Evaluation of NMU-Induced Breast Cancer Treated with Sirolimus and Sunitinib on Breast Cancer Growth

Objective: To analyze the effect of sirolimus and sunitinib in blocking the tumor growth and to evaluate the expressions of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2/neu) after treated with sirolimus and sunitinib. Methods: Thirty-two female Sprague Dawley rats at age 21-days old were administered intraperitoneally with N-Methyl-N-Nitroso Urea (NMU), dosed at 70mg/kg body weight. The rats were divided into 4 groups; Group 1 (Control, n=8), Group 2 (Sirolimus, n=8), Group 3 (Sunitinib, n=8) and Group 4 (Sirolimus+Sunitinib, n=8), being treated twice when the tumor reached the size of 14.5±0.5 mm and subsequently sacrificed after 5 days. The protein expressions of ER, PgR and HER2/neu of the tumor tissues were evaluated by using immunohistochemistry analysis. Results: Treatment with sirolimus alone lowered expressions of ER and PgR of breast cancer and reduced tumor size. There was no significant difference of ER and PgR expressions between control and sunitinib treated tumor. Sunitinib treated tumors reduce in diameter after the first treatment, however the diameter increases after the second treatment. Histologically, sunitinib treated tumor did not show any aggressive invasive carcinoma of no special type (NST) histological subtypes. In addition, all NMU-induced tumors are HER2/neu-negative scoring. Conclusion: Sirolimus is neither synergistic nor additive with sunitinib for breast cancer treatment.     

A nutraceutical extract from Inula viscosa leaves: UHPLC-HR-MS/MS based polyphenol profile,and antioxidant and cytotoxic activities

Nowadays, advanced extraction techniques and highly sensitive metabolic profiling methods are effectively employed to get new information on plant chemical constituents. Among them wild medicinal plants or their parts, with large and ancient use in folk medicine, are investigated for their potential functional use and cultivation. In this context, Inula viscosa leaves engaged our attention. A simple experimental design, based on Soxhlet extraction and chromatographic fractionation, allowed us to obtain the investigated polyphenol fraction (IvE). UHPLC-HRMS analyses revealed shikimoyl depsides of caffeic acid and unusual dihydrobenzofuran lignans as main secondary metabolites. These compounds, together with cinchonain-type phenols, and hydroxycinnamoyl flavonol glycosides, are reported for the first time in inula. Overall, forty-three secondary metabolites were identified. The extract exerted a remarkable antiradical activity towards DPPH^? and ABTS^+?. Furthermore, it was able to inhibit cell viability and mitochondrial redox activity of neuroblastoma, hepatoblastoma and colon carcinoma cells, whereas it did not affect cell density of HaCaT cells immortalized human keratinocytes. As detected by the oxidant-sensing probe 2′,7′-dichlorodihydrofluorescein diacetate, the inhibitory responses seemed to be related to IvE-induced increase of intracellular reactive oxygen species (ROS). The obtained results highlighted that inula leaves, nowadays even undervalued and unexplored, could be considered a renewable source of nutraceutical compounds.     

HCV-specific CD27- CD28- memory T cells are depleted in hepatitis C virus and Schistosoma mansoni co-infection

Factors that influence the generation and maintenance of memory CD8+ T cells are not fully understood. The homeostasis of memory T cells is highly dynamic and tightly regulated by various stimuli, including cytokines and antigen-major histocompatibility complex ligands. We characterized the hepatitis C virus (HCV)-specific CD8+ T-cell responses in a cohort of HCV-infected individuals with or without Schistosoma mansoni co-infection from Egypt. We observed a significantly decreased CD27- CD28- (late differentiated) memory T-cell population in the HCV co-infected individuals compared to those with HCV infection alone. In contrast, there was no significant difference in the CD27+ CD28+ (early differentiated) memory T cells between the two groups. Analysis of human cytomegalovirus-specific CD8+ T-cell responses in the same individuals failed to reveal a similar pattern of altered memory T-cell differentiation. Thus, S. mansoni co-infection targets a specific subset of memory CD8+ T cells in HCV infection.     

Rehabilitation in Charles Bonnet syndrome: a review of treatment options

People with vision loss sometimes experience visual hallucinations associated with Charles Bonnet syndrome. The appearance of these hallucinations often causes anxiety for the sufferer and can be difficult for the attending eye care professional to manage. A review of the literature highlighted a range of visual, pharmacological and social management regimes that may alleviate these hallucinations, albeit using small samples in uncontrolled trials. Eye care practitioners should be aware of methods of rehabilitation in Charles Bonnet syndrome that may lead to resolution of the visual hallucinations.     

Tc-99m diethylenetriamine pentaacetic acid (DTPA): Is it reliable for assessment of methotrexate-induced cumulative effect on renal filtration in rheumatoid arthritis patients?

Methotrexate[MTX] is commonly employed as the initial DMARD used for treatment of Rheumatoid arthritis[RA]. We aimed to contribute to the safety profile of MTX by assessing its cumulative effect on renal filtration. Fifty two RA adult females with normal base-line serum creatinine and GFR at the initial diagnosis of the disease were included. Group-1[G1] included 30 patients[mean age 40.4 ± 4.4 years] on MTX and NSAIDS, while 22 RA patients[mean age 38.5 ± 8.2 years] who received NSAIDs only served as the control group[G2]. Renal function was assessed by GFR-measurement using Technetium diethylenetriamine-pentaacetic acid[Tc-99 m-DTPA] at the point of the study time corresponding to disease duration. 21/30[70%] in G1 showed reduced GFR compared to 6/22[27.3%] in G2[P0.007] with 3.3 ± 0.5% annual reduction of GFR. Reduced GFR in G1 showed significant negative correlation with age[r = ?0.396, P = 0.005], MTX-cumulative dose[r = ?0.263, P = 0.049], MTX-intake duration[r = ?0.293, P = 0.031] and NSAID-intake duration[r = ?0.344, P = 0.014]. Low dose MTX has a slow cumulative effect on renal filtration manifested by GFR reduction over time that could be monitored by Tc-99 m DTPA.     

Return to illicit drug use post-incarceration among formerly incarcerated Black Americans

Aims: The number of drug-dependent individuals incarcerated in the USA is exceptionally high, and reportedly up to 60% of incarcerated Black Americans have a substance abuse disorder. The purpose of this study was to identify factors associated with return to illicit drug use post-incarceration.

Methods: A cross-sectional study was conducted with 121 formerly incarcerated Black Americans in New York City to examine predictors of return to illicit drug use. Kaplan–Meier curves were generated on the outcome of time-to-drug use for various predictors and compared using the log-rank test. Cox proportional hazards models were used to identify significant predictors of return to illicit drug use post-incarceration.

Findings: Approximately 83% (n?=?100) of the participants reported a history of illicit drug use, not including participants who have only used marijuana. Out of 121 participants, 36 (29.8%) had used drugs within 1?day after release. By 2 weeks post-release, half had used drugs. Gender and history of heroin use were significant predictors of time-to-drug use according to the log-rank test.

Conclusions: The potential for immediate return to drug use among our sample suggests that discharge support programmes that focus specifically on healthy decision-making among women and heroin users are especially critical.