Iván Delgado-Enciso

Folate levels and N(5),N(10)-methylenetetrahydrofolate reductase genotype (MTHFR) in mothers of offspring with neural tube defects: a case-control study.

BACKGROUND Neural tube defects (NTDs) have been associated with biochemical factors involved in the conversion of homocysteine to methionine as folate deficiency and the mutation 677T in the N(5),N(10)-methylenetetrahydrofolate reductase gene (MTHFR). METHODS A case-control study was performed to detect this mutation in 38 unrelated women with NTD deceased products and 31 mothers without antecedents of NTD offspring. All products were born in Nuevo León (northeastern Mexico) during 1997. Erythrocyte and plasmatic folate levels and the genotype of the 677 polymorphism at the MTHFR locus were analyzed in both groups. RESULTS Although no significant differences were found in mean blood folate levels, the percentage of women in the case group with erythrocyte folate levels <160 ng/mL was significantly higher than in the control group (75 vs. 51.2%, p <0.05). The proportion of women with plasma folate levels <3.5 ng/mL was higher in the case group (16.2 vs. 0%, p <0.01). Genotype analysis demonstrated a significantly higher proportion of 677T homozygous mothers with NTD products (39.6 vs. 9.1%, p <0.05). Allele frequencies for the 677T mutation were 0.55 and 0.36 for cases and controls, respectively. The odds ratio (OR) for having a NTD product was 6.1 (95%, CI 1.56-23.6) for homozygous 677T mothers vs. homozygous 677C and heterozygous mothers. Significantly low levels of erythrocyte folate were found in the 677C homozygous case group and in plasma folate in the 677C/677T heterozygous case mothers. CONCLUSIONS Our study suggests that folate deficiency and MTHFR unfavorable genotype in mothers are important risk factors for severe NTD phenotype in our population.

Kbg and Kv1.3 channels mediate potassium efflux in the early phase of apoptosis in Jurkat T lymphocytes

Microelectrode ion flux estimation (MIFE) and patch-clamp techniques were combined for noninvasive K(+) flux measurements and recording of activities of the dominant K(+) channels in the early phases of apoptosis in Jurkat cells. Staurosporine (STS, 1 microM) evoked rapid (peaking around 15 min) transient K(+) efflux, which then gradually decreased. This transient K(+) efflux occurred concurrently with the transient increase of the K(+) background (K(bg)) TWIK-related spinal cord K(+) channel-like current density, followed by a drastic decrease and concomitant membrane depolarization. The Kv1.3 current density remained almost constant. Kv1.3 activation was not altered by STS, whereas the inactivation was shifted to more positive potentials. Contribution of K(bg) and Kv1.3 channels to the transient and posttransient STS-induced K(+) efflux components, respectively, was confirmed by the effects of bupivacaine, predominantly blocking K(bg) current, and the Kv1.3-specific blocker margatoxin. Channel-mediated K(+) efflux provoked a substantial cellular shrinkage and affected the activation of caspases.

Matrix Metalloproteinase-2 Promoter Polymorphism Is Associated with Breast Cancer in a Mexican Population

Background:Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity on matrix proteins, particularly basement membrane constituents. A single nucleotide polymorphism C>T transition at –1306 displayed a strong association with several cancers. Our study investigated whether or not the MMP-2 –1306C>T polymorphism contributed to the development of breast cancer (BC) in a Mexican population. Methods: 90 patients with BC and 96 control subjects were analyzed to detect MMP-2 –1306C>T polymorphism. Results: The frequency of MMP-2 CC genotype was significantly higher in BC patients when compared with the control group (OR 2.15; 95% CI 1.1–4.1). MMP-2 CC genotype frequency was more pronounced in younger subjects (≤50 years) at diagnosis (OR 2.66; 95% CI 1.04–6.96). Conclusion: The data suggest that MMP-2 –1306C>T polymorphism strongly contributes to the development of BC in the population studied, especially among women 50 years old and younger.

Detection of sequences from a potentially novel strain of cell fusing agent virus in Mexican Stegomyia ( Aedes ) aegypti mosquitoes

Flaviviruses (FVs) are a very heterogeneous group of viruses that includes viruses capable of infecting insects and/or vertebrates. Different human-disease-causing FVs are disseminated by mosquitoes, and therefore, the search for FV in these insects has recently been proposed in order to evaluate their potential transmission in a given community. An entomological survey was carried out in Colima (the hyperendemic dengue fever transmission zone in Mexico) to collect culicidae in urban and wild areas. No human-pathogenic FVs were found, but sequences related to a potentially novel strain of cell fusing agent virus (CFAV) were detected in Stegomyia (Aedes) aegypti mosquitoes.

Mechanosensitive Ca2 +-permeable channels in human leukemic cells: Pharmacological and molecular evidence for TRPV2

Mechanosensitive channels are present in almost every living cell, yet the evidence for their functional presence in T lymphocytes is absent. In this study, by means of the patch-clamp technique in attached and inside-out modes, we have characterized cationic channels, rapidly activated by membrane stretch in Jurkat T lymphoblasts. The half-activation was achieved at a negative pressure of ~50mm Hg. In attached mode, single channel currents displayed an inward rectification and the unitary conductance of ~40 pS at zero command voltage. In excised inside-out patches the rectification was transformed to an outward one. Mechanosensitive channels weakly discriminated between mono- and divalent cations (PCa/PNa~1) and were equally permeable for Ca²⁺ and Mg²⁺. Pharmacological analysis showed that the mechanosensitive channels were potently blocked by amiloride (1mM) and Gd³⁺ (10 μM) in a voltage-dependent manner. They were also almost completely blocked by ruthenium red (1 μM) and SKF 96365 (250 μM), inhibitors of transient receptor potential vanilloid 2 (TRPV2) channels. At the same time, the channels were insensitive to 2-aminoethoxydiphenyl borate (2-APB, 100 μM) or N-(p-amylcinnamoyl)anthranilic acid (ACA, 50 μM), antagonists of transient receptor potential canonical (TRPC) or transient receptor potential melastatin (TRPM) channels, respectively. Human TRPV2 siRNA virtually abolished the stretch-activated current. TRPV2 are channels with multifaceted functions and regulatory mechanisms, with potentially important roles in the lymphocyte Ca²⁺ signaling. Implications of their regulation by mechanical stress are discussed in the context of lymphoid cells functions.

Intraprostatic distribution and long-term follow-up after AdV-tk immunotherapy as neoadjuvant to surgery in patients with prostate cancer

A phase I-II study to evaluate gene-mediated cytotoxic immunotherapy in newly diagnosed prostate cancer before radical prostatectomy was conducted in Monterrey, Mexico. First, to investigate delivery of adenovirus to the prostate, fluorescently labeled vector was injected into fresh prostatectomy specimens and distribution was visually analyzed. The optimal volume and site instillation was then used for transrectal ultrasound guided intraprostatic injection in 10 patients with adenocarcinoma scheduled for radical prostatectomy. Each received two apical and two basal 0.5 ml injections of AdV-tk for a total of 1 × 1011 vp followed by 14 days of prodrug. Nine patients continued to tumor resection: six high risk, one intermediate and two low risk. In vivo vector distribution was analyzed from the resected tissue of four patients. Patients were monitored for tumor progression and acute and long-term safety. For vector delivery, two apical and two basal injections of 0.5 ml led to optimal organ-wide distribution ex vivo and in vivo. Cytotoxicity was evidenced by transient rise in PSA and tumor histology. There were no significant adverse events deemed related to the treatment and no late toxicities after median follow-up of 11.3 years. All six high-risk patients had positive surgical margins and one had seminal vesicle involvement. Despite slow PSA rise post surgery in three of these patients, none developed metastases. The intermediate- and low-risk patients had complete resections and none have progressed. In conclusion, in vivo transrectal ultrasound guided instillation of an adenoviral vector into four sites in the prostate was practical as an outpatient procedure, well tolerated and led to distribution throughout the intraprostatic tumor mass. AdV-tk demonstrated no significant acute or late toxicities. Trends in PSA and disease progression conveyed the possibility of a sustained immune response against residual disease.

Association of matrix metalloproteinase-2 gene promoter polymorphism with myocardial infarction susceptibility in a Mexican population

1School of Medicine, Universidad de Colima, Av. Universidad 333, Colonia Las Viboras, CP 28040, Colima, Col., Mexico 2General Hospital N◦ 1, Instituto Mexicano del Seguro Social, Colima, Zaragoza 377, Colonia, CP 28040, Mexico 3Hospital Regional Universitario, Secretaria de Salud del Estado de Colima, Km 2.0 Carretcra Colima-Guadalajara, CP 28019, Colima, Mexico 4School of Medicine, Universidad Autonoma de Nuevo Leon, Av. Madero Y Aguirre Peqeno, Mitras Centro, CP 64460, Monterrey Nuevo Leon, Mexico

A280V Polymorphism in the Histamine H3 Receptor as a Risk Factor for Migraine

BACKGROUND AND AIMS Activation of histamine H3 receptors blocks the release of peptides responsible for headache. Our objective was to investigate the association between the genotypes of A280V polymorphism in the H3 receptor and migraine risk. METHODS We evaluated the frequency of the genotypes of A280V, polymorphism A280V and allelic variants of H3 receptor in 147 migraine patients and 186 healthy controls using a PCR-RLFP method. RESULTS V allele frequency was 6.46% and 2.68% for the cases and controls, respectively (p = 0.02) (OR 2.67; 95% CI 1.20-5.93). The frequency of V/V + V/A genotypes was 12.92% in migraine patients, significantly higher when compared to the 3.22% frequency in the control group (p = 0.001) (OR 4.45; 95% CI 1.7-11.46). CONCLUSIONS The results of this study suggest that V-allele genotypes in the H3 receptor gene are related to migraine risk in the Mexican population. We propose the hypothesis that the V-allele genotypes in the H3 receptor gene increase the population of inactive receptors, enhancing the inhibition of the negative feedback mechanism on the H3 receptor and increasing histamine release, which correlates with migraine attacks in susceptible patients. The case-control study reinforces the role of histamine in migraine pathogenesis.

A potent replicative delta-24 adenoviral vector driven by the promoter of human papillomavirus 16 that is highly selective for associated neoplasms.

Several human epithelial neoplasms are associated with high‐risk strains of human papillomavirus (HPV) such as cervical, anorectal, and other carcinomas. For some tumor types the current therapeutic tools are only palliative. Conditionally replicative adenoviruses (CRAds) are promising antineoplastic agents, which also can trigger confined antitumor effects.

Positive association between vascular endothelial growth factor (VEGF) -2578 C/A variant and prostate cancer

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.