Mefloquine loaded niosomes as a promising approach for the treatment of acute and chronic toxoplasmosis.

Toxoplasmosis is a disease with a worldwide distribution and significant morbidity and mortality. In search of effective treatment, mefloquine (MQ) was repurposed and loaded with niosomes to treat acute and chronic phases of toxoplasmosis in experimental mice. Mice were orally inoculated with 20 cysts of Toxoplasma gondii (ME 49 strain) for the acute model of infection and 10 cysts for the chronic model of infection. Infected mice were dosed with MQ solution or MQ-niosomes at 50 mg/kg/day, starting from the second day post-infection (PI) (acute model) or the fifth week PI (chronic model), and this was continued for six consecutive days. The effects of MQ solution and MQ-niosomes were compared with a pyrimethamine/sulfadiazine (PYR/SDZ) dosing combination as mortality rates, brain cyst number, inflammatory score, and immunohistochemical studies that included an estimation of apoptotic cells (TUNEL assays). In the acute infection model, MQ solution and MQ-niosomes significantly reduced the mortality rate from 45% to 25 and 10%, respectively, compared with infected untreated controls, and decreased the number of brain cysts by 51.5% and 66.9%, respectively. In the chronic infection model, cyst reduction reached 80.9% and 12.3% for MQ solution and MQ-niosomes treatments, respectively. MQ-niosomes significantly decreased inflammation induced by acute or chronic T. gondii infection. Additionally, immunohistochemical analysis revealed that MQ solution and MQ-niosomes significantly increased the number of TUNEL-positive cells in brain tissue, indicative of induction of apoptosis. Collectively, these results indicate that MQ-niosomes may provide a useful delivery strategy to treat both acute and chronic toxoplasmosis.

Evaluation of the efficacy and safety of platelet rich plasma injection in treatment of rosacea.

Rosacea is a chronic relapsing inflammatory skin disease, with a high prevalence among adults. Treatment of rosacea is difficult, with high rate of recurrence. Due to the strong anti- inflammatory and antibacterial effects of platelet rich plasma (PRP), it was used in the medicine for treating many inflammatory diseases. To evaluate the role of PRP injection in treatment of rosacea. The study was carried on 40 patients with rosacea. They were treated by PRP injection in right side of the face (group A) and platelet poor plasma injection in left side (group B). They underwent one session every 2 weeks for 3 months (6 sessions). The patients were assessed clinically before and after treatment by the rosacea grading scale. Skin biopsies were taken to evaluate the clinical results. There was a statistically significant decrease in rosacea grading scale after treatment with PRP injection, 50% of the patients showed excellent improvement and 50% showed good improvement. The improvement was significantly better in group A than B. There was marked decrease in inflammatory cells by hematoxylin and eosin stain, and decrease in expression of nuclear factor kappa ßeta after treatment with PRP. PRP was effective and safe technique in treatment of rosacea and alternative to other systemic modalities, especially if they are contraindicated.

Immunohistochemical and morphometrical evaluation of well-differentiated thyroid tumor of uncertain malignant potential.

CONTEXT: Well-differentiated tumor of uncertain malignant potential (WDT-UMP) were encapsulated follicular pattern tumors with diffuse equivocal or focal unequivocal papillary thyroid carcinoma (PTC) type nuclear changes without definite invasion. These tumors are suggested to be borderline in its nature. Immunohistochemistry by CD56, P63, and CK19 are common markers used in differentiation between benign and malignant thyroid tumor. Computerized nuclear morphometry is an inexpensive objective and reproducible tool to evaluate histological features of thyroid tumors. AIMS: To categorize WDT-UMP using combined nuclear morphometry and immunohistochemistry of CD56, P63, and CK19. SUBJECTS AND METHODS: We used CD56, P63, and CK19 immunostaining and mean nuclear area and perimeter morphometry on 20 cases of WDT-UMP, 25 cases malignant thyroid tumors, and 25 cases benign thyroid lesions. STATISTICAL ANALYSIS USED: Student's t-test (Unpaired), analysis of variance (ANOVA) test, and Chi-square tests by SPSS V. 20. RESULTS: Significant differences were obtained between WDT-UMP and benign group according to the three markers, but no significant difference between WDT-UMP and malignant group. The mean nuclear area and mean nuclear perimeter were significantly higher in WDT-UMP group in comparison with the benign group while there were no significant differences with the malignant group. CONCLUSION: WDT-UMP are intermediate lesions differing from benign lesions of the thyroid and sharing some criteria with PTC to a certain extent.

Significance of Tissue Expression and Serum Levels of Angiopoietin-like Protein 4 in Breast Cancer Progression: Link to NF-κB /P65 Activity and Pro-Inflammatory Cytokines.

BACKGROUND: The molecular mechanisms linking breast cancer progression and inflammation still remain obscure. The aim of the present study was to investigate the possible association of angiopoeitin like protein 4 (ANGPTL4) and its regulatory factor, hypoxia inducible factor-1 α (HIF-1α), with the inflammatory markers nuclear factor kappa B/p65 (NF-κB /P65) and interleukin-1 beta (IL-1ß) in order to evaluate their role in inflammation associated breast cancer progression. MATERIALS AND METHODS: Angiopoietin-like protein 4 (ANGPTL4) mRNA expressions were evaluated using quantitative real time PCR and its protein expression by immunohistochemistry. DNA binding activity of NF-κB /P65 was evaluated by transcription factor binding immunoassay. Serum levels of ANGPTL4, HIF-1α and IL-1ß were immunoassayed. Tumor clinico-pathological features were investigated. RESULTS: ANGPTL4 mRNA expressions and serum levels were significantly higher in high grade breast carcinoma (1.47±0.31 and 184.98±18.18, respectively) compared to low grade carcinoma (1.21±0.32 and 171.76±7.58, respectively) and controls (0.70±0.02 and 65.34±6.41, respectively), (p<0.05). Also, ANGPTL4 high/moderate protein expression was positively correlated with tumor clinico-pathological features. In addition, serum levels of HIF-1α and IL-1ß as well as NF-κB /P65 DNA binding activity were significantly higher in high grade breast carcinoma (148.54±14.20, 0.79±0.03 and 247.13±44.35 respectively) than their values in low grade carcinoma ( 139.14±5.83, 0.34±0.02 and 184.23±37.75, respectively) and controls (33.95±3.11, 0.11±0.02 and 7.83±0.92, respectively), (p<0.001). CONCLUSION: ANGPTL4 high serum levels and tissue expressions in advanced grade breast cancer, in addition to its positive correlation with tumor clinico-pathological features and HIF-1α could highlight its role as one of the signaling factors involved in breast cancer progression. Moreover, novel correlations were found between ANGPTL4 and the inflammatory markers, IL-1ß and NF-κB/p65, in breast cancer, which may emphasize the utility of these markers as potential tools for understanding interactions for axes of carcinogenesis and inflammation contributed for cancer progression. It is thus hoped that the findings reported here would assist in the development of new breast cancer management strategies that would promote patients' quality of life and ultimately improve clinical outcomes. However, large-scale studies are needed to verify these results.

Toxocara-induced hepatic inflammation: immunohistochemical characterization of lymphocyte subpopulations and Bcl-2 expression.

Toxocariasis is a soil-transmitted helminthic disease due to infection of humans by larvae of Toxocara canis (T. canis). It is one of the most commonly reported zoonotic infections in the world. The aim of this study was to characterize the key immune cells and activity of Bcl-2 in hepatic inflammation during the course of experimental infection by T. canis. Mice experimentally infected with T. canis were divided into two groups: mice with primary infection by Toxocara, and those infected after sensitization by Toxocara excretory-secretory antigen. CD4+, CD8+, and Bcl-2-expressing T lymphocytes were identified in the liver by immunohistochemistry at different durations post-infection. Recruitment of both CD4+ and CD8+ T lymphocytes within the inflammatory reaction in the liver was observed, with difference in count and localization. These cells were detected within and around Toxocara-induced granulomas as well as in isolated inflammatory foci in the portal tracts or within the hepatic parenchyma. The antiapoptotic protein Bcl-2 showed no significant change at different periods post-infection. On the other hand, immunization of mice with Toxocara excretory-secretory antigen prior to experimental infection caused earlier and more pronounced recruitment of CD4+ and CD8+ T cells to the liver and enhanced expression of Bcl-2. Moreover, CD8+ cells became more diffuse within the inflammatory infiltrate. These results suggest a dynamic change in key immune cells according to the duration of infection as well as the immune status of the host.