Aquaporin-4 inhibition attenuates Pentylenetetrazole-induced behavioral seizures and cognitive impairments in kindled rats.

Epilepsy is a neurological condition distinguished by recurrent and unexpected seizures. Astrocytic channels and transporters are essential for maintaining normal neuronal functionality. The astrocytic water channel, aquaporin-4 (AQP4), which plays a pivotal role in regulating water homeostasis, is a potential target for epileptogenesis. In present study, we examined the effect of different doses (10, 50, 100 µM and 5 mM) of AQP4 inhibitor, 2-nicotinamide-1, 3, 4-thiadiazole (TGN-020), during kindling acquisition, on seizure parameters and seizure-induced cognitive impairments. Animals were kindled by injection of pentylenetetrazole (PTZ: 37.5 mg/kg, i.p.). TGN-020 was administered into the right lateral cerebral ventricle 30 min before PTZ every alternate day. Seizure parameters were assessed 20 min after PTZ administration. One day following the last PTZ injection, memory performance was investigated using spontaneous alternation in Y-maze and novel object recognition (NOR) tests. The inhibition of AQP4 during the kindling process significantly decreased the maximal seizure stage and seizure duration (two-way ANOVA, P = 0.0001) and increased the latency of seizure onset and the number of PTZ injections required to induce different seizure stages (one-way ANOVA, P = 0.0001). Compared to kindled rats, the results of the NOR tests showed that AQP4 inhibition during PTZ-kindling prevented recognition memory impairment. Based on these results, AQP4 could be involved in seizure development and seizure-induced cognitive impairment. More investigation is required to fully understand the complex interactions between seizure activity, water homeostasis, and cognitive dysfunction, which may help identify potential therapeutic targets for these conditions.

Combined administration of gallic acid and glibenclamide mitigate systemic complication and histological changes in the cornea of diabetic rats induced with streptozotocin.

PURPOSE: To determine the effect of gallic acid or its combination with glibenclamide on some biochemical markers and histology of the cornea of streptozotocin (STZ) induced diabetic rats. METHODS: Following induction of diabetes, 24 male albino rats were divided into four groups of six rats each. Groups 1 and 2 (control and diabetic) received rat pellets and distilled water; group 3 (gallic acid) received rat pellets and gallic acid (10 mg/kg, orally) dissolved in the distilled water; and group 4 (gallic acid + glibenclamide) received rat pellets, gallic acid (10 mg/kg, orally), and glibenclamide (5 mg/kg, orally) dissolved in the distilled water. The treatments were administered for three months after which the rats were sacrificed after an overnight fast. Blood and sera were collected for the determination of biochemical parameters, while their eyes were excised for histology. RESULTS: STZ administration to the rats induced insulin resistance, hyperglycemia, microprotenuria, loss of weight, oxidative stress, inflammation, and alteration of their cornea histology, which was abolished following supplementation with gallic acid or its combination with glibenclamide. CONCLUSIONS: The study showed the potentials of gallic acid and glibenclamide in mitigating systemic complication and histological changes in the cornea of diabetic rats induced with STZ.

The effect of hydrogen-rich water on letrozole-induced polycystic ovary syndrome in rats.

RESEARCH QUESTION: What is the effect of hydrogen-rich water on rats with polycystic ovary syndrome (PCOS)? DESIGN: Female rats were divided into four groups, each consisting of eight animals. The control group received a carboxymethyl cellulose (CMC) solution, the molecular hydrogen (H2) group was given hydrogen-rich water and a CMC solution, the PCOS group was administered letrozole dissolved in a CMC solution and the PCOS + H2 group was given hydrogen-rich water and letrozole dissolved in a CMC solution. Blood and tissue samples were then collected, and biochemical and histopathological analyses were conducted on the samples. RESULTS: The histopathological analysis showed a reduction in the number of cysts in the PCOS + H2 group compared with the PCOS group (P < 0.0001). Additionally, the malondialdehyde, cortisol and testosterone data revealed a significant decrease in the PCOS + H2 group compared with the PCOS group (P = 0.0458, P = 0.0003, P = 0.0041, respectively). The glutathione also showed a statistically significant increase in the PCOS + H2 group compared with the PCOS group (P = 0.0012). CONCLUSION: The study findings demonstrate that hydrogen-rich water reduces the number of cysts and oxidative damage in rats with PCOS.

Protective effect of water extracts of Veronicastrum latifolium (Hemsl.) Yamazaki on carbon tetrachloride-induced liver fibrosis in mice and its effect on intestinal flora.

Liver fibrosis refers to a reversible event of repair and reconstruction following injury due to various etiologies, and its continuous development will lead to cirrhosis and liver cancer. Abnormal alterations in intestinal microbiota can hasten the development of hepatic fibrosis and damage. Veronicastrum latifolium (Hemsl.) Yamazaki (VLY) is a classic drug applied extensively for managing acute and chronic hepatitis, liver cirrhosis and ascites in ethnic minority areas of Guizhou Province, China, which possesses broad-spectrum pharmacological activities. In view of the crucial role of intestinal microbiota in the development of liver fibrosis, the present study attempted to investigate the effects of VLY aqueous extract on ameliorating CCl4-elicited liver fibrosis in mice and on intestinal microbiota and to explore its possible mechanism. Phytochemical analysis showed that VLY water extract contained a variety of components, particularly rich in organic acids and their derivatives, flavonoids, phenolic acids, nucleotides and their derivatives, carbohydrates and other compounds. VLY water extract remarkably alleviated CCl4-induced liver damage and fibrosis in mice, improved liver histology, and improved liver function abnormalities. VLY water extract also inhibited the activation of hepatic stellate cells and invasion of intrahepatic inflammatory cells. Additionally, sequencing the 16 s rDNA gene revealed that VLY water extract changed the intestinal microbiota composition in liver fibrotic mice. It elevated the Firmicutes/Bacteroidota ratio and enriched the relative Lactobacillus richness, which is capable of mitigating fibrosis and inflammation in impaired liver. In summary, through modulation of inflammation and intestinal microbiota, VLY water extract can reduce the CCl4-elicited liver fibrosis.

Quercus floribunda Lindl. Ex A. Camus; a tremendous remedy against inflammation and associated symptoms.

Crude extracts prepared from aerial parts and nut galls of Quercus floribunda Lindl. Ex. A. Camus were evaluated for phytochemical screening, in vitro antioxidant, and in vivo analgesic, anti-inflammatory and antipyretic activities. Various solvents including methanol (M), acetone (A), distilled water (DW), distilled water + methanol (DWM) were used for extraction. Highest total phenolic (66.9 ± 0.05 µg GAE/mgE) and flavonoid content (38.4 ± 0.72 µg QE/mgE) were measured in QFAA extract by colorimetric methods. Cumulative maximum concentrations of polyphenols were quantified in QFMG, QFAA, and QFMA extracts i.e. 19.036, 15. 574 and 11.647 µg/mg of extract by RP-HPLC analysis. From aerial parts extracts, apentacyclic tritepenoid, glutinol was isolated using column chromatography techniques and structure was elucidated using spectroscopic techniques. QFDWMA (205.5 ± 0.56 µg AAE/mg of extract) showed highest total reducing power while highest total antioxidant capacity (207.1 ± 0.49 AAE/mg of extract) and free radical scavenging potential (96.1 ± 0.42%) were observed in QFAA extract. QFAA extract showed significant (p ≤ 0.001) analgesic potential in different pain models i.e. hot plate method, cold plate method, Haffner's tail clip method and acetic acid induced writhing assay having 50.20%, 62.07%, 57.26% and 70.49% analgesia respectively at 300 mg/kg. QFAA extract showed maximum anti-inflammatory activity in croton oil induced edema (68.83%) and in carrageenan induced paw edema models (72.32%) at 300 mg/kg concentration. QFAA extract markedly reduced the rectal temperature at 300 mg/kg concentration, in brewer's yeast induced pyrexia model. Detailed investigations can be executed in future to determine the molecular mechanisms of these pharmacological attributes.

Running water while bathing is a risk factor for pediatric scald burns.

INTRODUCTION: Scalds are the most common mechanism of burn injury in pediatric populations and scald burns sustained during bathing present a unique opportunity for injury prevention. Evidence-based infant bathing educational resources recommend checking water temperature and having a caregiver present for the duration of the bath, but do not explicitly recommend avoiding running water or explain the associated risks. This study seeks to determine the incidence and role of running water in bathing scald burns at our institution. METHODS: This is a retrospective review of pediatric patients (<3 years) admitted to the University of Chicago Burn Center with scald injury from bathing between 2010 and 2020. Cases were reviewed to assess the following risk factors: whether there was running water, whether water temperature was checked before placing the child in water, and whether a caregiver was present for the entire bath. Injuries in which the manner of injury was abuse or indeterminate were excluded. RESULTS: The study cohort included 101 cases of scalds due to bathing, with a mean age of 13 months and mean burn size of 7% TBSA. Of these 101 cases, 96 (95%) involved running water. Thirty-seven cases (37%) had only one of the three risk factors and 95% of those 37 cases involved running water. Twenty-nine cases (29%) involved all three risk factors while only two cases (2%) involved none of the three risk factors. Sixty-one cases (60%), thirty-nine cases (39%), and one case (1%) occurred in a sink, bathtub, or infant tub, respectively. CONCLUSION: We found that the vast majority of bathing scald burns involved running water, identifying a specific bathing recommendation that should be added to existing guidelines to reduce the incidence of bathing scald burns.

Effects of Sideritis scardica Extract on Scopolamine-Induced Learning and Memory Impairment in Mice.

BACKGROUND: The neurodegenerative process in Alzheimer's disease, one of the most common types of dementia worldwide, mostly affects the cholinergic neurotransmitter system and, to a lesser extent, the monoaminergic one. The antioxidant acetylcholinesterase (AChE) and triple monoamine reuptake inhibitory activity of Sideritis scardica (S. scardica) and other Sideritis species has already been reported. OBJECTIVE: To investigate the effects of S. scardica water extracts on the learning and memory processes, anxiety-like behavior, and locomotor activities in scopolamine (Sco)-induced dementia in mice. METHODS: Male Albino IRC mice were used. The plant extract was administered for 11 consecutive days in the presence or absence of Sco (1 mg/kg, i.p). The behavioural performance of the animals was evaluated by passive avoidance, T-maze, and hole-board tests. The effects of extract on AChE activity, brain noradrenalin (NA), and serotonin (Sero) content, and antioxidant status were also monitored. RESULTS: Our experimental data revealed that the S. scardica water extract caused a reduction in degree of memory impairment and anxiety-like behaviour in mice with scopolamine-induced dementia. The extract did not affect changed by the Sco AChE activity but impact reduced brain NA and Sero levels and demonstrated moderate antioxidant activity. In healthy mice we did not confirm the presence of anxiolytic-like and AChE inhibitory effects of the S. scardica water extract. The extract did not change the control Sero brain levels and reduce those of NA. CONCLUSION: S. scardica water extract demonstrated memory preserving effect in mice with scopolamine-induced dementia and deserve further attention.

Differences between aquagenic and non-aquagenic pruritus in myeloproliferative neoplasms: An observational study of 500 patients.

BACKGROUND: Pruritus is a frequent symptom experienced by patients with myeloproliferative neoplasms (MPN). Aquagenic pruritus (AP) is the most common type. The Myeloproliferative Neoplasm-Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) self-report questionnaires were distributed to MPN patients before consultations. OBJECTIVES: The aim of this study was to assess clinical incidence (phenotypical evolution and response to treatment) of pruritus, especially AP, in MPN patients during their follow-ups. PATIENTS AND METHODS: We collected 1444 questionnaires from 504 patients [54.4% essential thrombocythaemia (ET) patients, 37.7% polycythaemia vera (PV) patients, and 7.9% primary myelofibrosis (PMF) patients]. RESULTS: Pruritus was reported by 49.8% of the patients, including 44.6% of AP patients, regardless of type of MPN or driver mutations. Patients suffering from pruritus were more symptomatic and had a higher rate of evolution into myelofibrosis/acute myeloid leukaemia (19.5% vs. 9.1%, OR = 2.42 [1.39; 4.32], p = 0.0009) than MPN patients without pruritus. Patients with AP had the highest pruritus intensity values (p = 0.008) and a higher rate of evolution (25.9% vs. 14.4%, p = 0.025, OR = 2.07) than patients with non-AP. Disappearance of pruritus was observed in only 16.7% of AP cases, compared to 31.7% of cases with other types of pruritus (p < 0.0001). Ruxolitinib and hydroxyurea were the most effective drugs to reduce AP intensity. CONCLUSIONS: In this study, we demonstrate the global incidence of pruritus across all MPN. Pruritus, especially AP, which is a major constitutional symptom observed in MPN, should be assessed in all MPN patients due to higher symptom burden and higher risk of evolution.

Sugar-sweetened beverages exacerbate high-fat diet-induced inflammatory bowel disease by altering the gut microbiome.

High-fat diets (HFDs) and frequent consumption of sugar-sweetened beverages (SSBs) are potential contributors to increasing inflammatory bowel disease (IBD) incidences. While HFDs have been implicated in mild intestinal inflammation, the role of sucrose in SSBs remains unclear. Therefore, we studied the role of SSBs in IBD pathogenesis in a mouse model and humans. C57BL6/J mice were given ad libitum access to a sucrose solution or plain water for 10 weeks, with or without an HFD. Interestingly, sucrose solution consumption alone did not induce gut inflammation in mice; however, when combined with an HFD, it dramatically increased the inflammation score, submucosal edema, and CD45+ cell infiltration. 16S ribosomal RNA gene-sequencing revealed that sucrose solution and HFD co-consumption significantly increased the relative abundance of IBD-related pathogenic bacteria when compared with HFD consumption. RNA sequencing and flow cytometry showed that co-consumption promoted pro-inflammatory cytokine and chemokine synthesis, dendritic-cell expansion, and IFN-γ+TNF-α+CD4+ and CD8+ T-cell activation. Fecal microbiota transplantation from HFD- and sucrose water-fed mice into gut-sterilized mice increased the susceptibility to dextran sulfate sodium-induced colitis in the recipient mice. Consistent herewith, high consumption of SSBs and animal fat-rich diets markedly increased systemic inflammation-associated IBD marker expression in humans. In conclusion, SSBs exacerbate HFD-induced colitis by triggering a shift of the gut microbiome into a pathobiome. Our findings provide new insights for the development of strategies aimed at preventing IBD.

Safety and Feasibility of Contrast-Enhanced Computed Tomography with a Nanoparticle Contrast Agent for Evaluation of Diethylnitrosamine-Induced Liver Tumors in a Rat Model.

RATIONALE AND OBJECTIVES: Safety and feasibility of contrast-enhanced computed tomography (CECT) with a nanoparticulate contrast agent, ExiTron nano 12000, was evaluated in a rat liver tumor model. MATERIALS AND METHODS: This study employed eighteen 8-week-old male F344 rats. Six rats given tap water for 8 weeks further divided into two: Control group and Normal Liver with CECT group. Six rats each were given tap water containing diethylnitrosamine (DEN) at 100 ppm for 8 or 14 weeks; Adenoma group and Hepatocellular carcinoma (HCC) group, respectively. Biochemical marker values and adverse events were evaluated after CT imaging. ExiTron nano 12000 was evaluated for the hepatic contrast enhancement, and the detection and measurement of liver nodules by CECT after 8- and 14-weeks administration of DEN. Post-mortem liver specimens were evaluated by hematoxylin-eosin (HE) staining, and the number and size of liver nodules were measured. The HCC group was evaluated for diagnostic concordance between HE-stained and CECT-detected nodules. RESULTS: The contrast agent enhanced liver and was tolerated after CECT in 15 rats. Biochemical parameter values did not differ significantly between the Control and Normal Liver groups. The numbers of CECT-detected nodules in the Adenoma and HCC groups were 14.8 ± 5.1, and 32.4 ± 8.1, respectively. The HCC group had 3.6 ± 2.7 of pathological HCCs, which were identified by CECT. The size of CECT-detected HCCs correlated significantly with that of pathological HCCs (r = 0.966, p < 0.0001). CONCLUSION: CECT with ExiTron nano 12000 is a safe and feasible method to measure tumors in a rat liver tumor model.

Morphological, Biochemical and Molecular Docking Evaluation of the Anti-inflammatory Effects of Methanolic Extract of Bridelia ferruginea stem bark on Acetic acid-induced Ulcerative Colitis in Rats.

Ulcerative colitis (UC) is a chronic disorder that involves inflammation. This study was carried out to examine the anti-inflammatory effect of the methanol extract of Brideliaferrugineastem barkinAcetic acid-induced ulcerative colitis inmaleWistarrats. Twenty-four rats were randomly divided into 6 groups of 4 animals each, colitis was thereafter induced by intrarectal administration of4% (v/v)Aceticacidin all except group 1, which received distilled water. For post-colitis induction treatment group 2 received distilled water, groups 3, 4 and 5 were orally administeredthe extract at doses of 100mg/kg, 200mg/kg and 400mg/kg, respectively while group 6 received sulfasalazine 500mg/kg orally.Post colitis induction, treatment lasted for 7 days and at the end of the experiment, colon samples were collected for estimation of antioxidant, inflammatory and histological parameters. Molecular docking study was also carried out to gain more insights about the promising anti-inflammatory compounds earlier identified in the extract.Results revealed that the extract significantly (p<0.05) attenuated the increased MDA, nitrite,TNF-α and IL-6 levels. Activities of SOD, CAT, MPO and GSH levelswere also, significantly (p<0.05) increased. Furthermore, molecular docking study revealed that α-amyrin may have contributed significantly to the anti-inflammatory activity of the extract because of its remarkable binding affinity for IL-6, iNOS, IL1-ß,TNF-α and COX-2 relative to prednisolone and celecoxib. This study suggests that the extract attenuated acetic acid-induced colitis via antioxidative and anti-inflammatory mechanisms. .

Antidiarrheal Activity of Dialium guineense Willd Fruit Pulp in Wistar Rats.

Objective: This study is aimed at evaluating the effects of Dialium guineense Willd fruit pulp powder on diarrhea induced by castor oil in Wistar rats. Materials and Methods: Three different tests were carried out. A preventive test by administration of a single dose of 250, 500, 1000, 2000, and 4000 mg/kg before the induction of diarrhea by castor oil. Another preventive test after repeated administration of Dialium guineense at 250, 500, and 1000 mg/kg/day for 8 days, before the induction of diarrhea, was done. The third test was a curative test with a single dose of 250, 500, 1000, and 2000 mg/kg after the induction of diarrhea by castor oil. Results: D. guineense fruit pulp at 1000, 2000, and 4000 mg/kg administered before the induction of diarrhea, has significantly delayed diarrhea; reduced the frequency of defecation, reduced the amount of diarrheal stools, and also reduced the purging index, with a degree of inhibition comparable to that of loperamide. But the water content of the stools of the group treated with D. guineense does not change significantly compared to the controls. D. guineense has reduced significantly from 500 mg/kg the diarrhea induced by castor oil after 8 days of treatment. It appears that the doses of 250 and 500 mg/kg, which were not effective with the single-dose preventive test, significantly delayed diarrhea; reduces the frequency of diarrheal stools and also reduces the purging index. D. guineense administered, after the induction of diarrhea, by castor oil has significantly reduced the diarrhea from 250 mg/kg. Conclusion: The fruit pulp of D. guineense has showed antidiarrheal activities in Wistar rats by reducing the frequency of defecation, the amount of diarrheal fecal matter emitted as well as the water content. It also delayed the onset of diarrhea and significantly reduced the purging index like loperamide.

[Activation of cannabinoid receptor 2 alleviates acute lung injury in rats with lipopolysaccharide-induced sepsis].

OBJECTIVE: To investigate the protective effect of cannabinoid receptor 2 (CB2) activation against acute lung injury in rats with lipopolysaccharide (LPS)-induced sepsis and explore the underlying mechanism. METHODS: Forty-eight SD rats were randomly assigned into control group, model group, CB2 agonist group and P38 MAPK inhibitor group (n=12). In the latter 3 groups, the rats received intraperitoneal injection of LPS to induce sepsis, and the control rats were given saline injection. In CB2 agonist group, JWH133 (3 mg/kg) was injected intraperitoneally 30 min before LPS injection; in P38 MAPK inhibitor group, the rats received intraperitoneal injection of SB203580 (5 mg/kg) 30 min prior to JWH133 injection. The changes in lung histopathology, water content, fluid clearance rate, inflammatory factors, pulmonary expressions of CB2 and tight junctionrelated genes, and phosphorylation of P38 MAPK in the lung tissues were examined. RESULTS: The rat models of sepsis showed severe damage of alveolar structures with significantly decreased fluid clearance rate, lowered pulmonary expressions of CB2, occludin and ZO-1 mRNA and proteins, increased water content in the lung tissue, and increased phosphorylation level of P38 MAPK and TNF-α and IL-1ß levels in lung lavage fluid (all P < 0.05). Treatment with JWH133 improved alveolar pathology in the septic rats, but there was still inflammatory infiltration; lung tissue water content, phosphorylation of P38 MAPK, and TNF-α and IL-1ß levels in lung lavage fluid were all significantly decreased, and the fluid clearance rate, pulmonary expressions of CB2, occludin and ZO-1 were significantly increased (all P < 0.05). Additional treatment with SB203580 resulted in further improvements of alveolar pathologies, lowered phosphorylation levels of P38 MAPK in the lung tissue and TNF-α and IL-1ß levels in lung lavage fluid, and increased the protein expressions of occludin and ZO-1 (P < 0.05) without causing significant changes in mRNA and protein expression of CB2 (P > 0.05). CONCLUSION: In rats with LPS-induced sepsis, activation of CB2 can inhibit the p38 MAPK signaling pathway, reduce the release of inflammatory factors in the lung tissues, promote tight junction protein expressions, and thus offer protection against acute lung injury.