Erythropoietin improves spatial learning and memory in streptozotocin model of dementia

Alzheimer's disease is associated to impairments of learning and memory. Because studies demonstrated that erythropoietin has positive effects on central nervous system, the aim of this study was to evaluate the effect of erythropoietin on spatial learning and memory in a well defined model for Alzheimer's disease. Rat model of Alzheimer's was created by injecting streptozotocin in lateral ventricles of the brain. Two weeks later, the rats were assessed through passive avoidance learning test to confirm the induction of Alzheimer's. After that, they received erythropoietin (5000 IU/kg) every other day, for two weeks and then spatial learning and memory were assessed by a 5-day protocol of Morris water maze test in them. The results showed that streptozotocin severely damaged learning and memory in rats. Erythropoietin had no significant effect in the control rats; however, it significantly improved learning and memory in rats with Alzheimer's disease, as the task performance of the rats treated with erythropoietin was like the control group. The results suggest that erythropoietin can be considered as an effective treatment for neurodegenerative damages.     

Evaluation of the efficacy of topical sucralfate on healing haemorrhoidectomy incision wounds and reducing pain severity: A randomised clinical trial

The healing of haemorrhoidectomy wounds is a main concern of surgeons and patients. Various modalities can improve the quality of wound care after surgery. Antibiotics and topical agents, such as solutions and ointments, have been evaluated. The current research investigates the effects of sucralfate ointment on wound healing (epithelialisation) and postoperative pain after open haemorrhoidectomy. This trial involves two groups of randomly collected patients (n = 40) who underwent open haemorrhoidectomy surgery by the Milligan‐Morgan method. A 10% topical sucralfate ointment was applied to the investigated group''s wounds, while the control group patients used Vaseline as a placebo. The present work measured the two outcomes as follows: pain severity by a Visual Analogues Scale (VAS) score and epithelialisation by a surgeon''s visual inspection. During the postoperative phase, the mean VAS was 3.70 for the investigated group and 6.90 for the control group. On the average, the completion of epithelialisation for the investigated group was on day 13 as opposed to day 20 for the control group. The topical application of sucralfate ointment on post‐haemorrhoidectomy wound is an effective method for the promotion of healing, also lessens the severity of pain, and reduces the need for analgesics.     

Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib-IX complex: studies using optical tweezers

Ultralarge von Willebrand factor (ULVWF) multimers have been implicated in the pathogenesis of the catastrophic microangiopathic disorder, thrombotic thrombocytopenic purpura. Spontaneous ULVWF binding to platelets has been ascribed to increased avidity due to the greatly increased number of binding sites for platelets (the A1 domain) per molecule. To address the mechanism of enhanced ULVWF binding to platelets, we used optical tweezers to study the unbinding forces from the glycoprotein Ib-IX (GP Ib-IX) complex of plasma VWF, ULVWF, and isolated A1 domain. The unbinding force was defined as the minimum force required to pull ligand-coated beads away from their attachment with GP Ib-IX-expressing cells. Beads coated with plasma VWF did not bind to the cells spontaneously, requiring the modulators ristocetin or botrocetin. The force required to break the ristocetin- and botrocetin-induced plasma VWF-GP Ib-IX bonds occurred in integer multiples of 6.5 pN and 8.8 pN, respectively, depending on the number of bonds formed. In contrast, beads coated with either ULVWF or A1 domain bound the cells in the absence of modulators, with bond strengths in integer multiples of approximately 11.4 pN for both. Thus, in the absence of shear stress, ULVWF multimers form spontaneous high-strength bonds with GP Ib-IX, while plasma VWF requires exogenous modulators. The strength of individual bonds formed with GP Ib-IX was similar for both ULVWF and the isolated A1 domain and greater than those of plasma VWF induced by either modulator. Therefore, we suggest that the conformational state of ULVWF multimers is more critical than their size for interaction with platelets.     

Current status of glucose,blood pressure and lipid management in type 2 diabetes clinic attendees in Isfahan,Iran

Aims/Introduction

To estimate the prevalence of meeting American Diabetes Association clinical practice recommendations for hemoglobin A1c (HbA1c), blood pressure (BP) and low-density lipoprotein cholesterol (LDLC) among Iranian type 2 diabetes clinic attendees, and to identify the factors associated with therapeutic target achievement.

Materials and Methods

A total of 2,640 patients with type 2 diabetes (944 men and 1,696 women) from Isfahan Endocrine and Metabolism Research Center outpatient clinics, Iran, were examined. The main outcome measures were HbA1c, BP and LDLC, in accordance with the American Diabetes Association recommendations. The mean (standard deviation) age of participants was 49.6 years (9.3 years) with a mean (standard deviation) duration of diabetes of 5.0 years (4.9 years) at initial registration.

Results

The percentages of patients who had HbA1c <7%, BP <140/90 mmHg and LDLC <100 mg/dL was 37.4% (95% confidence interval [CI] 35.6–39.3), 35.3% (95% CI 33.5–37.3) and 48.9% (95% CI 47.0–50.8), respectively. The proportion of patients meeting all three goals was 7.7% (95% CI 6.7–8.8). Lower BP, cholesterol level and higher education at registration, and higher follow up but lower number of follow-up visits affected achievement of all three goals.

Conclusions

The present study highlights that a substantial proportion of Iranian type 2 diabetes clinic attendees did not meet the American Diabetes Association clinical practice recommendations, and shows the difficult challenges physicians face when treating patients with type 2 diabetes.     

Development of an In-House TaqMan Real Time RT-PCR Assay to Quantify Hepatitis C Virus RNA in Serum and Peripheral Blood Mononuclear Cells in Patients With Chronic Hepatitis C Virus Infection

Background:

Viral load measurements are commonly used to monitor HCV infection in patients with chronic diseases or determining the number of HCV-genomes in serum samples of patients after sustained virological response. However, in some patients, HCV viral load in serum samples is too low to be detected by PCR, especially after treatment.

Objectives:

The aim of this study was to develop a highly specific, sensitive, and reproducible in-house quantitative PCR using specific primers and probe cited in highly conservative region of HCV genome that allows simultaneous detection of HCV genotypes 1 - 4.

Materials and Methods:

In this study, three sets of primer pairs and a TaqMan probe for amplification and detection of selected region within 5’-non-coding (5’NCR) of four HCV genotypes were used. Using plasmid containing 5’NCR region of HCV, standard curve, threshold, and threshold cycle (CT) values were determined. Real-time and nested PCR were performed on HCV genotypes 1 - 4 extracted from plasma and peripheral blood mononuclear cells (PBMCs) samples collected from patients with chronic HCV infection.

Results:

The lower limit detection of this in-house HCV real-time RT-PCR was determined as 100 RNA copies/mL. Inter- and intra-assay coefficient of variation (CV) of this in-house HCV real-time RT-PCR ranged from 0.9% to 1.8% and 1.76% to 3.94%, respectively. The viral load of the genotyped samples ranged from 2.0 × 10⁶ ± 0.31 to 2.7 × 10⁵ ± 0.46 copies/mL in serum samples and 5 × 10² ± 0.36 to 4.0 × 10³ ± 0.51 copies/10⁶ cells/mL of PBMCs.

Conclusions:

The quite sensitive in-house TaqMan real time RT-PCR assay was able to detect and quantify all four main HCV genotypes prevailing around all geographical regions of Iran.     

Prognostic Significance of T‐Wave Amplitude in Lead aVR on the Admission Electrocardiography in Patients with Anterior Wall ST‐Elevation Myocardial Infarction Treated by Primary Percutaneous Intervention

Background: T‐wave positivity in aVR lead patients with heart failure and anterior wall old ST‐segment elevation myocardial infarction (STEMI) are shown to have a higher frequency of cardiovascular mortality, although the effects on patients with STEMI treated with primary percutaneous coronary intervention (PCI) has not been investigated. In this study, we sought to determine the prognostic value of T wave in lead aVR on admission electrocardiography (ECG) for in‐hospital mortality in patients with anterior wall STEMI treated with primary PCI. Methods: After exclusion, 169 consecutive patients with anterior wall STEMI (mean age: 55 ± 12.9 years; 145 men) undergoing primary PCI were prospectively enrolled in this study. Patients were classified as a T‐wave positive (n = 53, group 1) or T‐wave negative (n = 116, group 2) in aVR based upon the admission ECG. All patients were evaluated with respect to clinical features, primary PCI findings, and in‐hospital clinical results. Results: T‐wave positive patients who received primary PCI were older, multivessel disease was significantly more frequent and the duration of the patient's hospital stay was longer than T‐wave negative patients. In‐hospital mortality tended to be higher in the group 1 when compared with group 2 (7.5% vs 1.7% respectively, P = 0.05). After adjusting the baseline characteristics, positive T wave remained an independent predictor of in hospital mortality (odds ratio: 4.41; 95% confidence interval 1.2–22.1, P = 0.05). Conclusions: T‐wave positivity in lead aVR among patients with an anterior wall STEMI treated with primary PCI is associated with an increase in hospital cardiovascular mortality.     

Optimizing results in endoscopic forehead rejuvenation

Endoscopic forehead rejuvenation has several advantages over traditional open techniques. First, large incisional scars are avoided. Second, the chances of forehead elongation are less. However, the technique requires a significant learning curve for best results. Suboptimal results may occur and are typically due to underresection or uneven resection of the glabellar musculature, overdissection of the medial periosteum, and under or overcorrection when repositioning of the lateral brow. This article reviews the pertinent anatomy and techniques for endoscopic forehead rejuvenation, and describes the authors' technique for more consistent, predictable results.     

Regional expression of NO synthase, NAD(P)H oxidase and superoxide dismutase in the rat brain

Nitric oxide (NO) derived from the endothelial NO synthase (eNOS) contributes to regulation of cerebral circulation, whereas that produced by neuronal NOS (nNOS) participates in the regulation of brain function. In particular, NO plays an important role in modulation of sympathetic activity and hence central regulation of arterial pressure. Superoxide derived from NAD(P)H oxidase avidly reacts with and inactivates NO and, thereby, modulates its bioavailability. Calmodulin (CM) is required for activation of NOS and soluble guanylate cyclase (sGC) serves as a NO receptor. Superoxide is dismutated to H2O2 by superoxide dismutase (SOD) and H2O2 is converted to H2O by catalase or glutathione peroxidase (GPX). Given the importance of NO in the regulation of brain perfusion and function, we undertook the present study to determine the relative expressions of immunodetectable nNOS, eNOS, CM, sGC, NAD(P)H oxidase and SOD by Western analysis in different regions of the normal rat brain. nNOS was abundantly expressed in the pons cerebellum and hypothalamus and less so in the cortex and medulla. sGC abundance was highest in the hypothalamus and pons, and lowest in the cerebellum and medulla. eNOS and calmodulin were equally abundant in all regions. NAD(P)H oxide was most abundant in the pons compared to other regions. Cytoplasmic SOD was equally distributed among different regions but catalase and GPX were more abundant in pons, hypothalamus and medulla and less so in the cortex and cerebellum. Thus, the study documented regional distributions of NOS, NAD(P)H oxidase, antioxidant enzymes, sGC and calmodulin which collectively regulate production and biological activities of NO and superoxide, the two important small molecular size signaling molecules.     

Deposition of ultrafine (nano) particles in the human lung

Increased production of industrial devices constructed with nanostructured materials raises the possibility of environmental and occupational human exposure with consequent adverse health effects. Ultrafine (nano) particles are suspected of having increased toxicity due to their size characteristics that serve as carrier transports. For this reason, it is critical to refine and improve existing deposition models in the nano-size range. A mathematical model of nanoparticle transport by airflow convection, axial diffusion, and convective mixing (dispersion) was developed in realistic stochastically generated asymmetric human lung geometries. The cross-sectional averaged convective-diffusion equation was solved analytically to find closed-form solutions for particle concentration and losses per lung airway. Airway losses were combined to find lobar, regional, and total lung deposition. Axial transport by diffusion and dispersion was found to have an effect on particle deposition. The primary impact was in the pulmonary region of the lung for particles larger than 10 nm in diameter. Particles below 10 nm in diameter were effectively removed from the inhaled air in the tracheobronchial region with little or no penetration into the pulmonary region. Significant variation in deposition was observed when different asymmetric lung geometries were used. Lobar deposition was found to be highest in the left lower lobe. Good agreement was found between predicted depositions of ultrafine (nano) particles with measurements in the literature. The approach used in the proposed model is recommended for more realistic assessment of regional deposition of diffusion-dominated particles in the lung, as it provides a means to more accurately relate exposure and dose to lung injury and other biological responses.