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.     

Refractory Ascites After Liver Transplantation: An Analysis of 1058 Liver Transplant Patients at a Single Center

A retrospective study of 1058 liver transplant recipients was performed to determine: (i) the incidence, etiology, timing, clinical features and treatment of refractory ascites (RA), (ii) risk factors for RA development, (iii) predictors of RA disappearance, (iv) predictors of survival following RA and (v) the impact of RA on patient survival. Sixty-two patients (5.9%) developed RA and its disappearance occurred in 27/62 cases. Patients having hepatitis C virus (HCV) had a significantly higher hazard rate of developing RA (p < 0.00001). No other baseline characteristic was associated with RA. Cox stepwise regression analysis of the hazard rate of RA disappearance found two significant factors: HCV recurrence as the reason for developing RA implied a poorer outcome (p = 0.006), whereas an unknown reason implied a favorable outcome (p = 0.02). In addition, survival following RA was significantly poorer among patients having bacterial peritonitis or HCV recurrence. Finally, the mortality rate was significantly (nearly 8.6 times) higher in patients following RA development while it was ongoing (p < 0.00001); however, if the RA disappeared, then the additional risk of death also disappeared. This study illustrates the importance of developing an optimal treatment strategy to (i) effectively treat RA if it develops and (ii) prevent hepatitis C recurrence.     

苦碟子抗肿瘤作用的实验性研究

目的 研究苦碟子对动物移植性肿瘤的作用。方法 以小鼠移植性肉瘤180（S180)和艾氏腹水瘤（EAC）为模型，观察苦碟子的抗肿瘤作用，并分别计算出抑瘤率和生命延长率。结果 不同剂量的苦碟子对小鼠肉瘤S180的抑制率分别为39．86％，38．14％和35．73％（与对照组相比差异有显著性，P＜0．01），苦碟子也能延长荷艾氏腹水瘤（EAC）小鼠的存活期，生命的延长率分别为41．27％、29．79％和17．88％（高剂量组和中等剂量组与对照组相比差异有显著性，P＜0．01）。结论 苦碟子在动物体内可能具有抗肿瘤作用，可作为一种有前途的抗肿瘤药物进行研究。     

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。     

腹腔镜检查对不明原因腹水的诊断价值

①目的 探讨腹腔镜检查对不明原因腹水的诊断价值。②方法 我科于2001年7月～2002年12月利用腹腔镜技术对14例顽固性腹水病人进行探查。③结果 14例病人均通过腹腔镜检查明确诊断，其中癌性腹膜炎腹水占64．3％(9／14)，结核性腹膜炎腹水占21．4％(3／14)，肝硬化腹水占14．3％(2／14)。所有病人术后均恢复顺利，无并发症发生。④结论 腹腔镜检查对不明原因的顽固性腹水是一种安全、准确的诊断方法。     

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.     

Optic chiasm glioma associated with inappropriate secretion of antidiuretic hormone,cerebral ischemia,nonobstructive hydrocephalus and chronic ascites following ventriculoperitoneal shunting

An optic chiasm glioma may cause loss of vision, endocrine disturbances, hydrocephalus and cerebral ischemia due to its proximity to the pituitary, hypothalamus, III ventricle and internal carotids. A 3-month-old infant with optic chiasm glioma developed hypopituitarism and inappropriate secretion of antidiuretic hormone with plasma hypo-osmolality. The cerebrospinal fluid (CSF) protein concentration was markedly elevated. The impairment of fluid absorption via arachnoid villi and peritoneum by the high protein content, and reversed osmotic gradient between protein-rich CSF and hypo-osmolar plasma may have contributed to both nonobstructive hydrocephalus and recurrent ascites following ventriculoperitoneal shunting. Cerebral ischemia from carotid compression may have led to cerebral atrophy.