genotyped to estimate population admixture proportions. Results: After adjusting for age, sex and admixture, PNPLA3, LYPLAL1, GCKR and PPP1R3B polymorphisms were associated with higher HTG content (P<0.05 for PNPLA3, LYPLAL1, GCKR polymorphisms and P=0.086 for PPP1R3B). The GRS was significantly associated with higher HTG and HTC content (P=1.0×10-4 and 0.048, respectively), steatosis stage (P=0.029), and higher ALT levels (P=0.002). Subjects with GRS ≥6 showed a significantly increased risk of NASH (OR=2.55, P=0.045) compared to those with GRS ≤5. However, the GRS did not predict NASH status, as AUC of ROC curves was 0.56 (P=0.219). Conclusion: NAFLD associated loci in Europeans and a GRS based on these loci contribute to the accumulation of hepatic lipids and NASH in morbidly obese Mexican individuals. © 2015 Elsevier Inc..

PubMed | Instituto Nacional Of Cardiologia Ignacio Chavez Incich, CINVESTAV, INCMNSZ, National Autonomous University of Mexico and 4 more.
Type: Journal Article | Journal: Annals of hepatology | Year: 2015

Secreted frizzled-related protein 5 (SFRP5) was recently described as a new adipokine protective for hepatic steatosis and other obesity-related complications in the mouse model. To date, SFRP5 expression in non-alcoholic fatty liver disease (NAFLD) has not been fully assessed in humans. We measured circulating SFRP5 levels and its expression in liver and adipose tissue, and evaluated its association with NAFLD in morbidly obese women.Fifty-four morbidly obese women undergoing bariatric surgery were included in the study. Liver biopsies were used for histology and hepatic triglyceride content quantification. Circulating SFRP5 levels were measured through enzyme-linked immunoabsorbent assay, and SFRP5 expression was performed in hepatic and adipose tissue (subcutaneous and visceral).Although circulating SFRP5 levels showed a tendency to decrease with NAFLD progression, no significant differences were observed among non-alcoholic steatosis, steatohepatitis, and control subjects. Hepatic SFRP5 expression showed a negative correlation with hepatic triglyceride content (r = -0.349, P = 0.016 for mRNA and r = -0.291, P = 0.040 for SRFP5 protein) and ALT serum levels (r = -0.437, P = 0.001 for SRFP5 protein). In addition, hepatic SFRP5 protein levels were significantly lower in NASH than in control subjects (P = 0.006).This is the first study reporting an association of hepatic SFRP5 expression with NAFLD in humans.

PubMed | Autonomous University of Guadalajara, Hospital General Dr Miguel Silva, Hospital Angeles Torreon, Hospital Of Especialidades and 15 more.
Type: Journal Article | Journal: Revista de gastroenterologia de Mexico | Year: 2016

Since the publication in 2009 of the Guidelines on the Diagnosis and Treatment of Irritable Bowel Syndrome of the Asociacin Mexicana de Gastroenterologa (2009 Guidelines), there have been significant advances in our knowledge of the epidemiology, pathophysiology, diagnosis, and treatment of this disease.To present a consensus review of the most current knowledge of IBS, updating the 2009 Guidelines by incorporating new internationally published scientific evidence, with a special interest in Mexican studies.The PubMed literature from January 2009 to March 2015 was reviewed and complemented through a manual search. Articles in English and Spanish were included and preference was given to consensuses, guidelines, systematic reviews, and meta-analyses. Statements referring to the different aspects of the disease were formulated and voted upon by 24 gastroenterologists employing the Delphi method. Once a consensus on each statement was reached, the quality of evidence and strength of recommendation were determined through the GRADE system.Forty-eight statements were formulated, updating the information on IBS and adding the complementary data that did not appear in the 2009 Guidelines regarding the importance of exercise and diet, diagnostic strategies, and current therapy alternatives that were analyzed with more stringent scientific vigor or that emerged within the last 5 years.We present herein a consensus review of the most relevant advances in the study of IBS, updating and complementing the 2009 Guidelines. Several studies conducted in Mexico were included.

Guevara-Lopez U.,National Polytechnic Institute of Mexico | Covarrubias-Gomez A.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz | Elias-Dib J.,INCMNSZ | Reyes-Sanchez A.,Instituto Nacional Of Ortopedia Y Rehabilitacion | Rodriguez-Reyna T.S.,INCMNSZ
Cirugia y Cirujanos | Year: 2011

It has been documented that pain in its diverse modalities is the most common cause of medical attention. In Mexico, an increase in its frequency has promoted its consideration in several health programs. On the other hand, inadequate pain management will cause severe physical, psychoaffective, and socioeconomic repercussions for patients, families, and public health services. Despite this panorama, there has not been an agreement to establish better diagnostic and therapeutic methods for the management of chronic pain. A consensus group was reunited and was integrated by medical experts from private and public institutions and from various states of the Mexican Republic. To assure the development of these practice guidelines, these experts had experience in the assessment and treatment of conditions causing pain. With the guidelines used by other consensus groups, meetings were held to analyze and discuss published literary evidence for the management of low back pain. The recommendations were classified according to their methodological strength. As a result of this meeting, consensus recommendations were based on evidence and operational conclusions of such proactive educational plans, institutional policies and diagnostic recommendations for pharmacological and nonpharmacological treatment in order for Mexican physicians to provide a better therapeutic approach to low back pain.

Espino-Urbina L.A.,Subespecialidad Cirugia de Colon y Recto INCMNSZ | Espinosa-De-Los-Monteros A.,Direccion de Cirugia INCMNSZ | Dominguez-Cherit J.,INCMNSZ | Chable-Montero F.,Fundacion Clinica Medica Sur | Vergara-Fernandez O.,Direccion de Cirugia INCMNSZ
Revista de Gastroenterologia de Mexico | Year: 2013

The literature reports an annual incidence of 5,900 cases of anal cancer in the developed countries. These involve three different anatomic zones: carcinoma of the anal canal, perianal carcinoma (formerly known as carcinoma of the anal margin, located at a distance of less than 5 cm from the anal margin), and carcinoma of the perianal skin (at a distance greater than 5 cm from the anal margin). Basal cell carcinoma of the perianal region is an uncommon tumor (0.27% of all diagnosed basal cell carcinomas) that in the majority of cases is treated by resection with disease-free margins. It must be differentiated from the basaloid and epidermoid variants of carcinoma, given that it has good outcome and its spread potential is practically null. © 2012 Asociación Mexicana de Gastroenterología.

Rodriguez-Cruz M.,Laboratorio Of Biologia Molecular | Sanchez R.,Laboratorio Of Biologia Molecular | Sanchez A.M.,Laboratorio Of Biologia Molecular | Kelleher S.L.,Pennsylvania State University | And 3 more authors.
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2011

Metabolic adaptations are triggered in the maternal organism to synthesize milk with an adequate concentration of long-chain polyunsaturated fatty acids (LC-PUFAs) required to the newborn. They may be a high uptake of dietary linoleic acid and its conversion to LC-PUFAs by desaturases of fatty acids (FADS) 1 and 2 in the mammary gland (MG). It is unknown if they also occur from onset of pregnancy. The aim of this study was to explore the participation of the MG as a mechanism involved in LC-PUFAs synthesis to support their demand during pregnancy and lactation in rats. The expression of desaturases in MG was significantly (P < 0.05) higher (12.3-fold for FADS1 and 41.2-fold for FADS2) during the late pregnancy and throughout lactation (31.7-fold for FADS1 and 67.1-fold higher for FADS2) than in nonpregnant rats. SREBF-1c showed a similar pattern of increase during pregnancy but remained higher only during the early lactation (11.7-fold, P < 0.005). Transcript of ELOVL6 and FASN increased throughout pregnancy and lactation, respectively. ELOVL5 mRNA increased in MG only during lactation (2.8 to 5.3-fold, P < 0.005). Accordingly, a higher content of LC-PUFAs was found in lactating MG than in nonpregnant rats. Results suggest that MG participates from late pregnancy and throughout lactation by expressing desaturases and elongases as a mechanism involved in LC-PUFAs synthesis, probably by SREBF-1c. Because desaturases and ELOVL5 were expressed in cultured lactocytes and such expression was downregulated by linoleic and arachidonic acid, these cells may be a useful model for understanding the regulatory mechanisms for LC-PUFAs synthesis in MG. © 2011 Elsevier B.V. All rights reserved.

Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

4169 Background: Hepatocellular carcinoma (HCC) is a malignant neoplasia that is associated with liver cirrosis in up to 60-80% of the cases. The incidence of HCC varies between 3 and 9% and it is one of the principal causes of death in patients with cirrhosis. The viral causes of liver cirrhosis, particularly by infection of hepatitis C virus, are associated with a greater risk of HCC, the pathologic mechanisms involved are probably a consequence of the inflammatory reaction. Colchicine is an anti-inflammatory agent, which inhibits the formation of intracellular microtubules, causing disturbances in the process of mitosis and in the formation of fibrosis. Diverse random studies have failed to demonstrate if colchicine has any benefit over mortality in patients with liver cirrhosis of any etiology.We made a retrospective study of a cohort of 350 patients with postnecrotic liver cirrhosis, to evaluate the effect of the administration of colchicine over the time of HCC development. We analyzed the clinical and pathological factors that are associated with the presence of hepatocarcinoma.The average follow-up was of 84+/- 2.8 months. Two hundred and twenty patients received 1mg during 5 days per week of colchicine and 130 patients just received symptomatic treatment. The patients who received colchicine had the same Child- Pugh classification that the group that didnt. Colchicine didnt affect the progression of the Child score, during the first three years of follow-up. The percentage of patients that develop HCC was significantly less in the group who received colchicine in comparison with those that didnt receive it (26 vs 10.3% p=0.0001). With the multivariate analysis we found that age greater than 52 and having less than 116 000 platlelets at the moment of diagnosis, as well as not receiving treatment with colchicine, were associated with developing HCC in lesser time. The protective mechanisms of colchicine over the development of HCC could be related with its effect as an anti-inflammatory drug and mithosis inhibition.Colchicine prevents the development of HCC, independently from the liver reserve nor the patient s age. No significant financial relationships to disclose.

PubMed | Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmncsz, INCMNSZ, University of Manitoba, Emory University and University of Chicago
Type: | Journal: Sleep medicine | Year: 2016

Although obstructive sleep apnea (OSA) has long been associated with daytime sleepiness, far less is known about its association with the ability to remain awake. The aim of this study was to examine the relative importance of inter-correlated measures of OSA severity (eg, various indices of oxygen saturation and sleep fragmentation) in the ability to stay alert as measured objectively by the Maintenance of Wakefulness Test (MWT), defined by a mean sleep latency of 12min.Seventy-eight obese women and men of similar age and body mass index living at altitude (Mexico City) underwent standard polysomnography, MWT, and completed validated sleep-related questionnaires.Men had more severe sleep apnea than women (p=0.002) and were also less alert on MWT (p=0.022). Logistic regression models indicated that measures of desaturation consistently predicted MWT-defined alertness, whereas varied measures of sleep fragmentation did not. Nearly a third of the variance (r(2)=0.304) in MWT-defined alertness was accounted for by the number of desaturations per hour of sleep (p=0.003), which is considerably higher than other studies have reported in different populations.The ability to remain awake in obese patients is best accounted for by hypoxemia rather than sleep fragmentation. Whether the size of this effect reflects differences in the population under study (eg, extent of obesity, racial background, residence at moderate altitude) and/or is a function of the measurement of alertness with the MWT remains uncertain.

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