Fernando Vazquez-Alaniz

Lack of association between Toxoplasma gondii infection and hypertensive disorders in pregnancy: a case–control study in a Northern Mexican population

BackgroundThe outcome of pregnancy is often threatened by hypertension disorders, i.e. eclampsia. Rate of infection with the protozoan parasite Toxoplasma gondii can be as high as 80% in pregnant women, and infection acquired during pregnancy can lead to fetal death. Very little is known about a potential association between infections, i.e. those with Toxoplasma gondii, and hypertensive disorders during pregnancy.MethodsThrough a case–control study design, we investigated the presence of anti-Toxoplasma IgG and anti-Toxoplasma IgM antibodies in 146 pregnant women suffering from hypertensive disorders (cases) and 146 age-matched normotensive pregnant women (controls) attending a public hospital in Durango City, Mexico. Obstetric and blood pressure characteristics from cases and controls were also obtained.ResultsSeroprevalence of anti-Toxoplasma IgG antibodies and IgG titers did not differ significantly in controls (8/146; 5.5%) and cases (9/146; 6.2%). Anti-Toxoplasma IgM antibodies were found in 2 (1.2%) controls and none of the cases. Seroprevalence of T. gondii in controls (5.5%) was similar to seroprevalences found in patients with mild preeclampsia (4/27: 14.8%), severe preeclampsia (5/95: 5.3%), eclampsia (0/16: 0%) and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) (0/8: 0%) (P = 0.23).ConclusionsOur results suggest that latent infection with T. gondii is not associated with hypertensive disorders in pregnant women in Northern Mexico. Further studies with larger sample sizes are needed to elucidate the association of infection with T. gondii with hypertensive disorders in pregnancy.

Association of COMT G675A and MTHFR C677T polymorphisms with hypertensive disorders of pregnancy in Mexican mestizo population

OBJECTIVE To investigate the relationship between COMT G675A and MTHFR C677T polymorphisms and hypertension disorders of pregnancy (HDP) in a Mexican mestizo population. DESIGN AND METHODS This case-control study involved 194 HDP and 194 normoevolutive pregnant women. The polymorphisms were genotyped by real time PCR. RESULTS Our results showed that the COMT AA genotype increases the risk to HDP (OR: 2.67; 95% CI 1.33-5.35), preeclampsia (OR: 2.69; 95% CI 1.00-7.22) and gestational hypertension (OR: 3.87; 95% CI 1.25-12.0). Furthermore, the double mutant genotype (COMTAA/MTHFRTT) potency the risk to HDP more than two times (OR: 5.21; 95% CI 1.12-24.3, p=0.019). CONCLUSION Our work provides evidence that COMT 675AA genotype is a risk factor for HDP and that this risk is increased by the presence of MTHFR 677TT genotype in a Mexican mestizo population.

Polymorphisms in DNA Repair Genes (APEX1, XPD, XRCC1 and XRCC3) and Risk of Preeclampsia in a Mexican Mestizo Population

Variations in genes involved in DNA repair systems have been proposed as risk factors for the development of preeclampsia (PE). We conducted a case-control study to investigate the association of Human apurinic/apyrimidinic (AP) endonuclease (APEX1) Asp148Glu (rs1130409), Xeroderma Pigmentosum group D (XPD) Lys751Gln (rs13181), X-ray repair cross-complementing group 1 (XRCC) Arg399Gln (rs25487) and X-ray repair cross-complementing group 3 (XRCC3) Thr241Met (rs861539) polymorphisms with PE in a Mexican population. Samples of 202 cases and 350 controls were genotyped using RTPCR. Association analyses based on a χ2 test and binary logistic regression were performed to determine the odds ratio (OR) and a 95% confidence interval (95% CI) for each polymorphism. The allelic frequencies of APEX1 Asp148Glu polymorphism showed statistical significant differences between preeclamptic and normal women (p = 0.036). Although neither of the polymorphisms proved to be a risk factor for the disease, the APEX1 Asp148Glu polymorphism showed a tendency of association (OR: 1.74, 95% CI = 0.96–3.14) and a significant trend (p for trend = 0.048). A subgroup analyses revealed differences in the allelic frequencies of APEX1 Asp148Glu polymorphism between women with mild preeclampsia and severe preeclampsia (p = 0.035). In conclusion, our results reveal no association between XPD Lys751Gln, XRCC Arg399Gln and XRCC3 Thr241Met polymorphisms and the risk of PE in a Mexican mestizo population; however, the results in the APEX1 Asp148Glu polymorphism suggest the need for future studies using a larger sample size.

Comparative expression profiles for KiSS-1 and REN genes in preeclamptic and healthy placental tissues

OBJECTIVE The aim of the present work was to look at differences in the placental tissue expression of KiSS-1 and REN genes from preeclamptic and healthy pregnant women, that could account for a possible synergistic function for both genes in the pathogenesis of preeclampsia. STUDY DESIGN This case-control study involved 27 preeclamptic women and 27 normoevolutive pregnant women. cDNA was obtained from placental tissue to carry out qPCR for both KiSS-1 and REN genes in order to compare mRNA expression levels in the studied groups. Statistical analysis showed expression differences that correlate with clinical and/or biochemical variables. RESULTS Higher expression for KiSS-1 in PEE vs. control woman (p=0.001) was observed, whereas no difference was observed for REN expression (p=0.300) when all the subjects were included. However, REN expression was significant higher when the samples were stratified according to preeclampsia severity. For 18 mild preeclamptic patients the p-value was p=0.001 compared to their controls, while for the remaining nine with severe preeclampsia the expression became significant (p=0.001). CONCLUSION Our results suggest that the high KiSS-1 expression seen in preeclamptic patients is in accordance with its role as an inhibitor of trophoblast invasiveness and maintained until the end of gestation. On the other hand, aggressive therapeutic management and/or severity status of patients have a direct effect on placental REN expression levels, masking the natural high expression of this gene on preeclamptic placental tissue. Therefore it was not possible to establish a real concordant expression profile for KiSS-1 and REN genes.

Genetic variation in oxidative stress and DNA repair genes in a Mexican population.

Abstract Background: Oxidative stress has been associated with several complex diseases. Effects generated as a result of oxidative stress may be modulated by various genes. Variation in these genes, particularly when located within coding or regulating regions, may be the primary cause of this modulation. The aim of this work was to determine the allelic and genotypic frequencies of CAT C-262T, SOD3 Ala58Thr, APEX1 Asp148Glu, XPD Lys751Gln and XRCC3 Thr241Met genetic markers in a northern Mexican population. Subjects and methods: This study analysed 250 unrelated individuals by RT-PCR. Results: A high allele mutant frequency was found in SOD3 Ala58Thr and APEX1 Asp148Glu genetic markers (0.395 and 0.38, respectively). A correspondence analysis showed that northern Mexicans are close to European populations. A linkage disequilibrium test between XPD Lys751Gln and CAT C-262T and XPD Lys751Gln and SOD3 Ala58Thr genetic markers was significant (p = 0.000). Conclusion: The genetic markers described in this work will be a valuable resource for future functional studies in the northern Mexican population to explore comprehensively their role in the aetiology of human diseases. Furthermore, it will be necessary to replicate these studies in other regions of Mexico due to differences between Mexican sub-populations.

Oxidative stress equilibrium during obstetric event in normal pregnancy

Abstract Objective: The aim of this study was to determine malondialdehyde (MDA) concentration as an oxidative stress marker and total antioxidant capacity (TAC) in pregnancy before and after perinatal event. Methods: This study was performed on 200 healthy full-term pregnant women admitted to pregnancy resolution in Maternal-Child Hospital of Durango, Mexico. Oxidative stress and TAC were assessed through detection of lipid peroxidation by quantitation of thiobarbituric acid-reactive substances (TBARS) and TAC through ferric reducing ability of the plasma (FRAP). Results: Our results showed increased levels of MDA after vaginal delivery (VD). TAC was also increased after obstetric event, but it did not differ between VD and caesarean section. Conclusions: We demonstrated that MDA concentrations are increased two hours after obstetric event, and this increase correlates with VD. The TAC was increased as a compensatory mechanism during obstetric event. Another important finding is that women receiving analgesia administration in VD, as well as dexamethasone administration in caesarean section, experienced a protector effect that decreased MDA levels.

Apoptosis in pancreatic β-cells is induced by arsenic and atorvastatin in Wistar rats with diabetes mellitus type 2

INTRODUCTION Diabetes Mellitus type 2 (T2D) is a multifactorial disease. However, it is known that there is an important effect in pancreatic β-cells caused by apoptosis of pro-apoptotic proteins, possibly related to arsenic exposure and atorvastatin treatment. OBJECTIVE The goal of this study was to evaluate the effects of atorvastatin treatment on apoptosis of pancreatic β-cells in Wistar rats with induced diabetes type 2 exposed to arsenic. MATERIAL & METHODS T2D in Wistar rats was induced by administration of Streptozotocin. The plasmatic glucose concentrations were measured using the glucose oxidase method, and the concentration of glycated hemoglobin (HbA1c) in whole blood was determined. Exposure to arsenic was measured from urine using atomic absorption with hydride generation, and pro-apoptotic proteins in pancreatic β-cells were observed using the Western blotting technique. RESULTS Caspase-3 was present in rats that were treated with 10 mg/kg of oral atorvastatin and exposed to 0.01 and 0.025 mg/L of arsenic, but no others proteins were present, such as pro Caspase-8, bcl-2, and Fas. The glycemic levels were 129.2 ± 7.0 mg/dL in the control group and 161.8 ± 14.6 mg/dL and 198.3 ± 18.2 mg/dL (p < .05) in the study groups. HbA1c increased from 2.53% to 3.64% (p < .05) in the control and study groups. CONCLUSIONS Atorvastatin treatment and arsenic exposure alone are capable of generating apoptosis in pancreatic β-cells of Wistar rats with T2D. Together, all of these factors induce apoptosis in pancreatic cells.

Full Atrioventricular Block Secondary to Acute Poisoning Mercury: A Case Report

Background: The biological behaviour and clinical significance of mercury toxicity vary according to its chemical structure. Mercury differs in its degree of toxicity and in its effects on the nervous, digestive and immune systems as well as on organs such as the lungs, kidneys, skin, eyes and heart. Human exposure occurs mainly through inhalation of elemental mercury vapours during industrial and artisanal processes such as artisanal and small-scale gold mining. Case presentation: A 52-years-old female, housewife, with a body mass index of 25.3 kg/cm2, without smoking or alcohol habits or any important clinical or chronic cardiovascular history, was admitted to the emergency room due to probable accidental poisoning by butane gas. Clinical manifestations with a headache, dizziness, cough, and dyspnoea of medium to small efforts. An initial physical exploration with Glasgow scored at 15, with arrhythmic heart sounds, pulmonary fields with bilateral subcrepitant rales and right basal predominance. Electrocardiographic findings were as follows: a cardiac frequency of 50 beats per minute and atrioventricular dissociation. Laboratory parameters were: white blood cells at 15.8 × 109/L; aspartate aminotransferase at 38 U/L; lactate dehydrogenase at 1288 U/L; creatine-kinase at 115 U/L; CK-MB fraction at 28 U/L; and other biochemical parameters were within the reference values. A radiographic evaluation showed flow cephalization, diffuse bilateral infiltrates with right basal predominance. In addition, the patient presented data of low secondary expenditure to third-degree atrioventricular (AV) block for which the placement of a transvenous pacemaker was decided, substantially improving the haemodynamic parameters. Subsequently, after a family interrogation, the diagnosis of mercury inhalation poisoning was established. An initial detection of mercury concentration (Hg(0)) was carried out, reporting 243.5 µg/L. In view of this new evidence, mercury chelation therapy with intravenous calcium disodium ethylenediamine tetraacetic acid (CaNa2·EDTA) was initiated. After 8-days of hospital stay, she presented a favourable evolution with both clinical and radiological improvements, so that the mechanical ventilation progressed to extubating. Subsequently, she was referred for cardiology because of her persistent 3rd-degree atrioventricular block, deciding to place a definitive bicameral pacemaker. The patient was discharged from the hospital 14 days after admission due to clinical improvements with mercury plasma levels at 5 µmol/L and a heart rhythm from the pacemaker. Conclusions: We show evidence that acute exposure to elemental mercury can affect the heart rhythm, including a complete atrioventricular blockage.

Hypocholesterolemia is an independent risk factor for depression disorder and suicide attempt in Northern Mexican population

BackgroundCholesterol has been associated as a risk factor for cardiovascular disease. Recently, however, there is growing evidence about crucial requirement of neuron membrane cholesterol in the organization and function of the 5-HT1A serotonin receptor. For this, low cholesterol level has been reported to be associated with depression and suicidality. However there have been inconsistent reports about this finding and the exact relationship between these factors remains controversial. Therefore, we investigated the link between serum cholesterol and its fractions with depression disorder and suicide attempt in 467 adult subjects in Mexican mestizo population.MethodsPlasma levels of total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-c) and low density lipoprotein cholesterol (LDL-c) were determined in 261 MDD patients meeting the DSM-5 criteria for major depressive disorder (MDD), 59 of whom had undergone an episode of suicide attempt, and 206 healthy controls.ResultsA significant decrease in total cholesterol, LDL-cholesterol, VLDL-cholesterol and triglyceride serum levels was observed in the groups of MDD patients and suicide attempt compared to those without suicidal behavior (p < 0.05). After adjusting for covariates, lower cholesterol levels were significantly associated with MDD (OR 4.229 CI 95% 2.555 – 7.000, p<.001) and suicide attempt (OR 5.540 CI 95% 2.825 – 10.866, p<.001)ConclusionsThese results support the hypothesis that lower levels of cholesterol are associated with mood disorders like MDD and suicidal behavior. More mechanistic studies are needed to further explain this association.

Association between Blood Lead Levels and Delta-Aminolevulinic Acid Dehydratase in Pregnant Women

Blood lead levels (BLLs) and delta-aminolevulinic acid dehydratase (ALAD) activity are considered biomarkers of lead exposure and lead toxicity, respectively. The present study was designed to investigate the association between BLLs and ALAD activity in pregnant women from Durango, Mexico. A total of 633 pregnant women aged 13–43 years participated in this study. Blood lead was measured by a graphite furnace atomic absorption spectrometer. ALAD activity was measured spectrophotometrically. Mean blood lead was 2.09 ± 2.34 µg/dL; and 26 women (4.1%) crossed the Centers for Disease Control (CDC) recommended level of 5 µg/dL. ALAD activity was significantly lower in women with levels of lead ≥5 µg/dL compared to those with BLLs < 5 µg/dL (p = 0.002). To reduce the influence of extreme values on the statistical analysis, BLLs were analyzed by quartiles. A significant negative correlation between blood lead and ALAD activity was observed in the fourth quartile of BLLs (r = −0.113; p < 0.01). Among women with blood lead concentrations ≥2.2 µg/dL ALAD activity was negatively correlated with BLLs (r = −0.413; p < 0.01). Multiple linear regression demonstrated that inhibition of ALAD in pregnant women may occur at levels of lead in blood above 2.2 µg/dL.