Effectiveness of Ramadan diurnal intermittent fasting and concurrent training in the management of obesity: is the combination worth the weight?

BACKGROUND AND AIMS: We investigated, in men with obesity, the efficacy of the combination of two strategies (Ramadan diurnal intermittent fasting 'RDIF' strategy vs RDIF plus concurrent training program 'RDIF-CT' strategy) known for their positive impact on body composition and then we explored the possible impact on metabolic and inflammatory biomarkers. METHODS AND RESULTS: Twenty obese men, age: 31.8 ± 7.05 years, BMI: 33.1 ± 4.2 kg m-2, performing regularly RDIF, were randomized into two groups: RDIF-CT (n = 10) and RDIF without training (RDIF-NCT) (n = 10). The RDIF-CT group participated in High intensity interval training (HIIT) program combined with resistance exercises for 4 weeks. Body composition, blood glucose, lipid profile, liver biomarkers and inflammation were assessed before and after 4-week RDIF. Both groups showed a significant decrease in weight, fat mass (FM), fat percentage (Fat%) and waist circumference (WC) and an improvement in blood glucose, lipid profile and inflammation. Fat free mass decreased significantly in RDIF-NCT (p < 0.05) while remaining unchanged in RDIF-CT. However, RDIF-CT induced greater improvements in body composition (i.e., weight, FM, Fat% and WC (p < 0.05, p < 0.01, p < 0.01 and p < 0.05; respectively)) as well as greater decrease in lipid biomarkers (i.e., TC, TG and LDL (p < 0.01 for all)), inflammation (i.e., CRP (p < 0.05)), and liver damage (i.e., ASAT, ALAT and Gamma-GT (p < 0.01, p < 0.05 and p < 0.001; respectively)) compared to RDIF-NCT group pre-post intervention. CONCLUSIONS: Our results suggest that a combination of RDIF and CT induces greater changes in body composition, lipid profile, inflammation and liver biomarkers compared to RDIF strategy alone. CLINICAL TRIAL REGISTER: PACTR202203475387226.

Is moderate-intensity interval training more tolerable than high-intensity interval training in adults with obesity?

Interval training (IT) has been shown to be a time-effective alternative to traditional training programmes in the management of obesity. Nevertheless, studies comparing the effects of different IT intensities on inflammation, muscle and liver damage, and perceptual responses in people with obesity are relatively scarce. This study aimed to compare the acute effects of two different IT protocols matched by the mean load and duration on biochemical and perceptual responses in sedentary adults with obesity. Twenty-two volunteers (age = 33.40 ± 10.01 years, BMI = 38.29 ± 7.09 kg/m²) were randomized to perform two conditions: moderate-intensity IT (MIIT) 5 × 3 min (70% of peak power output (PPO))/2 min (45%PPO) and high-intensity IT (HIIT) 8 × 1 min (90%PPO)/2 min (45%PPO). Blood samples were drawn before and after exercise for biochemical and haematological measurements. Rating of perceived exertion (RPE) was assessed during and after exercise. Perceptual pain was evaluated before, throughout and after exercise. C-reactive protein, white blood cells and neutrophils increased only after HIIT (p < 0.001, for all). Aspartate aminotransferase, alanine aminotransferase, creatine kinase and lactate dehydrogenase increased in both HIIT and MIIT (p < 0.001, for all), without any difference between sessions. HIIT induced a greater increase of blood lactate compared to MIIT (p < 0.05). Pain and RPE scores were higher during HIIT vs. MIIT (p < 0.001 and p < 0.01, respectively). MIIT induced fewer immune system perturbations and less muscle pain and was perceived as more tolerable compared to HIIT session. Therefore, MIIT could be used as a first step to promote body adaptations before starting a HIIT programme in sedentary people with obesity.

Correction: Saoudi et al. The Role of Allium subhirsutum L. in the Attenuation of Dermal Wounds by Modulating Oxidative Stress and Inflammation in Wistar Albino Rats. Molecules 2021, 26, 4875.

The authors wish to make the following change to their paper [...].

Phytochemical Characterization, Antioxidant and Anti-Inflammatory Effects of Cleome arabica L. Fruits Extract against Formalin Induced Chronic Inflammation in Female Wistar Rat: Biochemical, Histological, and In Silico Studies.

In recent decades, the use of herbs and plants has been of great interest, as they have been the sources of natural products, commonly named as bioactive compounds. In specific, the natural compounds from the Capparaceae family which has been proved to have antioxidant, anti-inflammatory, antimicrobial and anti-carcinogenic activities, by several studies. Cleome arabica L. (CA) specie is the most used medicinal plants in Tunisia and elsewhere in North African countries for treatment of various diseases including diabetes, rheumatism, inflammation, cancer, and digestive disorders. The current work was undertaken to estimate the total phenolic, flavonoid and condensed tannin contents, to identify and quantify the polyphenolic compounds, and to evaluate the antioxidant and the anti-inflammatory proprieties of CA fruits extract against formalin induced chronic inflammation in Female Wistar rats. In fact, the antioxidant activity was tested by Diphenyl-1-Picrylhydrazyl free radical scavenging (DPPH), Ferric reducing antioxidant power (FRAP) and Nitric Oxide radical (NO·). Anti-inflammatory effect of fruits extract was examined using formalin (2%) induced paw edema in rats. Molecular docking tools were used to investigate the interaction of some compounds from CA fruits extract with the cyclooxygenase-2 (COX-2) target protein. Our results showed that, the total phenolic, flavonoid and tannins contents, which were assessed by the Folin-Ciocalteu, Quercetin, and Catechin methods, respectively, were 230.22 mg gallic acid equivalent/g dry weight (mg GAE/g DW), 55.08 mg quercetin equivalent/g dry weight (QE/g DW) and 15.17 mg catechin equivalents/g dry weight (CatE/g DW), respectively. HPLC analysis revealed the presence of five polyphenolic compounds whose catechin was found to be the most abundant compounds. The antioxidant activity of extract was quantified by DPPH, FRAP and NO· tests and IC50 reached the values of 3.346 mg/mL, 2.306 and 0.023 mg/mL, respectively. Cleome fruits ameliorated the histological integrity of the skin and alleviated the disruptions in hematological parameters (WBC, LYM, RBC, and HGB), inflammatory cytokines (IL-1ß, IL-6, TNF-α), C-reactive protein, and some oxidative stress markers (TBARS (-49%) and AOPP (-42%) levels, SOD (+33%) and GPx (+75%) activities, and GSH (+49%) content) induced by formalin injection. Moreover, the in-silico investigation had shown that CA fruits extract compounds have a stronger interaction with COX-2 active site, more than the reference drug "indomethacin" (two H-bonds). Our research gives pharmacological backing to the healthcare utilization of Cleome plant in the treatment of inflammatory diseases and oxidative harm.

MTHFR (C677T, A1298C), FV Leiden polymorphisms, and the prothrombin G20210A mutation in arterial ischemic stroke among young tunisian adults.

Arterial ischemic stroke (AIS) in young adults is less common in older adults, but the underlying pathogenesis and risk factors are more multi-faceted. The role of inherited thrombophilia such as 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism, (C677T and A1298C), factor V of Leiden (FVL) polymorphism, and the prothrombin G20210A mutations remains unclear. This study aims to evaluate the role of prothrombin genetic factor in AIS among young adults in Tunisia and to assess the synergistic effect between thrombogenic mutations in the pathogenesis of AIS. In this case-control study, blood samples were collected from patients and healthy controls, all matched for age and gender. The difference between them is evaluated by using the chi-square test. The odds ratio (OR) was carried out to evaluate the associations between each polymorphism and AIS risk using a binary logistic regression model. Values were considered statistically significant when p < 0.05. Patients carrying simultaneously the MTHFR polymorphisms (677T and 1298C) have a higher risk to develop AIS compared to controls. The heterozygous variants FVL increased the risk of AIS only when it is associated with MTHFR C677T or MTHFR A1298C polymorphisms. In conclusion, our study confirmed the involvement of MTHFR polymorphisms as AIS's important risk factors. The existence of FVL polymorphism or prothrombin G20210A mutation alone doesn't correlate with the occurrence of stroke. We assume that the presence of both MTHFR and FVL polymorphisms has a synergistic effect and increased the risk of the AIS.

The Role of Allium subhirsutum L. in the Attenuation of Dermal Wounds by Modulating Oxidative Stress and Inflammation in Wistar Albino Rats.

In our study, Allium subhirsutum L. (AS) was investigated to assess its phenolic profile and bioactive molecules including flavonoids and organosulfur compounds. The antioxidant potential of AS and wound healing activity were addressed using skin wound healing and oxidative stress and inflammation marker estimation in rat models. Phytochemical and antiradical activities of AS extract (ASE) and oil (ASO) were studied. The rats were randomly assigned to four groups: group I served as a control and was treated with simple ointment base, group II was treated with ASE ointment, group III was treated with ASO ointment and group IV (reference group; Ref) was treated with a reference drug "Cytolcentella® cream". Phytochemical screening showed that total phenols (215 ± 3.5 mg GAE/g) and flavonoids (172.4 ± 3.1 mg QE/g) were higher in the ASO than the ASE group. The results of the antioxidant properties showed that ASO exhibited the highest DPPH free radical scavenging potential (IC50 = 0.136 ± 0.07 mg/mL), FRAP test (IC50 = 0.013 ± 0.006 mg/mL), ABTS test (IC50 = 0.52 ± 0.03 mg/mL) and total antioxidant capacity (IC50 = 0.34 ± 0.06 mg/mL). In the wound healing study, topical application of ASO performed the fastest wound-repairing process estimated by a chromatic study, percentage wound closure, fibrinogen level and oxidative damage status, as compared to ASE, the Cytolcentella reference drug and the untreated rats. The use of AS extract and oil were also associated with the attenuation of oxidative stress damage in the wound-healing treated rats. Overall, the results provided that AS, particularly ASO, has a potential medicinal value to act as effective skin wound healing agent.

HPLC-DAD Analysis, Antioxidant and Protective Effects of Tunisian Rhanterium suaveolens against Acetamiprid Induced Oxidative Stress on Mice Erythrocytes.

The present study was performed to assess the HPLC-DAD analysis as well as antioxidant and protective effects of Tunisian Rhanterium suaveolens (Rs) against acetamiprid (ACT) induced oxidative stress on mice erythrocytes. The in vitro assays showed that the methanolic extract of Rs has an impressive antioxidant effect proved by testing the total antioxidant and scavenging activities using BCB, DPPH and ABTS assays, respectively. Moreover, qualitative and quantitative analysis using HPLC-DAD revealed the richness of Rs in polyphenols where p-Coumaric, Apigenin-7-glucoside and Ferulic acid were detected as the most abundant polyphenols. In the in vivo experiment, ACT, used as a toxicity model, was given to mice at a dose of 20 mg/kg. The latter was the origin of hemolytic anemia characterized by a significant decrease in red blood cells, hemoglobin and hematocrit levels and an increase in bilirubin, LDH, osmotic fragility, reticulocytes and white blood cells number. Characteristic erythrocyte morphological alterations were also determined as spherocytosis, schistocytosis and dacryocystitis. The oxidative status of ACT-treated mice was also altered manifested by a significant increase in MDA and GSH levels and a decrease in SOD, CAT and GPx activities. When receiving the Rs methanolic extract at a dose of 300 mg/kg, all the parameters cited above were restored in mice. These remarkable corrections could only confirm the important antioxidant effect and the noticeable protective properties that possess Rs owing to its broad range of secondary bioactive metabolites.

Therapeutic potential of polysaccharide extracted from fenugreek seeds against thiamethoxam-induced hepatotoxicity and genotoxicity in Wistar adult rats.

This study aimed to evaluate the protective effect of a polysaccharide extracted from fenugreek seeds (Trigonella foenum-graecum) (FWEP) against insecticide-thiamethoxam (TMX)-induced hepatotoxicity. Obtained data exhibited potent antioxidant and antibacterial potentialities. On other trend, in vivo, adult female rats were divided into four groups: controls; TMX (100 mg/kg of body weight); TMX + FWEP at two graded doses, respectively (100 and 200 mg/kg of body weight) for 30 d. Up to TMX treatment, our data showed a significant increase in plasma markers of hepatotoxicity including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and in lactate dehydrogenase (LDH) activities, which is coordinated with decline in total protein and albumin levels. Remarkably, a clear sign of genotoxicity was delivered by total disruption in hematological parameters and micronucleus (MN) test shown by severe chromatin degradation. These data were also associated with oxidative stress set up, histological and DNA injuries. However, co-administration with FWEP succeeded significantly in a dose-dependent manner in reducing and healing liver's hematological and genotoxic induced by TMX injuries.

Modulatory effects of quercetin on liver histopathological, biochemical, hematological, oxidative stress and DNA alterations in rats exposed to graded doses of score 250.

This study investigated the morphological, biochemical and molecular aspects of liver injury in rats after the exposure to difenoconazole and the protective effects of quercetin against hepatotoxicity and genotoxicity induced by this fungicide. Rats were given graded doses of difenoconazole associated or not to quercetin daily for 20 days. Our results showed a significant increase in PLT (platelets) and WBC (white blood cells) in rats treated with higher doses of difenoconazole (1/38 and 1/9 of LD50). However, a significant decrease in Hb (hemoglobin) rate and RBC (red blood cells) number in rats treated with higher doses of difenoconazole (1/38 and 1/9 of LD50) was obtained. Besides, difenoconazole treatment caused an increase in hepatic enzyme activities of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). Difenoconazole increased the levels of malondialdehyde (MDA) and advanced oxidation protein products (AOPPs), and decreased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and vitamin C levels in liver tissues compared to the control group. We also noted a degradation of nucleic acids, testifying difenoconazole genotoxicity. Changes in hepatic tissues were confirmed by histological findings. Co-administration of quercetin (20 mg/kg) improved hematological and biochemical parameters and showed a significant liver protective effect by decreasing MDA levels and producing advanced oxidation protein, along with increased antioxidative enzyme activities and vitamin C levels. Results were confirmed by the improvement of histological impairments. Thus, it appears that quercetin was effective in preventing acute liver injury induced by exposure to difenoconazole.

Frequent Infections, Hypotonia, and Anemia in a Breastfed Infant.

Vitamin B12 deficiency may be responsible of serious hematologic and neurodevelopmental abnormalities. We report the case of an infant who was hospitalized because of recurrent infections, failure to thrive, hypotonia, and weakness. He was 8 months old and had been exclusively breastfed. Blood cell count showed pancytopenia with megaloblastic bone marrow. The serum IgG concentration was low. Vitamin B12 level was very low and associated with increased urinary methylmalonic acid. Cobalamin deficiency was caused by mother's unrecognized pernicious anemia. Vitamin B12 supply led to rapid clinical and hematologic improvement.

Increasing maneb doses induces reactive oxygen species overproduction and nephrotoxicity in adult mice.

BACKGROUND AND PURPOSE: The aim of this study was to elucidate the biochemical, molecular and histopathological aspects of the kidney injuries as well as the hematological perturbations induced after adult mice exposure to increasing doses of maneb (MB). MATERIAL AND METHOD: Adult mice were intraperitoneally treated for seven days with four graded doses of MB, corresponding to 1/8, 1/6, 1/4 and 1/2 of its lethal dose (LD50=1500 mg/kg body weight). RESULTS: Hematological analysis revealed a significant disruption in total white blood cells and platelets and a significant decrease in the plasmatic levels of ferrozine in mice treated with 1/8, 1/6 and 1/4 of MB LD50. However, the ferrozine levels increased significantly in the group treated with 1/2 of MB LD50. Evenly, our results showed a significant increase in the levels of malondialdehyde, lipid hydroperoxides, hydrogen peroxide and advanced oxidation protein products in all treated groups. The activities of catalase and glutathione peroxidase decreased significantly in all MB treated mice. Additionally, all treated groups exhibited strong nephrotoxicity signs, including increases in plasma urea, creatinine and albumin levels and lactate dehydrogenase activity, as well as a significant decrease in uric acid levels. Electrophoresis analysis revealed nucleic acid degradation, testifying the genotoxicity of MB. Moreover, the histopathological observations showed severe renal injuries, which could be related to the above mentioned data. CONCLUSIONS: Our data showed, for the first time, that the MB tested doses led to oxidative stress installation causing renal cell damages and lowering all defense systems capacities.

Beneficial effects of fermented sardinelle protein hydrolysates on hypercaloric diet induced hyperglycemia, oxidative stress and deterioration of kidney function in wistar rats.

This study investigated the potential effects of fermented sardinelle protein hydrolysates (FSPHs) obtained by two proteolytic bacteria, Bacillus subtilis A26 (FSPH-A26) and Bacillus amyloliquefaciens An6 (FSPH-An6), on hypercaloric diet (HCD) induced hyperglycemia and oxidative stress in rats. Effects of FSPHs on blood glucose level, glucose tolerance, α-amylase activity and hepatic glycogen content were investigated, as well as their effect on the oxidative stress state. Biochemical findings revealed that, while undigested sardinelle proteins did not exhibit hypoglycemic activity, oral administration of FSPHs to HCD-fed rats reduced significantly α-amylase activity as well as glycemia and hepatic glycogen levels. Further, the treatment with FSPHs improved the redox status by decreasing the levels of lipid peroxidation products and increasing the activities of the antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase) and the level of glutathione in the liver and kidneys, as compared to those of HCD-fed rats. FSPHs were also found to exert significant protective effects on liver and kidney functions, evidenced by a marked decrease in alkaline phosphatase activity and a modulation of creatinine and uric acid contents. These results indicated the beneficial effect of FSPHs on the prevention from hyperglycemia and oxidative stress.

Protective effects of pomegranate peel against hematotoxicity, chromosomal aberrations, and genotoxicity induced by barium chloride in adult rats.

CONTEXT: Pomegranate peel (PP) has health benefits including antibacterial, antioxidant, anti-inflammatory, and antimutagenic properties. OBJECTIVE: This study investigated the biochemical composition and protective effects of PP against hematotoxicity and genotoxicity induced by barium chloride (BaCl2) in adult rats. MATERIALS AND METHODS: Adult Wistar rats were divided into four groups of six each: control, barium (67 ppm via drinking water), PP (5% via diet), and their combination during 21 d. Oxidative stress was determined by MDA, AOPP, and antioxidant status: CAT, GPx, GSH, Vit C. Osmotic fragility (OF), chromosomal aberrations (CAs), and micronucleus (MN) assays were also studied. RESULTS: PP showed a rich composition of antioxidant compounds. DPPH test found IC50 value= 5.3 µg/mL and a high polysaccharides content (315 ± 5 mg/g of extract). In vivo study showed a decrease in red blood cells (70%) and platelet counts (46%), hemoglobin content (8%), hematocrit percent (7%), and an 80% increase of white blood cells in Ba-treated rats. A reduction in antioxidant status: catalase, glutathione peroxidase activities, glutathione, and vitamin C levels by 31, 21, 28, and 29%, respectively, and an increase in MDA (46%) and AOPP levels (72%) were also observed compared with controls. BaCl2-treatment showed a significant increase in the frequencies of total chromosomal aberrations with abnormal metaphases and micronucleus in bone-marrow cells. Oxidative stress induced by BaCl2 might be the major cause for chromosomal abnormalities leading to DNA damage. DISCUSSION AND CONCLUSION: A decrease in hematotoxic and genotoxic effects induced by PP is due to its powerful antioxidant capacity.

Hyparrhenia hirta: A potential protective agent against hematotoxicity and genotoxicity of sodium nitrate in adult rats.

The present study was carried out to examine the adverse hematotoxic and genotoxic effects of water nitrate pollution on male adult rats and the use of hyparrhenia hirta methanolic extract in alleviating these effects. Sodium nitrate (NaNO3 ) was administered to adult rats by oral gavage at a dose of 400 mg kg(-1) bw daily for 50 days, while hyparrhenia hirta methanolic extract was given by drinking water at a dose of 1.5 mg mL(-1) (200 mg kg(-1) bw). The NaNO3 -treated group showed a significant decrease in red blood cell count, hemoglobin and hematocrit and a significant increase in total white blood cell, in neutrophil and eosinophil counts. Platelet count, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration remained unchanged in treated groups compared to those of controls. Meanwhile, the results showed a marked reduction in the antioxidant enzyme activities, such as superoxide dismutase, catalase, and glutathione peroxidase, along with an elevation in the level of lipid peroxidation and a reduction in the total glutathione content, indicating the induction of oxidative stress in the erythrocytes of NaNO3 -treated group. Interestingly, NaNO3 treatment showed a significant increase in the frequencies of total chromosomal aberrations, aberrant metaphases and micronucleus in bone-marrow cells. The oxidative stress induced by nitrate treatment might be the major cause for chromosomal rearrangements as free radicals leading to DNA damage. Hyparrhenia hirta methanolic extract appeared to be effective against hematotoxic and genotoxic changes induced by nitrate, as evidenced by the improvement of the markers cited above.

Impact of breast cancer stage, time from diagnosis and chemotherapy on plasma and cellular biomarkers of hypercoagulability.

BACKGROUND: In breast cancer patients routine thromboprophylaxis is not recommended but individualized risk assessment is encouraged. The incorporation of hypercoagulability biomarkers could increase the sensitivity of risk assessment models (RAM) to identify patients at VTE risk. To this aim we investigated the impact of cancer-related characteristics on hypercoagulability biomarkers. METHODS: Thrombin generation (TG) assessed with the Thrombogramme-Thrombinoscope®, levels of platelet derived microparticles (Pd-MP) assessed with flow cytometry, procoagulant phospholid dependent clotting time (PPL-ct) measured with a clotting assay and D-Dimers (were assessed in a cohort of 62 women with breast cancer and in 30 age matched healthy women. RESULTS: Patients showed significantly higher TG, Pd-MP, D-Dimers levels and shortened PPL-ct compared to the controls. The PPL-ct was inversely correlated with the levels of Pd-MP, which were increased in 97% of patients. TG and D-Dimers were increased in 76% and 59% of patients respectively. In any stage of the disease TG was significantly increased as compared to the controls. There was no significant difference of TG in patients with local, regional of metastatic stage. There was no significant difference in Pd-MP or Pd-MP/PS+ between the subgroups of patients with local or regional stage of cancer. Patients with metastatic disease had significantly higher levels of Pd-MP and Pd-MP/PS+ compared to those with regional stage. The D-Dimers increased in patients with metastatic stage. In patients on chemotherapy with less than 6 months since diagnosis TG was significantly higher compared to those on chemotherapy who diagnosed in interval > 6 months. Patients with metastatic disease had significantly higher levels of Pd-MP and D-Dimers compared to those with non-metastatic disease. CONCLUSION: In breast cancer patients the stage, the time elapsed since the diagnosis and the administration of chemotherapy are determinants of cellular and plasma hypercoagulability. The levels and the procoagulant activity of Pd-MP are interconnected with the biological activity and the overall burden of cancer. TG reflects the procoagulant properties of both breast cancer and chemotherapy in the initial period of cancer diagnosis. Thus the weighted incorporation of the biomarkers of cellular and plasma hypercoagulabilty in RAM for VTE might improve their predictive value.

Methyl-thiophanate increases reactive oxygen species production and induces genotoxicity in rat peripheral blood.

Methylthiophanate is one of the widely used fungicides to control important fungal diseases of crops. The aim of this study was to elucidate the short-term hematoxicity and genotoxicity effects of methylthiophanate administered by intraperitoneal way at three doses (300, 500 and 700 mg/kg of body weight) after 24, 48 and 72 h. Our results showed, 24 h after methylthiophanate injection, a hematological perturbation such as red blood cells (p < 0.05, p < 0.05 and p < 0.01) and hemoglobin content (p < 0.05), respectively, and a noticeable genotoxic effect in WBC evidenced by a significant increase in the frequency of the micronuclei and a decrease in cell viability. An increase in erythrocyte osmotic fragility was also noted after 24 and 48 h of methylthiophanate treatment at graded doses. A significant increase in hydrogen peroxide, advanced oxidation of protein products and malondialdehyde levels, in erythrocytes of methylthiophanate-treated rats with 300, 500 and 700 mg/kg of body weight, was also observed after 24 h of treatment (p < 0.05, p < 0.01 and p < 0.001, respectively), suggesting the implication of oxidative stress in its toxicity. Antioxidants activities of superoxide dismutase and glutathione peroxidase in erythrocytes significantly increased (p < 0.001) 24 h after the highest dose injected. While all these parameters were improved after 72 h of methylthiophanate injection (300, 500 and 700 mg/kg body weight). In conclusion, these data showed that the exposure of adult rats to methylthiophanate resulted in oxidative stress leading to hematotoxicity and the impairment of defence system, confirming the pro-oxidant and genotoxic effects of this fungicide.

Ischemic Stroke in Young Tunisian Adults.

INTRODUCTION: Ischemic Stroke in young adults is a real public health problem; it's a major cause of disability, alters quality of life and has a great socio-economic impact. AIM: determine risk factors and specify the etiology of arterial ischemic stroke in young Tunisian adults. METHODS: In this 5 years retrospective study (2015-2020), we included all young adults (18-50 years) admitted for arterial ischemic stroke (AIS). Risk factors were registered and analyzed. All patients were investigated using a standard protocol: biological tests, brain imaging, carotid ultrasound and cardiac assessment. Additional investigations were carried out at the discretion of the treating physician. The cause of ischemic stroke was classified according to the TOAST criteria. RESULTS: We collected 200 patients with AIS. The mean age was 41.37 years ± 6.99. Traditional vascular risk factors were observed in more than 1/4 patients. A definite cause of stroke was identified in 120 patients. Cardio-embolic causes were the most common among our patients (19%) followed by atherosclerosis of the large arteries (11.5%). Other determined etiologies were found in 27.5% of patients. The etiology remained unclear in 40% of cases: undetermined despite complete investigation in 17.5%, undetermined and incompletely investigated 14.5 % and more than one potential pathomechanisms in 8%. CONCLUSION: Through this study, we demonstrated the diversity of etiology of stroke in young Tunisian adults. Changes of lifestyle are responsible for the occurrence of the traditional risk factors at an early age. Rheumatic heart diseases remain a frequent cause of AIS in our area.

GC-MS/MS Analysis and Wound Repair Potential of Urtica dioica Essential Oil: In silico Modeling and In vivo Study in Rats.

BACKGROUND: The study aimed to assess the antioxidant and wound healing properties of Urtica dioica essential oil (UDEO) through a comprehensive evaluation involving in silico, in vitro, and in vivo analyses. The phytochemistry of UDEO was also investigated to identify trace compounds crucial. METHODS: Various injection methods of the multimode inlet (MMI) in chromatography were investigated to attain lower instrumental detection limits. Subsequently, in silico studies were employed to delve deeper into the potential biological activities of the identified compounds. Standard antioxidative tests, encompassing ABTS•+ and TAC, were performed. In vivo tests centered on wound healing were implemented using rat models. The rats were randomly allocated to four groups: saline solution, vaseline vehicle, cytol centella, and 5% UDEO ointment. Wound healing progress was evaluated through a chromatic study. RESULTS: Gas chromatography combined with triple quadrupole mass spectrometry (GC-MS/MS) analysis revealed the presence of 97 thermolabile compounds in UDEO. Subsequent in silico studies unveiled the potential of identified compounds to inhibit COX-2, TNF-α, and IL-6, suggesting a possible enhancement of anti-inflammatory responses and healing processes. In vitro tests elucidated the notable antioxidant capacity of UDEO, a finding reinforced by wound healing data, revealing a substantial closure rate of 89% following the topical application of UDEO. Notably, fibrinogen and C-reactive protein (CRP) levels were significantly reduced, indicating minimized oxidative stress damage compared to control. Additionally, UDEO exhibited an increase in antioxidant enzyme activities compared to control. CONCLUSION: The study concludes that UDEO possesses significant antioxidant and wound-healing properties, supported by its rich phytochemical composition. The findings suggest its potential application in therapeutic interventions for oxidative stress and inflammatory conditions.

Anti-Vasculogenic, Antioxidant, and Anti-Inflammatory Activities of Sulfated Polysaccharide Derived from Codium tomentosum: Pharmacokinetic Assay.

The purpose of this paper was to investigate the anti-inflammatory and anti-angiogenic activities of sulfated polysaccharide from C. tomentosum (PCT) using carrageenan (CARR)-induced paw edema in a rat model and anti-vasculogenic activity on a chorioallantoic membrane assay (CAM) model. Based on in vitro tests of anti-radical, total antioxidant, and reducing power activities, PCT presents a real interest via its antioxidant activity and ability to scavenge radical species. The in vivo pharmacological tests suggest that PCT possesses anti-inflammatory action by reducing paw edema and leukocyte migration, maintaining the redox equilibrium, and stabilizing the cellular level of several pro-/antioxidant system markers. It could significantly decrease the malondialdehyde levels and increase superoxide dismutase, glutathione peroxidase, and glutathione activities in local paw edema and erythrocytes during the acute inflammatory reaction of CARR. PCT pretreatment was effective against DNA alterations in the blood lymphocytes of inflamed rats and reduced the hematological alteration by restoring blood parameters to normal levels. The anti-angiogenic activity results revealed that CAM neovascularization, defined as the formation of new vessel numbers and branching patterns, was decreased by PCT in a dose-dependent manner, which supported the in silico bioavailability and pharmacokinetic findings. These results indicated the therapeutic effects of polysaccharides from C. tomentosum and their possible use as anti-proliferative molecules based on their antioxidant, anti-inflammatory, and anti-angiogenic activities.

Sex-related differences in toxic manifestations induced by Bothrops atrox venom in mice.

Lancehead snakes of the genus Bothrops are responsible for 90% of the snakebites in Latin America. The objective of this study was to assess the LD50, physical, and hematological manifestations induced by B. atrox venom in male and female mice inoculated by different routes. B. atrox venom was inoculated in male and female mice by intramuscular (IM), subcutaneous (SC), intravenous (IV), and intraperitoneal (IP) routes. B. atrox venom LD50 was lower in male than female groups, regardless of the injection route. However, it was the lowest when the venom was inoculated by the IP route. Moreover, comparisons between male and female responses according to the injected venom dose showed higher edema-forming, local hemorrhagic, dermonecrotic, and myotoxic activities in male than in female mice. While the minimal hemorrhagic, and necrotic doses were not statistically different between the two groups, the difference between males and females was more pronounced at high venom doses. Hematological parameter changes were also more significant in male than in female mice. The venom decreased the levels of total leukocytes after 24 h of injection in male and female mice, with a more profound decrease in the male group. The micronucleus test, a tool for genotoxicity assessment, documented the mutagenic effects of B. atrox on leucocytes. We demonstrate the higher susceptibility of male mice to B. atrox venom than females. Sex differences must be considered when conducting experimental studies on snake venoms.