Quantifiable urine glyphosate levels detected in 99% of the French population, with higher values in men, in younger people, and in farmers

France is the first pesticide-consuming country in Europe. Glyphosate is the most used pesticide worldwide and glyphosate is detected in the general population of industrialized countries, with higher levels found in farmers and children. Little data was available concerning exposure in France. Our objective was to determine glyphosate levels in the French general population and to search for an association with seasons, biological features, lifestyle status, dietary habits, and occupational exposure. This study includes 6848 participants recruited between 2018 and 2020. Associated data include age, gender, location, employment status, and dietary information. Glyphosate was quantified by a single laboratory in first-void urine samples using ELISA. Our results support a general contamination of the French population, with glyphosate quantifiable in 99.8% of urine samples with a mean of 1.19 ng/ml + / − 0.84 after adjustment to body mass index (BMI). We confirm higher glyphosate levels in men and children. Our results support glyphosate contamination through food and water intake, as lower glyphosate levels are associated with dominant organic food intake and filtered water. Higher occupational exposure is confirmed in farmers and farmers working in wine-growing environment. Thus, our present results show a general contamination of the French population with glyphosate, and further contribute to the description of a widespread contamination in industrialized countries.

Effect of biotherapy T. cruzi 7x in several therapeutic schemes on experimental infection by Trypanosoma cruzi

Background: Biotherapy is used against infectious diseases treatment and prophylaxis and has been investigated by many researchers [1,2]. Aim: Assess the effect of biotherapy 7x T. cruzi on several treatment schemes, upon experimental infection by T. cruzi. Methodology: A blind, controlled and randomized by drawing experiment was performed. Male Swiss mice, four weeks old were utilized. Groups evaluated: IC – Infection Control (treated with water – 9 animals); TBBA7x3days – Treated with biotherapy 7x 3 days before and 3 days after infection (5 animals); TBB7x3days – Treated with 7x biotherapy 3 days before infection (5 animals); TBBAI7x3days – Treated with 7x biotherapy 3 days before infection and after infection indefinitely (6 animals). Animals were inoculated intraperitoneally with 1400 blood trypomastigotes Y strain. Biotherapy: prepared according to Farmacopéia Homeopática Brasileira [3]. Treatment plan: offered ad libitum, in the water (10µL/mL). Parasitological parameters: parasitemia was assessed according Brener’s technique. [4]. Clinical parameters: body hair aspect, edema, movement, diarrhea, body weight, temperature, food and water intake. Ethics: Registration 030/2008 UEM Ethics Committee for Experiments in Animals. Statistical analysis: was performed using the tests Kruskal Wallis and Mann-Whitney testes, significance 5%. Results: The best effect obtained was with the TBBA7x3days, both for clinical and parasitological parameters. It was expressed by lower parasitemia curve (p=0.04) and decrease of patent period tendency, of total parasitemia, of mortality and survival of the animals increase (Table 1). Evolution of parasitemia was distinct for the several treatment schemes. Survival of at least one mouse by treated groups is an extremely important data, since Y strain causes 100% mortality in Swiss mice. TBBAI7x3days group showed begger tendency in raising total parasitemia compared with IC. Although it might have occurred, this group presented 80% mortality rate compared with other groups. Animals from TBBA7x3days also showed better evolution of weight body, temperature, food (p=0.078-10%) and water intake, body hair aspect and edema development. Diarrhea and paralysis were only observed in IC group mice, highlighting the biotherapy use benefits. Conclusions: Best effect was obtained TBBA7x3days, both for clinical and parasitological parameters. It’s possible to speculate that in this regimen, biotherapy was able to modulate, more effectively, the host’s immune system, decreasing the number of parasites.

Evaluation of biotherapies T.cruzi 15x, 16x, 17x and "potency chords" in experimental infection by Trypanosoma cruzi.

Background: The biotherapies are drugs widely utilized against infectious diseases. Biotherapies’ profylatic and therapeutic action against Chagas Disease is currently being investigated, but it is needed to develop further controlled experiments “in vivo”, which could define more clearly: dilution, dose, time of use and, if possible, the action mechanisms of these ultradiluted medicaments [1,2]. Aim: Evaluate the effect biotherapies T. cruzi 15x, 16x, 17x and “potency chords”, on experimental infection by T. cruzi. Methodology: A blind, controlled and randomized by drawing test was performed. Animals: 29 male Swiss mice, four weeks old were utilized. The animals were kept at Parasitology Vivarium/State University of Maringá (UEM), in ideal conditions of temperature (22±2)ºC and photoperiod (light / dark cycle 12h). Mice have been inoculated intraperitoneally with 1400 blood trypomastigotes Y strain and divided in groups: IC – Infection control (treated with distilled water – 9 animals); TBBA15x3days – Treated with biotherapy 15x 3 days before and 3 days after infection (5 animals); TBBA16x3days – Treated with biotherapy 16x 3 days before and 3 days after infection (5 animals); TBBA17x3days – Treated with biotherapy 17x 3 days before and 3 days after infection (5 animals); TBBAChords3days – Treated with biotherapy 15x, 16x, 17x “potency chords”, 3 days before and 3 days after infection (5 animals). Biotherapies: prepared by a homeopathic pharmacist from UEM, according to Farmacopéia Homeopática Brasileira [3]. Biotherapies treatment schedule: diluted in distilled water (10µL/mL in ambar bottles – renewed each two days) offered ad libitum, 3 days before and 3 days after infection in all groups. Parasitological parameters: parasitemia was assessed from infection until death, according to Brener’s technique [4] with 5µL of blood collected from the tail vein and examined in optical microscope. Pre-patent period, patent period, total parasitemia, survival and morbidity were obtained from the parasitemia curve. Clinical parameters: Visually assessed (presence or absence): body hair aspect (bristling), edema, movement and diarrhea. Measured: body weight, temperature, food and water intake. Ethics: This study has been approved by the UEM Ethics Committee for Experiments in Animals - Registration 030/2008. Statistical analysis: was performed using the tests Kruskal Wallis and Mann-Whitney tests, significance of 5%. Results: There was not statistical difference between total parasitemia of the groups treated with biotherapies and the IC group (p=0.6819). The parasitemia curve of group TBBAChords3days was greater then the IC (p=0.0418). Despite this increase, patent period and mortality both showed a decreasing tendency, while pre patent period and survival time increased (p=0.373). The same tendency results were observed for TBBA17x3days results (Table 1). Survival of at least one mice in groups TBBA17x3days and TBBAChords3days is worthy of discussion, since Y strain causes 100% mortality in these experimental conditions. Groups TBBA17x3days and TBBAChords3days showed better evolution than IC group for body weight, temperature, food and water intake (p=0.05), body hair aspect and edema developing. Diarrhea and hind legs paralysis were only observed in mice belonging to groups IC and TBAA16x3days. Conclusions: Superior effect was obtained with biotherapies 17x and “Potency Chords”, both for clinical and parasitological parameters. “Potency chords” has proper effect which distinguishes it from the individual effects of the dilutions that compound it.

Growth Hormone Secretagogue Receptor 1A Antagonist JMV2959 Effectively Prevents Morphine Memory Reconsolidation and Relapse

Relapse to drug seeking after prolonged abstinence is a major problem in the clinical treatment of drug addiction. The use of pharmacological interventions to disrupt established drug reward memories is a promising strategy for the treatment of drug addiction. A growth hormone secretagogue receptor 1 A antagonist, JMV2959, has been shown to reduce morphine-induced conditioned place preference (CPP) in rats within hours of intervention; thus, JMV2959 is a potential candidate for drug addiction treatment. However, the effect of JMV2959 on reconsolidation to disrupt drug seeking remains unknown. In this study, we assessed the effect of JMV2959 on morphine induced memory reconsolidation to inhibit drug seeking after drug withdrawal. Our results showed that the administration of JMV2959 (6 mg/kg) significantly reduced environmental cue induced CPP, which suggested a preventive effect of JMV2959 on morphine induced memory reconsolidation. Additionally, JMV2959 administration significantly altered the locomotor activity and food and water intake but did not significantly alter the natural reward preference. We concluded that JMV2959 may be an effective candidate to treat drug addiction.

Effect of flaxseed on systemic inflammation and oxidative stress in diabetic rats with or without chronic kidney disease

Background Diabetes mellitus (DM) and chronic kidney disease (CKD) are common causes of morbidity and mortality. Flaxseed contains several bioactive compounds that have been shown to possess anti-inflammatory and antioxidative properties. The aim of the present study was to investigate the possible effect of flaxseed in diabetic rats with adenine–induced CKD. Methods Male Wister rats (n = 48) were randomly divided into seven equal groups and treated for 33 consecutive days as follows: G1: control. G2 adenine, G3: streptozotocin (STZ), G4: flaxseed, G5: adenine+flaxseed, G6: STZ+flaxseed, G7: adenine+STZ+flaxseed). DM or CKD were experimentally induced by a single intraperitoneal injection of streptozotocin (STZ) or by adenine via oral gavage, respectively. Results Rats fed adenine alone exhibited several changes including decreased body weight, increased food and water intake and urine output, increased urinary albumin/creatinine ratio. They also showed an increase in plasma urea and, creatinine, indoxyl sulfate, neutrophil gelatinase-associated lipocalin and cystatin C, and a decrease in renalase activity. These were associated with significant changes in inflammatory and oxidative biomarkers, e.g., increase in 8-isoprostane, 8 -hydroxy -2-deoxy guanosine and decrease in antioxidant enzymes, as well as increase in interleukins 1β and 6, and NF-κB, and a decrease in interlukin-10. Histopathologically, there was increased tubular necrosis and fibrosis. Concomitant administration of adenine and STZ further worsened the renal damage induced by adenine alone. Flaxseed significantly ameliorated the changes caused by adenine and STZ, given either singly or in combination. Conclusion These findings suggest that flaxseed is a potential therapeutic agent in attenuating the progression of CKD in diabetes.

Chemogenetic activation of endogenous arginine vasopressin exerts anorexigenic effects via central nesfatin-1/NucB2 pathway

We examined whether the chemogenetic activation of endogenous arginine vasopressin (AVP) affects central nesfatin-1/NucB2 neurons, using a transgenic rat line that was previously generated. Saline (1 mL/kg) or clozapine-N-oxide (CNO, 1 mg/mL/kg), an agonist for hM3Dq, was subcutaneously administered in adult male AVP-hM3Dq-mCherry transgenic rats (300–370 g). Food and water intake were significantly suppressed after subcutaneous (s.c.) injection of CNO, with aberrant circadian rhythmicity. The percentages of Fos expression in nesfatin-1/NucB2-immunoreactive neurons were significantly increased in the hypothalamus and brainstem at 120 min after s.c. injection of CNO. Suppressed food intake that was induced by chemogenetic activation of endogenous AVP was ablated after intracerebroventricularly administered nesfatin-1/NucB2-neutralizing antibody in comparison with vehicle, without any alteration of water intake nor circadian rhythmicity. These results suggest that chemogenetic activation of endogenous AVP affects, at least in part, central nesfatin-1/NucB2 neurons and may exert anorexigenic effects in the transgenic rats.

Ghrelin receptor signalling is not required for glucocorticoid-induced obesity in female mice.

Chronic exposure to high circulating glucocorticoid or ghrelin concentrations increases food intake, weight gain and adiposity, suggesting that ghrelin could contribute to the metabolic effects of chronic glucocorticoids. In male mice, however, blocking ghrelin receptor (GHSR) signalling increased the weight gain and adiposity induced by chronic corticosterone (CORT), rather than attenuating them. In the current study, we investigated the role of GHSR signalling in the metabolic effects of chronic exposure to high circulating CORT in female mice. To do this, female WT and GHSR KO mice were treated with either CORT in a 1% ethanol (EtOH) solution or 1% EtOH alone in their drinking water for 32 days (N=5-8/group). Body weight, food, and water intake as well as vaginal cyclicity were assessed daily. As expected, CORT treatment induced significant increases in body weight, food intake, adiposity and also impaired glucose tolerance. In contrast to results observed in male mice, WT and GHSR KO female mice did not differ on any of these parameters. Neither plasma levels of ghrelin, LEAP-2, the endogenous GHSR antagonist produced by the liver, nor their ratio were altered by chronic glucocorticoid exposure. In addition, CORT treatment disrupted vaginal cyclicity, produced a reduction in sucrose consumption and increased locomotor activity regardless of genotype. Chronic CORT also decreased exploration in WT but not GHSR KO mice. Collectively, these data suggest that most metabolic, endocrine, reproductive and behavioral effects of chronic CORT exposure are independent of GHSR signalling in female mice.

Polyphenol-rich extract of Ocimum gratissimum leaves Prevented Toxic Effects of Cyclophosphamide on the kidney Function of Wistar rats

Background Cyclophosphamide (CP) is one of the potent and low cost chemotherapy used in clinical setting against a variety of tumors. However, its association with nephrotoxicity limits its therapeutic use. Ocimum gratissimum leaf is a natural plant with numerous pharmacological and therapeutic efficacies, such as antioxidant, anti-inflammation, and anti-apoptotic properties.Methods The present study was designed to evaluate the protective effect of Ocimum gratissimum (OG) against CP-induced kidney dysfunction in rats. Rats were pre-treated with 400 mg/kg b.w. of polyphenol-rich Ocimum gratissimum leaves (PREOG) for 4 days and then 50 mg/kg b.w. of CP was co-administered from day 5 to day 7 along with PREOG. Markers of renal function and oxidative stress, food and water intake, electrolytes, aldosterone, leukocytes infiltration, inflammation and histopathological alteration were evaluated.Results Obvious renal inflammation and kidney injuries were observed in CP treated groups. PREOG administration prevented oxidative stress, kidney injuries, attenuated inflammation, increased aldosterone production and reduced sodium and water loss in rats. PREOG also decreased the plasma concentrations of Interleukin-(IL)-6, C-reactive protein and activity of myeloperoxidase and malondialdehyde in CP treated rats.Conclusion OG prevented kidney injury and enhanced renal function via inhibiting inflammation and oxidant-induced CP toxicity. The efficacy of OG is related to the presence of various phytochemicals in the plant.

Physical Activity during Ramadan and COVID-19

Ramadan is a holy month in Islamic calendar where fasting is observed for 29-30 days. Fasting causes a lot of changes in the body’s physical activity as food and water intake timings are altered. Physical activity is a key to fight the novel corona virus. Timing of the exercises should be adjusted in a manner that does not lead to severe starvation or dehydration. Fasting in the month of Ramadan during the pandemic is more of a personalised decision. Key words: Fasting, Ramadan, fitness, Conid-19 fitness.

Effects of GPR18 Ligands on Body Weight and Metabolic Parameters in a Female Rat Model of Excessive Eating

GPR18 has been proposed to play a role in the progression of metabolic disease and obesity. Therefore, the aim of this study was to determine the effects of selective GRP18 ligands (the antagonists PSB-CB5 and PSB-CB27 and the agonist PSB-KK1415) on body mass and the development of metabolic disorders commonly accompanying obesity. Experiments were carried out on female Wistar rats. In order to determine the anorectic activity of the investigated ligands, their effect on food and water intake in a model of excessive eating was assessed. Lipid profile, glucose and insulin levels as well as alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase activity in plasma were also evaluated. Potential side effects were examined in rat models of pica behavior and conditioned taste aversion. Animals treated with different ligands gained significantly less weight than rats from the obese control group. Effects of GPR18 antagonists on food intake and body weight were specific and unrelated to visceral illness, stress or changes in spontaneous activity. However, the GPR18 agonist is likely to affect body weight by inducing gastrointestinal disorders such as nausea. The presented preliminary data support the idea that the search for selective GPR18 antagonists for the treatment of obesity might be promising.