Health Risk Assessment in Children Occupationally and Para-Occupationally Exposed to Benzene Using a Reverse-Translation PBPK Model.

Benzene is a known human carcinogen and one of the ten chemicals of major public health concern identified by the World Health Organization. Our objective was to evaluate benzene's carcinogenic and non-carcinogenic health risks (current and projected) in highly exposed children in Yucatan, Mexico. Benzene exposure was estimated through a reverse-translation, four-compartment, physiologically based pharmacokinetic model (PBPK) based on previously performed urine trans, trans-muconic acid (benzene metabolite) determinations. Using a risk assessment methodology, the carcinogenic and non-carcinogenic risks of benzene were estimated for 6-12-year-old children from a family of shoemakers. The children's hazard quotients for decreased lymphocyte count were 27 and 53 for 4 and 8 h/day exposure, respectively, and 37 for the projected 8 h/day exposure in adults. The risks of developing leukemia were 2-6 cases in 1000 children exposed 4 h/day; 4-10 cases in 1000 children exposed 8 h/day, and 2-9 cases in 1000 adults with an 8 h/day lifetime exposure. Children in Yucatan working in shoe-manufacturing workshops, or living next to them, are exposed to benzene concentrations above the reference concentration and have unacceptably high risks of presenting with non-carcinogenic and carcinogenic hematologic symptoms, now and in the future. Interventions to prevent further exposure and mitigate health risks are necessary.

Arsenic: A Perspective on Its Effect on Pioglitazone Bioavailability.

Arsenic (As) is a common contaminant in drinking water in northeastern Mexico, which reduces the expression of cytochrome P450 (CYP 450). This enzyme group metabolizes numerous drugs, such as oral antidiabetic drugs such as pioglitazone (61% CYP 3A4, 49% CYP 2C8). When CYP 450's function is inadequate, it has decreased therapeutic activity in type 2 diabetes mellitus (T2DM). This study aimed to establish the effect of As on pioglitazone metabolism in patients with T2DM. METHODOLOGY: Urine, water, and plasma samples from a healthy population (n = 11) and a population with T2DM (n = 20) were obtained. Samples were analyzed by fluorescence spectroscopy/hydride generation (As) and HPLC (pioglitazone). Additionally, CYP 3A4 and CYP 2C8 were studied by density functional theory (DFT). RESULTS: The healthy and T2DM groups were exposed via drinking water to >0.010 ppm, Ka values with a factor of 4.7 higher, Cl 1.42 lower, and ABCt 1.26 times higher concerning the healthy group. In silico analysis (DFT) of CYP 3A4 and CYP 2C8 isoforms showed the substitution of the iron atom by As in the active sites of the enzymes. CONCLUSIONS: The results indicate that the substitution of Fe for As modifies the enzymatic function of CYP 3A4 and CYP 2C8 isoforms, altering the metabolic process of CYP 2D6 and CYP 3A4 in patients with T2DM. Consequently, the variation in metabolism alters the bioavailability of pioglitazone and the expected final effect.

Synergistic interaction between 4-allyl-1-hydroxy-2-methoxybenzene (eugenol) and diclofenac: An isobolograpic analysis in Wistar rats.

Clinical and preclinical research that contributes pain palliation has suggested that drugs favor the expected effects and minimize the adverse effects. Among the most widely used strategies is the combination of analgesic drugs among those in the same group, with those in another group of analgesics or with co-adjuvants (nonanalgesic drugs or elements of traditional medicine). This work aims to evaluate the interaction between eugenol (EUG) and diclofenac (DFC) on nociception in the presence of a noxious stimulus through the formalin test and isobolographic analysis. The results indicate that EUG, DFC, or the combination of both produce an antinociceptive effect in rodents (p ≤ 0.05). Local co-administration of EUG and DFC gave a theoretical effective dose (Zadd ) 2,936.27 ± 155.33 µg/kg (p ≤ 0.05) significantly higher as compared to the effective experimental doses (Zmix ) of 866.89 ± 0.02 µg/kg in phase 1 and 292.88 ± 0.05 µg/kg in phase 2, with an interaction index of 0.29 and 0.09, respectively. These data allow concluding that the interaction derived from the joint administration of EUG and DFC, in the rodent at a local level, is synergistic.

Toxoplasma gondii infection in pregnant women: a cross-sectional study in Matehuala City, Mexico.

OBJECTIVES: This study aimed to determine the seroprevalence of Toxoplasma gondii (T. gondii) infection in pregnant women in Matehuala City, Mexico; and the associated risk factors. DESIGN: A cross-sectional study. SETTING: Matehuala City, Mexico. PARTICIPANTS: 311 pregnant women. PRIMARY AND SECONDARY OUTCOME MEASURES: Sera of women were analysed for anti-T. gondii IgG and IgM antibodies by commercially available immunoassays. Bivariate and multivariate analyses were used to assess the association between T. gondii seroprevalence and the characteristics of the pregnant women. RESULTS: Thirteen (4.2%) of the 311 pregnant women studied were positive for anti-T. gondii IgG antibodies. No anti-T. gondii IgM antibodies were found in anti-T. gondii IgG seropositive women. No association between seropositivity and history of blood transfusion, transplantation, caesarean sections, deliveries, miscarriages or number of pregnancies was found. Logistic regression analysis of sociodemographic, behavioural and housing variables showed that availability of potable water at street represented a risk factor for T. gondii infection (age-adjusted OR=2.18; 95% CI: 1.05 to 4.53; p=0.03), whereas being born in Mexico was a protective factor for infection (age-adjusted OR=0.01; 95% CI: 0.001 to 0.35; p=0.008). CONCLUSIONS: In this first study on the seroepidemiology of T. gondii infection in pregnant women in Matehuala, we conclude that the seroprevalence of T. gondii infection is low and similar to those reported in pregnant women in other Mexican cities. However, the seroprevalence found is lower than those reported in pregnant women in other countries in the Americas and Europe. Two risk factors associated with T. gondii infection were identified. Results of the present study may help for the optimal planning of preventive measures against toxoplasmosis in pregnant women.

Determination of sialic acid levels by using surface-enhanced Raman spectroscopy in periodontitis and gingivitis.

OBJECTIVES: To compare the sialic acid (SA) levels in saliva among periodontitis-affected, gingivitis and control patients. METHODS: The study involved 93 subjects. The participants were divided into three groups: (1) 30 subjects without periodontal disease (control group); (2) 30 subjects with gingivitis; and (3) 33 subjects with periodontitis. The oral parameters examined were as follows: (a) Simplified Oral Hygiene Index; (b) Calculus Index; (c) Gingival Index; (d) probing pocket depth; and (e) level of epithelial attachment. SA levels in saliva were measured by means of surface-enhanced Raman spectroscopy (SERS). This method has demonstrated the capacity to detect extremely low concentrations of molecules. The spectrum was calibrated using analytical reagent SA. RESULTS: The obtained median values for SA concentrations were 5.98, 7.32, and 17.12 mg/dl for control, gingivitis, and periodontitis patients, respectively. CONCLUSIONS: Our measurements by SERS corroborate that in periodontitis-affected patients, the SA concentration is larger than their concentrations in either control or gingivitis patients. This confirms previous reports and opens the possibility of using SERS as a diagnostic tool.

Antinociceptive local activity of 4-allyl-1-hydroxy-2-methoxybenzene (eugenol) by the formalin test: an anti-inflammatory effect

Eugenol has been employed for decades as a condiment, an antimycotic, an antibacterial, an antiviral, and an antioxidant, and it is one of the natural analgesics most frequently utilized for pain and inflammation. Our objective was to determine the analgesic/anti-inflammatory effect of eugenol compared with diclofenac, naproxen, and tramadol using the formalin test. The formalin method was used in 6- to 10-week-old Wistar rats (weighing 250 g each) divided into six groups: saline (0.9%); formalin (5%); diclofenac (250 µg/kg); naproxen (400 µg/kg); tramadol (500 µg/kg), and eugenol (1,400 µg/kg), in the intraplantar part of the hind-end trunk of the rats, with n = 5 per group. Eugenol diminished 44.4% of nociceptive behavior in phase 1 and 48% in phase 2 (p ≤0.05 vs formalin). Eugenol was shown to be 1.14 times more effective than diclofenac, but 1.62 and 1.75 times less effective than naproxen and tramadol, respectively, in phase 1 and 1.45 times less effective than diclofenac and naproxen and 1.66 less effective than tramadol in phase 2 (p ≤0.05). These data suggest that eugenol possesses moderate activity in the acute pain phase and greater activity in inflammatory-type pain, and both effects are comparable to those produced by diclofenac and are less than the effects produced by naproxen and tramadol in the formalin test

Apoptosis in pancreatic ß-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 ß-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 ß-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 ß-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 ±â€¯7.0 mg/dL in the control group and 161.8 ±â€¯14.6 mg/dL and 198.3 ±â€¯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 ß-cells of Wistar rats with T2D. Together, all of these factors induce apoptosis in pancreatic cells.

Parecoxib Increases Blood Pressure Through Inhibition of Cyclooxygenase-2 Messenger RNA in an Experimental Model.

BACKGROUND: Cyclooxygenase-2 selective inhibitors have been developed to alleviate pain and inflammation; however, the use of a selective cyclooxygenase-2 inhibitor is associated with mild edema, hypertension, and cardiovascular risk. AIM: To evaluate, in an experimental model in normotensive rats, the effect of treatment with parecoxib in comparison with diclofenac and aspirin and L-NAME, a non-selective nitric oxide synthetase, on mean arterial blood pressure, and cyclooxygenase-1 and -2 messenger RNA and protein expression in aortic tissue. METHODS: Rats were treated for seven days with parecoxib (10 mg/kg/day), diclofenac (3.2 mg/kg/day), aspirin (10 mg/kg/day), or L-NAME (10 mg/kg/day). Mean arterial blood pressure was evaluated in rat tail; cyclooxygenase-1 and -2 were evaluated by reverse transcription-polymerase chain reaction and Western blot analysis in aortic tissue. RESULTS: Parecoxib and L-NAME, but not aspirin and diclofenac, increased mean arterial blood pressure by about 50% (p < 0.05) without changes in cardiac frequency. Messenger RNA cyclooxygenase-1 expression in aortic tissue was not modified with any drug (p < 0.05). L-NAME and parecoxib treatment decreased messenger RNA cyclooxygenase-2 and cyclooxygenase-2 (p < 0.05). While cyclooxygenase-1 protein decreased with the three drugs tested but not with L-NAME (p < 0.05), the cyclooxygenase-2 protein decreased only with aspirin and parecoxib (p < 0.05). CONCLUSION: Parecoxib increases the blood pressure of normotensive rats by the suppression of COX-2 gene expression, which apparently induced cardiovascular control.

[Pioglitazone hydrochloride a instrumental analytical perspective by Raman spectroscopy and HPLC]. / Clorhidrato de pioglitazona: una perspectiva analítico-instrumental por espectroscopia Raman y HPLC.

INTRODUCTION: The thiazolidinediones (pioglitazone) increases the action of insulin and produces the glycemic control in the patients with type 2 diabetes mellitus. Also, the pharmacological effect may be affected by the purity and pioglitazone plasma concentration. Therefore, the instrumental techniques offer a tool for characterization, identification and/or quantification of the pioglitazone; Raman spectroscopy offers several advantages due to its easy application methodology and structural analysis and the HPLC technique is the gold standard vs. other qualitative and quantitative techniques. OBJECTIVE: The aim of this work is to develop and validate analytical techniques for the characterization of pioglitazone hydrochloride by Raman spectroscopy and quantitative analysis in human plasma by HPLC. MATERIAL AND METHODS: The pioglitazone hydrochloride was analyzed by Raman spectroscopy with a 678 mW power and 3 integration time seconds. The analytical method for quantification by HPLC was validated with the guidelines of the NOM-177SSAl-1998. RESULTS: The Raman technique allowed us to elucidate the functional groups of the pioglitazone hydrochloride and the HPLC technique was linear, accurate, precise, specific and sensitive in the range of 30 to 2000 ng/mL under the chromatographic conditions specified. CONCLUSIONS: The structure analysis by Raman spectroscopy allowed us a complete characterization of the functional groups of pioglitazone hydrochloride effectively and non-destructively. Likewise, the analytical technique for the pioglitazone hydrochloride quantification by HPLC was linear, accurate, precise and sensitive in the range of 30 to 2000 ng/mL under the guidelines.