中药自拟方联合西医治疗慢性阻塞性肺病的疗效和安全性研究

目的 探讨中药自拟方联合西医治疗慢性阻塞性肺病的疗效和安全性.方法 选取80例慢性阻塞性肺疾病患者,随机分为对照组和观察组,对照组给予单纯西医的治疗方式,观察组患者给予中药自拟方联合西医治疗的方式,两组患者治疗开始和2个疗程后肺功能指标、呼吸困难量表、6 min步行的距离和药物不良反应比较.结果 观察组患者的肺功能指标、呼吸困难评价、6 min步行距离差异与治疗前的差异有统计学意义(P＜0.05),两组患者肺功能指标、呼吸困难评价、6 min步行距离,差异有统计学意义(P＜ 0.05);两组患者的药物不良反应,差异无统计学意义(P＞0.05).结论 中药自拟方联合西医治疗慢性阻塞性肺病的疗效要优于单纯西医治疗的方式,两者的安全性无差异,所以值得临床推广.     

中草药库房管理的现状分析及经验探讨

为了探讨和分析中草药库房管理的现状以及经验,在谷歌学术、中国知网、万方医学网等网站以中草药库房管理、现状及经验为关键词进行检索,然后结合本院中草药库房管理的实际经验,对近年来有关中草药库房管理的文献进行分析、总结,探讨和分析中草药库房管理的现状及经验。通过总结分析发现,在入库时对药品的质量进行验收,在储存时控制储存药材的条件,对库房进行微机化管理,能够有效保证中草药的质量和中草药的临床用药安全。加强对中草药库房的质量安全管理,可以保证患者的临床用药安全,更好的服务于临床。     

Subchronic toxicity of Sipjeondaebo-tang (SDT) in Sprague-Dawley rats

Sipjeondaebo-tang (SDT, Juzen-taiho-to in Japanese), a traditional Korean herbal medicine, is used as a supplemental treatment for the adverse effects of chemotherapy, radiation therapy, and surgical treatment. However, limited information is available about the long-term safety of SDT. Therefore, we evaluated the potential adverse effects of SDT in Sprague-Dawley rats over a period of 13-weeks. The SDT was administered once daily by gavage to male and female rats at dose levels of 0, 250, 500, 1000 and 2000 mg/kg/day for 13 weeks. The SDT treatment did not result in any toxicologically significant changes in mortality, clinical signs, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights, histopathology, estrus cycle, serum testosterone levels and sperm analysis. We concluded that the 13-week repeated oral administration of SDT did not cause any adverse effects in rats at dose levels of ≤ 2000 mg/kg/day. Under these experimental conditions, the no-observed-adverse-effect level (NOAEL) was more than 2000 mg/kg/day for both genders. Here, we demonstrated the safety of a 13-week repeated oral dose and considered that it is a safe herbal medicine for human consumption.     

复方蒿甲醚对Beagle犬的长期毒性

给 Beagle犬 po复方蒿甲醚 (蒿甲醚∶本芴醇 1∶ 6,W/W) 1 1 2 ,556,1 0 0 0 mg· kg-1· d-1,每天 1次 ,连服 1 4d.给药结束后 ,各组活杀 2 /3,留 1 /3继续观察 2 8d.观测了临床症状和生理指标 ,血液学 ,血生化 ,尿 ,心电图 ,眼底及病理组织学 .主要毒性反应为 1 0 0 0 mg·kg-1·d-1组给药早期出现网织红细胞降低 ,骨髓红系细胞的中幼红与早幼红比值降低 ,心电图 Q- T间期延长 ,生化检查谷草转氨酶 ,碱性磷酸酶轻度升高 .组织学检查可见肝 ,肾轻度损伤 .所有上述变化停药后均可恢复正常 . 556mg· kg-1· d-1及以下剂量组未见明显毒副作用 ,可视为基本安全剂量 .     

复方蒿甲醚对Beagle犬的长期毒性

给Ｂｅａｇｌｅ犬ｐｏ复方蒿甲醚（蒿甲醚：本芴醇１：６,Ｗ／Ｗ）１１２,５５６,１０００ｍｇ．ｋｇ＾－１．ｋｇ＾－１,ｄ＾－１。第天１次, 取１４ｄ,给药结束后,各级一积少成多样２／３,留１／３继续观察２８ｄ,观测了临床症状和生理指标,血液学,血生化,尿,心电图,眼底及病理组织学,主要毒性反应为１０００ｍｇ．ｋｇ＾－１．ｄ＾－１组给药早期出现网织红细胞降低,心电图Ｑ－Ｔ间期延长,生化检查从中草转氨酶     

Non-clinical safety assessment of Hwangryunhaedok-tang: 13-week toxicity in Crl:CD Sprague Dawley rats

Hwangryunhaedok-tang (Huang-Lian-Jie-Du-Tang in Chinese, Oren-gedoku-to in Japanese) is a traditional herbal medicine with a long history of use for anti-inflammatory purposes. In this study, subchronic toxicity of daily oral administration of a Hwangryunhaedok-tang water extract (HHT) at 0, 250, 750, and 2000 mg/kg for 13 weeks was examined in rats. Mortality, clinical signs, and changes in body weight, food consumption, clinical signs, ophthalmological examination, urinalysis, hematology, serum biochemistry, gross observation, organ weight, and histopathology were monitored in accordance with Good Laboratory Practice and OECD guidelines. We found no mortality or abnormality in clinical signs, body weight, serum biochemistry, or organ weight in HHT-treated groups in either sex. However, there were significant changes in glucose, bilirubin, urobilinogen, protein (only male) in urine after 2000 mg/kg/day HHT treatment for both sexes. In hematological examinations, we found a significant decreased number of red blood cells (RBC), whereas, an increased the mean corpuscular volume, number of platelets, and rate of reticulocyte (RET) after 2000 mg/kg/day HHT treatment of male rats. In male and female rats, 750 and 2000 mg/kg/day HHT treatment decreased the number of RBC and increased RET. Histopathological examinations revealed stomach mucosal erosion in female rats (2000 mg/kg/day). No-observed-adverse-effect levels were established for 750 mg/kg HHT in rats under the conditions of this study. However, other toxicological studies are necessary to evaluate the safety of HHT fully.     

Effects of the Japanese herbal medicine 'Sho-saiko-to' as a cytokine inducer

The herbal medicine, Sho-saiko-to (TJ-9), has been widely prescribed to chronic viral liver disease patients in Japan. This study examined the inductions of such sytokines as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and granulocyte-colony stimulating factor (G-CSF), on some fractions of peripheral blood mononuclear cells (PBMC) by TJ-9 and each of its seven components. IL-1β, TNF-α, and G-CSF were highly induced by scutellaria root and glycyrrhiza root on monocytes/macrophages. By repeating the same experiments using taxol (an LPS antagonist)-treated substances, authors confirmed that these inductions were not attributable to the presence of quite low LPS in TJ-9 solution, and the cytokine inductions are the specific effect of TJ-9. Because TJ-9's macrobiotic effect in liver cirrhosis patients has been proven statistically in an etiological study, TJ-9 could be a new important therapy in chronic liver diseases.     

Dose-dependent emetic effects of the Amaryllidaceous alkaloid lycorine in beagle dogs

Ingestions of plant material from Amaryllidaceae, especially the bulbs of daffodils, are known to be toxic, representing a persistent cause of poisoning in human and animals. Empiric data from case reports suggested, that the alkaloid lycorine could be the toxic constituent of the multi-component mixture responsible for symptoms like nausea and emesis. Systematic studies of the in vivo effects of the amaryllidaceaeous-type alkaloids are not available. Therefore, in an open, prospective, randomized and controlled trial we studied the dose-effect relationship of lycorine-induced nausea and emesis and the toxicokinetics of lycorine in beagle dogs. Subcutaneously administered lycorine-induced nausea and emesis starting at 0.5 mg/kg body weight reaching statistical significance at 1.0 mg/kg. The maximum emetic dose of lycorine (ED₁₀₀) was 2 mg/kg body weight. There was a correlation between dose and nausea score as well as between dose and number of the induced emetic events. Nausea and emesis were short-lasting and occurred not later than 2.5 h post dose. Lycorine showed linear plasma kinetics with a mean elimination half-life of 0.67 and 0.3 h after single s.c. and i.v. administration, compatible with the clinical course of nausea and emesis. The mean oral bioavailability was calculated to be about 40%. Biochemical and haematological parameters of safety showed no pathological signs. The results provide evidence that lycorine can be considered as a main, if not the crucial constituent responsible for nausea and emesis in human and animals in poisoning due to ingestion of plant material of the Amaryllidaceae.     

Herbal Medicines: challenges in the modern world. Part 5. status and current directions of complementary and alternative herbal medicine worldwide

Introduction: Herbal medicine (HM) use is growing worldwide. Single herb preparations, ethnic and modern HM formulations are widely used as adjunct therapies or to improve consumer wellbeing.

Areas covered: This final part in the publication series summarizes common tendencies in HM use as adjunct or alternative medicine, education of healthcare professionals and consumers, current and proposed guidelines regulating of production. We discuss potential HM-HM and HM-drug interactions that could lead to severe adverse events in situations where HMs are taken without proper medical professional oversight.

Expert commentary: A number of serious problems have arisen with the steady global increase in HM use. HM interaction with conventional drugs (CD) may result in inadequate dosing of CD or adverse reactions; HM-HM interaction within herbal supplements could lead to toxicity of formulations. Inadequate education of clinicians and patients regarding medicinal properties of HMs must be addressed regionally and globally to ensure consumer safety.     

Scientific evaluation of the subchronic toxicity of musca domestica larvae extracts in Sprague Dawley rats

Musca domestica larvae extracts (MDLE) is a potential drug used to treat lipopolysaccharide-induced atherosclerosis pro-inflammatory responses. The purpose of the study was to evaluate the safety of MDLE via a 13-week repeated dose subchronic toxicity test in rats. Both male and female Sprague Dawley rats were divided into four groups, eight animals each from the control and high-dose group (33.0 g/kg) were allocated into recovery groups. The four groups of rats were administrated with MDLE (0, 13.2, 22.0, 33.0 g/kg) in the diet for 13 weeks respectively. During the experimental period, the rats were observed for symptoms and signs of gross toxicity daily, food consumption and body weight were measured weekly. Urinalysis, thrombotest, blood biochemical and hematological analyses were performed regularly; Expression of peroxide dismutase gene in liver was quantified and a histopathological examination was also performed. There were no MDLE-induced abnormalities in any of the groups during or after the 13 weeks except the relative weight of liver of high-dose group and middle-dose group was significantly higher than that of control group in male rats (P < 0.05). The results indicate a no observed adverse effect level for MDLE is 13.2 and 33.0 g/kg bw/day in male and female rats, respectively.     

Subchronic toxicity of the new quinolone antibacterial agent irloxacin in beagle dogs

The subchronic oral toxicity of the new quinolone antibacterial agent irloxacin (6-fluorine-7-(pyrrol-1-yl)-1-ethyl-1,4-dihydro-4-oxo-quinolone- 3-carboxylic acid, CAS 91524-15-1) in Beagle dogs was investigated in studies of 4 and 29 weeks of duration. In both studies animals received dosages of 10, 120 and 1400 mg/kg/d. Pale coloured faeces were seen on animals receiving 1400 mg/kg/d. Animals receiving 1400 mg/kg/d for 29 weeks showed an increased incidence of wax in the ears during the latter half of the treatment period, and one male and one female experienced transitory locomotive difficulties at the end of the first week of treatment. The liver was identified as the target organ for toxicity with presence of lipofuscin in the hepatocytes of animals receiving 120 or 1400 mg/kg/d for 29 weeks. Slight increases in liver weights were observed in animals receiving 120 or 1400 mg/kg/d for 4 weeks, and in all groups receiving irloxacin for 29 weeks. However, no histopathological findings were observed in the liver of animals receiving irloxacin for 4 weeks or those receiving 10 mg/kg/d for 29 weeks. Other relevant findings observed in the 29 week study were increased triglyceride, phospholipid and cholesterol levels in males receiving 120 mg/kg/d and animals receiving 1400 mg/kg/d, increased albumin and decreased beta-globulin concentrations in females receiving 1400 mg/kg/d, and prolonged activated partial thromboplastin time in animals receiving 1400 mg/kg/d. On the basis of the results obtained it is concluded that 10 mg/kg/d can be considered as the non-toxic dose after 29 week oral administration of irloxacin in dogs.     

A four-year evaluation of the chronic toxicity of megestrol acetate in dogs.

A 4-year evaluation of the chronic toxicity of megestrol acetate in dogs is reported. .01, .1 or .25 mg of megestrol acetate/kg/day or .25 mg of chlormadinone acetate/kg/day was administered orally for 4 years t o female beagle dogs. The hormone-treated dogs tended to gain more weig ht than did the controls (controls vs. .25 mg megestrol acetate every month after the 3rd p less than .01). All treated dogs revealed decreased evidence of estrus. Mucoid vaginal discharges were more prevalent among the middle and high dose groups. Mean hemoglobin, packed cell volume and total erythrocyte values were slightly decreased while mean total leucocyte count and erythrocyte sedimentation rates were slightly increased in the middle and high dose groups. Clotting me chanism did not reveal any disturbances. Evidence of diabetes consistin g of bilateral cataracts, elevated serum glucose concentrations and glycosuria after 4 years in 2 of 16 high-dose megestrol acetate and in 6 of 15 chlormadinone acetate-treated dogs was revealed. It is concluded that the effects of megestrol acetate were similar but less severe than those of chlormadinone acetate.     

Pharmacokinetics and toxicity of the oxime HGG 12 in dogs

The pharmacokinetics, pharmacodynamics, and toxicity of the oxime HGG 12 were studied in conscious and anesthetized dogs. IV administration. The mean value of the half-time for terminal elimination of HGG 12 was 47 min; plasma clearance amounted to 4.6ml kg^–1 min^–1 and V_app to 0.3151 kg^–1. At doses above 1 umol/kg heart rate, left ventricular pressure and mean arterial pressure decreased, while central venous pressure and femoral blood flow increased. The dose-response curves were very flat. Repetitive administration of various doses of HGG 12 in 30 min intervals did not enhance the negative chronotropic effect when the preceding total dose amounted to about 1 mol/ kg. IM administration. The half-times for the absorption of HGG 12 dichloride and HGG 12 dinitrate were about 3.5 min; the corresponding value for HGG 12 dibromide was 9.4 min. In the elimination phase the half-time was comparable with that of the IV experiments. About 60% of the oxime was excreted unchanged in the urine within 24 h. The circulatory changes showed the same tendency as after IV injection. Conscious dogs tolerated well daily doses of 10 mol/kg for 6 weeks. At 30 umol/kg all dogs survived, displaying symptoms reminiscent of a cholinergic syndrome. Five out of eight dogs survived at 90 mol/ kg. Macroscopic and microscopic examinations and blood chemistry data showed no abnormality.     

天麻细粉片毒性及安全性的实验研究

目的观察天麻细粉片在实验动物中的毒性和安全性。方法急性毒性试验采用昆明种小鼠和SD大鼠各20只,雌雄各半,天麻细粉片剂量为15．0异,kg体重,观察14d,记录中毒表现。Ames试验采用了菌株TA97、TA98、TA100和TA102,在加S9与不加S9的条件下加入天麻细粉片,剂量分别为8、40、200、1000、5000μg／皿。小鼠骨髓细胞微核试验和精子畸变试验均采用昆明种小鼠,天麻细粉片剂量为1．25、2．50、5．00g／kg体重,用环磷酰胺40mg/kg体重为阳性对照。30d喂养试验采用SD大鼠,雌、雄各40只,天麻细粉片剂量为2．81、5．62、11．25g/kg体重,连续给予30d,观察动物一般状况和体重,测定血液学及血液生化学指标、脏器系数。并进行组织病理学检查。结果急性毒性试验结果显示天麻细粉片在小鼠和大鼠中的最大耐受剂量（MTD）均〉15．0g／kg体重,属无毒级。天麻细粉片的Ames试验、小鼠骨髓细胞微核试验和精子畸变试验结果均为阴性。30d喂养试验显示动物一般状况良好,各剂量天麻细粉片对动物的体重、进食量、食物利用率以及脏器重量和脏器系数均无明显影响．对动物的血常规和血清生化指标也无明显影响。病理检查显示高剂量天麻细粉片对动物的肝、肾、胃肠、脾、卵巢（睾丸）等组织无明显毒性。结论本实验条件下天麻细粉片未见明显毒性或致畸和致突变作用。     

Risks and benefits of commonly used herbal medicines in Mexico

In Mexico, local empirical knowledge about medicinal properties of plants is the basis for their use as home remedies. It is generally accepted by many people in Mexico and elsewhere in the world that beneficial medicinal effects can be obtained by ingesting plant products. In this review, we focus on the potential pharmacologic bases for herbal plant efficacy, but we also raise concerns about the safety of these agents, which have not been fully assessed. Although numerous randomized clinical trials of herbal medicines have been published and systematic reviews and meta-analyses of these studies are available, generalizations about the efficacy and safety of herbal medicines are clearly not possible. Recent publications have also highlighted the unintended consequences of herbal product use, including morbidity and mortality. It has been found that many phytochemicals have pharmacokinetic or pharmacodynamic interactions with drugs. The present review is limited to some herbal medicines that are native or cultivated in Mexico and that have significant use. We discuss the cultural uses, phytochemistry, pharmacological, and toxicological properties of the following plant species: nopal (Opuntia ficus), peppermint (Mentha piperita), chaparral (Larrea divaricata), dandlion (Taraxacum officinale), mullein (Verbascum densiflorum), chamomile (Matricaria recutita), nettle or stinging nettle (Urtica dioica), passionflower (Passiflora incarnata), linden flower (Tilia europea), and aloe (Aloe vera). We conclude that our knowledge of the therapeutic benefits and risks of some herbal medicines used in Mexico is still limited and efforts to elucidate them should be intensified.     

胺碘酮治疗慢性心房颤动毒副作用探讨

目的分析胺碘酮在治疗慢性心房颤动时出现的毒副作用、诊断及处理方法。方法回顾性分析45例应用胺碘酮治疗慢性心房颤动引起毒副作用患者的临床表现、X线、CT表现及治疗转归。结果5例出现胃肠不适、恶，心、胸闷、Ⅰ度房宣传导阻滞及皮肤光敏反应。均发生在200mg／d雏持治疗期。经采取积极治疗措施后副作用消失。未停药治疗。有3例出现转氨酶轻度升高，但无明显的临床症状，经减量、对症处理后，复查肝功能恢复正常。2例发现肺毒性．出现干咳症状，经复查X线胸片、呼吸功能检查、肺CT检查而明确诊断。诊断肺间质病变后，立即停用胺碘酮，改为莫雷西嗪，控制心房颤动，同时给予口服阿奇霉素。连续服用3个月，此后随访未出现呼吸系统症状，X线胸片无变化。结论胺碘酮的副作用彤式多样且轻重不一，对于出现的常见副作用经积极对症处理，可不予停药。但肺毒性是胺碘酮的严重毒副作用，典型表现为肺间质纤雏化。定期检查X线胸片并对可艇病例行肺CT检查，有利于早期诊断，早期表现为肺问质增厚。激素治疗有效。预后较好。     

Safety assessment of heated diacylglycerol oil: Subchronic toxicity study in rats

Diacylglycerol oil is an edible oil with similar taste and usability characteristics as conventional edible oil rich in triacylglycerol oil. The objective of the present study was to evaluate potential adverse effects of heated diacylglycerol and triacylglycerol oil in rats following subchronic administration. The heated diacylglycerol and triacylglycerol oils were prepared separately following deep frying potato slices at 180 degrees C for 8h per day for three days. Sprague Dawley rats were fed diets containing different ratios (concentrations) of heated to unheated diacylglycerol oil. The ratio of heated to unheated diacylglycerol was as follows: 0%/5.5% (control-1; Group 1), 1.0%/4.5% (Group 2), 2.75%/2.75% (Group 3), and 5.5%/0% (Group 4). Two additional groups received the feed containing 5.5% of unheated or 5.5% of heated triacylglycerol oil. Compared to the unheated oils, feeding of heated diacylglycerol or triacylglycerol oil did not reveal any toxicologically significant changes in clinical observation, body weights, body weight gains, feed consumption, ophthalmic examinations, functional observational battery and motor activity, clinical pathology evaluations and organ weights. Similarly, terminal necropsy did not reveal treatment-related gross or histopathology findings. Based on the results of this subchronic study, the no-observed-effect levels (NOELs) of heated diacylglycerol or triacylglycerol oil were 5.5%, the highest levels tested. The mean dietary exposure levels at the highest dose for the heated diacylglycerol and triacylglycerol oil for male and female rats ranged from 3,178 to 4,120 mg/kg/day.