Conventional- versus high-dose vancomycin regimen in patients with acute bacterial meningitis: a randomized clinical trial

Objective: Efficacy of the conventional- versus high-dose vancomycin regimen in patients with acute bacterial meningitis was compared.

Methods: In a randomized clinical trial 44 patients with acute bacterial meningitis were randomly assigned to the conventional- or high-dose vancomycin groups. Clinical and laboratory parameters were used for evaluation of response to the treatment regimens.

Results: In the high-dose group, leukocytosis and fever resolved significantly faster than those in the conventional group. Furthermore, the length of hospitalization was shorter and Glasgow Coma Scale at the end of 10th day was significantly lower in the high dose compared to the conventional group. Trend of creatinine clearance changes did not differ significantly between the two groups.

Conclusion: In comparison to the conventional-dose regimen, the high-dose vancomycin regimen was associated with significantly more favorable clinical response without increase in the incidence of nephrotoxicity in patients with acute bacterial meningitis.     

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.     

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...     

Inhibitory effect of Crocus sativus L. ethanol extract on adjuvant-induced arthritis

Saffron is a well-known spice produced from dried stigmas of Crocus sativus L. flowers. Apart from its wide use in food preparations, it also has a broad range of medical properties. We examined the potential anti-inflammatory effects of saffron ethanolic extract (SEE) using an animal model of arthritis. Adjuvant-induced arthritis was induced in Wistar rats by injection of Complete Freund's Adjuvant. The rats were then injected intraperitoneally every other day with 25–600 mg SEE/kg or dexamethasone (DEX, 2 mg/kg). Changes in body weight, paw oedema and arthritis indices were recorded over the subsequent 12 days of treatment. Results revealed that SEE particularly at the higher concentrations significantly reduced paw and tibiotarsal joint diameters and comparing with DEX caused no significant change in body weight. These observations suggest that SEE displays a considerable anti-inflammatory potency and could potentially be used as an anti-arthritic agent in control of inflammation in rheumatoid arthritis.     

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.     

Screening of different interactions in oxo-manganese porphyrin dimers containing axial N-donor ligands: a theoretical study

A theoretical analysis for describing the dimeric assemblies of high-valent manganese(v)-oxo meso-tetraphenylporphyrin (TPP) ([(TPP)Mn^VO]₂²⁺) and meso-tetrakis(pentafluorophenyl)porphyrin (TPFPP) ([(TPFPP)Mn^VO]₂²⁺) in the presence of axial N-donor ligands is presented. Our theoretical results revealed two types interactions in dimers: a sandwich-like interaction between phenyl rings of porphyrin molecules, and a non-bonded T-shape interaction between nitrogen donors attached to Mn centers. The curvature in the geometry of porphyrin in the [(TPP)Mn^VO]₂²⁺/N-donor system is significantly smaller than that of [(TPFPP)Mn^VO]₂²⁺/N-donor system. Moreover, the Mn–N_(ax) distances in [(TPFPP)Mn^VO]₂²⁺/N-donor system are shorter than those of [(TPP)Mn^VO]₂²⁺/N-donor system. Also, the donor–acceptor interaction between the imidazoles and the Mn centers are stronger than those of the other ligands in both porphyrins. These results are supported by atoms in molecules (AIM) and natural bond orbital (NBO) analysis.

A DFT analysis for describing the dimeric assemblies of high-valent manganese(v)-oxo meso-tetraphenylporphyrin ([(TPP)Mn^VO]₂²⁺) and meso-tetrakis(pentafluorophenyl)porphyrin ([(TPFPP)Mn^VO]₂²⁺) in the presence of axial N-donor ligands is presented.     

Effects of melatonin supplementation on disease activity,oxidative stress,inflammatory, and metabolic parameters in patients with rheumatoid arthritis: a randomized double-blind placebo-controlled trial

Clinical Rheumatology - Considering the pathologic significance of inflammation and oxidative stress in rheumatoid arthritis (RA) as well as the antioxidant, anti-inflammatory and hypolipidemic...     

Evaluation of LKB1 and Serine-Glycine Metabolism Pathway Genes (SHMT1 and GLDC) Expression in AML

LKB1 is a significant tumor suppressor and epigenetic regulator playing a vital role in different types of cancers. SHMT1 and GLDC are two critical genes of the epigenetic pathway influenced by LKB1. As epigenetic is the major cause of AML pathogenesis, this study aimed at investigating LKB1, SHMT1, and GLDC gene expression levels in acute myeloid leukemia patients. The present study was conducted on LKB1, SHMT1, and GLDC gene expression levels in 60 de novo AML samples and 30 normal controls using real-time RT-PCR. The results showed that LKB1 and SHMT1 have respectively a significantly lower (P < 0.05) and higher (P < 0.05) expression level than that of normal controls. Furthermore, the correlation between LKB1 with SHMT1 and GLDC was significant and positive (P value: 0.015, r: 0.299). Positive findings confirm that metabolic pathways alongside the LKB1 association drive the epigenetic axis and its substrate production. Therefore, it can be concluded that the newly-discovered pathway in the pathogenesis of this disease provides new insights into the design of therapeutic targets.