Uso de agrotóxicos e mortes por câncer no estado do Rio Grande do Sul / Pesticide use and cancer deaths in Rio Grande do Sul, Brazil

Resumo Este estudo teve como objetivo caracterizar as regiões de saúde do estado do Rio Grande do Sul (RS) quanto ao uso de agrotóxicos e à mortalidade por câncer de próstata, linfoma não Hodgkin (LNH) e leucemias. Para cada região de saúde foram estimados o volume total de agrotóxicos utilizado, o volume usado por área plantada, a proporção de lavouras com uso, a proporção de agricultura familiar e o grau de desigualdade na distribuição das terras. A mortalidade pelos três tipos de câncer foi descrita com base na mortalidade proporcional e na taxa de mortalidade ajustada por idade. A associação entre as variáveis foi estimada pelo coeficiente de correlação de Spearman. A mortalidade por câncer de próstata mostrou-se relacionada à produção agrícola intensa, utilização de elevado volume de agrotóxicos e menor proporção de agricultura familiar. Já a mortalidade por linfoma não Hodgkin e leucemias esteve associada positivamente à proporção de agricultura familiar. Mortalidade proporcional e taxa de mortalidade ajustada por idade mostraram-se positivamente correlacionadas para os três tipos de câncer. Este estudo demonstrou que, nas regiões de saúde do RS, a mortalidade pelos três tipos de câncer investigados está vinculada, em diferentes intensidades, ao uso de agrotóxicos e a características da agricultura praticada.

Abstract This study characterizes the health regions of the Rio Grande do Sul State regarding pesticide use and mortality by prostate cancer, Non-Hodgkin's Lymphoma and leukemias. Total volume of pesticide used, volume used per planted area, the proportion of crops using pesticides, the proportion of family farming and the degree of inequality in land distribution were estimated for each region. Mortality from the three types of cancer was described by proportional mortality and age-adjusted mortality rate. Association between variables was estimated using Spearman's correlation coefficient. Prostate cancer mortality was associated with intense agricultural production, high volume of pesticide use and a lower proportion of family farming. Mortality from Non-Hodgkin's Lymphoma and leukemias, in turn, was positively associated with the proportion of family farming. Proportional mortality and age-adjusted mortality rate were positively correlated for the three types of cancer. In conclusion, in the health regions of Rio Grande do Sul, mortality by the three types of cancer investigated is associated, albeit at different intensities, with pesticide use and the type of agriculture practiced.

Copper induces damage, oxidative stress and cell death in endothelium of chronic intoxicated Wistar rats / El cobre induce daño, estrés oxidativo y muerte celular en el endotelio de ratas Wistar intoxicadas

SUMMARY: Reactive Oxygen Species (ROS) are part of the functional balance of various systems, they can generate cellular damage by oxidative stress associated with disease processes such as atherosclerosis, cardiovascular disease, diabetes, and aging. Some studies report that copper induces damage to the endothelium, which could be associated with cardiovascular pathologies. This study was an experimental comparative, prospective, longitudinal, and controlled clinical trial in a murine animal model. Twenty-four male Wistar rats were included, the distribution of the groups was time-depending chronic exposition to copper, and a control group. Results show gradual alterations in the groups treated with copper: areas with loss of the endothelium, signs of disorganization of smooth muscle fibers in the tunica media, as well as areas with the fragmentation of the elastic sheets. A significant statistical difference was observed in the active- Caspase-3 analysis expression in the aortic endothelium and endothelium of the capillaries and arterioles of the lung between the control group vs 300 ppm of copper. Expression of eNOS was detected in the endothelium of the aorta and vessels of the lung. Our study shows histological changes in the walls of the great vessels of intoxicated rats with copper, and the increment of inflammatory cells in the alveoli of the study model, mainly at a high dose of copper exposition. These results will be useful to understand more about the mediators involved in the effect of copper over endothelium and cardiovascular diseases in chronic intoxication in humans.

RESUMEN: Las Especies Reactivas de Oxígeno (ROS) son parte del equilibrio funcional de varios sistemas, pueden generar daño celular por estrés oxidativo asociado a procesos patológicos como aterosclerosis, enfermedades cardiovasculares, diabetes y envejecimiento. Algunos estudios informan que el cobre induce daños en el endotelio, lo que podría estar asociado a patologías cardiovasculares. Este estudio fue un ensayo clínico experimental comparativo, prospectivo, longitudinal y controlado en un modelo animal murino. Se incluyeron veinticuatro ratas Wistar macho, la distribución de los grupos fue la exposición crónica al cobre en función del tiempo y un grupo de control. Los resultados muestran alteraciones graduales en los grupos tratados con cobre: áreas con pérdida del endotelio, signos de desorganización de las fibras musculares lisas en la túnica media, así como áreas con la fragmentación de las láminas elásticas. Se observó una diferencia estadística significativa en la expresión del análisis de caspasa-3 activa en el endotelio aórtico y el endotelio de los capilares y arteriolas del pulmón entre el grupo de control frente a 300 ppm de cobre. Se detectó expresión de eNOS en el endotelio de la aorta y los vasos del pulmón. Nuestro estudio muestra cambios histológicos en las paredes de los grandes vasos de ratas intoxicadas con cobre, y el incremento de células inflamatorias en los alvéolos del modelo de estudio, principalmente a una alta dosis de exposición de cobre. Estos resultados serán útiles para comprender más sobre los mediadores involucrados en el efecto del cobre sobre el endotelio y las enfermedades cardiovasculares en la intoxicación crónica en humanos.

Antioxidant effect of ethanolic onion (Allium cepa) husk extract in ageing rats.

The role of natural antioxidants in preventing of age-relating diseases is evident. The vegetable industry generates a large amount of waste, which is a good source of antioxidants. The aim of the study was the investigation of the antioxidant effect of long-term consumption of ethanolic yellow onion husk extract in ageing laboratory rodents. Twenty male Wistar albino rats were divided randomly into two groups (n = 10): a control group and an experimental group that received ethanolic yellow onion husk extract (2 mL/rat diluted with distilled water; activity of 4.44 µmol-equiv. quercetin) for 188 days. Oxygen radical absorbance capacity and ferric reducing antioxidant power assays were used to determine the total antioxidant capacity of the extract, which amounted to 941.4 ± 32.7 µmol equiv. Trolox/g raw material and 167.4 ± 16.4 µmol-equiv. quercetin/g raw material, respectively. Oral intake of the onion husk extract affected the indicators of the antioxidant system of the liver and the brain but not of the blood and plasma, mainly due to elevations in the activity of catalase and superoxide dismutase in the liver by 44.4% and 79.1%, respectively, and in the brain by three-fold and 79.1%, respectively. The availability, cheapness and high antioxidant potential of onion waste qualifies it a good source of functional ingredients and bioactive substances applicable in the food and pharmaceutical industries.

Chronic methanol toxicity through topical and inhalational routes presenting as vision loss and restricted diffusion of the optic nerves on MRI: A case report and literature review.

Methanol intoxication can cause irreversible neurologic sequelae if unrecognized and untreated. Ingestion is the most common form of toxicity; however, dermal and inhalational exposures likewise occur but are documented rarely. While acute intoxication is commonly encountered, chronic exposure to methanol should also be highlighted. We report a case of a 57-year old female presenting in the emergency room with progressive dyspnea, metabolic acidosis with high anion gap, and metabolic encephalopathy. After emergency hemodialysis, the patient complained of vision loss on both eyes. Initial non-contrast cranial magnetic resonance imaging (MRI) revealed restricted diffusion of the intraorbital segment of both optic nerves. A thorough history revealed that she was applying a clear colorless liquid bought online all over her body for alleged pruritus for more than a year. The syndrome of metabolic acidosis with high anion gap, metabolic encephalopathy, vision loss, and laboratory findings led us to suspect a diagnosis of chronic methanol poisoning with an acute component. The liquid in question was sent for chemical analysis and result showed that it consisted of 95.5% Methanol. This case highlights the need for high index of clinical suspicion for methanol toxicity in the absence of oral consumption, the complications of chronic form of methanol intoxication, and the uncommon radiologic finding seen in diffusion-weighted imaging (DWI).

Curcumin prevents the midbrain dopaminergic innervations and locomotor performance deficiencies resulting from chronic aluminum exposure in rat.

Aluminum (Al) among the abundant metals on the earth crust, is able to cross the biological barriers via the gastrointestinal and lung tissues. Once in the body, this heavy metal accumulates in different organs, especially the central nervous system. Though its influence is evidently shown in the substantia nigra of Parkinson's disease patients and other brain areas in other neurodegenerative diseases, few studies have demonstrated that Al could trigger profound changes in neurotransmission systems including the dopaminergic (DAergic) system. A variety of medicinal plants may be prescribed in such contamination, including some culinary spices such as Curcumin (Cur). Several studies have proven Cur to exhibit a wide variety of biological and pharmacological activities, especially its antioxidant potential. Using the immunohistochemistry, of tyrosine hydroxylase (TH), in the midbrain substantia nigra pars compact (SNc) and the ventral tegmental area (VTA) and the open field test, we examined the DAergic system together with the locomotor behavior respectively in rats exposed chronically to Al (0,3%) in drinking water during 4 months since the intra-uterine age, as well as the neuroprotective effect of the concomitant administration of Cur I (30 mg/kg B.W) of chronic Al exposed rats. Our results have shown a significant decrease of TH immureactivity in both SNc and VTA associated to a loss of the number of crossed boxes, leading to a difficient locomotor performance in the Al group while Cur I prevents such TH immunoreactivity impairment and maintains a higher locomotor activity in the Al-CurI group. Our findings lead to suppose a powerful and obvious neuroprotective potential of CurI against Al-induced neurotoxicity of the DAergic system involved in the control of the locomotor behavior.

Clinical analysis of severe visual loss caused by inhalational methanol poisoning in a chronic process with acute onset:a retrospective clinical analysis.

BACKGROUND: To analyze the clinical features and prognosis of the visual loss resulted from inhalational methanol poisoning in 8 Chinese patients. METHODS: Eight consecutive patients seen at the Beijing Tongren Hospital of Capital Medical University, Beijing, China between January 2003 to August 2017, with complains of vision loss in both eyes, identified as inhalational methanol poisoning. Detailed medical history was extracted. All patients underwent optic nerve and brain magnetic resonance imaging (MRI) scan, laboratory tests, and visual function analysis. Treatment protocols were large dosage of methylprednisolone and B vitamins over 3 months. Patients were seen at 3-month intervals until a year. RESULTS: Eight patients with optic neuropathy caused by inhalation toxicity of methanol were under observation, whose methanol-contact time spans were form 4 days to 5 years for occupational exposure. All the patients had acute onset, transient systemic symptoms on early stage, both eyes involved with severe visual impairment (visual acuity 0.1 or even worse). Retrobulbar optic nerves (ONs) were the major sites involved. Optic nerve MRI scan showed increased signal of bilateral ONs in the orbit and the canal parts, with enhancement. After treatment, the visual function of these patients got improved in different degree in a year follow-up, but not satisfactorily. CONCLUSIONS: Inhalational methanol toxicity may lead to serious damage to ON in a process of chronic intoxication with acute attack, and with poor prognosis.

Chronic Mercury Intoxication Masquerading as Systemic Disease: A Case Report and Review of the Literature.

BACKGROUND: Mercury is a highly toxic environmental metal that exists in three different forms: elemental, inorganic and organic. Intoxication occurs in either occupational or non-occupational settings, mainly after the inhalation of vapour and fumes in work places, laboratories or homes. Chronic mercury toxicity ranges from mild and insignificant to severe and life-threatening. We describe the case of a young male patient who presented with multiple organ dysfunction after chronic mercury exposure. CASE PRESENTATION: We report the case of 28-year-old male artisanal gold miner who was admitted to hospital for severe neurological impairment associated with inflammatory bowel disease-like symptoms and a skin rash after mercury exposure. Symptomatic treatment and corticosteroid administration assured rapid clinical improvement. Chronic mercury poisoning can masquerade as an autoimmune or systemic inflammatory disease. CONCLUSION: Physicians should be aware that low exposure to mercury, even from artisanal gold mining, may be harmful to health. Management can be simple without the need for aggressive or invasive therapeutic measures. Larger case series are required in order to establish a clear management plan. LEARNING POINTS: Mercury intoxication has a wide the variety of clinical manifestations that may involve the neurological, gastrointestinal and dermatological systems.Therefore, it can mimic degenerative neurological conditions, autoimmune diseases, as well as metabolic and mitochondrial disorders.Once diagnosed, mercury intoxication is easily treated.

The role of PON1 and CYP2D6 genes in susceptibility to organophosphorus chronic intoxication in Egyptian patients.

BACKGROUND: Paraoxonase-1 (PON1) activity toward organophosphorus(OP) compounds shows inter-individual variations, rendering the identification of individuals' PON1 allozymes valuable in treating patients suffering from organophosphorus intoxication. One of the most important cytochrome P450 monooxygenases (CYPs) is CYP2D6. The CYP2D6 G1934A polymorphism leads to good, poor or no enzyme activity. Genetic testing helps identification of high risk individuals as well as management of chronic intoxicated patients. OBJECTIVE: to investigate a possible association between genetic polymorphisms of PON1 Q192R, and CYP2D6 G1934A as well as PON1 and pseudo-cholinesterase (PChE) enzyme activity levels and chronic organophosphate exposed patients, and hence, susceptibility for organophosphorus chronic poisoning. DESIGN AND METHODS: Thirty chronic organophosphate exposed farm workers were compared to 29 healthy controls as regards PON1 Q192R and CYP2D6 G1934A polymorphisms using PCR-RFLP technique. Also serum PON1 and PChE activities were determined spectrophotometrically. RESULTS: Serum PChE was significantly reduced in chronic intoxicated patients compared to the control group (p=0.02), while PON1 activity was increased, but just failed to reach significance (p=0.06). PON1 192 RR genotype and R allele were significantly increased in chronic OP intoxicated patients (p=0.005 &p=0.002 respectively). CYP2D6 1934A allele was significantly increased in chronic OP patients (p=0.045). combining the two SNPs showed a significant statistical difference between the two groups with PON1QQ and CYP2D6 GG genotypes being more represented in the healthy controls (p=0.001). Fatigue and motor weakness were the most prevalent neurological symptoms seen in chronic cases (56.7%), followed by headache and lacrimation (30% each), depression (23%), tingling and sensory symptoms (20%), sleep disorders and limb pain (13%). The mean duration of environmental exposure to organophosphates was 7.7±5.2years and no association was found between chronic symptoms of intoxication and duration of exposure, provided that all workers were exposed for at least 3 years. CONCLUSION: PON1 192RR genotype and CYP2D6 1934A allele were found to be related to the susceptibility to organophosphate chronic toxicity in Egyptians. Larger scale gene-environmental interaction studies are recommended to confirm results and Genotyping is recommended during selection of agricultural pesticide workers to exclude high risk group.

Effect of hydroxymethylfurfural (HMF) on mortality of artificially reared honey bee larvae (Apis mellifera carnica).

Hydroxymethylfurfural (HMF) is a heat-formed, acid-catalyzed contaminant of sugar syrups, which find their way into honey bee feeding. As HMF was noted to be toxic to adult honey bees, we investigated the toxicity of HMF towards larvae. Therefore we exposed artificially reared larvae to a chronic HMF intoxication over 6 days using 6 different concentrations (5, 50, 750, 5000, 7500 and 10,000 ppm) and a control. The mortality was assessed from day 2 to day 7 (d7) and on day 22 (d22). Concentrations ranging from 5 to 750 ppm HMF did not show any influence on larval or pupal mortality compared to controls (p > 0.05; Kaplan-Meier analysis). Concentrations of 7500 ppm or higher caused a larval mortality of 100%. An experimental LC50 of 4280 ppm (d7) and 2424 ppm (d22) was determined. The calculated LD50 was 778 µg HMF per larva on d7 and 441 µg HMF on d22. Additionally, we exposed adult honey bees to high concentrations of HMF to compare the mortality to the results from larvae. On d7 larvae are much more sensitive against HMF than adult honey bees after 6 days of feeding. However, on d22 after emergence adults show a lower LC50, which indicates a higher sensitivity than larvae. As toxicity of HMF against honey bees is a function of time and concentration, our results indicate that HMF in supplemental food will probably not cause great brood losses. Yet sublethal effects might decrease fitness of the colony.

Plasma profile of pro-inflammatory cytokines and chemokines in cocaine users under outpatient treatment: influence of cocaine symptom severity and psychiatric co-morbidity.

The treatment for cocaine use constitutes a clinical challenge because of the lack of appropriate therapies and the high rate of relapse. Recent evidence indicates that the immune system might be involved in the pathogenesis of cocaine addiction and its co-morbid psychiatric disorders. This work examined the plasma pro-inflammatory cytokine and chemokine profile in abstinent cocaine users (n = 82) who sought outpatient cocaine treatment and age/sex/body mass-matched controls (n = 65). Participants were assessed with the diagnostic interview Psychiatric Research Interview for Substance and Mental Diseases according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Tumor necrosis factor-alpha, chemokine (C-C motif) ligand 2/monocyte chemotactic protein-1 and chemokine (C-X-C motif) ligand 12 (CXCL12)/stromal cell-derived factor-1 (SDF-1) were decreased in cocaine users, although all cytokines were identified as predictors of a lifetime pathological use of cocaine. Interleukin-1 beta (IL-1ß), chemokine (C-X3-C motif) ligand 1 (CX3CL1)/fractalkine and CXCL12/SDF-1 positively correlated with the cocaine symptom severity when using the DSM-IV-TR criteria for cocaine abuse/dependence. These cytokines allowed the categorization of the outpatients into subgroups according to severity, identifying a subgroup of severe cocaine users (9-11 criteria) with increased prevalence of co-morbid psychiatric disorders [mood (54%), anxiety (32%), psychotic (30%) and personality (60%) disorders]. IL-1ß was observed to be increased in users with such psychiatric disorders relative to those users with no diagnosis. In addition to these clinical data, studies in mice demonstrated that plasma IL-1ß, CX3CL1 and CXCL12 were also affected after acute and chronic cocaine administration, providing a preclinical model for further research. In conclusion, cocaine exposure modifies the circulating levels of pro-inflammatory mediators. Plasma cytokine/chemokine monitoring could improve the stratification of cocaine consumers seeking treatment and thus facilitate the application of appropriate interventions, including management of heightened risk of psychiatric co-morbidity. Further research is necessary to elucidate the role of the immune system in the etiology of cocaine addiction.

Chronic aluminum intoxication in rat induced both serotonin changes in the dorsal raphe nucleus and alteration of glycoprotein secretion in the subcommissural organ: Immunohistochemical study.

Aluminum (Al) causes multiple impairments in several body systems including the central nervous system. In fact, Al exposure has been mostly associated with neurological dysfunctions that occur in some brain diseases. The effect of Al neurotoxicity on the dopaminergic system is well documented, but this effect on the serotoninergic system is poorly studied. The aim of this work is to evaluate the effect of chronic Al intoxication (0.3% of aluminum chloride exposure from the intra-uterine age until 4 months of adult age) on dorsal raphe nucleus (DRN) which is the main source of serotonin, and also on the glycoprotein secretion of subcomissural organ (SCO), receiving important serotoninergic innervation. This will be executed using immunohistochemistry procedure, with both the anti serotonin and the anti Reissner's fiber antibodies in the rat. Our results showed a significant increase of serotonin immunoreactivity in the DRN, accompanied by a noticeable decrease of RF immunoreactivity in the SCO ependymocytes. This study provides further evidence confirming the toxic effect of Al exposure on serotonin neurotransmission in the brain likely through increased synthesis or decreased release. Al exposure was also shown to decrease RF glycoprotein which is involved in the detoxification of cerebrospinal fluid.