Enhanced antitumour activity of doxorubicin and simvastatin combination loaded nanoemulsion treatment against a Swiss albino mouse model of Ehrlich ascites carcinoma

Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX‐SIM‐Solution) or nanoemulsions (NEs) (DOX‐SIM‐NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX‐SIM‐Solution group (265.30) that was double the %ILS of the DOX‐SIM‐NE group (134.70). However, DOX‐SIM‐NE had a non‐toxic effect on the haematological parameters, whereas DOX‐SIM‐Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX‐SIM‐Solution. A reduction in the side effects of DOX‐SIM‐NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX‐SIM‐NE treatment than with the DOX‐SIM‐Solution treatment. The study showed that incorporating SIM into the DOX‐loaded‐NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects.     

奥沙利铂持续腹腔热灌注治疗癌性腹水的临床研究

目的研究奥沙利铂(L-OHP)持续腹腔热灌注治疗癌性腹水的疗效和毒副作用。方法将76例癌性腹水患者随机分为三组:奥沙利铂持续腹腔热灌注化疗组(热化组)26例,引出腹水后,在加热的5%葡萄糖溶液2500～3500ml中加入L-OHP200mg/m2,持续体外循环腹腔热灌注,腹腔内温度保持在41～43℃,持续60min;腹腔内注射奥沙利铂化疗组(单化组)26例,常规腹腔穿刺引流腹水后注射L-OHP200mg/m2。单纯腹腔热灌注组(单热组)24例,加热5%葡萄糖溶液2500～3500ml,持续热灌注60min。结果总有效率(CR PR)54%(41/76)。热化组、单化组和单热组的有效率分别为76.9%(20/26)、50.0%(13/26)、33.3%(8/24),P<0.05。急性腹痛:热化组53.8%(14/26),单热组16.7%(4/24)。单化组无急性腹痛病例,P<0.05。麻痹性肠梗阻:热化组19.2%(5/26),单化组7.7%(2/26),单热组16.7%(4/24),P>0.05。结论奥沙利铂持续腹腔热灌注治疗恶性腹水是一种新的有效的治疗方法,毒副作用不大。     

Management of ascites in cirrhosis

Ascites is one of the earliest and most common complications of patients with cirrhosis. A typical circulatory dysfunction characterized by arterial vasodilation, high cardiac output and stimulation of vasoactive systems is commonly present in these patients and is associated with a poor prognosis. The treatment of ascites has been based on the combination of a low-sodium diet and the administration of diuretics. The reintroduction of paracentesis and the recent introduction of the transjugular intrahepatic portosystemic shunt (TIPS) are the most relevant innovations in the treatment of ascites during the past two decades, although controlled trials in large series of patients are needed to delineate whether TIPS is a safe and useful treatment for these patients.     

Fractionation of a chalone-containing preparation from Ehrlich's ascites tumor by high performance liquid chromatography

Department of Biology, Medico-Biological Faculty, and Applied Research Laboratory of Ecology, Toxicology, and Metabolism of Medicinal Preparations, attached to the Department of Biochemistry, Medico-Biological Faculty, N. I. Pirogov Second Moscow Medical Institute. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 10, pp. 418–419, October, 1991.     

Update on ascites and hepatorenal syndrome

Ascites is the most common complication occurring during liver cirrhosis. Even if a significant decrease in renal clearance may be observed in the first step of chronic active liver disease, renal impairment, at times complicated by the typical signs of hepatorenal syndrome, occurs only in patients with ascites, especially when tense and refractory. Experimental and clinical data seem to suggest a primary sodium and water retention in the pathogenesis of ascites, in the presence of an intrahepatic increase of hydrostatic pressure, which, by itself, physiologically occurs during digestion. Abnormal sodium and water handling leads to plasma volume expansion, followed by decreased peripheral vascular resistance and increased cardiac output. This second step is in agreement with the peripheral arterial vasodilation hypothesis, depicted by an increase in total blood volume, but with a decreased effective arterial blood volume. This discrepancy leads to the activation of the sympathetic nervous and renin-angiotensin-aldosterone systems associated with the progressive activation of the renal autacoid systems, especially, that of the arachidonic acid. During advanced cirrhosis, renal impairment becomes more sustained and renal autacoid vasodilating substances are less available, possibly due to a progressive exhaustion of these systems. At the same time ascites becomes refractory inasmuch as it is no longer responsive to diuretic treatment. Various pathogenetic mechanisms leading to refractory ascites are mentioned. Finally, several treatment approaches to overcome the reduced effectiveness of diuretic therapy are cited. Paracentesis, together with simultaneous administration of human albumin or other plasma expanders is the main common approach to treat refractory ascites and to avoid a further decrease in renal failure. Other effective tools are: administration of terlipressin together with albumin, implantation of the Le Veen shunt, surgical porto-systemic shunting or transjugular intrahepatic portosystemic stent-shunt, or orthotopic liver transplantation, according to the conditions of the individual patient.     

Palliative treatment of malignant ascites by intraperitoneal bleomycin after dialytic ultrafiltration with haemofilter

Dialytic ultrafiltration with haemofilter was performed in 16 patients with malignant ascites refractory to treatment with sodium restriction, diuretic and systemic chemotherapy. A continuous flow of ascitic fluid at a rate of 300–400 ml/min through a haemofilter was maintained by a blood pump. The protein-rich ascitic fluid was re-infused into the peritoneal cavity with sodium and water removed. An average of 5.2 1 of filtrate was removed over a mean interval of 3.5 h. Bleomycin (60 mg) was administered intraperitoneally following the procedure. Complete response was observed in six patients (37.25%) and partial response occurred in four (25%). The remaining patients showed no response. Complications of the dialytic ultrafiltration procedure and toxicity of intraperitoneal administration of bleomycin were minimal. The technique of dialytic ultrafiltration is simple, safe and cost-effective and could be used as an adjuvant therapy for intraperitoneal chemotherapy.     

Pharmacokinetics of famotidine in patients with cirrhosis and ascites

Summary The pharmacokinetics of famotidine has been investigated in ascitic cirrhotic patients. 10 decompensated cirrhotic patients were studied (9 m, 1 f), who had normal renal function, and six healthy control subjects (4 m, 2 f), matched for age, sex and weight. Each subject received on two occasions, at least four days apart, a single oral (40 mg) or intravenous dose (20 mg) of famotidine, at 21.00 h in a randomised manner. Serial blood samples were collected and famotidine in plasma was determined by a HPLC/UV method. Plasma data were subjected to non compartmental pharmacokinetic analysis.There were no statistically significant differences in pharmacokinetic parameters between the two groups after either the intravenous or oral administration of famotidine.The findings suggest that the dose of famotidine may not require any adjustment in ascitic patients without renal failure.     

腹水良恶性细胞核仁组成区定量研究

使用胶质银染色技术，对２８例良性腹水和２６例恶性腹水进行核仁组成区（ＡｇＮＯＲｓ）形态定量研究。结果表明：良性腹水间皮细胞与恶性腹水癌细胞二者在ＡｇＮＯＲｓ数目、形态、大小及核内分布方面均存在显著差异。另外，对５例临床上疑诊恶性腹水而常规脱落细胞学（ＨＥ）染色阴性或未肯定者进行上述定量分析，确定腹水良恶性质，结果与组织病理学诊断相一致。提示该技术在一定程度上可弥补常规脱落细胞形态学之不足。