Acetaminophen toxicity up-regulates MRP2 expression in the liver of cats: an old story with new vision

This study was conducted to clarify the role of efflux transporter MRP₂ in acetaminophen-induced hepatotoxicity in cats. Sixteen mixed bred male cats and four liver samples from mixed breed male dogs were used. The cats were assigned into four groups (n?=?4), received saline and 2, 10 and 50?mg/kg doses of acetaminophen orally for 14 days. Unlike the intact dogs, the MRP₂ was not detectable in control cats. MRP₂ at mRNA level was expressed in the liver of cats, which received the medium and high doses. Data suggest that the MRP₂ expression may involve in the acetaminophen-induced hepatotoxicity in cats.     

Effect of peptide length on the conjugation to the gold nanoparticle surface: a molecular dynamic study

Background

Gold nanoparticles now command a great deal of attention for medical applications. Despite the importance of nano-bio interfaces, interaction between peptides and proteins with gold surfaces is not still fully understood, especially in a molecular level.

Methods

In the present study computational simulation of adsorption of 20 amino acids, in three forms of mono-amino acid, homo di-peptide and homo tri-peptide, on the gold nanoparticles was performed by Gromacs using OPLSAA force field. The flexibility, stability, and size effect of the peptides on the gold nanoparticles were studied as well as the molecular structure of them.

Results

According to our results, adsorbed homo tri-peptides on the gold surface had more flexibility, more gyration, and the farthest distance from the GNP in comparison with homo di-peptides and mono-amino acids.

Conclusion

Our findings provide new insights into the precise control of interactions between amino acids anchored on the GNPs.

     

Improved anticancer delivery of paclitaxel by albumin surface modification of PLGA nanoparticles

Background

Nanoparticles (NPs) play an important role in anticancer delivery systems. Surface modified NPs with hydrophilic polymers such as human serum albumin (HSA) have long half-life in the blood circulation system.

Methods

The method of modified nanoprecipitation was utilized for encapsulation of paclitaxel (PTX) in poly (lactic-co-glycolic acid) (PLGA). Para-maleimide benzoic hydrazide was conjugated to PLGA for the surface modifications of PLGA NPs, and then HSA was attached on the surface of prepared NPs by maleimide attachment to thiol groups (cysteines) of albumin. The application of HSA provides for the longer blood circulation of stealth NPs due to their escape from reticuloendothelial system (RES). Then the physicochemical properties of NPs like surface morphology, size, zeta potential, and in-vitro drug release were analyzed.

Results

The particle size of NPs ranged from 170 to 190 nm and increased about 20–30 nm after HSA conjugation. The zeta potential was about -6 mV and it decreased further after HSA conjugation. The HSA conjugation in prepared NPs was proved by Fourier transform infrared (FT-IR) spectroscopy, faster degradation of HSA in Differential scanning calorimetry (DSC) characterization, and other evidences such as the increasing in size and the decreasing in zeta potential. The PTX released in a biphasic mode for all colloidal suspensions. A sustained release profile for approximately 33 days was detected after a burst effect of the loaded drug. The in vitro cytotoxicity evaluation also indicated that the HSA NPs are more cytotoxic than plain NPs.

Conclusions

HSA decoration of PLGA NPs may be a suitable method for longer blood circulation of NPs.     

miRNA-binding site polymorphism in IL-15RA gene in rheumatoid arthritis and systemic lupus erythematosus: correlation with disease risk and clinical characteristics

Clinical Rheumatology - MiRSNPs may interfere with mRNA stability through effects on microRNAs (miRNAs)-mRNA interactions via direct changes in miRNA binding site or effect on the secondary...     

Expression analysis of mTOR-associated lncRNAs in multiple sclerosis

Metabolic Brain Disease - mTOR has been shown to be involved in the regulation of immune responses and differentiation of immune cells. This protein is a candidate molecule for unraveling the...     

Pattern of in-hospital pediatric mortality over a 3-year period at University teaching hospitals in Iran

Introduction:

Causes of death are different and very important for policy makers in different regions. This study was designed to analyze the data for our in-patient children mortality.

Materials and Methods:

In this cross-sectional study from March 2011 to March 2013, all patients from 2 months to 18 years who died in pediatric intensive care unit, emergency room or medical pediatric wards in the teaching hospitals were studied.

Results:

From a total of 18,915 admissions during a 2-year-period, 256 deaths occurred with a mean age of 4.3 ± 5 years and mortality 1.35%. An underlying disease was present in 70.7% of the patients and in 88.5% of them the leading causes of death were related to the underlying diseases. The most common underlying diseases were congenital heart disease and cardiomyopathy in 50 (27.6%). The four main causes of deaths were sepsis (14.8%), pneumonia (14.5%), congestive heart failure (9.8%), and hepatic encephalopathy (9.8%).

Conclusion:

We may conclude that after sepsis and pneumonia, congestive heart failure, and hepatic encephalopathy are the leading causes of death. Most patients who died had underlying diseases including malignancies, heart and liver diseases as the most common causes.     

Nitric oxide and cyclic GMP levels in sickle cell patients receiving hydroxyurea

Recent studies suggest that nitric oxide (NO) may partly be responsible for the beneficial effect of hydroxyurea (HU) in sickle cell disease (SCD) patients. NO stimulates cyclic guanosine monophosphate (cGMP) production, which mediates vasodilatation. We investigated the association between NO, cGMP and fetal haemoglobin (HbF) levels after HU administration. Our data showed that chronic HU significantly increased NO, cGMP, and HbF levels in SCD. Recently it was shown that HbF production was stimulated by cGMP-dependent protein kinase. Our results suggest that NO stimulates cGMP production, which then activates a protein kinase and increases the production of HbF.     

Oral Zinc Sulfate as Adjuvant Treatment in Children With Nephrolithiasis: a Randomized,Double-Blind,Placebo-Controlled Clinical Trial

Background:

Nephrolithiasis in children is associated with a high rate of complications and recurrence.

Objectives:

Since some evidences reported that zinc has an important place amongst inhibitors of crystallization and crystal growth, we decided to assess the effectiveness of oral zinc sulfate as adjuvant treatment in children with nephrolithiasis.

Patients and Methods:

This was a randomized, double-blind, placebo-controlled clinical trial. 102 children in the age range 1 month to 11 years with first nephrolithiasis were recruited. Patients were randomly divided into two equal groups (intervention and control groups). Intervention group received conservative measures for stones and 1 mg/kg/day (maximum 20 mg/day) oral zinc sulfate syrup for 3 months. Control group received placebo in addition to conservative measures, also for 3 months. Patients were followed up by ultrasonography for 9 months, in 5 steps (at the end of 1st, 2nd, 3rd, 6th and 9th month after treatment) assessing size and number of stones in the kidneys.

Results:

Only at the end of the first month, the average number (intervention: 1.15 ± 3.78, control: 1.3 ± 2.84) (P = 0.001) and size (cm) (intervention: 0.51 ± 1.76, control: 0.62 ± 1.39) (P = 0.001) of stones was significantly lower in the intervention group, and in other points there was no significant therapeutic efficacy in oral zinc adjuvant treatment compared to conservative treatment alone. Also, during the 9-month follow-up, the number and size of stones in both groups decreased significantly (both: P < 0.0001) in a way that the decrease in the intervention group showed no difference with the control group.

Conclusions:

Adjuvant treatment with zinc is not more effective than consecutive treatment in children with nephrolithiasis. However, further studies are recommended due to the lack of clinical evidence in this field.     

Intellectual and Developmental Status in Children With Hyperphenylalaninemia and PKU Who Were Screened in a National Program

Background:

Hyperphenylalaninemia (HPA) and Phenylkeonuria (PKU) are metabolic errors caused by deficiency of phenylalanine hydroxylase enzyme, which results in increased level of phenylalanine. This increase is toxic to the growing brain.

Objectives:

The purpose of this study was to compare the intellectual and developmental status in HPA and PKU children with normal population in national screening program.

Patients and Methods:

In a historical cohort study, 41 PKU patients who had the inclusion criteria and 41 healthy children were evaluated. Wechsler preschool and primary scale of intelligence-3rd edition (WPPI-3) was used in order to assess the intellectual status of children 4 years and older and Ages and stages questionnaire (ASQ) was used to assess the developmental status of children 5 years and younger.

Results:

In intellectual test comparison, the two groups showed significant difference in Wechsler’s performance intelligence score and some performance subscales (P-value < 0.01). In comparison of developmental status, no significant difference was observed between the two groups (P-value > 0.05).

Conclusions:

Even with early diagnosis and treatment of PKU patients, these children show some deficiencies intellectually compared to normal children. This study emphasizes on necessity for screening intellectual and developmental status of PKU patients so that effective medical or educational measures can taken in case of deficiencies.