Fusogenic pH sensitive liposomal formulation for rapamycin: Improvement of antiproliferative effect

Context: Liposomes are increasingly employed to deliver chemotherapeutic agents, antisense oligonucleotides, and genes to various therapeutic targets.

Objective: The present investigation evaluates the ability of fusogenic pH-sensitive liposomes of rapamycin in increasing its antiproliferative effect on human breast adenocarcinoma (MCF-7) cell line.

Materials and methods: Cholesterol (Chol) and dipalmitoylphosphatidylcholine (DPPC) (DPPC:Chol, 7:3) were used to prepare conventional rapamycin liposomes by a modified ethanol injection method. Dioleoylphosphatidylethanolamine (DOPE) was used to produce fusogenic and pH-sensitive properties in liposomes simultaneously (DPPC:Chol:DOPE, 7:3:4.2). The prepared liposomes were characterized by their size, zeta potential, encapsulation efficiency percent (EE%), and chemical stability during 6 months. The antiproliferative effects of both types of rapamycin liposomes (10, 25, and 50?nmol/L) with optimized formulations were assessed on MCF-7 cells, as cancerous cells, and human umbilical vein endothelial cells (HUVEC), as healthy cells, employing the diphenyltetrazolium bromide (MTT) assay for 72?h.

Results and discussion: The particle size, zeta potential, and EE% of the liposomes were 165?±?12.3 and 178?±?15.4?nm, ?39.6?±?1.3, and ?41.2?±?2.1?mV as well as 76.9?±?2.6 and 76.9?±?2.6% in conventional and fusogenic pH-sensitive liposomes, respectively. Physicochemical stability results indicated that both liposome types were relatively stable at 4?°C than 25?°C. In vitro antiproliferative evaluation showed that fusogenic pH-sensitive liposomes had better antiproliferative effects on MCF-7 cells compared to the conventional liposomes. Conversely, fusogenic pH-sensitive liposomes had less cytotoxicity on HUVEC cell line.     

Hysteroscopic resection of a symptomatic uterine leiomyoma in an adolescent

Background

Uterine leiomyomas or fibroids are rare in the adolescent population. Hysteroscopic resection is an ideal approach for adolescents with symptomatic intracavitary myomas.

Case

A 17-year-old female had a history of menometrorrhagia and symptomatic anemia, and had been hospitalized twice for acute management of heavy bleeding. On pelvic ultrasound and subsequent MRI, a 2 × 3 cm mass was visualized and appeared to distort the uterine cavity. Due to recurrent heavy bleeding, operative hysteroscopy was performed, and a 3-cm intracavitary mass was identified and resected; pathology evaluation confirmed a leiomyoma.

Summary and Conclusion

Surgical intervention for abnormal bleeding due to a submucosal myoma was more successful than medical treatment. In adolescents, hysteroscopic resection of a symptomatic submucosal myoma is a reasonable minimally invasive management option.     

Acute treatment with metformin improves cardiac function following isoproterenol induced myocardial infarction in rats

BackgroundIt has been proposed that metformin exerts protective effects on ischemic hearts. In the present study, we evaluated the effects of metformin on cardiac function, hemodynamic parameters, and histopathological changes in isoproterenol-induced myocardial infarction (MI).MethodsMale Wistar rats were divided into six groups (n = 6) of control, isoproterenol (100 mg/kg; MI), metformin alone (100 mg/kg; sham), and metformin (25, 50, 100 mg/kg) with isoproterenol. Subsequently, isoproterenol was injected subcutaneously for two consecutive days and metformin was administered orally twice daily for the same period.ResultsIsoproterenol elevated ST-segment and suppressed R-amplitude on ECG. All doses of metformin were found to significantly amend the ECG pattern. Isoproterenol also caused an intensive myocardial necrosis along with a profound decrease in arterial pressure indices, left ventricular contractility (LVdP/dt_max) and relaxation (LVdP/dt_min), and an increase in left ventricular enddiastolic pressure (LVEDP). Histopathological analysis showed a marked attenuation of myocyte necrosis in all metformin treated groups (p < 0.001). Metformin at 50 mg/kg strongly (p < 0.01) increased LVdP/dt_max from 2988 ± 439 (mmHg/s) in the MI group to 4699 ± 332 (mmHg/s). Similarly, treatment with 50 mg/kg of metfromin lowered the elevated LVEDP from 27 ± 8 mmHg in the myocardial infarcted rats to a normal value of 5 ± 1.4 (mmHg; p < 0.01) and the heart to body weight ratio as an index of myocardial edematous from 4.14 ± 0.13 to 3.75 ± 0.08 (p < 0.05).ConclusionThe results of this study demonstrated that a short-term administration of metformin strongly protected the myocardium against isoproterenol-induced infarction, and thereby suggest that patients suffering from myocardial ischemia could benefit from treatment with metformin.     

Seroprevalence of Toxoplasma gondii Infection in Dogs in Tehran,Iran

Background

Toxoplasma gondii infects a wide range of animals; felines are definitive hosts and other animals including the dogs are intermediate hosts. The aim of this study was to determine the seroprevalence of T. gondii infection in dogs in Tehran, capital of Iran and to investigate possible associated risk factors.

Methods

Three hundreds ninety six serum samples were collected during 2007–8 from the dogs. Collected samples were tested using an indirect fluorescent antibody test (IFAT) in dilutions of 1:16 and more. All procedures were carried out in Shahrekord University, Iran. All the data were analyzed using SPSS software, qui square test with confidence interval of 0.95.

Results

From evaluated samples, 89 (22.47%) were positive in titers of at least 1:16. further evaluations in other dilutions showed positive results in dilutions of maximum 1:16, 1:32, 1:64, 1:128 and 1:256 in 38, 29, 15, 2 and 5 dogs respectively. Investigation of the role of risk factors showed no sex predisposition while infection rate was significantly higher in dogs older than one year old. Living places were of significant importance; infection rate was significantly higher in stray or guard dogs in compare with household dogs (P<0.05).

Conclusion

Relatively high seroprevalence of T. gondii infection in dogs in Tehran shows high environmental contamination. It is recommended that the dogs with suspected clinical signs be tested for T. gondii infection.