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Carbohydrate intake restriction positively affects markers related to metabolic syndrome (MS). However, the effects of long-term carbohydrate-free diets (CFD) have yet to be studied. The main objective of this study was to report the effects on biochemical and morphometric parameters in a rat model of MS. Male Wistar rats were initially divided into two groups: the standard diet group (SD, n = 20); and the MS group ( n = 30) fed a high-glucose diet. Ten animals from each group were sacrificed after 20 weeks on their respective diets to verify MS development. The remaining MS animals were divided into two subgroups: one continued with the MS diet ( n = 10); and the other transitioned to a carbohydrate-free diet (MS + CFD group, n = 10) for 20 more weeks. At week 40, parameters, including glucose, insulin, lipid profile, ketone bodies, C-reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, liver and muscle glycogen, and serum, hepatic, renal, and pancreatic malondialdehyde (MDA) levels were assessed. Transitioning to CFD resulted in decreased caloric intake and body weight, with normalized parameters including MDA, insulin, lipid profile, ALT, liver glycogen, creatinine, and CRP levels. This shift effectively reversed the MS-induced alterations, except for glycemia and uremia, likely influenced by the diet's high protein content stimulating gluconeogenesis. This research underscores the potential benefits of long-term carbohydrate restriction in mitigating MS-related markers.

Crataegus oxyacantha is used in the treatment of cardiovascular diseases. The aim of this study was to evaluate the transplacental genotoxicity effect of aqueous (AE) and hydroalcoholic extract (HE) of leaves C. oxyacantha in a rat model and the quantification of malondialdehyde (MDA) in the liver. Three different doses of the AE and HE of the C. oxyacantha leaf were administered orally (500, 1000 and 2000 mg/kg) to Wistar rats during 5 days through the pregnancy term (16-21 days), and sampling in rats occurred every 24 h during the last 6 days of gestation, while only one sample was taken in neonates at birth. A sample of the mother's and the neonate's liver was taken for the determination of MDA. The results show that, at the hepatic level, the evaluated doses of extracts C. oxyacantha in pregnant rats and their pups did not show cytotoxicity. However, the AE and HE generated cytotoxic and genotoxic damage in the short term. On the other hand, only the AE showed a teratogenic effect. Based on these results, the AE and HE of the C. oxyacantha leaf should not be administered during pregnancy.

Annona muricata have been extensively used in traditional medicine to treat multiple diseases, including cancers. This study evaluated the genotoxic potential and antigenotoxic activities of A. muricata aqueous and ethanolic leaf extracts by employing an in vivo erythrocyte rodent micronucleus assay. Different doses (187.5, 375, and 750 mg/kg) of both extracts were administered orally for 5 days alone and combined with cyclophosphamide (CP, 60 mg/kg) to BALB/c mice. Also, it was administered orally to Wistar rats for 5 days through the final stage of gestation. No genotoxic or cytotoxic effects were observed in the two adult rodent models when A. muricata was administered orally nor in newborn rats transplacentally exposed to the extracts. Moreover, A. muricata aqueous and ethanolic leaf extracts demonstrated a protective effect against CP-induced DNA damage. Due to its lack of genotoxic effect and its capacity to decrease DNA damage, A. muricata is likely to open an interest field regarding its potential safe use in clinical applications., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Susana Vanessa Sánchez-De-La-Rosa et al.)

Few studies have addressed how selective pressures have shaped the genetic structure of the current Native American populations, and they have mostly limited their inferences to admixed Latin American populations. Here, we searched for local adaptation signals, based on integrated haplotype scores and population branch statistics, in 325 Mexican Indigenous individuals with at least 99% Native American ancestry from five previously defined geographical regions. Although each region exhibited its own local adaptation profile, only PPARG and AJAP1 , both negative regulators of the Wnt/β catenin signaling pathway, showed significant adaptation signals in all the tested regions. Several signals were found, mainly in the genes related to the metabolic processes and immune response. A pathway enrichment analysis revealed the overrepresentation of selected genes related to several biological phenotypes/conditions, such as the immune response and metabolic pathways, in agreement with previous studies, suggesting that immunological and metabolic pressures are major drivers of human adaptation. Genes related to the gut microbiome measurements were overrepresented in all the regions, highlighting the importance of studying how humans have coevolved with the microbial communities that colonize them. Our results provide a further explanation of the human evolutionary history in response to environmental pressures in this region.

Objective: Levetiracetam (LEV) is an antiseizure medication prescribed to women during childbearing age. The impact of LEV on placental transporters is poorly understood. This study aimed to assess the effect of LEV exposure on the messenger RNA (mRNA) expression of placental transporters for hormones and nutrients and to correlate their expression with the drug's serum concentration in pregnant mice., Methods: Studies were conducted on gestational days (GD) 13 and 18, following oral treatment with 100 mg/kg LEV or the vehicle every 24 h after weaning. Serum LEV measurements were performed by High-performance liquid chromatography with a UV detector (HPLC-UV). The weight, height, and width of the fetuses were also analyzed. In addition, the placental expression of transporters xCt, Lat1, Oatp4a1, Fr-α, Rfc, and Snat4 was evaluated through semi-quantitative real-time polymerase chain reaction (qPCR). The Kruskal-Wallis and the Mann-Whitney U tests were used to determine the statistical significance (p < .05). The correlation between serum LEV concentration and placental gene expression was evaluated using the Spearman test., Results: The weight, height, and width were lower in the fetuses exposed to LEV compared with the control group (p < .05). The number of fetuses was lower in the LEV-exposed group than in the control GD 13 group (p < .001). No significant differences were detected in the mRNA expression level at GD 13. At GD 18, the expression of Lat1, Oatp4a1, xCT, and Snat4 was higher in the group treated with LEV compared with the control group (p < .05), whereas the expression of Rfc was lower (p < .05). No correlation was identified between serum LEV concentrations and gene expression levels., Significance: The repression of the Rfc transcript by LEV at GD 18 suggests that the protein expression would be abolished contributing to the observed intrauterine growth restriction (IUGR). Furthermore, the significant increase in mRNA of xCt, Snat4, Oatp4a1, and Lat1 might be a compensatory mechanism for fetal survival at GD 18., (© 2022 International League Against Epilepsy.)

Crataegus oxyacantha has been mainly used in traditional medicine for the treatment of cardiovascular diseases. However, its safety profile has not been fully established, since only the genotoxic effects of C. oxyacantha fruit have been described. Therefore, the objective of this work was evaluating the cytotoxicity and genotoxicity of the aqueous and hydroalcoholic leaf and bark extracts of C. oxyacantha by means of the micronucleus test in a murine model. Doses of 2000, 1000, and 500 mg/kg of both extracts were administered orally for 5 days in mice of the Balb-C strain. Peripheral blood smears were performed at 0, 24, 48, 72, and 96 h after each administration. The number of polychromatic erythrocytes (PCEs), micronucleated polychromatic erythrocytes (MNPCEs), and micronucleated erythrocytes (MNEs) was determined at the different sampling times. Our results showed that the leaf and bark of C. oxyacantha increase the number of MNEs at the 2000 mg/kg dose, and only the aqueous leaf extract decreases the number of PCEs at the same dose. Therefore, the aqueous and hydroalcoholic leaf and bark extracts of C. oxyacantha showed genotoxic effects, and only the aqueous leaf extract exhibited cytotoxic effects.

The genetic makeup of Indigenous populations inhabiting Mexico has been strongly influenced by geography and demographic history. Here, we perform a genome-wide analysis of 716 newly genotyped individuals from 60 of the 68 recognized ethnic groups in Mexico. We show that the genetic structure of these populations is strongly influenced by geography, and our demographic reconstructions suggest a decline in the population size of all tested populations in the last 15-30 generations. We find evidence that Aridoamerican and Mesoamerican populations diverged roughly 4-9.9 ka, around the time when sedentary farming started in Mesoamerica. Comparisons with ancient genomes indicate that the Upward Sun River 1 (USR1) individual is an outgroup to Mexican/South American Indigenous populations, whereas Anzick-1 was more closely related to Mesoamerican/South American populations than to those from Aridoamerica, showing an even more complex history of divergence than recognized so far., (© 2021. The Author(s).)

Aims: The 5HTT gene has been associated with obesity; this study aimed to determine the association between L- and S-alleles at the 5HTTLPR polymorphism with obesity in indigenous Mexican populations. Materials and Methods: A total of 362 individuals, 289 belonging to eight Native American (NA) groups; 40 Mexican mestizos; and 33 Caucasian Mennonites were enrolled in a cross-sectional study. High (≥90%) and low (<90%) NA ancestry was molecularly determined. A body mass index >30 kg/m 2 was considered as obese. The L- and S-alleles of the 5HTTLPR locus were identified by PCR; the association between alleles and obesity was performed by logistic regression analysis. Results: A significantly lower prevalence of obesity (35%) was observed in participants from communities with high NA ancestry ( p  < 0.005). Under a dominant heritance model the L-allele was associated with obesity in women with high NA ancestry (odds ratio [OR] 7.27; 95% confidence interval [CI] 1.6-32.5; p  = 0.009) but not in women with low NA ancestry (OR 0.83; 95% CI 0.3-2.2; p  = 0.71); no association was observed in men. Conclusion: Our results suggest that the 5HTTLPR L-allele is a risk factor for developing obesity in Mexican women with high NA ancestry (≥90%).

Genomic instability is associated with increased oxidative stress in patients with human immunodeficiency virus (HIV). The aim of this study was to determine the effect of intake of methanolic and aqueous extracts of Rosmarinus officinalis on genomic instability in HIV patients. We studied 67 HIV patients under pharmacological treatment with ATRIPLA who were divided into three groups: group 1, patients under ATRIPLA antiretroviral therapy; group 2, patients with ATRIPLA and rosemary aqueous extract (4 g/L per day); and group 3, patients with ATRIPLA and rosemary methanolic extract (400 mg/day). The genomic instability was evaluated through the buccal micronucleus cytome assay. Oral epithelial cells were taken at the beginning and 1 and 4 months later. The groups that received the pharmacological therapy with ATRIPLA and the complementary therapy with R. officinalis extracts showed a decrease in the number of cells with micronuclei and nuclear abnormalities compared with the group that only received ATRIPLA. The complementary therapy with R. officinalis decreased the genomic instability in HIV patients.

CYP3A5 metabolizes endogenous substrates and ~30% of prescription drugs. The CYP3A5 gene contains an active CYP3A5*1 allele, and a non-functional version, the CYP3A5*3 (rs776746), with consequences for drug therapeutic responses and side effects. Both CYP3A5*1 and *3 have been associated with hypertension. The frequency of CYP3A5*3 varies between populations of different ancestries, with Europeans having the highest allele frequency (> 90%). Given the importance of CYP3A5*3 in drug response and hypertension development, the aim of the present study was to evaluate the frequency of this polymorphism and its association with hypertension in vulnerable indigenous populations in Mexico. A total of 372 subjects were recruited from eight ethnic groups in Northwest Mexico. Systolic (SBP), diastolic (DBP), and median (MBP) blood pressures as well as body mass index (BMI) were measured. Ancestry was evaluated through STR analysis, and the CYP3A5*1/*3 polymorphisms were identified using real-time PCR with TaqMan® probes. Higher frequencies of CYP3A5*1 and *3 were observed in groups with higher (>90%) and lower (<90%) Amerindian ancestry, respectively. The CYP3A5*3 / *3 genotype was more frequent in indigenous women with higher SBP and DBP values. On the other hand, the * 1 allele showed a protective effect against both high SBP (OR, 0.38; 95% CI, 0.17-0.83, p = 0.001) and DBP (OR 0.38, 95% CI 0.18-0.81, p = 0.007) in women. This association remained significant after adjusting for BMI and age for diastolic (OR, 0.38; 95% CI, 0.17-0.84, p = 0.011) and systolic BP (OR, 0.33; 95% CI, 0.15-0.76, p = 0.005) BP levels in women. Thus, the frequency of CYP3A5*3 varies between groups and seems to depend on ancestry, and CYP3A5*1 decreases the risk of hypertension in Mexican indigenous women. This population analysis of CYP3A5*1/*3 has profound implications not only for the susceptibility to diseases, such as hypertension, but also for safer drug administration regimens, assuring better therapeutic responses and fewer side effects., (Copyright © 2020 Galaviz-Hernández, Lazalde-Ramos, Lares-Assef, Macías-Salas, Ortega-Chavez, Rangel-Villalobos and Sosa-Macías.)

Background: Rosemary leaves powder has been reported to reduce in a dose-dependent manner, glucose levels, lipid profile and lipid peroxidation in humans. However, patients should ingest high doses of powder contained in capsules. This formulation constitutes the intake of 10 capsules per day, so the active metabolite must first, be released and then absorbed (for which, rosemary leaf powder must be mixed with gastric juice)., Aim: Evaluate whether a shortened dose and time of treatment as well as the pharmaceutical presentation in rosemary tea (Rosmarinus officinalis) instead of powder have a therapeutic effect in the treatment of T2D., Method: The complementary therapy with Rosemary tea (2g/1 litre of water per day) were evaluate on resistance to insulin, oxidative stress, biochemical parameters and anthropometric measurements in forty patients T2D under treatment with metformin and/or glibenclamide afther giving your authorization through informed consent., Results: The data indicated that Rosemary tea intake after 90 days, statistically decreased (p < 0.05) anthropometric parameters like the body mass index and waist-hip ratio. Remarkably, this treatment decreased the percentages of glycated hemoglobin, insulin resistance, and the pancreatic β-cell function and lastly, a significant difference in lipid peroxide levels was found., Conclusion: These data show that shortening time and dose, as well as changing the formulation of the Rosemary plant constitutes a promising treatment for drug-resistant T2D patients., Competing Interests: The authors declare no conflicts of interest., (© 2019 Journal of Population Therapeutics and Clinical Pharmacology. All rights reserved.)

Jatropha dioica is traditionally used owing to its antiviral, antifungal, and antimicrobial properties. But, toxicological information regarding J. dioica root total extract is currently limited. The aim of this work was to evaluate in a rat model, the transplacental genotoxicity effect of J. dioica aqueous root total extract. Three different J. dioica aqueous root total extract doses (60, 100, and 300 mg/kg) were administered orally to Wistar rats during 5 days through the pregnancy term (16-21 days). Pregnant rats were sampled every 24 h during the last 6 days of gestation, and pubs were sampled at birth. Genome damage in dams and their newborn pups transplacentally exposed to J. dioica was evaluated by in vivo micronuclei assay. We evaluated the frequency of micronucleated erythrocytes (MNE), micronucleated polychromatic erythrocytes (MNPCE), and polychromatic erythrocytes (PCE) in peripheral blood samples from pups and MNPCE and PCE in pregnant rats. No genotoxic effect was observed after oral administration of the three different doses of aqueous root total extract of J. dioica in pregnant or in their newborn pubs, after transplacental exposure. A significant decrease in PCE frequency was noted in samples from pubs of rats treated with the highest dose of J. dioica extract. The aqueous total root extract of J. dioica at the highest dose tested in our research do have cytotoxic effect in pups transplacentally exposed to this plant extract. Moreover, neither a genotoxic nor a cytotoxic effect was observed in pregnant rats. In the present work, there was no evidence of genome damage in the rat model after transplacental exposure to J. dioica aqueous root total extract., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Gabriela Morales-Velazquez et al.)

Chronic periodontitis (CP) is an infection that affects the teeth supporting structure. Macrophage migration inhibitory factor (MIF) is an important effector cytokine of the innate immune system. Due to its functional characteristics, MIF may be involved in the immunopathology of CP. The aim of the present study was to evaluate MIF levels in gingival crevicular fluid (GCF), saliva, and serum of CP patients. A cross-sectional study was conducted on 60 subjects divided into two groups: subjects with CP (n= 30) and periodontally healthy subjects without CP (n=30). MIF was quantified in GCF, saliva, and serum of all participants by enzyme-linked immunosorbent assay. MIF concentrations were higher in GCF, saliva, and serum in the group with CP compared with the group without CP and a higher MIF concentration was observed in GCF (p=0.001) and saliva (p=0.009) in the group with CP. MIF intragroup comparisons between fluids demonstrated significant high levels of MIF in saliva compared with GCF and serum in both study groups (p<0.05). A positive correlation was found between clinical signs and MIF concentration in GCF (p<0.05). There is an association between the MIF and the clinical signs of the disease. Therefore, MIF could have an important role in the pathology and progression of CP.

Preeclampsia is a condition associated with high rates of maternal-fetal morbidity and mortality. It usually occurs in 3-10% of nulliparous women and 18% of previously affected women. Different lines of evidence have demonstrated the role of the father in the onset of preeclampsia. The placenta is the cornerstone of preeclampsia and poses important paternal genetic determinants; in fact, the existence of a "paternal antigen" has been proposed. Nulliparity is a well-known risk factor. Change of partner to a woman without history of preeclampsia increases the risk; however, this change decreases in women with history of the condition. High interval between pregnancies, short sexual intercourse before pregnancy, and conception by intracytoplasmic sperm injection suggest a limited exposure to the so-called paternal antigen. A man who was born from a mother with preeclampsia also increases the risk to his partner. Not only maternal but also paternal obesity is a risk factor for preeclampsia. Fetal HLA-G variants from the father increased the immune incompatibility with the mother and are also significantly associated with preeclampsia in multigravida pregnancies. An analysis of a group of Swedish pregnant women showed that the risk for preeclampsia is attributable to paternal factors in 13% of cases, which could be related to genetic interactions with maternal genetic factors. This review aimed to evaluate the evidences of the father's contribution to the onset of preeclampsia and determine the importance of including them in future studies.

Objective: To determine the number of micronuclei and nuclear anomalies in Mexico's indigenous population., Materials and Methods: One hundred twenty indigenous individuals were evaluated, including thirty from the ethnicities Cora, Huichol, Tarahumara and Tepehuano. The number of micronuclei (MN) and any nuclear abnormality (NA) in oral mucosa cells, including cells with nuclear buds, binucleated cells, cells with karyolysis, karyorrhetic, condensed chromatin and pyknotic cells were determined for each participant., Results: Tepehuano and Tarahumaras showed the greatest damage to DNA. The Tepehuano group presented the highest number of MN and NA, this being a significant difference (p < 0.05) compared with the rest of the studied groups. This group also presented the highest herbicide exposure (46.7%). In relation to the smoking and drinking habits, these were more frequent in the Tarahumara group (33.3 and 50% respectively)., Conclusion: The ethnic diversity, habits and customs may influence the DNA nuclear integrity in the Amerindian groups.

Jatropha dioica Sessé ex Cerv. is a medicinal plant credited with low cytotoxicity in vitro. Thus, the objective of this work was to evaluate the possible genotoxic and cytotoxic effect in vivo of the J. dioica aqueous extract by means of micronucleus assay in mouse peripheral blood. Four different J. dioica aqueous extract dose-units were evaluated (30, 60, 100, and 300 mg/kg). The extract was administered orally to male Balb-C-strain mice every 24 h during 5 days. Blood samples were taken at 0, 24, 48, 72, 96, and 120 h from the mouse's tail and were performed in duplicate extensions. The number of Polychromatic Erythrocytes (PCE), Polychromatic Micronucleus Erythrocytes (PCEMN), and Micronucleus Erythrocytes (MNE) was determined at the different sampling times in the different study groups. Our results showed that the group that received 60 mg/kg of cyclophosphamide (positive control) presented a significant decrease in the PCE (p = 0.044) proportion and a significant increase in MNE (p = 0.032, p = 0.0001). The groups that received the different J. dioica aqueous extract doses did not present either a PCE decrease or an increase in PCEMN and MNE. J. dioica exerts neither a genotoxic nor a cytotoxic effect on mouse peripheral blood at high doses., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Exposure to ultraviolet-A (UVA) light can accidentally cause adverse effects in the skin and eyes. UVA induces DNA damage directly by creating pyrimidine dimers or by the formation of reactive oxygen species that can indirectly affect DNA integrity. UVA radiation is emitted by lamps from everyday devices. In adult rats, micronucleated erythrocytes (MNE) are removed from the circulation by the spleen. However, in newborn rats, MNE have been observed in peripheral blood erythrocytes. The objective of this study was to use micronucleus tests to evaluate the DNA damage caused in newborn rats exposed to UVA light from three different types of UVA lamps obtained from commonly used devices: counterfeit detectors, insecticide devices, and equipment used to harden resins for artificial nails. Rat neonates were exposed to UVA lamps for 20min daily for 6days. The neonates were sampled every third day, and the numbers of MNE and micronucleated polychromatic erythrocytes (MNPCE) in the peripheral blood were determined. The rat neonates exposed to the three types of UVA lamps showed increased numbers of MNE and MNPCE from 48h to 144h (P<0.05 and P<0.001 respectively). However, no relationship was observed between the number of MNE and the wattage of the lamps. In conclusion, under these conditions, UVA light exposure induced an increase in MNE without causing any apparent damage to the skin., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To evaluate whether the maternal, paternal or the combined maternal/paternal contribution of SNP rs5370 of the EDN1 gene is associated with preeclampsia and drove its expression in placenta., Study Design: This case-control study included 61 preeclamptic patients and their partners and 49 healthy pregnant women and their partners. The population was sub-divided into three groups: women-only, men-only and combined (women/men). The analysis included genotyping of rs5370 in mothers and fathers and evaluating the expression profile of the EDN1 gene in placenta. Comparisons of categorical variables were performed using chi-square and/or Fisher's exact tests. The intergroup comparisons were analysed with the Mann-Whitney U test. The association between the polymorphism and the disease was evaluated through multivariate regression analysis. Spearman's correlation was performed to test the relationship between pre-gestational history and clinical features of the affected patients with EDN1 gene expression., Results: The analysis of paternal risk factors associated with preeclampsia revealed no differences between groups. A negative association between SNP rs5370 and preeclampsia was found in men group (OR 0.42; CI 95% 0.18-0.94, p=0.034) but not in women or combined groups. The adjustment for paternal protective factors increased the observed negative association, and the opposite was observed in the presence of paternal risk factors. The expression of the EDN1 gene in the placenta was significantly higher in the group of cases and was not associated with the rs5370 polymorphism., Conclusion: The paternal rs5370 polymorphism decreases the risk for preeclampsia and is not associated with placental expression of the EDN1 gene., (Copyright © 2016 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background and Objective: Periodontal disease is a chronic bacterial infection characterized by connective tissue breakdown and alveolar bone destruction because of inflammatory and immune response caused by periodontopathogens and long-term release of reactive oxygen species. A high number of reactive oxygen species result in periodontal tissue damage through multiple mechanisms such as lipid peroxidation, protein denaturation and DNA damage. The aim of this study was to evaluate DNA and oxidative damage in subjects with chronic or aggressive periodontitis and healthy controls., Material and Methods: Buccal mucosa cells and whole saliva were collected from 160 subjects, who were divided into three groups: subjects with chronic periodontitis (CP) (n = 58), subjects with aggressive periodontitis (AgP) (n = 42) and a control group (n = 60). DNA damage was determined by counting micronuclei (MN) and nuclear abnormalities (NAs) in exfoliated cells, including binucleated cells, cells with nuclear buds and karyolitic, karyorrhectic, condensed chromatin and pyknotic cells. The degree of oxidative stress was determined by quantifying 8-hydroxy-2'-deoxyguanosine (8-OHdG) in whole saliva., Results: Subjects with CP or AgP presented significantly more ( p < 0.05) MN and NAs and higher levels of 8-OHdG ( p < 0.05) compared with the control group., Conclusion: Our results indicate that subjects with periodontitis (CP or AgP) exhibited an increase in the frequency of MN, NAs and 8-OHdG, which is directly related to DNA damage. In addition, a positive correlation exists between oxidative stress produced by periodontitis disease and MN., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Aims: High triglyceride levels are closely related to cardiovascular disease. Its development lays on age, diet, physical activity, ethnicity and genetic factors. Among the last, the CYP1A1*2C allele has an influence on the metabolism of cholesterol and other fatty acids. We undertook this study to determine the frequency of CYP1A1*2C and its association with triglyceride levels in Mexican indigenous Tarahumaras and Tepehuanos., Methods: Anthropometric and biochemical data were recorded. Genotyping of CYP1A1*2C by RT-PCR was done in 110 Tepehuano, 69 Tarahumara and 64 Mestizo., Results: Significant differences in age, waist diameter, BMI, creatinine, glucose, cholesterol, triglycerides, HDL and VLDL measurements were found between Tarahumaras and Tepehuanos (p <0.05). Additionally, Tarahumara women showed the highest values of waist diameter, BMI and triglycerides (p <0.05). It was found that Tarahumaras showed a significant association between high triglyceride levels and CYP1A1*2C allele (OR = 2.57; 95% CI 1.12-5.88, p = 0.024) under a recessive inheritance model. However, the Tepehuano group showed a significant protective association between normal triglyceride levels and CYP1A1*2C polymorphism (OR = 0.28; 95% CI 0.10-0.80, p = 0.015) following a dominant inheritance model. The same pattern was observed after analysis with females of both ethnicities., Conclusion: A significant association between CYP1A1*2C and high triglyceride levels in Amerindian Tarahumaras from Chihuahua has been found; this allele was significantly associated with normal triglyceride levels in Tepehuanos from Durango, Mexico. Further studies are needed to elucidate the genetic role of CYP1A1 in cardiovascular disease susceptibility., (Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.)

Aim: Polymorphisms in CYP2D6 impact the interindividual and interethnic variability of drug efficiency; therefore, we determined the CYP2D6 allele distribution in eight Amerindian groups from northwestern Mexico and compared them with the frequencies in Mexican Mestizos., Materials & Methods: A total of 508 Amerindians were studied. Genotyping of CYP2D6*5 and multiplication alleles was performed by long-range PCR, while CYP2D6*2, *3, *4, *6, *10, *17, *29, *35, *41 and copy number were evaluated by real-time PCR., Results: The most frequent alleles were CYP2D6*2 (0.05-0.28), CYP2D6*4 (0.003-0.21) and multiplications (0.043-0.107). CYP2D6*5, *6, * 10 and *41 were not observed in the majority of Amerindians, and CYP2D6*3, *17, *35 and *29 were not detected. The poor metabolizer genotype ( *4/*5) was lower (0.2%) in Amerindians than in Mestizos (5%); conversely, the ultrarapid metabolizer genotype was higher (12.6%) in indigenous groups than in Mestizos (7%)., Conclusion: Our data show a lower frequency of CYP2D6 inactive alleles and a higher frequency of duplication/multiplication of CYP2D6 active alleles in indigenous populations that in Mestizos. Original submitted 14 August 2013; Revision submitted 7 October 2013.

We previously documented the lowest frequency of CYP2C9*2 in Mexican indigenous Tepehuanos followed by Mestizos and Mexican-Americans populations, suggesting a negative correlation between the CYP2C9*2 frequency and the degree of Asian ancestry in indigenous Americans. We determined the influence of ethnic admixture components on the CYP2C9 allele distribution in 505 Amerindian from eight indigenous populations through genotyping CYP2C9*2, *3 and *6 alleles by real-time PCR and molecular evaluation of ancestry. The frequencies for CYP2C9*2 were 0.026 in Seris and 0.057 in Mayos, being higher than in Asians (P<0.001). CYP2C9*3 was found in Tarahumaras (0.104), Mayos (0.091), Tepehuanos (0.075), Guarijíos (0.067), Huicholes (0.033) and Coras (0.037), with East Asians having lower frequencies than the former three groups (P<0.001). CYP2C9*6 was not found. The frequency of CYP2C9*2 was lower in Amerindians than in European populations, and higher than their Asian ancestors. The presence of this allele in ethnic groups in Mexico can be explained by European admixture.

Allele frequency distributions for 15 STR loci (AmpFlSTR Identifiler kit) were estimated in 825 volunteers of the following eight Mexican-Amerindian populations from two geographical regions: (1) North: Tarahumara (204), Mayo (45), Seri (28), and Guarijío (17); (2) Northwest: Tepehuano (123), Mexicanero (84), Cora (85), and Huichol (239). Genotype frequency distribution was in agreement with Hardy-Weinberg expectations for all 15 STRs, excepting for two loci (D13S317 and FGA) in the Huichol population. The power of discrimination and power of exclusion values were both larger than 0.99999. These STR databases will support the correct interpreting of DNA profiles in paternity testing and forensic cases in Mexican-Amerindian groups from these regions, until know poorly studied. Genetic distances and pairwise comparisons were estimated between populations. A significant genetic differentiation was observed between these Mexican-Amerindian groups (F(ST)=3.43%; p=0.0000) that was 10 times larger than the observed between Mestizos (F(ST)=0.34%), which represent most of the Mexican population (~90%). This result was in agreement with the incapability to cluster these Native American populations by geographic criteria. Pre-Colombian descriptions of Aridoamerica, including the North region of Mexico, suggest genetic drift effects to explain this noticeable population differentiation of Mexican-Amerindian groups., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Interindividual differences in response to drug treatments are mainly caused by differences in drug metabolism, in which cytochrome P450 (CYP450) enzymes are involved. Genetic polymorphisms of these enzymes have a key role in this variability. However, environmental factors, endogenous metabolism and disease states also have a great influence on the actual drug metabolism rate (metabolic phenotype). Consequently, the genotype does not always correlate with the actual drug hydroxylation phenotype. In this sense, in vivo phenotyping strategies represent an alternative to evaluate the interindividual variability in drug metabolism. Therefore, the 'cocktail' approach is considered as an advantageous strategy to obtain actual and reliable information on several CYP activities in just one experiment. As reviewed, phenotyping studies on Latin-American populations, which comprise about 400 million people, are scarce, and only selective phenotyping methods were applied. Therefore, a novel cocktail approach is here proposed as a phenotyping tool to evaluate the relationship between genotype and phenotype of major CYP enzymes in Hispanic populations. This determination will allow adaptation of drug therapies to these populations and consequently to benefit from the application of pharmacogenetics in the reduction of drug adverse effects and in the improvement of therapeutic responses.

Background: Vascular endothelial growth factor (VEGF) gene is an important angiogenesis regulator related to cancer development and progression. We evaluated the association between -2578 C/A (rs699947) VEGF polymorphism and PCa in Mexican subjects, to contribute to knowledge of VEGF role in genetic epidemiology of prostate cancer (PCa)., Objective: The aim of this study was to evaluate the association between -2578 C/A VEGF variant and PCa in Mexican population., Methods: A total of 249 men (77 PCa cases and 172 controls) from the Northwestern region of Mexico were screened for the -2578 C/A VEGF variant. The polymorphism was determined by polymerase chain reaction-based restriction analysis., Results: Genotype frequencies for C/C, C/A, and A/A, were 0.48, 0.49, 0.03 for cases and 0.41, 0.45, 0.14 for controls respectively. Genotype A/A of -2578 VEGF variant reduces the risk of PCa in an 84% among studied population (Odds Ratio 0.16; 95% CI: 0.04-0.71, P=0.007). C/C carriers showed an increased PCa risk of 6.1 times among the study population., Conclusions: Inheritance of -2578 A/A genotype of VEGF gene may modify PCa susceptibility risk in Mexican population.

Background and Aims: Type 2 diabetes mellitus (T2DM) is a chronic degenerative disease that promotes autoxidation of sugars, leading to the production of reactive oxygen species. This damage occurs especially at the level of cellular proteins, carbohydrates, lipids and DNA, thus playing an important role in the pathogenesis of late complications of T2DM. We investigated the effect of folic acid on DNA and oxidative damage in patients with T2DM., Methods: We studied 30 individuals diagnosed with T2DM and 30 control individuals without disease. Individuals with T2DM were prescribed 5 mg of folic acid, taken orally three times daily for 1 month. Samples were taken 15 and 30 days after treatment. DNA damage was determined using the micronucleus test in oral mucosa and oxidative stress by quantifying 8-hydroxy-2'-deoxyguanosine (8-OHdG) as well as by quantifying total lipid peroxides., Results: Individuals with T2DM had a higher number of micronuclei as well as higher levels of 8-OHdG and lipid peroxides than the control group (p = 0.001). Individuals with T2DM showed a significant reduction in the number of micronuclei and the concentration of 8-OHdG and lipid peroxides over time with folic acid intake., Conclusions: A positive correlation exists between oxidative stress produced by T2DM and DNA damage, so the use of an antioxidant such as folic acid in DM2 therapy is advisable for delaying complications due to T2DM-induced oxidative stress and DNA damage., (Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.)

Methylphenidate (MPH; Ritalin®; Novartis Pharmaceuticals, Inc., Basel, Switzerland) has been prescribed to treat attention deficit/hyperactivity disorder (ADHD) since its approval by the U.S. Food and Drug Administration over 50 years ago. Due to concerns that MPH might induce cytogenetic alterations in children, treatment with this drug has been a controversial issue. In the present study, we assessed the frequency of micronucleated erythrocytes (MNEs), micronucleated polychromatic erythrocytes (MNPCEs), and polychromatic erythrocytes (PCEs) in peripheral blood samples from mice treated with three different doses of MPH (30, 60, or 125 mg/kg). We found no evidence of increased MNEs or MNPCEs, nor did PCEs decline. These results add to the accumulating evidence that MPH does not induce genotoxic or cytotoxic damage.

The aim of the present study was to modify and validate a high-performance liquid chromatographic (HPLC) method for determining 2,3 and 2,5 dihydroxybenzoic acid (2,3-DHBA and 2,5-DHBA) from salicylic acid in human plasma. The mobile phase was a mixture of sodium acetate/citrate (pH 2.5) 30 mM-methanol (93:7, v/v). The injection volume was 10 muL. Retention time for 2,5-DHBA, and 2,3-DHBA was 4.5 +/- 0.10 and 5.8 +/- 0.15 min, respectively. The detection and quantification limits were 10 and 40 nM for 2,3-DHBA and 8 and 20 nM for 2,5-DHBA. Linearity was evaluated in the range of 40-1600 nM for both metabolites. Inter- and intra-analysis variation coefficient was below 10%. Good recoveries of more than 99% were obtained for both metabolites using this method.

Background: Little is known about the epidemiology of Chlamydia trachomatis infection in female sex workers (FSWs) in Mexico., Goal: The goal of the study was to determine the prevalence of C trachomatis infection in registered FSWs from northern Mexico and to determine the sociodemographic characteristics associated with the infection., Study Design: An enzyme immunoassay was used to test 354 FSWs in three northern Mexican cities for cervical C trachomatis infection. All participants were registered in a government health office. Recruitment was consecutive and voluntary. The association between clinical and sociodemographic characteristics of FSWs and infection was evaluated., Results: The overall prevalence of C trachomatis infection among participants in the three cities was 12.4%. Women of low socioeconomic level and those younger than 25 years were the most frequently infected. Among FSWs in Durango, a higher frequency of C trachomatis infection was found for those who did not use condoms., Conclusion: C trachomatis is an important pathogen in the sexually transmitted diseases of registered FSWs in northern Mexico.