Low molecular-weight chitosan as a pH-sensitive stealth coating for tumor-specific drug delivery

When a nanoparticle is developed for systemic application, its surface is typically protected by poly(ethylene glycol) (PEG) to help prolonged circulation and evasion of immune clearance. On the other hand, PEG can interfere with interactions between nanocarriers and target cells and negatively influence the therapeutic outcomes. To overcome this challenge, we propose low molecular-weight chitosan (LMWC) as an alternative surface coating, which can protect the nanomedicine in neutral pH but allow cellular interactions in the weakly acidic pH of tumors. LMWCs with a molecular weight of 2-4 kDa, 4-6.5 kDa, and 11-22 kDa were produced by hydrogen peroxide digestion and covalently conjugated with poly(lactic-co-glycolic acid) (PLGA). Nanoparticles created with PLGA-LMWC conjugates showed pH-sensitive cell interactions, which enabled specific drug delivery to cells in a weakly acidic environment. The hydrophilic LMWC layer reduced opsonization and phagocytic uptake. These properties qualify LMWCs as a promising biomaterial for pH-sensitive stealth coating.     

BAK, BAX, and NBK/BIK Proapoptotic Gene Alterations in Iranian Patients with Ataxia Telangiectasia

Introduction

Ataxia telangiectasia (AT) is an autosomal recessive multisystem disorder characterized by variable immunodeficiency, progressive neurodegeneration, occulocutaneous telangiectasia, and an increased susceptibility to malignancies. This study was designed to study the role of proapoptotic BAK, BAX, and NBK/BIK genes in a group of patients with AT to elucidate the possible role of these genes in progression of malignancies in this disease.

Materials and Methods

Fifty Iranian patients with AT were investigated in this study. The entire coding regions of the BAK gene (exons 2–6), NBK/BIK gene (exons 2–5), and BAX gene (exons 1–7) were amplified using polymerase chain reaction (PCR). The PCR products were separated by 2% agarose gel electrophoresis, and all positive samples were verified by direct sequencing of PCR products using the same primers used for PCR amplification, BigDye chemistry, and Avent 3100 Genetic Analyzer following the manufacturer’s instructions (Applied Biosystems).

Results

Eight of fifty Iranian AT patients (16%) exhibited a C?>?T transition in exon 2 (c342C?>?T) of the BAK gene, while none of the healthy controls had such alteration (P?=?0.0001). Higher frequency of another nucleotide substitution in the noncoding region of exon 7 in BAX gene (6855G?>?A) was also identified in 68% of the patient group versus 24% in the controls (P?<?0.0001). Sequence alteration in intronic region of the NBK/BIK gene IVS4-12delTC was observed in 52% of AT patients, which was significantly higher than 20% in the control group (P?=?0.0023). Another variant IVS1146C?>?T in the intronic region of the BAX gene was found in 78% of patients, which was significantly higher than 10% in the controls (P?<?0.0001). Frequency of alteration in intronic region of exon 3 of the BAX gene (IVS3?+?14A?>?G) was also significantly higher in the AT patients (P?<?0.0001).

Discussion

Several alterations in the proapoptotic genes BAK, NBK/BIK, and BAX were found in our study, which could elucidate involvement of the mitochondrial pathway mediated apoptosis in accelerating and developing of cancers and in immunopathogenesis of AT. Such altered apoptosis in AT could play some roles in developing cancers in this group of patients.     

Leukocyte adhesion deficiency: report of two family related newborn infants

Leukocyte adhesion deficiency type 1 (LAD 1) is an autosomal recessive hereditary disorder resulting from deficiency of CD18, characterized by recurrent bacterial infections. We report two consanguineous patients with Leukocyte adhesion deficiency type 1( LAD1). These two infant boy patients were referred to us, within a short period of time, with the complaints of recurrent infections at the age of 38 and 75 days -old, respectively. Parents of two patients were first cousins and their grandmothers also were first cousins. The history of delayed umbilical cord separation was shown in both patients. Patient 1 had history of omphalitis, conjunctivitis, skin lesion of groin area and abscess formation of vaccination site, and had infective wound of eye-lid at the last admission. Patient 2 had history of omphalitis and soft tissue infection of right wrist at the last admission. Laboratory findings showed marked leukocytosis and low CD18 levels (6.6% in Patient 1 and 2.4 % in Patient 2). In Patient 1 recurrent infections were treated with antibiotic regimens and received bone marrow transplantation but Patient 2 died because of septicemia, generalized edema, ascites and progression to acute renal failure at 4 months of age. Due to considerable rate of consanguineous marriages in parents of Leukocyte adhesion deficiency patients, sequence analysis especially for prenatal diagnosis in subsequent pregnancies and genetic counseling is recommended.     

Low serum leptin serves as a biomarker of malnutrition in elderly patients

Anthropometric and classical biologic markers of malnutrition, such as serum albumin, are limited because they are influenced by nonnutritional factors. We propose that a biologic parameter that both predicts nutritional status and is unaffected by nonnutritional factors would facilitate the diagnosis of malnutrition in the elderly. This cross-sectional study included 179 randomized elderly patients. Nutritional status was assessed by the Mini-Nutritional Assessment (MNA) instrument; other end points included anthropometric measures and biologic parameters. Subjects were divided into 3 groups based on MNA-defined nutritional status, and end point means were compared using 2-way analyses of variance adjusted by sex. Correlations between the most accurate biologic marker in predicting malnutrition and other biologic and clinical variables were assessed using Pearson correlation test. Multiple linear regressions were then performed to relate the best biomarker of malnutrition to specific parameters. Finally, leptin levels that predict malnutrition were determined using receiver operating characteristic curve cutoff values. The well-nourished group had significantly higher leptin (P = .001), weight, body mass index, mid-arm circumference, and calf circumference (all, P < .001) compared with the malnourished group and the at risk of malnutrition group. Serum leptin was the optimal biomarker of MNA-defined malnutrition and had significant positive correlations with weight (P = .003) and with all anthropometric values (all P < .001), but no significant correlation with C-reactive protein. Sex, weight, and triglyceride were the best predictors of serum leptin (all P < .001). The optimal cutoff value of serum leptin to detect malnutrition was 4.3 ng/mL in men and 25.7 ng/mL in women. Serum leptin may be a good predictor of nutritional status in elderly patients.     

Cord Blood Lipid Profile in a Population of Iranian Term Newborns

Premature coronary artery disease (CAD) and its risk factors are highly prevalent in Iran. It is well documented that atherosclerosis starts in childhood and there is evidence that this association with adult levels may originate at birth, so assessment of serum lipid levels in neonates might be of importance. In this study we aimed to measure serum lipoprotein and apolipoprotein levels in a representative sample of Iranian newborns. Cord blood lipid profile, apolipoprotein A, apolipoprotein B, and lipoprotein a (LPa) were analyzed in 378 full-term, Iranian newborns. The mean values of total cholesterol (TC), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A, apolipoprotein B, and Lpa in girls were 81.4 ± 28.3, 35.9 ± 22.4, 31.1 ± 9.9, 87.9 ± 20.2, 34.2 ± 18.2, and 21.0 ± 2.8 mg/dL, respectively; these values in boys were 75.2 ± 21.1, 32.1 ± 16.3, 28.8 ± 8.7, 84.3 ± 16.0, 32.6 ± 14.2, and 19.5 ± 2.7 mg/dL, respectively. Median values of triglycerides (TGs) in boys and girls were 61 and 62 mg/dL, respectively. Female neonates had significantly higher concentrations of TC and HDL-C than males (81.4 ± 28.3 vs. 75.2 ± 21.1, p = 0.02, and 31.18 ± 9.97 vs. 28.8 ± 8.7, p = 0.02, respectively). Other biochemical factors were not significantly different between genders. The mean and median concentrations of LPa were 20.3 and 18.7 mg/dL, respectively, which are almost five times higher than those reported in some other studies. The TG concentration was 1.5–2 times higher than those previously reported. Our findings indicate that serum concentrations of LPa and TG in Iranian neonates are higher than those in previous studies; this disorder, which is likely placing Iranians at increased risk for future CADs, needs to be assessed in longitudinal studies.     

Assertiveness process of Iranian nurse leaders: A grounded theory study

The purpose of this study was to explore the assertiveness process in Iranian nursing leaders. A qualitative design based on the grounded theory approach was used to collect and analyze the assertiveness experiences of 12 nurse managers working in four hospitals in Iran. Purposeful and theoretical sampling methods were employed for the data collection and selection of the participants, and semistructured interviews were held. During the data analysis, 17 categories emerged and these were categorized into three themes: "task generation", "assertiveness behavior", and "executive agents". From the participants' experiences, assertiveness theory emerged as being fundamental to the development of a schematic model describing nursing leadership behaviors. From another aspect, religious beliefs also played a fundamental role in Iranian nursing leadership assertiveness. It was concluded that bringing a change in the current support from top managers and improving self-learning are required in order to enhance the assertiveness of the nursing leaders in Iran.