Assessment of hematological parameters in workers exposed to organophosphorus pesticides, carbamates and pyrethroids in Cundinamarca 2016-2017.

OBJECTIVE: To establish hematotoxic alterations through clinical and paraclinical exploration in workers who are exposed to organophosphorus pesticides, carbamates and pyrethroids (OPCP) due to their work in production, packaging, distribution and fumigation processes in Cundinamarca-Colombia between 2016 and 2017. MATERIALS AND METHODS: A cross-sectional descriptive epidemiological study was carried out on a sample of 92 workers from six companies, mostly aged between 18 and 30 years, of which 61 % were males and 39 % females, and 71 % were workers in the operational area and 29 % in the administrative area. Univariate, bivariate and multivariate analyses were performed. RESULTS: Clinical exploration reported findings in 17 % of the sample group, of which only 2 % presented with erythrocyte cholinesterase outside the reference range. The values of hematological parameters such as peripheral blood smear (PBS) and complete blood count (CBC) were outside the range in 15 % and 47 % of the sample, respectively. DISCUSSION: The results suggest that there are hematological alterations in this group that could possibly be associated with chronic exposure to OPCP.

Estrogen counteracts ozone-induced oxidative stress and nigral neuronal death.

Oxidative stress is implicated in the premature death of dopamine neurons in substantia nigra in Parkinson's disease. The incidence of Parkinson's disease is higher in men than in women, and estrogen may provide neuroprotection against oxidative damage. We examined the protective effects of estrogen on rat nigral death after chronic ozone inhalation. Ozone inhalation produced impaired nigral cell morphology and loss of dopamine neurons in ovariectomized rats. This was counteracted after 60 days of 17beta-estradiol treatment, when blood levels were highest. These results indicate that ozone exposure may be a useful Parkinson's disease model and neuroprotection afforded by 17beta-estradiol is dependent on the high levels achieved after its prolonged administration.

Resveratrol-induced apoptotic death in human U251 glioma cells.

Resveratrol (trans-3,4',5-trihydroxystilbene) is a naturally occurring polyphenolic compound highly enriched in grapes, peanuts, red wine, and a variety of food sources. Resveratrol has antiinflammatory and antioxidant properties, and also has potent anticancer properties. Human glioma U251 cells were used to understand the molecular mechanisms by which resveratrol acts as an anticancer agent, since glioma is a particularly difficult cancer to treat and eradicate. Our data show that resveratrol induces dose- and time-dependent death of U251 cells, as measured by lactate dehydrogenase release and internucleosomal DNA fragmentation assays. Resveratrol induces activation of caspase-3 and increases the cleavage of the downstream caspase substrate, poly(ADP-ribose) polymerase. Resveratrol-induced DNA fragmentation can be completely blocked by either a general caspase inhibitor (Z-VAD-FMK) or a selective caspase-3 inhibitor (Z-DEVD-FMK), but not by a selective caspase-1 inhibitor. Resveratrol induces cytochrome c release from mitochondria to the cytoplasm and activation of caspase-9. Resveratrol also increases expression of proapoptotic Bax and its translocation to the mitochondria. Resveratrol inhibits U251 proliferation, as measured by MTS assay [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt], and induces G0/G1 growth arrest, as determined by flow cytometry. The cyclin-dependent kinase inhibitor, olomoucine, prevents cell cycle progression and resveratrol-induced apoptosis. These results suggest that multiple signaling pathways may underlie the apoptotic death of U251 glioma induced by resveratrol, which warrants further exploration as an anticancer agent in human glioma.

Roles of Ras-Erk in apoptosis of PC12 cells induced by trophic factor withdrawal or oxidative stress.

To understand the role of Ras-MAPK (mitogen-activated protein kinase) in trophic factor withdrawal- and oxidative stress-induced apoptotic cell death processes, undifferentiated rat pheochromocytoma PC12 cells and a PC12 variant cell line stably expressing the Ras dominant-negative mutant (M-M17-26) were subjected to serum withdrawal in the absence or presence of H2O2 treatment. The extent of cell death was analyzed by lactate dehydrogenase release, internucleosomal DNA fragmentation, and caspase-3 assays. Both serum withdrawal and H2O2 treatment induced apoptotic cell death in PC12 cells, and the extent of cell death was greatly enhanced in M-M17-26 cells. DNA fragmentation induced by serum withdrawal or H2O2 treatment was blocked completely by a general caspase inhibitor, Z-VAD-FMK. A selective MAPK kinase inhibitor, U0126, blocked the H2O2-induced phosphorylation of Erk1/2 (extracellular signal-regulated kinase) in PC12 cells and increased the levels of active caspase-3 in M-M17-26 under serum withdrawal or H2O2 treatment. In addition, the short-term H2O2 treatment (5-30 min) was sufficient to cause DNA fragmentation in M-M17-26 cells even though H2O2 was removed and cells were incubated in regular growth medium with complete serum for 24 h. However, similar, short-term H2O2 treatment of PC12 cells did not induce DNA fragmentation 24 h later. These results suggest that the Ras-Erk pathway is critical in mediating protection against apoptotic cell death induced by either trophic factor withdrawal or increased oxidative stress.

Role of Bcl-2 family of proteins in mediating apoptotic death of PC12 cells exposed to oxygen and glucose deprivation.

Apoptotic cell death has been observed in many in vivo and in vitro models of ischemia. However, the molecular pathways involved in ischemia-induced apoptosis remain unclear. We have examined the role of Bcl-2 family of proteins in mediating apoptosis of PC12 cells exposed to the conditions of oxygen and glucose deprivation (OGD) or OGD followed by restoration of oxygen and glucose (OGD-restoration, OGD-R). OGD decreased mitochondrial membrane potential and induced necrosis of PC12 cells, which were both prevented by the overexpression of Bcl-2 proteins. OGD-R caused apoptotic cell death, induced cytochrome C release from mitochondria and caspase-3 activation, decreased mitochondrial membrane potential, and increased levels of pro-apoptotic Bax translocated to the mitochondrial membrane, all of which were reversed by overexpression of Bcl-2. These results demonstrate that the cell death induced by OGD and OGD-R in PC12 cells is potentially mediated through the regulation of mitochondrial membrane potential by the Bcl-2 family of proteins. It also reveals the importance of developing therapeutic strategies for maintaining the mitochondrial membrane potential as a possible way of reducing necrotic and apoptotic cell death that occurs following an ischemic insult.

Inhibitors of iNOS protects PC12 cells against the apoptosis induced by oxygen and glucose deprivation.

It has been shown that deletion of the gene encoding the inducible form of nitric oxide synthase (iNOS) results in a reduction of ischemia-induced apoptotic cell death, suggesting the detrimental role of iNOS. The signaling pathways by which iNOS mediates apoptotic cell death under ischemic conditions remain unclear. Understanding the molecular mechanisms of iNOS-mediated apoptotic cell death in ischemia may offer opportunities for potential therapeutic intervention. In the current study, undifferentiated rat pheochromocytoma PC12 cells, exposed to oxygen and glucose deprivation (OGD) followed by reperfusion (adding back oxygen and glucose, OGD-R), were used as an in vitro model of ischemia. The iNOS expression and activity were increased during OGD-R. OGD-R-induced apoptosis was demonstrated by the increase of LDH release, cytosolic release of cytochrome C and caspase-3 activity. Inhibition of iNOS activity by selective iNOS inhibitors, aminoguanidine and 1400W, reduces OGD-R-induced apoptotic cell death, as demonstrated by the decrease of LDH release, cytochrome C release, and caspase-3 activity. These results suggest the critical role of iNOS in mediating apoptosis under ischemic conditions, likely through the induction of caspase-3 activity.

Effects of Sertoli cell transplants in a 3-nitropropionic acid model of early Huntington's disease: a preliminary study.

Problems with immunosuppression and graft survival limit clinical applications of neurotransplantation protocols for neurodegenerative disease. Sertoli cells, testes-derived cells with immunosuppressive and trophic properties, may serve as an alternative cell source for transplantation. Sertoli cells were transplanted into the striatum of rats following two injections of 3-nitropropionic acid (3-NP) to determine whether they could ameliorate abnormalities in a model of early stage Huntington's disease. 3-NP-induced locomotor hyperactivity was significantly reduced in rats receiving Sertoli transplants compared to controls, with some behaviors returning to baseline. Sertoli cells survived in the striatum without systemic immunosuppression and some formed tubule-like structures. These results show that Sertoli transplants are able to ameliorate locomotor abnormalities in a 3-NP model of early HD. Thus, Sertoli cells should be further evaluated as a possible treatment strategy for the early stages of Huntington's disease.

Assessment of hematological parameters in workers exposed to organophosphorus pesticides, carbamates and pyrethroids in Cundinamarca 2016-2017 / Evaluación de parámetros hematológicos en trabajadores expuestos a pesticidas organofosforados, carbamatos y piretroides, Cundinamarca 2016-2017

ABSTRACT Objective To establish hematotoxic alterations through clinical and paraclinical exploration in workers who are exposed to organophosphorus pesticides, carbamates and pyrethroids (OPCP) due to their work in production, packaging, distribution and fumigation processes in Cundinamarca-Colombia between 2016 and 2017. Materials and Methods A cross-sectional descriptive epidemiological study was carried out on a sample of 92 workers from six companies, mostly aged between 18 and 30 years, of which 61 % were males and 39 % females, and 71 % were workers in the operational area and 29 % in the administrative area. Univariate, bivariate and multivariate analyses were performed. Results Clinical exploration reported findings in 17 % of the sample group, of which only 2 % presented with erythrocyte cholinesterase outside the reference range. The values of hematological parameters such as peripheral blood smear (PBS) and complete blood count (CBC) were outside the range in 15 % and 47 % of the sample, respectively. Discussion The results suggest that there are hematological alterations in this group that could possibly be associated with chronic exposure to OPCP.

RESUMEN Objetivo Determinar las alteraciones hematotóxicas a través de una exploración clínica y paraclínica, en trabajadores que por su oficio se exponen a pesticidas organofosforados, carbamatos y piretroides (POCP), en procesos de producción, envase, distribución y fumigación, en el departamento de Cundinamarca Colombia. Metodología Se realizó un estudio epidemiológico descriptivo de corte transversal. Se realizó un análisis univariado, bivariado y multivariado. La muestra se conforma por 92 trabajadores de seis empresas, la mayoría entre los 18 y 30 años, de los cuales el 61 % son hombres y el 39 % mujeres, 71 % se desempeñan en el área operativa y 29 % en el área administrativa. Resultados Es de resaltar que se tienen hallazgos en la exploración clínica en el 17 % del grupo participante, solo el 2 % presenta la colinesterasa eritrocitaria por fuera del rango de referencia. Los parámetros hematológicos como el frotis de sangre periférica (FSP) presentan valores por fuera de los rangos en el 15 % y el cuadro hemático (CH) tiene valores por fuera de los rangos en el 47 % de las personas. Discusión Los resultados sugieren que existen alteraciones hematológicas en este grupo y que posiblemente podrían estar asociadas con la exposición crónica a POCP.

Acupuncture versus venlafaxine for the management of vasomotor symptoms in patients with hormone receptor-positive breast cancer: a randomized controlled trial.

PURPOSE: Vasomotor symptoms are common adverse effects of antiestrogen hormone treatment in conventional breast cancer care. Hormone replacement therapy is contraindicated in patients with breast cancer. Venlafaxine (Effexor), the therapy of choice for these symptoms, has numerous adverse effects. Recent studies suggest acupuncture may be effective in reducing vasomotor symptoms in menopausal women. This randomized controlled trial tested whether acupuncture reduces vasomotor symptoms and produces fewer adverse effects than venlafaxine. PATIENTS AND METHODS: Fifty patients were randomly assigned to receive 12 weeks of acupuncture (n = 25) or venlafaxine (n = 25) treatment. Health outcomes were measured for up to 1 year post-treatment. RESULTS: Both groups exhibited significant decreases in hot flashes, depressive symptoms, and other quality-of-life symptoms, including significant improvements in mental health from pre- to post-treatment. These changes were similar in both groups, indicating that acupuncture was as effective as venlafaxine. By 2 weeks post-treatment, the venlafaxine group experienced significant increases in hot flashes, whereas hot flashes in the acupuncture group remained at low levels. The venlafaxine group experienced 18 incidences of adverse effects (eg, nausea, dry mouth, dizziness, anxiety), whereas the acupuncture group experienced no negative adverse effects. Acupuncture had the additional benefit of increased sex drive in some women, and most reported an improvement in their energy, clarity of thought, and sense of well-being. CONCLUSION: Acupuncture appears to be equivalent to drug therapy in these patients. It is a safe, effective and durable treatment for vasomotor symptoms secondary to long-term antiestrogen hormone use in patients with breast cancer.

[Chromium levels and their relationship with alterations in the health of tannery workers living and working in Bogotá, Colombia]. / Niveles de cromo y alteraciones de salud en una población expuesta a las actividades de curtiembres en Bogotá, Colombia.

OBJECTIVE: Determining whether chromium levels in urine samples were higher than limits and contrasting them with alterations in the health of people living and working in the San Benito neighbourhood of Bogotá. METHODS The total amount of chromium in urine was measured as a biological marker of exposure in a sample of 827 people. This was contrasted with health alterations attributed to chromium exposition. Exposure was defined by being whether current economic activity was related to working in a tannery. Two groups were defined: being directly exposed (26%) and having potentially high exposure (73%). RESULTS: 6.3% presented >10 ug/L chromium levels (4.64% to 7.96% confidence interval). No significant statistical differences were found between both groups. 34.3% presented a diagnosis of possible attribution to chromium exposure, of whom 23.3% were due to otorhinolaryngologic issues, 6.5% to dermatological ones, 2.9% to ophthalmologic ones and 1.6 % to oral cavity issues. The remaining 65.7% of cases were not related. >10 ug/L levels and living in the particular neighbourhood in question were associated (4.94 odds ratio; 1.18%-20.69% CI). The results suggested a connection between economic activity and health alterations due to chromium components. CONCLUSIONS: The people involved in producing leather have a significant risk of presenting clinical conditions attributed to chromium exposure (4.33 OR; 3.12-6.02 CI). San Benito s inhabitants are being exposed to chromium as if they were actually working in a tannery as they are in daily contact with chromium or its components through non work-related activities, such as environmental contamination. Concern at such exposure should lead to further in-depth studies.

Niveles de cromo y alteraciones de salud en una población expuesta a las actividades de curtiembres en Bogotá, Colombia / Chromium levels and their relationship with alterations in the health of tannery workers living and working in Bogotá, Colombia

Objetivo Determinar si los niveles de cromo en orina están más altos de los permitidos y contrastarlos con alteraciones de salud en personas del barrio San Benito en Bogotá. Métodos En una muestra de 827 personas, se cuantificó cromo total en orina como biomarcador de exposición y se contrastó con alteraciones de salud atribuibles a exposición a cromo. La exposición se definió, por la "Ocupación actual" relacionada con la labor en curtiembres. Se definieron dos estratos: "Directamente expuestos" 26 por ciento y "Potencial alta exposición" 73 por ciento. Resultados Un 6,3 por ciento presentó niveles de cromo >10 ug/L (intervalo de confianza: 4,64-7,96 por ciento). No se encontraron diferencias estadísticamente significativas entre los dos estratos. El 34,3 por ciento presentó diagnósticos posiblemente atribuibles a la exposición a cromo. El 23,3 por ciento otorrinolaringológico; 6,5 por ciento dermatológico; 2,9 por ciento oftalmológico; 1,6 por ciento cavidad oral y el 65,7 por ciento no relacionados. Se halló asociación entre niveles >10ug/L y residir en la zona (OR 4,94 IC:1,2- 20,7 por ciento). Los resultados sugieren asociación entre ocupación y alteraciones de salud atribuibles a la exposición a compuestos de cromo. Conclusiones Las personas que participan del proceso productivo del cuero tienen un riesgo significativo de presentar hallazgos clínicos posiblemente atribuibles a la exposición a cromo, OR 4,33 (3,12-6,02). La población general se esta viendo expuesta de manera no diferente a aquella con ocupación relacionada con las curtiembres, lo que puede deberse a que los habitantes del sector están en contacto con cromo o compuestos por vías diferentes a la ocupacional, como contaminación ambiental.

Objective Determining whether chromium levels in urine samples were higher than limits and contrasting them with alterations in the health of people living and working in the San Benito neighbourhood of Bogotá. Methods The total amount of chromium in urine was measured as a biological marker of exposure in a sample of 827 people. This was contrasted with health alterations attributed to chromium exposition. Exposure was defined by being whether current economic activity was related to working in a tannery. Two groups were defined: being directly exposed (26 percent) and having potentially high exposure (73 percent). Results 6.3 percent presented >10 ug/L chromium levels (4.64 percent to 7.96 percent confidence interval). No significant statistical differences were found between both groups. 34.3 percent presented a diagnosis of possible attribution to chromium exposure, of whom 23.3 percent were due to otorhinolaryngologic issues, 6.5 percent to dermatological ones, 2.9 percent to ophthalmologic ones and 1.6 percent to oral cavity issues. The remaining 65.7 percent of cases were not related. >10ug/L levels and living in the particular neighbourhood in question were associated (4.94 odds ratio; 1.18 percent-20.69 percent CI). The results suggested a connection between economic activity and health alterations due to chromium components. Conclusions The people involved in producing leather have a significant risk of presenting clinical conditions attributed to chromium exposure (4.33 OR; 3.12-6.02 CI). San Benito´s inhabitants are being exposed to chromium as if they were actually working in a tannery as they are in daily contact with chromium or its components through non work-related activities, such as environmental contamination. Concern at such exposure should lead to further in-depth studies.

Neurobehavioral assessment of transplanted porcine Sertoli cells into the intact rat striatum.

Sertoli cells, a testes-derived cell with immunosuppressive and trophic properties, may serve as an alternative cell source for transplantation in a number of neurodegenerative diseases. However, before Sertoli cells can be considered for clinical use, safety studies must be conducted to ensure that the cells themselves produce no adverse effects when transplanted into the central nervous system. The present study assessed the behavioral effects of transplanting porcine Sertoli cells into the striatum of normal rats and provided a histological examination of the graft site and host striatum. Activity monitors revealed significant increases in nocturnal locomotor activity over time following both sham and Sertoli transplants. Ambulation and rearing, but not stereotypic measures, were increased compared to pre-transplant levels. Sertoli animals exhibited less behavioral alteration than sham controls. Histological examination of the striatum demonstrated surviving Sertoli cell transplants in an intact striatum. These results indicated that Sertoli cell xenografts might be a safe alternative cell source for neurotransplantation procedures requiring immune or trophic support.

Antioxidant effects of taurine, vitamin C, and vitamin E on oxidative damage in hippocampus caused by the administration of 3-nitropropionic acid in rats.

The administration of 3-nitropropionic acid increases reactive oxygen species (ROS). Antioxidant defense mechanisms buffer these ROS converting them into non-damaging compounds. Taurine and vitamins C and E are antioxidants that play a role in the defense against cellular damage. This study examines the antioxidant effect of taurine, vitamin C, and vitamin E on acute hippocampal damage caused by 3-NP. Animals treated with 3-NP increased lipid peroxidation levels and astrocytic damage in the hippocampus. Administration of taurine, vitamin C, and vitamin E partially protected from oxidative damage, indicate that while all substances had antioxidant effects, only taurine showed morphological protection in surviving cells.