Design and Evaluation of Orally Dispersible Tablets Containing Amlodipine Inclusion Complexes in Hydroxypropyl-β-cyclodextrin and Methyl-β-cyclodextrin

The development of new orally dispersible tablets containing amlodipine (AML) inclusion complexes in hydroxypropyl-β-cyclodextrin (HP-β-CD) and in methyl-β-cyclodextrin (Me-β-CD) was studied. The methods of obtaining amlodipine and the physical and chemical properties of the inclusion complexes using the two cyclodextrins was investigated separately. Solid inclusion complexes were obtained by three methods: kneading, coprecipitation, and lyophilization, at a molar ratio of 1:1. For comparison, a physical mixture in the same molar ratio was prepared. The aim of the complexation process was to improve the drug solubility. As the lyophilization method leads to a complete inclusion of the drug in the guest molecule cavity, for both used cyclodextrins, these types of compounds were selected as active ingredients for the design of orally dispersible tablets. Subsequently, the formulation of the orodispersible tablets containing AML-HP-β-CD and AML-Me-β-CD inclusion complexes and quality parameters of the final formulation were evaluated. The results prove that F1 and F4 formulations, based on silicified microcrystalline cellulose, which contains insignificant proportions of very small or very large particles, had the lowest moisture degree (3.52% for F1 and 4.03% for F4). All of these demonstrate their porous structure, which led to good flowability and compressibility performances. F1 and F4 formulations were found to be better to manufacture orally dispersible tablets.     

Valorization of Grape Pomace and Berries as a New and Sustainable Dietary Supplement: Development,Characterization, and Antioxidant Activity Testing

Grape pomace and berries represent natural sources of phytochemicals that can increase the quality of life of consumers by contributing to the prevention of chronic diseases; thus, the development of a dietary supplement was necessary. The raw material (r.m.) used for the development of the dietary supplement consisted of dried and powdered bilberries (Vaccinium myrtillus L.), red currants (Ribes rubrum L.), and red fermented pomaces (Vitis vinifera L.) from Feteasca Neagra and Cabernet Sauvignon cultivars. The particle size distribution, powder flow, total phenolic content (TPC), HPLC-DAD phenolic profile assessment, and radical scavenging assay (RSA) were employed for the analysis of the raw material. After encapsulation, the average mass and uniformity of mass, the disintegration, and the uniformity of content for the obtained capsules were performed to obtain a high-quality dietary supplement. All the assays performed complied to the compendial requirements and the TPC was determined at 9.07 ± 0.25 mg gallic acid equivalents/g r.m. and RSA at 48.32 ± 0.74%. The highest quantities of phenolic compounds determined were 333.7 ± 0.50 µg/g r.m. for chlorogenic acid, followed by rutin, ferulic acid, and (+)-catechin with 198.9 ± 1.60 µg/g r.m., 179.8 ± 0.90 µg/g r.m. and 118.7 ± 0.75 µg/g r.m., respectively. The results of this study can be used for the manufacturing and assessing of pilot scale-up capsule batches and thinking of quality assurance, we recommend that the industrial batch extracts should be standardized in polyphenols, and the manufacturing process should be validated.     

Prognostic role of the recepteur d'origine nantais (RON) expression in ovarian cancer patients

ObjectiveThe aim of the study was to investigate the potential clinical relevance of immunohistochemically assessed RON expression in a large, single institution series of primary untreated advanced ovarian cancer patients.MethodsImmunohistochemical analysis was performed by using the polyclonal rabbit anti-RON-β antibody (C-20, clone sc-322, Santa Cruz, California). Results were expressed as the total proportion of immunostained tumor cells (RON positivity), or the percentage of cells showing strong staining of RON expression (H-RON positivity).ResultsIn the overall series RON positive immunoreaction was observed in 103/141 cases, while H-Ron positivity was detected in 577141 (40.4%) cases. No association between RON and H-RON expression with response to first-line treatment was documented. During the follow up period, progression and death of disease were observed in 111 (78.7%) and 76 (53.9%) cases, respectively. Cases with strong H-RON expression has a shorter overall survival (median = 35 months) than cases with low RON levels (median = 59 months) (X² = ? 2.1, p value = 0.032). In multivariate analysis, only platinum resistance, and extent of residual tumor retained an independent negative prognostic role for OS, with the percentages of H-RON positively immunostained cells showing a borderline statistical significance (p value = 0.0643). The unfavourable role of elevated percentages of H-RON expression was maintained only in the subgroup of platinum resistant recurrent ovarian cancer patients (X² = 3.89, p value = 0.048) compared to the platinum sensitive ones (X² = 1.98, p value = 0.16).ConclusionsThe assessment of RON expression deserves further attention as a parameter helpful to identify poor prognosis ovarian cancer patients potentially candidates to investigational agents.     

Jugular lymphatic maldevelopment in Turner syndrome and trisomy 21: different anomalies leading to nuchal edema

Increased nuchal translucency (NT), morphologically known as nuchal edema, is an ultrasound marker for aneuploidy. Turner syndrome presents with massive NT, called cystic hygroma. Conflicting data exist as to whether cystic hygroma and increased NT are different entities. Both are associated with jugular lymphatic distension. The authors investigated jugular lymphatics of trisomy 21, Turner syndrome, and normal karyotype fetuses. Fetuses were investigated using immunohistochemistry for blood vascular, lymphatic, and smooth muscle cell markers. Trisomy 21 fetuses showed nuchal cavities within the mesenchymal edema negative for endothelial markers. These were extremely large in Turner fetuses, showing similar characteristics. The skin showed numerous dilated lymphatics in the case of trisomy 21 and scanty small lymphatics in Turner fetuses. A jugular lymphatic sac was present in control and trisomy 21 fetuses and was enlarged in trisomy 21 cases. In Turner fetuses, no jugular lymphatic sac was observed. Nuchal edema in trisomy 21 and Turner syndrome appears to be a similar entity caused by different lymphatic abnormalities.     

Effect of Brazilian copaiba oils on Leishmania amazonensis

Ethnopharmacological relevance

Copaiba oil has been used in folk medicine since the 19th century. The use of copaiba oils to treat leishmaniasis is cited in several ethnopharmacological studies. Nevertheless, the potential antileishmania of copaiba oils had not been studied.

Aim of the study

Eight different kinds of Brazilian copaiba oils were screened for antileishmanial activity.

Materials and methods

The antiproliferative effect of copaiba oil on promastigote and amastigote axenic were determined. To determine the survival index peritoneal macrophage were infected with promastigotes of Leishmania amazonensis and treated with copaiba oil. The cytotoxic effect of copaiba oil was assessed on macrophage strain J774G8 by assay of sulforhodamine B.

Results

Copaiba oils showed variable levels of activity against promastigote forms with IC₅₀ values in the range between 5 and 22 μg/mL. The most active oil was that from Copaifera reticulata (collected in Pará State, Brazil) with IC₅₀ values of 5, 15, and 20 μg/mL for promastigote, axenic amastigote and intracellular amastigote forms, respectively. Amphotericin B showed IC₅₀ of 0.058 and 0.231 μg/mL against promastigote and amastigote forms, respectively. Cytotoxicity assay showed that this copaiba oil obtained from Copaifera reticulata showed low cytotoxicity against J774G8 macrophages.

Conclusion

Copaiba oils showed significant activity against the parasite Leishmania amazonensis.     

Seroprevalence and risk factors associated with herpes simplex virus infection among pregnant women

OBJECTIVES: To estimate the type-specific seroprevalence and identify the risk factors associated with herpes simplex virus (HSV)-2 infection in pregnant women in Bucharest, Romania. METHODS: A prospective survey was conducted in 452 subjects, aged 15-39 years, at the Elias Hospital, during the years 2004-2005. We evaluated serum IgG anti-bodies to HSV-1 and HSV-2 using the HerpeSelect ELISA test. All subjects completed an epidemiological questionnaire. RESULTS: Seroprevalence was 87.3% and 15.1% for HSV-1 and HSV-2, respectively. The risk factors for HSV-2 infection were lower level of education and a greater number of sexual partners. Elementary school and high-school graduates were 6.28 and 2.26 times more exposed than University graduates. Having 2-3 partners and more than three partners was associated with 2.43 and 4.26 times the risk of acquiring HSV-2, compared with having one partner. CONCLUSIONS: In pregnant women, HSV-1 seroprevalence was higher than in Western Europe but similar to that in Eastern Europe. HSV-2 seroprevalence was within European ranges. Both were lower than in the USA. Risk factors for HSV-2 infection may lead to prevention programs.     

Extraosseous vulvar chondroma: a case report

BACKGROUND: Extraosseous chondromas are cartilaginous tissue tumors with a nodular appearance on the hands and feet. There are reports of these tumors occurring on the knee, neck, back, liver and testis and in the oral cavity. Occurrence in the pelvis is generally rare. The origin is metaplastic and may be mesenchymal or subcelomic. Treatment is by surgery and requires removing the tumor with a safety margin. Recurrences are infrequent, and distant metastasis has never been reported. CASE: An 11-year-old girl was referred for a painless solid tumor located on the mons pubis. Surgical removal of the tumor with a safety margin was performed. Macroscopically, the tumor was shiny when cut open and yellowish. Microscopic examination revealed a very distinct cartilage-forming tumor compatible with extraosseous chondroma. Two years after the operation, the patient had no recurrence. CONCLUSION: Extraosseous chondroma is a rare benign tumor. Finding it in children is even less frequent, and localization in the vulvar region has never before been reported. This appears to be the first such report of this type of tumor in this region and age range.     

Efficacy of barriers and hypoxia-inducible factor inhibitors to prevent CO(2) pneumoperitoneum-enhanced adhesions in a laparoscopic mouse model

STUDY OBJECTIVE: To investigate the effects of hypoxia-inducible factor (HIF) inhibitors, flotation agents, barriers, and a surfactant on pneumoperitoneum-enhanced adhesions in a laparoscopic mouse model. DESIGN: Prospective randomized trial (Canadian Task Force classification I). SETTING: Department of Obstetrics and Gynecology, University Hospital Gasthuisberg, Catholic University of Leuven. SUBJECTS: One hundred fourteen female BALB/c mice. INTERVENTIONS: Adhesions were induced during laparoscopy in BALB/c female mice. Pneumoperitoneum was maintained for 60 minutes with humidified CO(2). In 3 experiments the effects of HIF inhibitors such as 17-allylamino 17-demethoxygeldanamycin, radicicol, rapamycin, and wortmanin, flotation agents such as Hyskon and carboxymethylcellulose, barriers such as Hyalobarrier gel and SprayGel, and surfactant such as phospholipids were evaluated. MEASUREMENTS AND MAIN RESULTS: Adhesions were scored after 7 days during laparotomy. Adhesion formation decreased with the administration of wortmannin (p <.01), phospholipids (p <.01), Hyalobarrier Gel (p <.01), and SprayGel (p <.01). CONCLUSIONS: These experiments confirm the efficacy of barriers and phospholipids to separate or lubricate damaged surfaces. They also confirm the role of mesothelial hypoxia in this model by the efficacy of the HIF inhibitor wortmannin.