A geranyl acetophenone targeting cysteinyl leukotriene synthesis prevents allergic airway inflammation in ovalbumin-sensitized mice

Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The current use of corticosteroids in the management of asthma has recently raised issues regarding safety and lack of responsiveness in 5-10% of asthmatic individuals. The aim of the present study was to investigate the therapeutic effect of a non-steroidal small molecule that has cysteinyl leukotriene (cysLT) inhibitory activity, upon attenuation of allergic lung inflammation in an acute murine model. Mice were sensitized with ovalbumin (OVA) and treated with several intraperitoneal doses (100, 20, 2 and 0.2 mg/kg) of 2,4,6,-trihydroxy-3-geranylacetophenone (tHGA). Bronchoalveolar lavage was performed, blood and lung samples were obtained and respiratory function was measured. OVA sensitization increased pulmonary inflammation and pulmonary allergic inflammation was significantly reduced at doses of 100, 20 and 2 mg/kg with no effect at the lowest dose of 0.2 mg/kg. The beneficial effects in the lung were associated with reduced eosinophilic infiltration and reduced secretion of Th2 cytokines and cysLTs. Peripheral blood reduction of total IgE was also a prominent feature. Treatment with tHGA significantly attenuated altered airway hyperresponsiveness as measured by the enhanced pause (Penh) response to incremental doses of methacholine. These data demonstrate that tHGA, a synthetic non-steroidal small molecule, can prevent acute allergic inflammation. This proof of concept opens further avenues of research and development of tHGA as an additional option to the current armamentarium of anti-asthma therapeutics.     

Prophylactic neuroprotective efficiency of co-administration of Ginkgo biloba and Trifolium pretense against sodium arsenite-induced neurotoxicity and dementia in different regions of brain and spinal cord of rats

The present study was carried out to evaluate the potential protective role of co-administration of Ginkgo biloba, Trifolium pretenseagainst sodium arsenite-induced neurotoxicity in different parts of brain (Cerebral cortex, Hippocampus, striatum and Hind brain) and in the spinal cord of rats. Sodium arsenite caused impairment in the acquisition and learning in all the behavioral tasks and caused significant increase in tumor necrosis factor-α,thiobarbituric acid-reactive substances andlipid profile, while caused significant decrease in glutathione, total thiol content, total antioxidant capacity, acetylcholinesterase, monoamine oxidase and ATPases activities. These results were confirmed by histopathological, fluorescence and scanning electron microscopy examination of different regions of brain. From these results sodium arsenite-induced neurodegenerative disorder in different regions of brain and spinal cord and this could be mediated through modifying the intracellular brain ions homeostasis, cholinergic dysfunction and oxidative damage. The presence of Ginkgo biloba and/orTrifolium pretense with sodium arsenite minimized its neurological damages. It was pronounced that using Ginkgo biloba and Trifolium pretense in combination was more effective as protective agents compared to use eachone of them alone.     

Applicability of rat precision-cut lung slices in evaluating nanomaterial cytotoxicity,apoptosis, oxidative stress,and inflammation

The applicability of rat precision-cut lung slices (PCLuS) in detecting nanomaterial (NM) toxicity to the respiratory tract was investigated evaluating sixteen OECD reference NMs (TiO₂, ZnO, CeO₂, SiO₂, Ag, multi-walled carbon nanotubes (MWCNTs)). Upon 24-hour test substance exposure, the PCLuS system was able to detect early events of NM toxicity: total protein, reduction in mitochondrial activity, caspase-3/-7 activation, glutathione depletion/increase, cytokine induction, and histopathological evaluation. Ion shedding NMS (ZnO and Ag) induced severe tissue destruction detected by the loss of total protein. Two anatase TiO₂ NMs, CeO₂ NMs, and two MWCNT caused significant (determined by trend analysis) cytotoxicity in the WST-1 assay. At non-cytotoxic concentrations, different TiO₂ NMs and one MWCNT increased GSH levels, presumably a defense response to reactive oxygen species, and these substances further induced a variety of cytokines. One of the SiO₂ NMs increased caspase-3/-7 activities at non-cytotoxic levels, and one rutile TiO₂ only induced cytokines. Investigating these effects is, however, not sufficient to predict apical effects found in vivo. Reproducibility of test substance measurements was not fully satisfactory, especially in the GSH and cytokine assays. Effects were frequently observed in negative controls pointing to tissue slice vulnerability even though prepared and handled with utmost care. Comparisons of the effects observed in the PCLuS to in vivo effects reveal some concordances for the metal oxide NMs, but less so for the MWCNT. The highest effective dosages, however, exceeded those reported for rat short-term inhalation studies. To become applicable for NM testing, the PCLuS system requires test protocol optimization.     

快速尿素酶和组织病理学检测幽门螺杆菌的价值分析

分析快速尿素酶与组织病理学检测幽门螺杆菌(HP)的阳性率.2 305例患者行电子胃镜检查,并对其中102例患者应用快速尿素酶试验与组织病理学两项检测方法检测幽门螺杆菌,对两种检测方法所得HP结果进行分析.幽门螺杆菌阳性率在性别、年龄组间无显著性差异,不同疾病组间消化性溃疡患者幽门螺杆菌(HP)检出率较高.102例患者中...     

超声造影表现与肝硬化背景下肝细胞癌组织病理、分化程度及预后的关系分析

目的 探讨超声造影(CEUS)表现与肝硬化背景下肝细胞癌(HCC)组织病理、分化程度及预后的关系.方法 选择2014年1月至2017年1月在恩施州中心医院行根治性切除术的174例肝硬化背景下HCC病人为研究对象.收集病人的一般临床资料及微血管浸润(MVI)、微血管密度(MVD)及增殖细胞核抗原(Ki-67)等病理资料....     

Anti-ischemic effects of nimesulide, a cyclooxygenase-2 inhibitor on the ischemic model of rabbit induced by isoproterenol

The objective was to devise an animal model of myocardial infarction (MI) against which cardioprotective drugs might be tested. We describe the effects of nimesulide, a COX experience with development and validation of such a model. The rabbit was chosen in preference to rodents because its heart and cardiac circulation more closely resemble those of human. Thus, the cardiovascular system of anaesthetized male rabbits, 1 to 1.5 kg (n=11), was stressed by a single bolus intravenous injection of isoprenaline (ISP), 65 mg/kg. The effects of the injection were followed for sixteen days and were evaluated in four ways: 1) measurements of creatinine kinase isozyme and troponin-I (TPI) in serum 2) Electrocardiographic (ECG) changes (ST elevation and Q wave development) 3) Cardiac histopathology observed in tissue sections of the isolated of the heart. The histopathological analysis showed that rabbit heart on 2nd day after ISP injection showed changes of coagulation necrosis. Day 4 total coagulation with the loss of nuclear and striation associated with heavy interstitial infiltrate of neutrophils was found. Day 8 after infarction showed collagen deposition with capillary channels in between the remaining islands of myocytes in the infarcted area. On the 16th day scarring was complete. Coronary perfusion rates (CPR) and heart rate (HR) of the infarcted and nimesulide (a COX-2 inhibitor) treated rabbits displayed significant improvement (n=11) on each corresponding day after infarction as compared to the infarcted and saline treated rabbits (P<0.05). All four indices revealed similarities with effects commonly associated with MI in humans.     

柴油车尾气颗粒物对小鼠胚胎发育不良影响的初步研究

目的 初步探讨柴油车尾气颗粒对胚胎发育的不良影响.方法 从孕鼠妊娠起经腹腔注射从某交通繁华路段收集的柴油车尾气颗粒,按高剂量7.4mg/(kg·d)、低剂量组(4.4/(kg·d)和二甲亚砜对照组进行研究.结果 高剂量组非存活胎鼠发生率(23.8%)和活胎鼠宫内发育迟缓发生率(9.8%)均高于对照组;高低剂量组均出现外...     

In vivo studies on evaluation of potential toxicity of unspent tannins using albino rats (Rattus norvegicus)

The present study emphasizes the effect of unspent tannins on liver, kidney and heart of albino rats. Oral administration of unspent tannins at three different concentrations was made for a period of seven days. Carbon tetrachloride served as positive control. Tissues were removed carefully followed by sacrifice and were subjected to sectioning and H&E staining. Histopathological examination of the sections showed, major tissue damage with the highest concentration of tannins (1500 mg/kg body weight) irrespective of their nature and source, followed by moderate damage with the 1000 mg/kg bw and zero damage with 500 mg/kg bw. However, complete damage was observed with the tissues of positive control group. Lipid peroxidase assay using post-mitochondrial supernatant of liver, kidney and heart showed appreciable levels of malondialdehyde release at higher concentrations of tannins.     

Tubulointerstitial damage as the major pathological lesion in endemic chronic kidney disease among farmers in North Central Province of Sri Lanka

Chronic kidney disease of uncertain etiology (CKDu) in North Central Province of Sri Lanka has become a key public health concern in the agricultural sector due to the dramatic rise in its prevalence and mortality among young farmers. Although cadmium has been suspected as a causative pathogen, there have been controversies. To date, the pathological characteristics of the disease have not been reported. Histopathological observations of 64 renal biopsies obtained at Anuradhapura General Hospital from October 2008 to July 2009 were scored according to Banff 97 Working Classification of Renal Allograft pathology. The correlations between the histological observations and clinical parameters were statistically analyzed. Interstitial fibrosis and tubular atrophy with or without nonspecific interstitial mononuclear cell infiltration was the dominant histopathological observation. Glomerular sclerosis, glomerular collapse, and features of vascular pathology such as fibrous intimal thickening and arteriolar hyalinosis were also common. Although hypertension was identified as one of the common clinical features among the cases, it did not influence the histopathological lesions in all the cases. This study concludes that tubulointerstitial damage is the major pathological lesion in CKDu. Exposure(s) to an environmental pathogen(s) should be systematically investigated to elucidate such tubulointerstitial damage in CKDu.     

肺胚母细胞瘤6例免疫组化及病理分析

目的探讨肺胚母细胞瘤的临床病理特点及组织发生。方法对6例肺胚母细胞瘤进行光学显微镜检查及免疫组化、单克隆抗体分析。结果镜下示6例均以间叶细胞和上皮细胞为主,核分裂像较多,免疫组化示CK(+)、EMA(+)、鼠抗波形纤维蛋白单克隆抗体(+)。结论6例均为发生于肺中胚层细胞的恶性肿瘤,其病理特征均为双向性肉瘤样癌。应用免疫组化和单克隆抗体为6例疑难疾病的诊断提供了可靠的依据。随访病人均生存1年以上。