Effect of low-protein diet on anthracycline pharmacokinetics and cardiotoxicity

Objectives Anthracyclines are broad spectrum anticancer drugs with dose‐dependent cardiotoxicity. Protein malnutrition commonly occurs in cancer patients and is considered a risk factor for development of cardiotoxicity. This study was designed to assess the modulatory effect of protein malnutrition on the pharmacokinetics and drug disposition properties of a single dose of doxorubicin and epirubicin and how these possible changes will affect the degree of cardiotoxicity of these drugs. Methods A single interperitoneal dose of 15 mg/kg of either doxorubicin or epirubicin was injected into rats fed with either normal protein diet or low‐protein diet. The plasma concentration–time profiles of doxorubicin and epirubicin and their concentrations in different tissues were determined. Serum creatine kinase level was determined at different time intervals and histopathological examination of heart tissue was carried out. Key findings Protein malnutrition significantly altered the pharmacokinetics of doxorubicin and epirubicin, with a significant decrease in their elimination, and prolonged the exposure of the heart to these drugs. Histopathological examination and serum creatine kinase measurements supported the role of protein malnutrition in enhancement of anthracycline cardiotoxicity. Conclusions If similar alteration in anthracyclines' pharmacokinetics occurs in malnourished cancer patients, protein malnutrition will be a risk factor for development of anthracycline cardiotoxicity and dose adjustment will be required in nutritionally deprived patients.     

Biochemical and ultrasound parameters may help predict the need for therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in patients with a firm clinical and biochemical suspicion for choledocholithiasis

Background

Prediction of the need for therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in patients with suspected choledocholithiasis (CDL) remains a challenging task.

Aims

We aimed to evaluate the predictive value of biochemical and ultrasound parameters and to create a corresponding model for prediction of the need for therapeutic ERCP.

Methods

203 consecutive patients referred to our center due to a firm clinical and/or biochemical suspicion for CDL. All patients underwent ERCP. Biochemical and ultrasound variables were analyzed.

Results

The sample was divided into testing group (103; 50.7%) and validation group (100; 49.3%) which did not differ in their baseline characteristics. Elevated gamma glutamil transaminase (GGT), common bile duct (CBD) diameter and presence of hyperechoic structures in CBD were found to be significant predictors for presence of CBD stones on ERCP (p < 0.05) in the testing group. We used these variables to construct a predictive model for the presence of CBD stones on ERCP. The model was tested on a second, validation group of patients using ROC analysis with the area under the ROC curve of 0.81 (%95 CI = 0.75-0.86; p < 0.001). We identified a threshold (0.86) above which, patients had a high probability (93.1%) for the need for interventional ERCP.

Conclusion

Our predictive model may help predict the need for therapeutic ERCP in patients with a suspicion for choledocholithiasis.     

Non-invasive predictive score of fibrosis stages in chronic hepatitis C patients based on epithelial membrane antigen in the blood in combination with routine laboratory markers

Aim: The epithelial membrane antigen (EMA) could detect small deposits of liver malignant cells. However, no information exists regarding the use of EMA in patients with chronic hepatitis C (CHC). Therefore, we attempted to evaluate the diagnostic performance of EMA to distinguish patients with different liver fibrosis stages. Methods: Epithelial membrane antigen was identified in sera of 154 CHC patients using Western blot and enzyme linked immunosorbent assay (ELISA). Multivariate discriminant analysis (MDA) and receiver operating characteristic (ROC) curve analyses were used to create a predictive model including EMA in addition to a panel of routine blood markers. A combination algorithm was developed and validated prospectively in 170 CHC additional patients. Results: Epithelial membrane antigen at 130 kDa was identified, purified and quantified in sera of CHC patients using ELISA. Based on these encouraging results, we purified and developed a direct ELISA for the quantitation of EMA in sera of CHC. MDA selected a score for the prediction of significant liver fibrosis patients based on measurements of EMA, aspartate aminotransferase to platelet ratio index and albumin. Areas under the ROC curves (AUC) of the score for the three biomarkers were 0.82 for patients with liver fibrosis (F1–F4), 0.86 for significant liver fibrosis (F2–F4), 0.87 for advanced liver fibrosis (F3–F4) and 0.86 for liver cirrhosis (F4). The results of the validation study demonstrated that (74%) of patients could have avoided liver biopsy. Conclusion: This score was validated for the prediction of liver fibrosis stages and may minimize the need for liver biopsy.     

Assessment of Implicit Sexual Associations in Non-Incarcerated Pedophiles

Offences committed by pedophiles are crimes that evoke serious public concern and outrage. Although recent research using implicit measures has shown promise in detecting deviant sexual associations, the discriminatory and predictive quality of implicit tasks has not yet surpassed traditional assessment methods such as questionnaires and phallometry. The current research extended previous findings by examining whether a combination of two implicit tasks, the Implicit Association Task (IAT) and the Picture Association Task (PAT), was capable of differentiating pedophiles from non-pedophiles, and whether the PAT, which allows separate analysis for male, female, boy and girl stimulus categories, was more sensitive to specific sexual associations in pedophiles than the IAT. A total of 20 male self-reported pedophiles (10 offender and 10 non-offenders) and 20 male self-reported heterosexual controls completed the two implicit measures. Results indicated that the combination of both tasks produced the strongest results to date in detecting implicit pedophilic preferences (AUC = .97). Additionally, the PAT showed promise in decomposing the sexual associations in pedophiles. Interestingly, as there was an equal distribution of offenders and non-offenders in the pedophile group, it was possible to test for implicit association differences between these groups. This comparison showed no clear link between having these implicit sexual associations and actual offending.     

The effect of zinc sulfate on immunologic response to recombinant hepatitis B vaccine in elderly: Zinc sulfate and immunologic response to recombinant hepatitis B vaccine

Background

Hepatitis B is the major cause of chronic hepatitis and cirrhosis in Iran. Sanitation and immunization is one of the most effective measures for prevention of the disease which is now widely used in developing countries. However, the immune response to the vaccine varies by age.

Objectives

To determine the effect of zinc sulfate on immune response to hepatitis-B vaccine in elderly.

Patients and Methods

In a clinical trial on 140 subjects aged ?40 years with a body mass index (BMI) <30 kg/m2, and without any co-morbid disease were recruited. Those who had negative hepatitis B core antibody (102 persons) were randomly allocated to two groups. The trial group received hepatitis B vaccine plus 200 mg zinc sulfate daily for 30 days and the control group received vaccine plus placebo.

Results

52 of 102 people were female (51%). The two studied groups were comparable in terms of age, gender, and smoking habits. The mean antibody production in the intervention and control groups was 116.93 and 157.37 mIU/mL, respectively (p=0.22). No statistical differences were observed between the two groups in terms of proportion of people who were protected after vaccination (26.0% and 36.5% in people with and without zinc, respectively).

Conclusions

This study revealed that zinc sulfate has no effect in level of immunity among elderly.     

A review of allergy and allergen specific immunotherapy

Since 20th century, when allergy was defined, an ongoing attempt for discovering the mechanisms underlying it and its treatment began. Defining allergens as well as cells such as regulatory T-cells and characterizing the antibodies involved in the pathogenesis (including blocking antibodies) have helped very much towards a better understanding of the immunologic process. However, allergen specific immunotherapy (SIT), as a specific curative treatment for allergy also dates back to the beginning of the previous century and has progressed considerably during these years. SIT similar to natural immunomodulation, directs the immune response towards tolerance. New strategies in this field, such as using recombinant allergens, T- and B-cell-epitope-containing peptides, and DNA vaccination have shown promising results. Sublingual immunotherapy, although not yet FDA-approved, as an alternative strategy in SIT has demonstrated efficacy as well as safety. Furthermore, allergen extracts, their standardization and their modification have also been the focus of much research. Undoubtedly, specific immunotherapy is proven to be an efficacious method to treat allergy, so its cost-effectiveness should be estimated in developing countries in order to include it in the country's health priorities. Informing physicians about the new anti-vaccination movement is also crucial.