甘草酸对四氯化碳致小鼠肝纤维化及骨丢失的防治作用

目的　研究甘草酸对肝纤维化小鼠骨丢失的防治作用。方法　用体积分数为 4 0 %的CCl4花生油皮sc 5wk致小鼠肝纤维化 ,观察与肝损伤相关的各种生化指标和肝脏病理切片结果以及测定小鼠右股骨的骨Ca2 + 量和其他骨微量元素以及骨羟脯胺酸的含量。结果　单用CCl4小鼠呈现典型的慢性肝损伤后肝纤维化的改变 ,骨重量和骨钙总量及骨羟脯胺酸的含量减少 (P <0 0 5 ) ,而甘草酸治疗组有明显的护肝及对抗骨丢失作用。结论　甘草酸在所用的剂量下对肝纤维化及骨丢失有一定预防作用     

人参须对四氯化碳致小鼠肝纤维化的保护作用

目的：观察人参须对四氯化碳致小鼠肝纤维化的影响。方法：运用皮下多次注射四氯化碳(CCl4)致小鼠慢性肝损伤模型，观察人参须对小鼠肝组织病理变化、血清丙氨酸氨基转移酶(ALT／GPT)、天冬氨酸氨基转移酶(AST／GOT)、总蛋白(TP)、白蛋白(Alb)和白蛋白／球蛋白(A／G)的比值以及内脏器官重量的影响。结果：人参须能够显著降低由CCl4引起的肝、脾重量增加及血清ALT、TP的升高，明显减轻CCl4引起的肝坏死病变，与秋水仙碱无差别。结论：人参须对四氯化碳致小鼠肝纤维化有保护作用。     

小鼠肝硬化导致骨丢失及人参茎叶皂苷的防治作用

目的　探讨肝硬化与骨质疏松的关系并观察人参茎叶皂苷对肝硬化导致的骨丢失的防治作用。方法用CCl₄致小鼠肝纤维化,观察与肝损伤相关的各种指标及测定股骨的骨Ca²⁺量和其他矿物质含量。结果　单用CCl₄小鼠呈现典型的慢性肝损伤后肝硬化的改变,骨重量和骨钙总量明显减少,而骨铜和骨镁显著增高。而人参茎叶皂苷防治组有明显的护肝及对抗骨丢失作用。结论　人参茎叶皂苷在所用的剂量下对肝硬化及骨丢失有一定预防作用     

护肝降酶口服液对四氯化碳所致小鼠慢性肝损伤的保护作用

目的:观察护肝降酶口服液(Hugan Jiangmei oral medicinal liquid,HGJM)对四氯化碳(CCl4)所致小鼠慢性肝损伤的保护作用。方法:以CCl4诱发小鼠慢性肝纤维化模型,采用灌胃法给予HGJM,测定小鼠血清丙氨酸氨基转移酶(ALT)、天门冬酸氨基转移酶(AST)及肝组织病理改变。结果:HGJM在给药8周后,显著降低血清ALT和AST水平,减轻了肝脏的病理损伤。结论:HGJM对CCl4致小鼠的慢性肝损伤有一定的肝保护作用。     

罗汉果甜苷对小鼠实验性肝损伤保护作用的研究

目的:研究罗汉果甜苷(Mog)对实验性肝损伤小鼠的保护作用。方法:以四氯化碳诱导小鼠急性肝损伤;以卡介苗(BCG)加脂多糖(LPS)诱导小鼠免疫性肝损伤。检测血清中谷丙胺酸氨基转移酶(ALT)、谷草胺酸氨基转移酶(AST)的活性;检测肝组织中超氧化物歧化酶(SOD)的活性和丙二醛(MDA)的含量;并进行病理学检查。结果:Mog小鼠对急性、免疫性肝损伤,有降低血清中ALT、AST活性的作用;对免疫性肝损伤的肝组织匀浆有升高SOD活性、降低MDA含量的作用;并能显著减轻肝组织病理变化程度。结论:Mog对小鼠急性肝损伤、免疫性肝损伤有保护作用,其机制可能与Mog的抗脂质过氧化作用有关。     

肝乐宁粉针剂对实验性肝损伤的保护作用

研究肝乐宁粉针剂对实验性肝损伤的保护作用。方法：采用四氯化碳致小鼠和大鼠肝脏损伤,测定生化指标及观察病理组织学改变。结果：肝乐宁粉针剂能显著降低四氯化碳引起的急性肝损伤小鼠和慢性肝损伤大鼠血清丙氨酸氨基转换酶和天门冬氨酸氨基转换酶增高;亦能明显降低大鼠血清唾液酸和肝羟脯氨酸含量,升高血清总蛋白和白蛋白水平;病理组织学检查肝乐宁粉针剂明显减轻肝细胞的变性和坏死,并抑制慢性肝损伤胶原纤维形成。结论：肝乐宁粉针剂具有肝细胞保护及抗肝纤维化作用。     

五灵胶囊对实验性肝硬化大鼠的影响

目的 :观察五灵胶囊对大鼠肝纤维化的作用及其机制。方法 :采用以四氯化碳 (CCl4)为主的复合因素致大鼠肝纤维化 ,化学法测定血清羟脯酸 (HYP)含量 ,放免法测定血清与肝匀浆I型前胶原 (PCI)和Ⅲ型前胶原 (PCⅢ )水平 ,免疫组化法检测肝组织肿瘤坏死因子 (TNF)、纤维结合蛋白 (FN )的表达。同时 ,体外培养成纤维细胞 ,观察五灵胶囊对其的抑制作用。结果 :五灵胶囊能显著降低肝纤维化大鼠血清PCI、PCⅢ和肝匀浆HYP、PCI。五灵胶囊组大鼠肝FN表达量明显少于模型组。体外实验表明 ,五灵胶囊可抑制成纤维细胞的生长。结论 :五灵胶囊确有抗肝纤维化作用     

川芎嗪关节内注射对骨关节炎软骨基质内胶原蛋白含量变化的实验研究

目的观察川芎嗪关节内注射对骨关节炎软骨基质内胶原蛋白含量变化的影响,探讨其对关节软骨基质代谢的作用及对骨关节炎的防治作用。方法①建立兔膝骨关节炎模型,并用X片论证造模是否成功。②将造模后的兔子随机分成对照组(n=12)和治疗组(n=12),分别予生理盐水和川芎嗪关节内注射治疗;治疗后4、8、12周各处死4只兔子取膝关节软骨,测定软骨中羟脯氨酸含量。结果①造模后12周,X片见兔右膝关节关节间隙不对称、软骨下硬化,但无明显骨质增生表现,属于OA早期表现。②治疗组的羟脯胺酸的含量随治疗的延长而增加,对照组羟脯胺酸的含量随时间的延长而减少;且两组间各个时期羟脯胺酸的含量相比,具有显著差异(P<0.05)。结论说明川芎嗪关节内注射具有促进软骨基质胶原蛋白生长,抑制关节退变的作用。     

柴胡乳剂对急性化学性肝损伤的保护作用

目的研究中药柴胡乳剂对急性化学性肝损伤的保护作用。方法经预防给药7 d后,采用四氯化碳(CCl4)、扑热息痛两种肝毒剂复制小鼠急性肝损伤模型,采用四氯化碳复制大鼠急性肝损伤模型,16 h后眼眶取血,测定大鼠、小鼠血清中丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)含量及血清蛋白的变化,观察柴胡乳剂对四氯化碳、扑热息痛所致小鼠及大鼠急性化学性肝损伤的保护作用。结果柴胡乳剂大、中剂量组均能明显降低四氯化碳、扑热息痛所致急性肝损伤后小鼠血清ALT、AST含量(P<0.01);柴胡乳剂大剂量组能明显降低四氯化碳所致急性肝损伤大鼠血清ALT、AST(P<0.05)含量,增加血清白蛋白(Alb)含量(P<0.05),改善肝功能。结论柴胡乳剂对四氯化碳、扑热息痛所致化学性急性肝损伤有一定的保护作用。     

注射用鲨鱼肝再生因子对小鼠急性化学性肝损伤的影响

观察鲨鱼肝再生因子(sHRF)对小鼠急性化学性肝损伤的影响。采用化学药物引起小鼠急性肝损伤，测定血清中ALT、AST的含量以及对肝组织进行病理组织学检查。sHRF能显著降低四氯化碳、硫代乙酰胺及D-半乳糖胺所致的急性肝损伤小鼠血清中ALT、AST含量的升高；减轻对肝脏细胞的病理性损伤。实验表明sHRF对小鼠急性化学性肝损伤有保护作用。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.