Pesticide Exposure Alters Follicle-Stimulating Hormone Levels in Mexican Agricultural Workers

Organophosphorous pesticides (OPs) are suspected of altering reproductive function by reducing brain acetylcholinesterase activity and monoamine levels, thus impairing hypothalamic and/or pituitary endocrine functions and gonadal processes. Our objective was to evaluate in a longitudinal study the association between OP exposure and serum levels of pituitary and sex hormones. Urinary OP metabolite levels were measured by gas–liquid chromatography, and serum pituitary and sex hormone levels by enzymatic immunoassay and radioimmunoassay in 64 men. A total of 147 urine and blood samples were analyzed for each parameter. More than 80% of the participants had at least one OP metabolite in their urine samples. The most frequent metabolite found was diethylthiophosphate (DETP; 55%), followed by diethylphosphate (DEP; 46%), dimethylthiophosphate (DMTP; 32%), and dimethyldithiophosphate (DMDTP; 31%). However, the metabolites detected at higher concentrations were DMTP, DEP, DMDTP, and dimethylphosphate. There was a high proportion of individuals with follicle-stimulating hormone (FSH) concentrations outside the range of normality (48%). The average FSH serum levels were higher during the heavy pesticide spraying season. However, a multivariate analysis of data collected in all periods showed that serum FSH levels were negatively associated with urinary concentrations of both DMTP and DMDTP, whereas luteinizing hormone (LH) was negatively associated with DMTP. We observed no significant associations between estradiol or testosterone serum levels with OP metabolites. The hormonal disruption in agricultural workers presented here, together with results from experimental animal studies, suggests that OP exposure disrupts the hypothalamic–pituitary endocrine function and also indicates that FSH and LH are the hormones most affected

Outcomes of transsphenoidal surgery for pituitary adenomas in Spain: a retrospective multicenter study

Background The outcomes of transsphenoidal surgery (TSS) for pituitary adenoma (PA) depend on many factors, including the availability of an expert team and the volume of surgeries performed. Data on the outcomes of TSS for PA are scarce in our country. TESSPAIN evaluates TSS outcomes in Spanish centers to assess the influence of surgical volume and specialized neurosurgical teams on success and complication rates. Methods A retrospective, nationwide, study of Spanish centers performing TSS between January 2018 and December 2022. Centers were classified as high volume (HV) [n=11, defined as centers with recognized expertise in Spain or those performing more than 25 TSS/year] or non-HV. Data collection included surgical success rates, complications, and pituitary adenoma resectability (R-PA). Additional analyses evaluated the impact of dedicated neurosurgical teams (DNT) within HV centers. Results A total of 2815 TSS from 29 Spanish centers were included (1421 NSPA, 436 GH-secreting, 323 Cushing's disease, 127 PRL-secreting and 25 TSH-secreting PA). The overall success rate was 50.5%, 76.8% for R-PA. HV centers had a higher overall success rate (53.1 vs. 47.7%; p=0.03). Better TSS outcomes for NSPA accounted for this difference. The overall TSS complication rate was 22.1%, which was higher for NSPA than for SPA (25.0 vs. 17.7%). The overall complication rate of TSS for PA was significantly higher in non-HV centers than in HV centers (24 vs 20.4.0; p <0.01). Centers with a DNT showed a trend to higher success rate in R-PA, while having a lower overall incidence of complications in TSS for PA than HV centers without a DNT (18.5 vs. 23.0; p=0.058), mainly reducing the rate of permanent ADH deficiency in all TSS for PA (2.7 vs. 8.4%; p<0.001). Conclusion Higher surgical volume and DNT are associated with improved TSS outcomes for PA in Spain. Our results support the recommendation of concentration of pituitary surgery in a reduced number of centers of expertise in our country in order to improve the success rate and reduce complications, mainly postoperative ADH deficiency

Predictors of therapeutic failure in GH and prolactin co-secreting pituitary adenomas

Aim: To evaluate which factors are associated with a higher probability of failure to surgical and first-generation somatostatin receptor ligands (fgSRLs) treatment in patients with growth hormone and prolactin co-secreting pituitary adenomas (GH&PRL-PAs). Methods: Acromegaly patients with GH&PRL-PAs included in the ACRO-SPAIN study were enrolled. GH&PRL-PAs were defined as tumors with serum PRL levels above the upper limit of normal and positive immunostaining for GH and PRL, or with PRL levels >= 100 ng/mL when immunostaining data were not available. Results: A total of 126 acromegaly patients with GH&PRL-PAs who underwent transsphenoidal pituitary surgery were included, and 42.1% (n = 53) were biochemically cured at the immediate postoperative evaluation. Knosp grade >2 (odds ratio (OR) 3.48, 95% CI 1.28-9.38), higher serum GH (OR 1.01, 95% CI 1.01-1.08) and IGF-1 (OR 1.60, 95% CI 1.05-2.45) levels were associated with a lower probability of surgical cure. Sixty-eight patients received first-line medical therapy as follows: fgSRLs in monotherapy (n = 22), fgSRL plus cabergoline (n = 37), cabergoline in monotherapy (n = 7) and pegvisomant in monotherapy (n = 2). Among the cases treated with fgSRL in monotherapy, 18.2% (n = 4/22) were resistant. We identified as predictors of fgSRL resistance (in monotherapy and combined with cabergoline) a Knosp grade >2 (OR 8.75, P = 0.003), high GH levels at acromegaly diagnosis (OR 1.02, P = 0.031) and higher postoperative GH levels (OR 1.05, P = 0.006), but no predictors of response to fgSRL in monotherapy were identified. Conclusion: The clinical predictors of surgical failure and of fgSRL resistance in patients with GH&PRL-PAs are similar to those described in acromegaly without PRL, co-secretion

State of the Art of Genomic Technology in Toxicology: A Review

The rapid growth of genomics techniques has revolutionized and impacted, greatly and positively, the knowledge of toxicology, ushering it into a &ldquo;new era&rdquo;: the era of genomic technology (GT). This great advance permits us to analyze the whole genome, to know the gene response to toxicants and environmental stressors, and to determine the specific profiles of gene expression, among many other approaches. The aim of this work was to compile and narrate the recent research on GT during the last 2 years (2020&ndash;2022). A literature search was managed using the PubMed and Medscape interfaces on the Medline database. Relevant articles published in peer-reviewed journals were retrieved and their main results and conclusions are mentioned briefly. It is quite important to form a multidisciplinary taskforce on GT with the aim of designing and implementing a comprehensive, collaborative, and a strategic work plan, prioritizing and assessing the most relevant diseases, so as to decrease human morbimortality due to exposure to environmental chemicals and stressors

Association between the polymorphism of three genes involved in the methylation and efflux of arsenic (As3MT, MRP1, and P‐gp) with lung cancer in a Mexican cohort

Lung cancer is the most common neoplasm and the primary cause-related mortality in developed and in most of nondeveloped countries. Epidemiological studies have demonstrated that even at low arsenic doses, the lungs are one of the main target organs and that chronic arsenic exposure has been associated with an increase in lung cancer development. Among the risk factors for cancer, arsenic methylation efficiency (As3MT) and the clearance of arsenic from cells by two members of the ATP-binding cassette (ABC) transporter family (multidrug resistance protein 1 [MRP1] and P-glycoprotein [P-gp]) play an important role in processing of arsenic and decreasing its intracellular levels. This study aimed to evaluate the association between chronic exposure to arsenic with polymorphism of three proteins involved in arsenic metabolism and efflux of the metalloid in subjects with lung cancer. Polymorphism in As3MT, MRP1, and P-gp modified the arsenic metabolism increasing significantly the AsV urinary levels. A significant association between MRP1 polymorphisms with an increase in the risk for cancer was found. The high inorganic arsenic urinary levels registered in the studied subjects suggest a reduction in the efficiency of As3MT, MRP1, and P-gp firstly because of gene polymorphisms and secondarily because of high internal inorganic arsenic levels. MRP1 polymorphism was associated with a twofold increase in the risk of lung cancer. © 2020 John Wiley & Sons, Ltd.12 month embargo; first published: 19 December 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Assessment of YAP gene polymorphisms and arsenic interaction in Mexican women with breast cancer

The identification of gene-environment interactions related to breast cancer reveals the biological and molecular mechanisms underlying the disease and allows the distinction of women at high risk from women at lower risk, which could decrease the morbimortality of this neoplasm. The current study evaluated the association between polymorphisms rs1820453 and rs11225161 of the Yes-associated protein (YAP) gene in women with breast cancer exposed to arsenic (As) through drinking water. In total, 182 women were assessed for the frequency of YAP rs1820453 and rs11225161 polymorphisms and As urinary levels. The results demonstrated a positive and significant association between breast cancer and smoking, type of drinking water, and levels of AsIII , AsV and inorganic As (iAs) but not the YAP gene polymorphisms evaluated. In conclusion, our data showed that the source of drinking water and AsV and iAs urinary levels increased the risk for breast cancer, but no interactions between YAP gene polymorphisms and As urinary levels were found.University of Coahuila; Superfund National Institute of Environmental Health Sciences [NIH ES-04940, NIEHS/NIH P30ES006694, P42ES004940];[CONACyT-377059]12 month embargo; published online: 21 October 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

ATM polymorphisms IVS24-9delT, IVS38-8T>C, and 5557G>A in Mexican women with familial and/or early-onset breast cancer

Objective. To assess whether in Mexican population the frequencies of ATM polymorphisms IVS24-9delT, IVS38-8T mayor que C, and 5557G mayor que A in breast cancer (BC) cases and healthy controls were different from those found in other countries. Materials and methods. Frequencies of polymorphisms conferring BC risk IVS24-9delT, IVS38-8T mayor que C, and 5557G mayor que A were analyzed by PCR-RFLP in 94 patients with familial and/or early onset BC, and 97 healthy controls randomly selected. Allele frequencies analysis was done using χ2 and Hardy-Weinberg test. Results. Frequencies of heterozygous were: for 5557G mayor que A, 13% cases, 0%controls (p=0.0009); for IVS24-9delT, 21% cases, 8% controls (p=0.0122); for IVS38-8T mayor que C, only one case. 5557G mayor que A and IVS24-9delT were more frequent in cases than in controls. The allelic frequencies found in 5557G mayor que A are similar to those described by González-Hormazábal in Chile. Conclusion. The similarity of results in this polymorphism between Chilean and Mexican populations may be due to both being crossbred with an Amerindian-Spanish component, while differences may be due to fact that Chilean population has a greater European component than Mexican’s