Effect of sitagliptin on down-regulation of KAT7 and SIRT1 gene expression in breast cancer cell line MCF7.

BACKGROUND: To date, the main clinical interest in DPP4 is focused on its inhibition in diabetic patients to prolong the half-life of incretins. Epigenetic alterations resulting from DPP4 inhibition have been poorly explored. OBJECTIVE: The objective of this study was to determine, whether sitagliptin, a DPP4 inhibitor, has effects on the expression of KAT7 and SIRT1 (genes encoding a histone acetyltransferase and a histone deacetylase, respectively) in MCF7 breast cancer cells, which play an essential role in modulating the epigenetic landscape of chromatin. MATERIAL AND METHODS: MCF7 cells were incubated for 20 h with sitagliptin at concentrations of 0.5, 1.0 and 2.0 µM. Total RNA was isolated and the relative mRNA expression of KAT7 and SIRT1 was determined by RT-qPCR. RESULTS: There was downregulation in the relative expression of both genes; for KAT7, downregulation reached up to 0.49 (p = 0.027) and for SIRT1, it reached up to 0.55 (p = 0.037). CONCLUSIONS: These results suggest that sitagliptin has effects on the histone epigenetic landscape. This topic deserves further study due to the current sample use of DPP4 inhibitors in diabetic patients.

ANTECEDENTES: Hasta la fecha, el principal interés clínico de la DPP4 se centra en su inhibición en pacientes diabéticos para prolongar la vida media de las incretinas. Las alteraciones epigenéticas resultantes de la inhibición de DPP4 han sido poco exploradas. OBJETIVO: Determinar si la sitagliptina, un inhibidor de DPP4, tiene efectos sobre la expresión de KAT7 y SIRT1 (genes que codifican una histona acetiltransferasa y una histona desacetilasa, respectivamente) en células de cáncer de mama MCF7, que desempeñan un papel esencial en la modulación del paisaje epigenético de la cromatina. MÉTODO: Las células MCF7 se incubaron durante 20 h con sitagliptina a concentraciones de 0.5, 1.0 y 2.0 µM. Se aisló el ARN total y se determinó la expresión relativa de ARNm de KAT7 y SIRT1 mediante RT-qPCR. RESULTADOS: Hubo una regulación a la baja en la expresión relativa de ambos genes; para KAT7, la regulación negativa alcanzó hasta 0.49 (p = 0.027) y para SIRT1 alcanzó hasta 0.55 (p = 0.037). CONCLUSIONES: Estos resultados sugieren que la sitagliptina tiene efectos sobre el paisaje epigenético de las histonas. Este tema merece más estudios debido al uso actual de inhibidores de DPP4 en pacientes diabéticos.

Differential Methylation in Promoter Regions of the Genes NR3C1 and HSP90AA1, Involved in the Regulation, and Bioavailability of Cortisol in Leukocytes of Women With Preeclampsia.

Introduction: Hypertensive disorders are of interest in obstetrics and gynecology because they are the second place among causes of maternal mortality and a source of complications in the short, mid, and long term. Even if the pathophysiological process behind preeclampsia (PE) is still unknown, stress factors have been revealed to play an important role in the genesis of this pathologic process. Methods: A case-control study was designed with the purpose of determining if there is a differential methylation in NR3C1, HSD11B2, CYP11A1, CRHBP, TEAD3, and HSP90AA1 genes, related to signaling of the hypothalamic-pituitary-adrenal axis, and its regulation on early-onset PE (EOPE). Results: A total of 20 cases and 20 controls were studied by DNA methylation analysis, demonstrating differences among groups in the percentage of methylation of the NR3C1 gene. After a contingency analysis, an odds ratio (OR) for PE of 12.25 was identified for NR3C1 and 9.9 for HSP90AA1 genes. NR3C1, TEAD3, and HSP90AA1 genes showed a positive correlation with the systolic and diastolic blood pressure levels with a p ≤ 0.05. Conclusion: This study found a differential methylation in the glucocorticoid receptor (GR) NR3C1 and its co-chaperone HSP90AA1 in women with PE, with a possible regulatory role in the response to stress in pregnancy and is a likely physiopathological mechanism in PE.

Renal damage induced by the pesticide methyl parathion in male Wistar rats.

Little information is apparently available regarding the nephrotoxic effects induced by pesticides. The aim of this study was to examine the influence of low doses of methyl parathion (MP) on the structure and function of the kidney of male Wistar rats. A corn oil (vehicle) was administered to control rats, whereas treated rats received MP at 0.56 mg/kg orally (1/25 of LD50), every third day, for 8 weeks. At the end of each week following MP exposure, creatinine and glucose levels were measured in plasma, while glucose, inorganic phosphate, total proteins, albumin, and activity of γ-glutamyltranspeptidase (GGT) were determined in urine. Kidney histological study was also performed. Compared with control rats, MP significantly increased plasma glucose and creatinine levels accompanied by decreased urinary flow rate and elevated urinary excretion rates of glucose, phosphate, and albumin. Further, the activity of GGT in urine was increased significantly. The proximal cells exhibited cytoplasmic vacuolization, positive periodic acid Schiff inclusions, and brush border edge loss after 2 or 4 weeks following MP treatment. Finally, renal cortex samples were obtained at 2, 4, 6, and 8 weeks of MP treatment, and the concentrations of reduced glutathione (GSH) and glutathione peroxidase (GPx) activity were measured. The mRNA expression levels of BAX and tumor necrosis factor-α (TNF-α) were also determined (RT-PCR). MP significantly decreased renal GSH levels, increased GPx activity, as well as downregulated the mRNA expression of TNF-α and BAX. Densitometry analysis showed a significant reduction in TNF-α and BAX mRNA expression levels at 2 and 4 weeks following MP treatment. Low doses of MP produced structural and functional damage to the proximal tubules of male rat kidney.

Effect of oral magnesium supplementation on the transcription of TRPM6, TRPM7, and SLC41A1 in individuals newly diagnosed of pre-hypertension. A randomized, double-blind, placebo-controlled trial.

A stringent regulation of influx and efflux of magnesium by cation transporters seems to play an important role in the regulation of blood pressure (BP). With this regard, we evaluate the effect of oral magnesium supplementation on the transcription of TRPM6, TRPM7, and SLC41A1, in individuals with incident pre-hypertension (preHTN). For such purpose, we conducted a randomized, double-blind, placebo-controlled trial that compared 18 individuals who received oral magnesium lactate (360 mg elemental magnesium) versus 18 individuals who received placebo, during 4 months. Diagnosis of hypertension or normal BP, diabetes, alcohol intake, chronic diarrhea, use of diuretics, intake of magnesium supplementation, and reduced renal function were exclusion criteria. Regarding the transcription analysis of TRPM6, TRPM7, and SLC41A1 using RT-qPCR, leukocyte-rich plasma was obtained and total RNA was isolated with the kit Direct-zol™ RNA MiniPrep (Zymo). The leukocyte TRPM6 mRNA relative expression showed a significant increase (2.1 ± 1.37 and 0.8 ± 0.4, P<0.05), whereas the mRNA relative expression of both leukocyte TRPM7 (0.8 ± 1.1 and 0.9 ± 0.6, pNS) and SLC41A1 (0.9 ± 1.0 and 0.7 ± 0.6, pNS) showed no significant differences, between the magnesium and placebo groups, respectively. Oral magnesium supplementation increases the leukocyte TRPM6 mRNA relative expression, in subjects with new diagnosis of preHTN.

Alelo C del polimorfismo rs2209972 del gen de la enzima degradadora de insulina y enfermedad de Alzheimer en diabéticos tipo 2. Estudio de casos y controles / C allele of the rs2209972 single nucleotide polymorphism of the insulin degrading enzyme gene and Alzheimer's disease in type 2 diabetes, a case control study

Background and objective: In the last few decades we have witnessed an interesting transformation of the population pyramids throughout the world. As the population's life expectancy increases, there are more chronic diseases such as diabetes mellitus and dementias, and both of them have shown an association. General objetive: To determine the association between Alzheimer's disease in diabetic patients and the insulin degrading enzyme in outpatients of a second level Hospital in Monterrey, Mexico. Materials and methods: This was a case control study in which we included outpatients from the Geriatrics Clinic of a Hospital in Northeastern Mexico. Cases were patients with a Mini Mental Score Exam (MMSE) below 24 and DSM-IV criteria for Dementia. Controls were patients who had MMSE scores greater than 24. Results: Data from 97 patients were analyzed. Regarding physical examination and the results of laboratory tests, there were no differences between the two groups (p > 0.05). A 98% prevalence of the insulin degrading enzyme was documented in the sample studied. We found an association between a homozygous status for the CC genotype and Dementia with an estimated Odds Ratio (OR) of 2.5 (CI 95% 1.6–3.3) on the bivariate test, while, on the multivariate analysis, the OR was estimated 3.3 (CI 95% 1.3–8.2). Conclusions: Evidence shows that cognitive impairment is more frequent among those exposed to the C allele of the rs2209972 SNP of the insulin degrading enzyme gene (AU)

Fundamento y objetivo: En las últimas décadas se ha producido una transformación en las pirámides poblacionales, con un aumento en la expectativa de vida, lo que conlleva un mayor número de enfermedades crónico-degenerativas, como son la diabetes mellitus y la demencia, que han mostrado tener una asociación estrecha, pero cuya etiología aún está por discernir. El objetivo de este estudio fue determinar la asociación entre el alelo C de la enzima degradadora de insulina y la enfermedad de Alzheimer en pacientes con diabetes tipo 2. Material y métodos: Estudio de casos y controles, en el cual se incluyeron pacientes de la clínica de Geriatría del Hospital General del Noreste de México. Los casos fueron aquellos con una puntuación en el Mini-Mental State Examination (MMSE) menor de 24 y criterios para demencia de acuerdo con el DSM-IV. Los controles fueron pacientes con MMSE superior a 24. Resultados: Se analizaron datos de 97 pacientes. No hubo diferencias respecto a las características basales clínicas y de laboratorio entre los casos y los controles (p > 0,05). Se documentó una prevalencia de 98% del alelo C de la enzima degradadora de insulina. Encontramos una asociación entre homocigosidad para el genotipo CC de la enzima degradadora de insulina y enfermedad de Alzheimer, con una OR de 2,5 (IC 95% 1,6–3,3) en el examen bivariado, y en el examen multivariado se encontró asociación con una OR de 3,3 (IC 95% 1,3–8,2). Conclusiones: La evidencia muestra una asociación entre deterioro cognitivo y presencia del alelo C del polimorfismo rs2209972 del gen de la enzima degradadora de insulina (AU)

Risk of microalbuminuria in relatives of subjects with diabetic nephropathy: a predictive model based on multivariable dimensionality reduction approach.

AIM: To evaluate a predictive model of microalbuminuria by using anthropometric, clinical and genetic variables in relatives of subjects with diabetic nephropathy. METHODS: Eligible subjects, aged 18-63 years with body mass index<35 kg/m2, and first degree relatives of patients with type 2 diabetes and diabetic nephropathy were enrolled in a cross-sectional study. A total of 70 individuals with microalbuminuria were compared with 60 individuals without microalbuminuria. Based on a morning urinary sample, microalbuminuria was defined as albumin≥30<300 mg/dL. Genotyping of single nucleotide polymorphisms (SNPs) G-174C of IL6 (rs1800795), G-308A of TNF (rs1800629), and Pro12Ala of PPARγ2 (rs1801282) genes were determined. The multivariable dimensionality reduction analysis was performed using the software multifactor dimensionality reduction package. RESULTS: The multivariable dimensionality reduction analysis showed that obesity and SNP G-308A of TNF gene exhibited main effects with 1.10 and 1.98% of information gain (IG), respectively. The IL6 showed synergy (interaction) with HDL-c (IG 1.27%) and sex (IG 1.02%); also high-sensitivity C-reactive protein and triglycerides levels showed synergy (IG 1.08%). The consistency of the cross-validation for this model was 0.6836, with sensitivity and specificity of 0.58 and 0.76 (odds ratio 4.64; 95% CI 4.0-10.0, p<0.0001). CONCLUSION: Our results indicate that obesity and/or high blood pressure, in synergism with high-sensitivity C-reactive protein and high-density lipoprotein cholesterol levels, is the main predictive risk factor of diabetic nephropathy in healthy subjects, relatives of patients with type 2 diabetes and diabetic nephropathy.

[Risk factors associated with breast cancer women's in Durango, Mexico]. / Factores de riesgo asociados con el cáncer de mama en mujeres del estado de Durango, México.

BACKGROUND: Breast cancer is a public health problem worldwide and is a priority for developing countries like ours, to establish preventive and early detection measures. In Mexico since 2006 breast cancer than cervical cancer as a cause of death in women aged 30-54 years and threatens all socioeconomic groups. The known risk factors for the occurrence of this neoplasm are early menarche, nulliparity, late age parity and late menopause and family history of breast cancer. OBJECTIVE: To determine the risk factors associated with breast cancer in women in the State of Durango. MATERIAL AND METHODS: Epidemiological study of 50 cases and 100 con- trols aged between 35 and 69 years old. For the calculation of sample size Schlesselman tables were used. The data was collected and analyzed in SPSS V15. We used descriptive statistics and odds ratio was calculated. RESULTS: Age had a mean of 50.60 years and a deviation ±9,599 for cases and 50.73 (SD ± 10.08) for controls. The hereditary familial history of breast cancer OR = 5.182 (Cl 1694-15855), higher age at first pregnancy at 30 years of age OR = 3.582 (95% CI .1.121-11.439). CONCLUSIONS: The results of this study suggest that reproductive and hereditary familial history may influence the development of breast cancer, which is a multifactorial disease.

C allele of the rs2209972 single nucleotide polymorphism of the insulin degrading enzyme gene and Alzheimer's disease in type 2 diabetes, a case control study.

BACKGROUND AND OBJECTIVE: In the last few decades we have witnessed an interesting transformation of the population pyramids throughout the world. As the population's life expectancy increases, there are more chronic diseases such as diabetes mellitus and dementias, and both of them have shown an association. GENERAL OBJETIVE: To determine the association between Alzheimer's disease in diabetic patients and the insulin degrading enzyme in outpatients of a second level Hospital in Monterrey, Mexico. MATERIALS AND METHODS: This was a case control study in which we included outpatients from the Geriatrics Clinic of a Hospital in Northeastern Mexico. Cases were patients with a Mini Mental Score Exam (MMSE) below 24 and DSM-IV criteria for Dementia. Controls were patients who had MMSE scores greater than 24. RESULTS: Data from 97 patients were analyzed. Regarding physical examination and the results of laboratory tests, there were no differences between the two groups (p>0.05). A 98% prevalence of the insulin degrading enzyme was documented in the sample studied. We found an association between a homozygous status for the CC genotype and Dementia with an estimated Odds Ratio (OR) of 2.5 (CI 95% 1.6-3.3) on the bivariate test, while, on the multivariate analysis, the OR was estimated 3.3 (CI 95% 1.3-8.2). CONCLUSIONS: Evidence shows that cognitive impairment is more frequent among those exposed to the C allele of the rs2209972 SNP of the insulin degrading enzyme gene.

Asociación entre el polimorfismo c.1-765G>C del gen de la COX-2 y el deterioro cognitivo en individuos diabéticos de 65 o mas años de un Servicio de Geriatría en Monterrey, México / Association between polymorphism c.1-765G>C of the COX2 gene and cognitive impairment in individuals 65 years or more with diabetes from a Geriatric Service in Monterrey, Mexico

Background and objective: Cognitive impairment and dementia are common geriatric syndromes in diabetic patients. Inflammation plays a crucial role in the pathophysiology of Alzheimer's disease and cognitive impairment. Cyclooxygenases (COX) 1 and 2 participate in inflammation. The polymorphism c.1-765G>C of the COX2 gene might be protective against cognitive decline in Mexicans with diabetes mellitus through its reduced promotor activity. To determine the association between polymorphism c.1-765G>C of the COX2 gene and cognitive impairment in elderly adults with diabetes. Patients and methods: Case-control study. We included diabetic patients from the Geriatric Clinic of General Hospital No. 17 who were over 65 years and accepted to participate. Cases were patients with a score of 24 or less on the Mini Mental Status Examination (MMSE) and with DSM IV criteria for dementia. Controls were those with MMSE scores of 25 or greater. Results: We included 97 patients (50 cases and 47 controls). There were no differences regarding clinical and laboratory characteristics between cases and controls. The frequency of the C allele and the CG genotype was higher in controls than in cases and this difference remained significant in a multivariate analysis with an odds ratio of 0.012 (95% CI 0.001-0.091) and 0.009 (95% CI 0.001-0.076) in the bivariate and multivariate analysis, respectively, using the GG genotype frequency as a reference. Conclusion: Cognitive impairment in Mexican patients with diabetes is associated with less exposure to the CG genotype of the c.1-765G>C polymorphism of COX2 (AU)

Fundamento y objetivo: El deterioro cognitivo y la demencia son síndromes geriátricos frecuentes en los pacientes con diabetes. La inflamación es crucial en la fisiopatología de la enfermedad de Alzheimer y del deterioro cognitivo. Las ciclooxigenasas (COX) 1 y 2 participan en la inflamación. El polimorfismo c.1- 765G>C de la COX-2 protegería contra el deterioro cognitivo en adultos mayores diabéticos mexicanos por su menor actividad promotora. El objetivo de este estudio fue determinar la asociación entre el polimorfismo c.1-765G>C del gen de la COX-2 y el deterioro cognitivo en adultos mayores diabéticos. Pacientes y métodos: Estudio de tipo casos y controles. Se incluyeron pacientes diabéticos de la clínica de Geriatría del Hospital General de Zona No. 17, mayores de 65 años que aceptaron participar. Los casos fueron los pacientes con puntuación de 24 o menor en el Mini-Mental State Examination (MMSE) y criterios DSM-IV para demencia. Los controles tenían una puntuación de 25 o mayor en el MMSE. Resultados: Se incluyeron 97 pacientes (50 casos y 47 controles). No hubo diferencias respecto a las características clínicas y de laboratorio entre los casos y los controles. La frecuencia del alelo C y del genotipo CG fue mayor en los controles que en los casos, y dicha diferencia permaneció significativa en el análisis multivariado, con una razón de momios de 0,012 (IC 95% 0,001 a 0,091) y de 0,009 (IC 95% 0,001 a 0,076), en el análisis bivariado y multivariado, respectivamente, tomando como referencia la frecuencia genotípica GG. Conclusión: El deterioro cognitivo en pacientes mexicanos con diabetes se asocia con una menor exposición al polimorfismo c.1-765G>C del gen de la COX-2 (AU)

CTCFL (BORIS) mRNA Expression in a Peripheral Giant Cell Granuloma of the Oral Cavity.

Peripheral giant cell granuloma (PGCG) is a relatively common benign reactive lesion of the oral cavity which can occur at any age. CTCFL/BORIS (CTCF like/Brother of the Regulator of Imprinted Sites) and CTCF (CCCTC-binding factor) are paralogous genes with an important role in the regulation of gene expression, genomic imprinting, and nuclear chromatin insulators regulation. BORIS expression promotes cell immortalization and growth while CTCF has tumor suppressor activity; the expression pattern may reflect the reverse transcription silencing of BORIS. The aim of this work was to describe a histopathological and molecular approach of an 8-year-old pediatric male patient with PGCG diagnosis. It was observed that the PGCG under study expressed CTCF as well as BORIS mRNAs alongside with the housekeeping gene GAPDH, which may be related to possible genetic and epigenetic changes in normal cells of oral cavity.

ESR1 and PGR gene promoter methylation and correlations with estrogen and progesterone receptors in ductal and lobular breast cancer.

The aim of this work was to analyze methylation of the promoter sites of the ESR1 and PGR genes and to determine correlations with immunohistochemical expression of estrogen and progesterone receptors in ductal and lobular breast cancers. An observational, descriptive, molecular study was conducted on 20 ductal and 20 lobular breast cancer samples with immunohistochemical determination of estrogen and progesterone receptor expression. The methylation analysis of ESR1 and PGR promoter sites was carried-out by methylation-specific PCR. For correlation analysis, Kendall's tau coefficient was determined. Positive correlations were found between estrogen and progesterone receptors, estrogen receptor and unmethylated progesterone receptor, progesterone receptor, and unmethylated progesterone receptor. Negative correlations were found between estrogen receptor and methylated progesterone receptor, progesterone receptor and methylated progesterone receptor, methylated and unmethylated estrogen receptor, and methylated and unmethylated progesterone receptor. The results suggest that methylation of promoter sites of ESR1 and PGR is a relatively uncommon event in ductal and lobular breast cancer, and also suggest that the determination of epigenetic states of ESR1 and PGR could represent an alternative or complement to the histopathological expression analysis.

CTCF and CTCFL mRNA expression in 17ß-estradiol-treated MCF7 cells.

Estrogens play a key role in breast cancer, with 60-70% of the cases expressing estrogen receptors (ERs), which are encoded by the ESR1 gene. CTCFL, a paralogue of the chromatin organizer CTCF, is a potential biomarker of breast cancer, but its expression in this disease is currently controversial. A positive correlation has been reported between CTCFL and ERs in breast tumors and there also exists a coordinated interaction between CTCF and ERs in breast cancer cells. Therefore, there appears to be an association between CTCF, CTCFL and estrogens in breast cancer; however, there has been no report on the effects of estrogens on CTCF and CTCFL expression. The aim of this study was to determine the effect of 17ß-estradiol (E2) on the CTCF and CTCFL mRNA expression in the MCF7 breast cancer cell line. The promoter methylation status of CTCFL and data mining for estrogen response elements in promoters of the CTCF and CTCFL genes were also determined. The transcription of CTCF and CTCFL was performed by quantitative polymerase chain reaction (qPCR) and the promoter methylation status of CTCFL was determined by methylation-specific PCR. The MCF7 cells exhibited basal transcription of CTCF, which was significantly downregulated to 0.68 by 1 µM E2; basal or E2-regulated transcription of CTCFL was not detected. Under basal conditions, the CTCFL promoter was methylated. Through data mining, an estrogen response element was identified in the CTCF promoter, but no such element was found in CTCFL. These results suggested that estrogens may modulate CTCF expression, although there was no apparent association between ERs and CTCFL.

Association between polymorphism c.1-765G>C of the COX2 gene and cognitive impairment in individuals 65 years or more with diabetes from a Geriatric Service in Monterrey, Mexico.

BACKGROUND AND OBJECTIVE: Cognitive impairment and dementia are common geriatric syndromes in diabetic patients. Inflammation plays a crucial role in the pathophysiology of Alzheimer's disease and cognitive impairment. Cyclooxygenases (COX) 1 and 2 participate in inflammation. The polymorphism c.1-765G>C of the COX2 gene might be protective against cognitive decline in Mexicans with diabetes mellitus through its reduced promotor activity. To determine the association between polymorphism c.1-765G>C of the COX2 gene and cognitive impairment in elderly adults with diabetes. PATIENTS AND METHODS: Case-control study. We included diabetic patients from the Geriatric Clinic of General Hospital No. 17 who were over 65 years and accepted to participate. Cases were patients with a score of 24 or less on the Mini Mental Status Examination (MMSE) and with DSM IV criteria for dementia. Controls were those with MMSE scores of 25 or greater. Results We included 97 patients (50 cases and 47 controls). There were no differences regarding clinical and laboratory characteristics between cases and controls. The frequency of the C allele and the CG genotype was higher in controls than in cases and this difference remained significant in a multivariate analysis with an odds ratio of 0.012 (95% CI 0.001-0.091) and 0.009 (95% CI 0.001-0.076) in the bivariate and multivariate analysis, respectively, using the GG genotype frequency as a reference. CONCLUSION: Cognitive impairment in Mexican patients with diabetes is associated with less exposure to the CG genotype of the c.1-765G>C polymorphism of COX2.

Obesity and inflammation: epidemiology, risk factors, and markers of inflammation.

Obesity is a public health problem that has reached epidemic proportions with an increasing worldwide prevalence. The global emergence of obesity increases the risk of developing chronic metabolic disorders. Thus, it is an economic issue that increased the costs of the comorbidities associated. Moreover, in recent years, it has been demonstrated that obesity is associated with chronic systemic inflammation, this status is conditioned by the innate immune system activation in adipose tissue that promotes an increase in the production and release of pro-inflammatory cytokines that contribute to the triggering of the systemic acute-phase response which is characterized by elevation of acute-phase protein levels. On this regard, low-grade chronic inflammation is a characteristic of various chronic diseases such as metabolic syndrome, cardiovascular disease, diabetes, hypertension, non-alcoholic fatty liver disease, and some cancers, among others, which are also characterized by obesity condition. Thus, a growing body of evidence supports the important role that is played by the inflammatory response in obesity condition and the pathogenesis of chronic diseases related.

No positive effect of oral magnesium supplementation in the decreases of inflammation in subjects with prediabetes: a pilot study.

To determine whether oral magnesium supplementation modifies serum levels of high-sensitivity C-reactive protein (hsCRP), TNF-alpha, IL-6, and IL-10 in subjects with prediabetes, inflammation, and hypomagnesemia, a total of 26 subjects men and non-pregnant women were included and randomly allocated to receive 30 ml of MgCl(2) 5% solution (equivalent to 382 mg of magnesium) or placebo, daily during three months. At baseline conditions, there were not significant statistical differences between the groups. At end of the study, hsCRP levels were significantly lower in the intervention group (3.3 ± 2.5 vs 8.0 ± 5.9 mg/L, p = 0.03), as compared with the control group. However, the intra-group analysis of the individuals who received magnesium, did not shows significant statistical differences between baseline and final conditions (4.1 ± 3.0 and 3.3 ± 2.5, p = 0.45). In addition, TNF-alpha (1.2 ± 0.3 vs 1.1 ± 0.3 pg/mL, p = 0.69), IL-6 (0.3 ± 0.3 vs 5.0 ± 7.7 pg/mL, p = 0.08), and IL-10 (1.8 ± 0.4 vs 1.8 ± 0.5 pg/mL, p = 0.89) serum levels were not significantly different between the groups. Our results do not show a beneficial effect of oral magnesium supplementation on hsCRP, IL-6, TNF-alpha, and IL-10 levels in prediabetic subjects with hypomagnesemia and inflammation. Further studies with large sample sizes and longer time of follow-up are necessaries to verify the results of our pilot study.

C-reactive protein is directly associated with urinary albumin-to-creatinine ratio.

BACKGROUND AND AIMS: There are no studies that elucidate whether the role of inflammation in the increase of urinary albumin is independent, mediated by family history or by risk factors acquired during life in the offspring of subjects with type 2 diabetes. We undertook this study to evaluate whether elevated C-reactive protein (CRP) levels are independently associated with urinary albumin-to-creatinine ratio (UACR) in the offspring of subjects with diabetic nephropathy. METHODS: A total of 64 healthy males and healthy nonpregnant females, offspring of subjects with diabetic nephropathy, aged 18-69 years, and with body mass index ≤35 kg/m(2) were enrolled in a cross-sectional study. Hypertension, glucose metabolic disorders, metabolic syndrome, smoking, alcohol intake, chronic or acute infections, renal disease, neoplasm, cardiovascular disease, degenerative disease, intake of anti-inflammatory drugs, exercise, or sexual intercourse in the previous 72 h were exclusion criteria. Subjects with high-sensitivity CRP (hsCRP) levels ≥3.0 mg/dL were compared with a gender- and age-matched control group of subjects with hsCRP levels <3.0 mg/dL. RESULTS: The multivariate linear regression analysis showed that hsCRP (B = 0.50, ß = 0.583, p = 0.02), total body fat (B = -2.80, ß = 0.473, p = 0.03), BMI (B = -1.45, ß = 0.390, p = 0.04) and waist circumference (B = 0.89, ß = 0.407, p = 0.04) are predictors for elevation of UACR (Table 2). However, in the stepwise model only hsCRP (B = 0.674; ß = 0.314; p = 0.04) remained significantly associated with UACR. CONCLUSIONS: Our results show that independent of the primary risk factors, elevated hsCRP levels are associated with UACR.

The grade-response relation between severity of peritonitis and serum cytokine concentrations explains Mannheim Peritonitis Index threshold.

AIM: To explore the gradient between the acute-phase response (APR) and peritonitis of differing severity. METHODS: In 202 patients with peritonitis, we determined serum concentrations of interleukin (IL)-6, IL-10, IL-13, tumor necrosis factor (TNF)-alpha, and C-reactive protein (CRP). The severity of peritonitis was graded in accordance with the Mannheim Peritonitis Index (MPI). The grade-response relation between the severity of peritonitis and each analyte was explored. RESULTS: A statistically significant association was found between the medians of severity of peritonitis and IL-6 (p < 0.025), TNF-alpha (p < 0.01), CRP (p < 0.033), IL-10 (p < 0.0001), and IL-13 (p < 0.004). Both TNF-alpha and IL-10 had a direct, and IL-13 an indirect, relation to severity, whereas CRP and IL-6 tended toward linear behavior in equilibrium. A significant association persisted between individual MPI scores and IL-6 (p < 0.002), TNF-alpha (p < 0.002), CRP (p < 0.002), and IL-10 (p < 0.001), but not IL-13 (p = 0.646). CONCLUSION: Around the mean value of grade II peritonitis, the equilibrium between pro-inflammatory and anti-inflammatory cytokines is lost. This change coincides with the 26-point threshold for the MPI.

Leptin in sepsis: a well-suited biomarker in critically ill patients?

The value of monitoring serum leptin in critically ill patients is important for early diagnosis and differentiation between sepsis and non-infectious systemic inflammatory response syndrome (SIRS). The early diagnosis of sepsis, the identification of its origin, and an adequate therapeutic management are crucial to overcome sepsis-associated mortality. Cytokine levels are an obvious choice as sepsis markers, since cytokines are key mediators of the inflammatory response to sepsis. Leptin, a hormone mainly generated by adipocytes, acts centrally in the hypothalamus to regulate body weight and energy expenditure. There is, however, strong evidence that leptin is also involved in cell-mediated immunity and cytokine crosstalk. The finding that a serum leptin threshold of 38 microg/l can distinguish between sepsis and non-infectious SIRS (sensitivity 91.2%, specificity 85%) is the major finding in the article by Yousef and colleagues (in this issue). Much remains to be learned about the precise mechanisms by which leptin signaling participates in sepsis and non-infectious SIRS. This knowledge will potentially contribute to new therapeutic approaches.

Human papillomavirus infections in women seeking cervical Papanicolaou cytology of Durango, Mexico: prevalence and genotypes.

BACKGROUND: HPV infection in women from developing countries is an important public health problem. Therefore, we sought to determine the prevalences of HPV infection and HPV genotypes in a female population of Durango City, Mexico. Also to determine whether any socio-demographic characteristic from the women associated with HPV infection exists. METHODS: Four hundred and ninety eight women seeking cervical Papanicolaou examination in three public Health Centers were examined for HPV infection. All women were tested for HPV DNA PCR by using HPV universal primers. In addition, all positive HPV DNA PCR samples were further analyzed for genotyping of HPV genotype 16, 18 and 33. Socio-demographic characteristics from each participant were also obtained. RESULTS: Twenty-four out of four hundred and ninety-eight (4.8%) women were found infected by HPV. HPV genotype 16 was found in 18 out of the 24 (75%) infected women. Two of them were also coinfected by HPV genotype 18 (8.3%). In the rest 6 PCR positive women, genotyping for HPV genotypes 16, 18 and 33 were negative. CONCLUSION: The prevalence of HPV in women of Durango City is low; however, most infected women have high risk HPV genotype. The women who were studied showed low frequency of risk factors for HPV infection and this may explain the low prevalence of HPV infection. The high frequency of high risk HPV genotypes observed might explain the high rate of mortality for cervical cancer in our region.

Reciprocal modulation of matrix metalloproteinase-13 and type I collagen genes in rat hepatic stellate cells.

Collagen degradation by matrix metalloproteinases is the limiting step in reversing liver fibrosis. Although collagen production in cirrhotic livers is increased, the expression and/or activity of matrix metalloproteinases could be normal, increased in early fibrosis, or decreased during advanced liver cirrhosis. Hepatic stellate cells are the main producers of collagens and matrix metalloproteinases in the liver. Therefore, we sought to investigate whether they simultaneously produce alpha1(I) collagen and matrix metalloproteinase-13 mRNAs. In this communication we show that expression of matrix metalloproteinase-13 mRNA is reciprocally modulated by tumor necrosis factor-alpha and transforming growth factor-beta1. When hepatic stellate cells are co-cultured with hepatocytes, matrix metalloproteinase-13 mRNA is up-regulated and alpha1(I) collagen is down-regulated. Injuring hepatocytes with galactosamine further increased matrix metalloproteinase-13 mRNA production. Confocal microscopy and differential centrifugation of co-cultured cells revealed that matrix metalloproteinase-13 is localized mainly within hepatic stellate cells. Studies performed with various hepatic stellate cell lines revealed that they are heterogeneous regarding expression of matrix metalloproteinase-13. Those with myofibroblastic phenotypes produce more type I collagen whereas those resembling freshly isolated hepatic stellate cells express matrix metalloproteinase-13. Overall, these findings strongly support the notion that alpha1(I) collagen and matrix metalloproteinase-13 mRNAs are reciprocally modulated.