Zinc Protoporphyrin Polymeric Nanoparticles: Potent Heme Oxygenase Inhibitor for Cancer Therapy

Purpose

Oxidation therapy is an antitumor strategy in which, apoptosis or necrosis is caused by either excess delivery of reactive oxygen species (ROS) as an oxidant or anti-oxidant inhibition. Heme oxygenase (HO) is an anti-oxidant enzyme that plays an important role in cell growth and proliferation. The purpose of this study was to prepare poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with zinc protoporphyrin (ZnPP) to deliver the HO inhibitor into tumor.

Methods

PLGA NPs were prepared using nanoprecipitation technique and their characteristics were optimized by Box-Behnken experimental design. Scanning electron microscopy and in vitro studies consisting of drug release, HO inhibitory effect, cytotoxicity and cellular uptake followed by in vivo biodistribution and blood cytotoxicity were carried out. Internalization of coumerin-6 loaded NPs by PC3 cells was visualized by confocal laser scanning microscopy beside quantitatively analysis.

Results

NPs average size, entrapment efficiency and drug loading were 100.12?±?5.345 nm, 55.6%?±?2.49 and 7.98%?±?0.341 respectively. Equal HO inhibitory effect of NPs compared to free ZnPP was observed. The IC₅₀ value of ZnPP-NPs for PC3 human prostate cancer cells was found to be 2.14?±?0.083 μM.

Conclusion

In conclusion, ZnPP loaded PLGA NPs could exhibit enough HO inhibitory effect against cancer cells to be considered as a promising candidate for cancer treatment investigation.     

Correlation between creatinine clearance and Helicobacter pylori infection eradication with sequential and triple therapeutic regimens: A randomised clinical trial

Background and study aimsUraemic patients show susceptibility to gastrointestinal mucosal lesions and colonisation by Helicobacter pylori (HP). Antibiotic resistance constitutes a problem in treatment and bismuth preparations are toxic in uraemic patients. This study aimed to assess the correlation between creatinine clearance (CrCl) and eradication of HP infection with new sequential and standard triple therapeutic regimens.Patients and methodsA total of 120 HP-positive patients with renal function impairment and 60 control patients with HP infection were enrolled in this study. Patients were divided into four groups on the basis of CrCl and were randomly assigned to one of the two different regimens: A 14-day standard triple therapy with 20 mg omeprazole bid, 1000 mg amoxicillin bid and 500 mg clarithromycin bid and a new sequential regimen with 20 mg omeprazole bid and 1000 mg amoxicillin bid both for 14 days, 500 mg ciprofloxacin bid for the first 7 days and 200 mg furazolidone bid for the last 7 days. Doses of amoxicillin, clarithromycin and ciprofloxacin were reduced to 50% in the cases of CrCl <30 mg dl^?1.ResultsOne hundred and sixty two out of 180 HP-positive patients (54.3% male, 51.6 ± 12.1 years) completed treatment in the four groups and were studied. According to renal function they were classified into group A (n = 39), haemodialysis (HD) patients; group B (n = 37), CrCl <30 mg dl^?1 without HD; group C (n = 36), CrCl between 30 and 60 mg dl^?1; and group D (n = 50), control subjects with CrCl >90 mg dl^?1. HP was successfully eradicated in 77.7% of patients with standard triple therapy and in 81.4% of patients with the sequential therapy. There was no significant difference among the study groups in the rate of HP-infection eradication with both regimens.ConclusionHP eradication rates did not differ with both sequential and standard therapeutic regimens in uraemic and non-uraemic patients. We, therefore, prefer the standard triple therapy due to its simplicity and reported.     

Effects of a Healthy Lifestyle Education on the Incidence of Metabolic Syndrome in Children during a 13-Year Follow-up

Purpose

This study aimed to determine effects of community-based healthy lifestyle education on the incidence of metabolic syndrome (MetS) in Tehranian children considering parental factors during a 13-year follow-up.

Methods

This study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS) on 1603 healthy children, aged 8–18 years, who had complete parental data. Parental factors including MetS, education, age, occupation, and smoking were considered to distinguish parental clusters which could potentially predispose children to MetS. Lifestyle interventions were aimed at achieving healthy dietary patterns and increasing physical activity. Cluster analysis and survival Cox model were used to determine potential low and high risk parental clusters and the effect of intervention on the hazard of MetS in children respectively.

Results

In a model adjusted for children’s age and sex, the hazard of the MetS incidence was 36% higher in children from high-risk parental cluster than those from low-risk parental cluster (HR = 1.36, 95% CI = 1.07–1.73). Moreover, the intervention group showed a 39% lower risk for MetS incidence (HR = 0.61, 95% CI = 0.44–0.85) compared to controls, during the first 6 years after baseline assessment (short term), although the risk lowering effect of the intervention was not maintained long term.

Conclusion

A healthy lifestyle education was successful in reducing the short-term risk of MetS in children. To identify ways of maintaining long-term results, further research is definitely warranted.

Trial Registration

This study was funded by National Research Council and Planning and Management Organization and has been reviewed and approved by the Iranian registry of clinical trials (ISRCTN52588395).

     

Correlation between E-cadherin and CD44 adhesion molecules expression and cervical lymph node metastasis in oral tongue SCC: Predictive significance or not

The aim of this article was to evaluate the expression of E-cadherin and CD44 adhesion molecule in oral tongue squamous cell carcinoma (SCC) since inappropriate expression of adhesion molecules raises the metastatic ability of the tumor cells.Biopsy specimens from 92 patients with tongue SCC were examined for the expression of E-cadherin and CD44 by immunohistochemistry. The relationship of immunoreactivity with tumor stage and cervical lymph node metastasis was then analyzed.Sixty-one patients (66.3%) had reduced or negative staining for CD44. Weak or absent staining for E-cadherin was seen in 14 patients (15.21%). Cervical lymph node metastasis is associated with decreased or negative staining for CD44, but no association was found between E-cadherin immunoreactivity and nodal metastasis.Our study reveals that reduced expression of CD44 could be an indicator of high invasiveness of tumor by increasing cervical lymph node metastasis.     

TP53 gene expression in HPV-positive oral tongue SCC and its correlation with nodal metastasis

In this study, we investigated the prevalence of human papilloma virus (HPV) infection and TP53 expression in patients with squamous cell carcinoma (SCC) of the tongue and, subsequently, its significance in cervical lymph node metastases and tumor differentiation. Sections of formalin-fixed, paraffin-embedded tissue blocks from 94 histologically confirmed tongue SCC cases were investigated in this study. Immunohistochemistry was used to study TP53 expression, and polymerase chain reaction (PCR) was performed for the detection of high risk HPV types (16 and 18). The frequency of HPV-16 and HPV-18 infection was 10.6% and 16%, respectively. Overexpression of TP53 was observed in 70.2% of patients. Young patients (aged below 45 years) comprised 20% of all patients. There was no significant association between TP53, HPV-16, or HPV 18 presence and higher stages of the tumor, tumor differentiation, or presence of nodal metastasis. Although an association between head and neck SCC and HPV infection is being recognized and reported, our data implicate that HPV infection or TP53 expression does not play a significant role in oral tongue SCC pathogenesis, differentiation, or metastasis, as seen in our patients.     

Das Nierenzellkarzinom beim Kind

Renal cell carcinoma (RCC) is a very rare pediatric disease and should be treated as an entity of its own because of differences in symptoms, therapy, and prognosis from the adult form of the disease. Our objective is to discuss the difficulties in clinical diagnosis, prognosis, and therapy of this very rare disease in children and to provide a review of the current literature.     

Diagnostic accuracy of three screening questions (3Q/TMD) in relation to the DC/TMD in a specialized orofacial pain clinic

Objective: To determine the diagnostic accuracy of three screening questions (3Q/TMD) in relation to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD), in a specialized clinic.

Material and methods: Consecutive patients,?>18 years, referred with a possible TMD complaint to the Orofacial Pain and Dysfunction clinic, Academic Centre for Dentistry Amsterdam, the Netherlands, were included in the study. All patients (n?=?449; mean age 44 years; 72% females), answered the 3Q/TMD and the DC/TMD questionnaire before a DC/TMD examination. The 3Q/TMD constitutes of two questions on weekly pain from the jaw, face and temple region (Q1), and on function (Q2), and one function-related question on weekly catching and/or locking of the jaw (Q3). Q1 and Q2 were evaluated in relation to a DC/TMD pain diagnosis and Q3 in relation to a subgroup of DC/TMD intra-articular diagnosis, referred to as the reference standard.

Results: In total, 44% of patients received a pain-related DC/TMD diagnosis and 33% an intra-articular reference DC/TMD diagnosis. Sensitivity for the two pain screening questions was high (0.83–0.94), whereas specificity was low (0.41–0.55). For the function-related question, sensitivity was low (0.48), whereas specificity was high (0.96).

Conclusions: In a specialized pain clinic, the two pain questions (Q1, Q2) are positive in most patients with pain-related TMD. Therefore, in case of a positive response, further diagnostic procedures for TMD pain are warranted. For the functional screening question (Q3), a positive response is indicative for an intra-articular DC/TMD diagnosis, while in case of a negative outcome, an intra-articular TMD might still be present.     

Synthesis of novel N-substituted imidazolecarboxylic acid hydrazides as monoamine oxidase inhibitors

Novel 2-alkylsulfanyl-1-benzyl-5-imidazolecarboxylic acid hydrazides (15a,b) were synthesized as analogues of isocarboxazide, which is a known nonselective irreversible monoamine oxidase inhibitor and tested for monoamine oxidase A and B inhibitory activity. Neither of the compounds showed any inhibition of MAO B activity up to a high concentration of 100 microM. An MAO A activity was only slowly inhibited at this high concentration after prolonged incubation with either compound. This suggests any observed inhibition is not very specific.