The effect of sodium valproate on acetic acid-induced colitis in rats

Ulcerative colitis is a chronic recurrent disease with incomplete treatment options. The current article evaluated the effect of sodium valproate on acetic acid-induced ulcerative colitis in rats. Rats were randomly distributed into six groups including Sham group, colitis control group, sodium valproate treatment groups (50, 100 and 300 mg/kg, i.p.) and dexamethasone-treatment group. Dexamethasone was used as a reference drug. Colitis was induced by intracolonic instillation of 2 mL of 3% acetic acid solution. The efficacy of sodium valproate was evaluated by macroscopical and histopathological scoring systems, hematocrit measurement as well as biochemical analysis including myeloperoxidase (MPO) and pro-inflammatory cytokines assessment. Sodium valproate, particularly with doses of 100 and 300 mg/kg significantly improved weight loss, and macroscopic damage, reduced ulcer area, colon weight, microscopic colitis index and elevated hematocrit level. Biochemical experiments showed elevated levels of colonic MPO activity, interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in colitis control group. Treatment with sodium valproate at the doses of 100 and 300 mg/Kg) decreased the MPO activity and colonic concentrations of IL-1β, IL-6 and TNF-α. The results provide evidence that sodium valproate has a protective effect in acetic acid-induced ulcerative colitis which might be due to its anti-inflammatory activities, and it may be useful in patients with ulcerative colitis.     

Comparison among Ocular Response Analyzer, Corvis ST and Goldmann applanation tonometry in healthy children

AIM: To explore the relationship between different parameters of Ocular Response Analyzer (ORA) and Corvis ST (CST) in a sample of healthy Iranian school-aged children and the relationship between parameters of these 2 instruments against intraocular pressure (IOP), measured by the Goldmann applanation tonometer (GAT-IOP), age and gender, and find possible correlation between ORA and CST with GAT. METHODS: This cross-sectional study included 90 healthy children. A general interview and complete eye examination were performed. Following successful GAT-IOP measurement, ORA and CST were conducted. The CST parameters were A 1/2 length (A1L, A2L), A 1/2 velocity (A1V, A2V), highest concavity deformation amplitude (HCDA), radius of curvature (RoC), peak distance (PD), central corneal thickness (CCT) and IOP. The ORA parameters were corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated IOP (IOP-G) and corneal compensated IOP (IOP-CC). Extracted data was analyzed using the Statistical Package for Social Science software. RESULTS: Totally 39 males with age of 9.08±1.60 (6-12)y and 51 females with age of 8.96±1.55 (6-13)y were included. Many CST parameters were significantly correlated with CH, CRF, IOP-G and IOP-CC. Some CST parameters had a significant correlation with GAT-IOP, including IOP-CST in both eyes and HCDA, A2L, PD, and RoC in the left eye, but none with age, except A2L in the right eye. The CRF measurement showed a significant correlation with GAT-IOP in both eyes and CH in the right eye, yet, none with age. Among all CST and ORA parameters, CCT-CST in both eyes and A1L in right eye had a significant correlation with gender, although this was a negligible negative correlation. Comparison of mean IOP values by different devices showed a significantly highest IOP overestimation by CST and lowest by IOP-CC compared with GAT. Also, IOP-G versus IOP-CST significantly had the lowest IOP overestimation among others. Overall, either low positive correlation or negligible correlation was found between IOP measurements by 3 instruments. CONCLUSION: The study finds the highest IOP overestimation by CST and lowest by IOP-CC compared with GAT. Overall, either low positive correlation or negligible correlation is found between IOP measurements by the 3 instruments.     

黄豆提取物的雌激素依赖作用对戊四唑诱发的大鼠癫痫的影响

目的：研究黄豆提取物对经戊四唑（pentylenetrazole,PTZ）诱发癫病发作的女性荷尔蒙缺失雌性大鼠与正常雌性大鼠的不同作用,以及因性别差异引起的植物雌性激素对行为的影响。方法：雄性Wistar大鼠被随机分为雄性生理盐水组,雄性低、中、高剂量黄豆提取物治疗组,每组8只;雌性Wistar大鼠随机分为假手术生理盐水组,假手术低、中、高剂量黄豆提取物治疗组,去卵巢生理盐水组,去卵巢低、中、高剂量黄豆提取物治疗组,每组8只。去卵巢大鼠在氯胺酮麻醉下行卵巢切除术。分别给予各组大鼠生理盐水及不同剂量黄豆提取物治疗2周后腹腔内注射戊四唑。将大鼠放置在树脂玻璃笼内,记录最小阵挛性癫痫发作（minialclonicseizure,MCS）潜伏期和强直性阵挛性癫痫发作（generalizedtonic-clonicseizure,GTCS）潜伏期。结果：与雄性生理盐水组大鼠比较,雄性低、中剂量黄豆提取物治疗组的MSC和GTCS潜伏期显著缩短（P〈10．05或P〈0．01）。雌性假手术大鼠在给予黄豆提取物治疗后,其MSC和GTCS潜伏期没有显著改变。与去卵巢生理盐水组比较,去卵巢低、高剂量黄豆提取物治疗组的MSC和GTCS潜伏期明显缩短（P〈0．05或P〈0．01）。结论：黄豆的植物雌激素能影响由PTZ诱发的癫痫发作的轻重程度,但其影响程度与卵巢激素水平有关。机制还有待进一步研究。     

Altered Integration of Structural Covariance Networks in Young Children With Type 1 Diabetes

Type 1 diabetes mellitus (T1D), one of the most frequent chronic diseases in children, is associated with glucose dysregulation that contributes to an increased risk for neurocognitive deficits. While there is a bulk of evidence regarding neurocognitive deficits in adults with T1D, little is known about how early‐onset T1D affects neural networks in young children. Recent data demonstrated widespread alterations in regional gray matter and white matter associated with T1D in young children. These widespread neuroanatomical changes might impact the organization of large‐scale brain networks. In the present study, we applied graph‐theoretical analysis to test whether the organization of structural covariance networks in the brain for a cohort of young children with T1D (N = 141) is altered compared to healthy controls (HC; N = 69). While the networks in both groups followed a small world organization—an architecture that is simultaneously highly segregated and integrated—the T1D network showed significantly longer path length compared with HC, suggesting reduced global integration of brain networks in young children with T1D. In addition, network robustness analysis revealed that the T1D network model showed more vulnerability to neural insult compared with HC. These results suggest that early‐onset T1D negatively impacts the global organization of structural covariance networks and influences the trajectory of brain development in childhood. This is the first study to examine structural covariance networks in young children with T1D. Improving glycemic control for young children with T1D might help prevent alterations in brain networks in this population. Hum Brain Mapp 37:4034–4046, 2016. © 2016 Wiley Periodicals, Inc .     

Toxicity of thallium on isolated rat liver mitochondria: The role of oxidative stress and MPT pore opening

Thallium(I) is a highly toxic heavy metal; however, up to now, its mechanisms are poorly understood. The authors' previous studies showed that this compound could induce reactive oxygen species (ROS) formation, reduced glutathione (GSH) oxidation, membrane lipid peroxidation, and mitochondrial membrane potential (MMP) collapse in isolated rat hepatocyte. Because the liver is the storage site of thallium, it seems that the liver mitochondria are one of the important targets for hepatotoxicity. In this investigation, the effects of thallium on mitochondria were studied to investigate its mechanisms of toxicity. Mitochondria were isolated from rat liver and incubated with different concentrations of thallium (25–200 µM). Thallium(I)‐treated mitochondria showed a marked elevation in oxidative stress parameters accompanied by MMP collapse when compared with the control group. These results showed that different concentrations of thallium (25–200 µM) induced a significant (P < 0.05) increase in mitochondrial ROS formation, ATP depletion, GSH oxidation, mitochondrial outer membrane rupture, mitochondrial swelling, MMP collapse, and cytochrome c release. In general, these data strongly supported that the thallium(I)‐induced liver toxicity is a result of the disruptive effect of this metal on the mitochondrial respiratory complexes (I, II, and IV), which are the obvious causes of metal‐induced ROS formation and ATP depletion. The latter two events, in turn, trigger cell death signaling via opening of mitochondrial permeability transition pore and cytochrome c expulsion. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 232–241, 2015.     

[3H]2-(2-Benzofuranyl)-2-imidazoline,a highly selective radioligand for I2-imidazoline receptor binding sites Studies in rabbit kidney membranes

2-(2-Benzofuranyl)-2-imidazoline (2-BFI) has recently been characterised as a selective ligand for the I₂-type of imidazoline-receptor binding site(s) (I₂-RBS). The present studies determined the relative levels of specific [³H]2-BFI binding to membrane homogenates of brain and kidney from rat, guinea pig and rabbit and identified the pharmacological characteristics of [³H]2-BFI binding sites in rabbit kidney membranes. Rabbit kidney membranes had the highest relative density of specific [³H]2-BFI binding of all tissues studied (2000?fmol/mg protein). Rabbit brain and guinea pig kidney had moderate levels of specific [³H]2-BFI binding (350–500?fmol/mg protein), while rat kidney and guinea pig and rat brain displayed much lower densities of binding (40–65?fmol/mg protein). Studies of [³H]2-BFI binding kinetics in rabbit kidney homogenates revealed binding to two distinct sites with K _d values of 0.10?±?0.01?nmol/l and 1.00?±?0.36?nmol/l respectively. Equilibrium saturation studies were also consistent with the presence of two binding sites – [³H]2-BFI (0.01–20?nmol/l) bound to sites with affinities of 0.10?± 0.01?nmol/l and 0.92?±?0.13?nmol/l and binding densities of 470?±?80 and 840?±?60?fmol/mg protein (n=3), representing 36 and 64% respectively. Drug inhibition studies revealed that l-adrenaline; α₁-adrenoceptor drugs (prazosin, l-phenylephrine) and α₂-adrenoceptor drugs (rauwolscine, methoxyidazoxan, 2-(2,4-(O-methoxyphenyl)-piperazin-1-yl)-ethyl-4,4-dimethyl-1,3-(2H,4H)-isoquinolindione (ARC-239) had extremely low affinities for [³H]2-BFI binding sites (IC₅₀?≥?10?μmol/l). Putative I₁-RBS compounds, p-aminoclonidine, moxonidine, imidazole-4-acetic acid and cimetidine, inhibited [³H]2-BFI binding to rabbit renal membranes with low to very low affinities (K _i values 3 to ≥100?μmol/l), suggesting [³H]2-BFI does not label I₁-RBS in rabbit kidney membranes. I₂-RBS compounds – 2-(4,5-dihydroimidaz-2-yl)-quinoline (BU224), 2-(4,5-dihydroimidaz-2-yl)-quinoxaline (BU239), idazoxan and cirazoline – potently inhibited [³H]2-BFI binding (K _i values 0.37–1.6?nmol/l), confirming the labelling of I₂-RBS. Inhibition of [³H]2-BFI binding by certain compounds was consistent with their interaction with two binding site populations – for example (drug, K _i values) guanabenz, 0.65?nmol/l and 0.17?μmol/l; naphazoline, 0.94?nmol/l and 2.8?μmol/l; amiloride, 76?nmol/l and 26?μmol/l rilmenidine, 150?nmol/l and 50?μmol/l; and clonidine, 230?nmol/l and 70?μmol/l. The high affinity of amiloride for a high proportion (85%) of the binding is consistent with the presence of the I_2A-subtype of I-RBS in rabbit kidney. These results demonstrate that [³H]2-BFI is a highly selective and high affinity radioligand for I₂-RBS which should be useful for the further characterisation of these sites in mammalian tissues.     

Evolutionary puzzle of Toxoplasma gondii with suicidal ideation and suicide attempts: An updated systematic review and meta‐analysis

The World Health Organization has reported an annual global suicide rate of 14.5 per 100,000 people. On the other hand, it is estimated that approximately one‐third of the global population are infected with Toxoplasma gondii (T. gondii) parasite. It is widely assumed that microbial pathogens, such as T. gondii, are probably associated with affective and behavioural modulation. The present article aimed to assess the proposed role of toxoplasmosis in raising the risk of suicidal ideation (SI) and suicide attempts (SA) using the available epidemiological data. Seven major electronic databases and the Internet search engine Google were searched for all the studies published between the 1st of January 1950 and 31st of October 2019. The heterogeneity and the risk of bias within and across studies were assessed. Following data extraction, pooled odds ratios (ORs) with 95% confidence interval (CI) across studies were calculated using the random‐effects models. A total number of 9,696 articles were screened and 27 studies were regarded as eligible in our systematic review (SI with five papers and 22 papers on SA). A significant association was detected between antibodies against T. gondii with TA (ORs = 1.57; 95% confidence interval [CI] 1.23–2.00, p = .000). Exploration of the association between T. gondii and SA yielded a positive effect of seropositivity for IgG antibodies but not IgM. Despite the limited number of studies, a statistical association was detected between suicidal behaviours and infection with latent T. gondii.