PMID: 

Drugs Aging. 2019 Sep 4. Epub 2019 Sep 4. PMID: 31485926

Abstract Title: 

Proton Pump Inhibitors and Infection-Related Hospitalizations Among Residents of Long-Term Care Facilities: A Case-Control Study.

Abstract: 

OBJECTIVE: Our objective was to investigate associations between proton pump inhibitor (PPIs) use and infection-related hospitalizations among residents of long-term care facilities (LTCFs).METHODS: This was a case-control study of residents aged ≥ 65 years admitted to hospital between July 2013 and June 2015. Residents admitted for infections (cases) and falls or fall-related injuries (controls) were matched for age (± 2 years), sex, and index date of admission (± 6 months). Conditional logistic regression was used to estimate crude and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations between PPI use and infection-related hospitalizations. Analyses were adjusted for age, sex, polypharmacy, diabetes, heart failure, chronic obstructive pulmonary disease, myocardial infarction, cerebrovascular accident, and concomitant use of cancer and immunosuppressant medications. Subgroup analyses were performed for high- and low/moderate-intensity PPIs and for respiratory and non-respiratory infections. Logistic regression was used to compare the odds of infection-related hospitalizations among users of high- and low/moderate-intensity PPIs.RESULTS: Overall, 181 cases were matched to 354 controls. Preadmission PPI use was associated with infection-related hospitalizations (aOR 1.66; 95% CI 1.11-2.48). In subgroup analyses, the association was apparent only for respiratory infections (aOR 2.26; 95% CI 1.37-3.73) and high-intensity PPIs (aOR 1.93; 95% CI 1.23-3.04). However, the risk of infection-related hospitalization was not significantly higher among users of high- versus low/moderate-intensity PPIs (aOR 1.25; 95% CI 0.74-2.13).CONCLUSION: Residents who use PPIs may be at increased risk of infection-related hospitalizations, particularly respiratory infections. Study findings provide further support for initiatives to minimize unnecessary PPI use in the LTCF setting.

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PMID: 

Biochem Biophys Res Commun. 2019 Jun 11 ;513(4):1070-1075. Epub 2019 Apr 19. PMID: 31010672

Abstract Title: 

Glyphosate induces toxicity and modulates calcium and NO signaling in zebrafish embryos.

Abstract: 

Glyphosate, an herbicide used worldwide, has emerged as a pollutant. However, its toxic effects are debated by regulatory authorities. Therefore, it is essential to keep the use of such chemicals under continuous observation, and their effects must be re-evaluated. We used zebrafish embryos to evaluate the toxic effects of glyphosate and its mechanisms. We found that glyphosate induced significant toxicity in a time and concentration-dependent manner. We observed an LDof 66.04 ± 4.6 μg/mL after 48 h of exposure. Glyphosate significantly reduced the heartbeat in a time and concentration-dependent manner indicating cardiotoxicity. Selective downregulation of Cacana1C (L-type calcium channel) and ryr2a (Ryanodine receptor) genes along with selective upregulation of hspb11 (heat shock protein) gene was observed upon exposure to glyphosate indicating alterations in the calcium signaling. A reduction in the nitric oxide (NO) generation was also observed in the zebrafish embryos upon exposure to glyphosate. Our results indicate that glyphosate induces significant toxicity including cardiotoxicity in zebrafish embryos in a time and concentration-dependent manner. Further, cardiotoxicity may be due to changes in calcium and NO signaling.

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PMID: 

Comp Biochem Physiol C Toxicol Pharmacol. 2019 Aug ;222:145-155. Epub 2019 May 2. PMID: 31055068

Abstract Title: 

Acute exposure to chlorpyrifos and glyphosate induces changes in hemolymph biochemical parameters in the crayfish, Astacus leptodactylus (Eschscholtz, 1823).

Abstract: 

Acute and subacute toxicity tests for chlorpyrifos and glyphosate were performed on the crayfish, Astacus leptodactylus. The crayfish were divided into a control group and four experimental groups with exposure from 50.18 to 301.11 μg Lof chlorpyrifos for 96 h under semi-static test conditions. In the same experiment, the crayfish were exposed to different concentrations of glyphosate (from 0.0, 8.14 to 13.05 mg L) for 96 h. Mortality was recorded, and the median lethal concentrations (LC) were calculated using probit analysis. The 96 h LCvalues of chlorpyrifos and glyphosate to A. leptodactylus were 49.55 ± 4.66 μg Land 7.83 ± 0.50 mg L, respectively. The results showed that chlorpyrifos was a few hundred times more toxic than glyphosate for the crayfish. Then, the crayfish were exposed to different subacute concentrations of chlorpyrifos (12.5 and 25 μg L) and glyphosate (2 mg Land 4 mg L) for seven days, and their toxicity was evaluated through several hemolymph biochemical parameters. Chlorpyrifos and glyphosate exposure caused a significant (P 

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PMID: 

Sci Total Environ. 2019 Sep 1 ;681:541-550. Epub 2019 Apr 30. PMID: 31125929

Abstract Title: 

Analysis of scientific production on glyphosate: An example of politicization of science.

Abstract: 

Glyphosate is one of the most used herbicides worldwide. However there still exists a strong debate about its effects on the environment or people health. In this context, the metric analysis is a methodology increasingly used to quantify and evaluate the scope of the scientific production around a specific topic. The goal of this work was to characterize the context of knowledge generation about glyphosate. All the scientific production linked to glyphosate was analyzed in the period from 1974 to 2016, using the Web of Science (WOS) as a source of information and"glyphosate"as a search criterion. A total of 8174 records were found. The bibliographic production on this herbicide experienced a sustained increase. There was a concentration in knowledge generation led by the United States. Monsanto Company produced the largest number of articles during the first thirty years of the development of this topic. Research around glyphosate in South America gained importance as of the year 2000, with Brazil being the country with the highest production followed by Argentina. A large proportion of research was focused on agricultural science, while the analysis of toxicology or environmental effects did not begin until the year 2000, and it is still insufficient.

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PMID: 

Biomed Res Int. 2019 ;2019:4746283. Epub 2019 May 14. PMID: 31218226

Abstract Title: 

How Glyphosate Impairs Liver Condition in the Field Lizard(Rafinesque-Schmaltz, 1810): Histological and Molecular Evidence.

Abstract: 

The potential toxicity of glyphosate, a widely used broad-spectrum herbicide, is currently a great matter of debate. As vertebrate insectivores, lizards protect plants from herbivorous insects increasing plant biomass via the trophic cascade and represent an important link between invertebrates and higher predators. A negative effect of glyphosate on lizards' survival could have major impacts at the ecological levels. In this study, we investigated the effects of the exposure to low doses of glyphosate on the liver of the wall lizarda suitable bioindicator of soil pollution. Two different doses of pure glyphosate (0.05 and 0.5g/kg body weight) were orally administered every other day for 3 weeks to sexually mature males and females. The results demonstrated that both doses, despite being very low, are toxic for the liver that showed clear signs of suffering, regardless of sex. The histological analysis provided a scenario of severe hepatic condition, which degenerated until the appearance of fibrotic formations. The morphological observations were consistent with a loss of liver physiological functions. Immunocytochemical investigations allowed us to detect an involvement of antioxidant/cytoprotective proteins, such as superoxide dismutase 1 (Cu/Zn SOD, known as SOD1), glutathione peroxidase 1 (GPx1), metallothionein (MT), and tumor suppressor protein 53, (p53) suggesting that the liver was trying to react against stress signals and damage induced by glyphosate. Finally,hybridization and Real-Time PCR analysis showed the upregulation of estrogen receptorand vitellogenin gene expression, thus demonstrating the xenoestrogenic action of glyphosate. The imbalance of the hormonal homeostasis could threaten the lizards' reproductive fitness and survival, altering the trophic cascade.

PMID: 

Ecotoxicol Environ Saf. 2019 Oct 30 ;182:109405. Epub 2019 Jul 2. PMID: 31276886

Abstract Title: 

Imbalances in the male reproductive function of the estuarine crab Neohelice granulata, caused by glyphosate.

Abstract: 

The effect of glyphosate, both pure and formulated (Roundup Ultramax®), was evaluated on males of the estuarine crab Neohelice granulata, by means of both in vivo and in vitro assays. The in vivo assays comprised the exposure for 30 d to 1 mg/L of the herbicide, until finally assessing weight gain, levels of energy reserves, sperm number per spermatophore, proportion of abnormal spermatophores, and sperm viability. At the end of this assay, significant (p 

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PMID: 

Chemosphere. 2019 Jul 9 ;236:124311. Epub 2019 Jul 9. PMID: 31310974

Abstract Title: 

Single and joint effects of chronic exposure to chlorpyrifos and glyphosate based pesticides on structural biomarkers in Cnesterodon decemmaculatus.

Abstract: 

Worldwide freshwater bodies that cross agricultural or urban areas are exposed to mixtures of xenobiotics. In particular, pesticides are usually part of these mixtures and could come into direct or indirect contact with biota and therefore, organisms have to cope with this altered scenario and the detrimental effects of these substances. Commercial formulations of chlorpyrifos and glyphosate, and their mixtures were evaluated using a set of biomarkers in the native fish C. decemmaculatus exposed to relevant environmentally pesticides concentrations. The biomarkers measured were: histopathological indices and tissue ultrastructure in liver and nuclear abnormalities and micronuclei in erythrocytes. During 42 days adult females were exposed to the following concentrations of Clorfox and Roundup Max (chlorpyrifos and glyphosate, respectively): 0.84 nl/l and 8.4 nl/l of Clorfox (CF), 0.2 and 2 mg/l of Roundup Max (RM) and all the combinations of these concentrations. Being the low concentrations of both pesticides environmentally relevant. Nuclear abnormalities of erythrocytes were registered under CF, RM and only one mixture. Histological inflammatory alterations increased in individuals exposed to CF and two mixtures. Finally, some pesticide combinations increased the circulatory alterations in liver. Ultrastructural changes in hepatocytes were registered at all the pesticide treatments. The different biomarker responses showed in the mixtures treatments reflected complex interactions, showing the mixture of the low concentrations of both pesticides (the environmentally relevant), potentiated effects. According to our results the presence of these substances in freshwaters could impose important risks for natural populations by causing deleterious effects on the native fish species C. decemmaculatus.

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PMID: 

Neurotoxicology. 2019 Aug 20 ;75:1-8. Epub 2019 Aug 20. PMID: 31442459

Abstract Title: 

Gut microbiota and neurological effects of glyphosate.

Abstract: 

There are currently various concerns regarding certain environmental toxins and the possible impact they can have on developmental diseases. Glyphosate (Gly) is the most utilised herbicide in agriculture, although its widespread use is generating controversy in the scientific world because of its probable carcinogenic effect on human cells. Gly performs as an inhibitor of 5-enolpyruvylshikimate-3-phospate synthase (EPSP synthase), not only in plants, but also in bacteria. An inhibiting effect on EPSP synthase from intestinal microbiota has been reported, affecting mainly beneficial bacteria. To the contrary, Clostridium spp. and Salmonella strains are shown to be resistant to Gly. Consequently, researchers have suggested that Gly can cause dysbiosis, a phenomenon which is characterised by an imbalance between beneficial and pathogenic microorganisms. The overgrowth of bacteria such as clostridia generates high levels of noxious metabolites in the brain, which can contribute to the development of neurological deviations. This work reviews the impact of Gly-induced intestinal dysbiosis on the central nervous system, focusing on emotional, neurological and neurodegenerative disorders. A wide variety of factors were investigated in relation to brain-related changes, including highlighting genetic abnormalities, pregnancy-associated problems, diet, infections, vaccines and heavy metals. However, more studies are required to determine the implication of the most internationally used herbicide, Gly, in behavioural disorders.

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PMID: 

J Nutr Sci Vitaminol (Tokyo). 2019 ;65(4):318-327. PMID: 31474681

Abstract Title: 

Oral Supplementation of Tocotrienol-Rich Fraction Alleviates Severity of Ulcerative Colitis in Mice.

Abstract: 

Ulcerative colitis (UC) is characterized by damaged colonic mucosa and submucosa layers that are caused by excessive inflammatory reactions and oxidative stress. This study aimed to examine the use of tocotrienol-rich fraction (TRF) in mitigating damages caused by UC on the colon epithelium. Dextran sulfate sodium (DSS)-induced UC mice were treated with vehicle control, TRF, alpha-tocopherol (αTP) and 5-aminosalicylic acid (5-ASA). Observable clinical signs, quality of stool, histopathological scoring, inflammatory and oxidative markers were assessed. Vitamin E levels of colons and plasma were quantified. Oral supplementation of TRF significantly reduced the severity of DSS-induced UC by lowering the disease activity index (DAI) and histopathological inflammatory scoring. TRF also attenuated the DSS-induced enlargement of spleen and shortening of the colon. TRF has demonstrated marked anti-inflammatory and antioxidative properties indicated by the attenuation of DSS-induced upregulation of inflammation and oxidative stress markers including interleukin (IL)-6, IL-17, tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), nitric oxide (NO), malondialdehyde (MDA) and pNF-κB. These improvements were similar to that of 5-aminosalicylic acid (5-ASA) treatment. In contrast, αTP did not demonstrate evident clinical and histopathological improvements. The superior protective effect of TRF may be ascribed to the preferential absorption of TRF by the gut mucosa. TRF alleviated the signs and symptoms of acute UC in murine model via the reduction of local inflammatory reactions and oxidative stress. These effects suggested that TRF could serve as a gut health supplement for preventive measures for UC condition in patients.

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PMID: 

Melanoma Res. 2019 Aug 28. Epub 2019 Aug 28. PMID: 31469708

Abstract Title: 

Decreased vitamin D serum levels at melanoma diagnosis are associated with tumor ulceration and high tumor mitotic rate.

Abstract: 

The aim of this study is to evaluate the relation between 25-hydroxyvitamin D levels at diagnosis and pathological characteristics in primary invasive melanoma. A cross-sectional study was designed based on a series of 204 consecutive patients diagnosed of invasive melanomas in the 2013-2017 period at a single institution. 25-hydroxyvitamin D serum levels at diagnosis were assessed, and three groups were defined by vitamin D status: deficiency, insufficiency, and sufficiency. Clinical and pathological characteristics were compared between the groups by Chi-square test. Logistic regression models were performed to evaluate the association between vitamin D status and Breslow thickness, ulceration, and tumor mitotic rate. A significant association between vitamin D levels at diagnosis and location, tumor mitotic rate, and ulceration was found; and a borderline association with Breslow thickness and BMI. Deficient levels were found in 7.8% of patients and increased the risk of presenting ulcerated tumors [odds ratio: 6.8 (95% confidence interval: 1.5-29.7; P = 0.012)] and with a tumor mitotic rate greater than 1 mitosis/mm [odds ratio: 6.0 (95% confidence interval: 1.4-25.1; P = 0.014)]. A marginal increased risk of tumor thickness greater than 1 mm was also observed [odds ratio: 3.7 (95% confidence interval: 1.0-13.9; P = 0.057)]. Our study suggests a role of vitamin D levels in melanoma aggressiveness and raises the question as to whether vitamin D levels should be monitored, or even supplemented, in people with low yearly sun exposure.

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