Neuroprotective effects of IGF-I against TNFalpha-induced neuronal damage in HIV-associated dementia

Human immunodeficiency virus type 1 (HIV-1) infection often results in disorders of the central nervous system, including HIV-associated dementia (HAD). It is suspected that tumor necrosis factor-alpha (TNFalpha) released by activated and/or infected macrophages/microglia plays a role in the process of neuronal damage seen in AIDS patients. In light of earlier studies showing that the activation of the insulin-like growth factor I receptor (IGF-IR) exerts a strong neuroprotective effect, we investigated the ability of IGF-I to protect neuronal cells from HIV-infected macrophages. Our results demonstrate that the conditioned medium from HIV-1-infected macrophages, HIV/CM, causes loss of neuronal processes in differentiated PC12 and P19 neurons and that these neurodegenerative effects are associated with the presence of TNFalpha. Furthermore, we demonstrate that IGF-I rescues differentiated neurons from both HIV/CM and TNFalpha-induced damage and that IGF-I-mediated neuroprotection is strongly enhanced by overexpression of the wt IGF-IR cDNA and attenuated by the antisense IGF-IR cDNA. Finally, IGF-I-mediated antiapoptotic pathways are continuously functional in differentiated neurons exposed to HIV/CM and are likely supported by TNFalpha-mediated phosphorylation of I(kappa)B. All together these results suggest that the balance between TNFalpha and IGF-IR signaling pathways may control the extent of neuronal injury in this HIV-related experimental setting.     

The Effect of Intravenous Magnesium Sulphate as an Adjuvant in the Treatment of Acute Exacerbations of COPD in the Emergency Department: A Double-Blind Randomized Clinical Trial

BackgroundAcute exacerbations of chronic obstructive pulmonary disease (AECOPD) are serious complications that often require immediate intervention in an emergency department (ED). The aim of this study was to investigate the effect of intravenous magnesium sulphate as an adjuvant in the treatment of AECOPD in the ED.MethodsIn a double-blind, randomized clinical trial, a total of 60 patients with AECOPD presenting to the ED of Imam Khomeini Hospital in Sari, Iran, were included. The study was conducted between September 2016 and February 2018. Eligible patients were randomly allocated into two groups of intervention and control. Patients in the intervention and control groups received intravenous infusion of magnesium sulfate (2 gr) or normal saline over 30 minutes, respectively. For all patients, Borgdyspnea score, forced expiratory volume in one second (FEV1) result and clinical variables of interest were evaluated before the beginning of the intervention, and also 45 minutes and 6 hours after the commencement of intervention.ResultsRegardless of time of evaluation, pulse rate (PR), respiratory rate (RR) and Borg score in intervention group was lower than control group. Also, FEV1 and SPO2 were greater in intervention group compared to control group. However, these differences were not statistically significant (between-subject differences or group effect) (p<0.001). The trends of FEV1, SPO2, PR, RR and Borg score were similar between two groups of study (no interaction effect; P>0.05).ConclusionAccording to the results of this study, it seems that using intravenous magnesium sulfate has no significant effect on SPO2, FEV1, RR, and PR of patients with AECOPD who presented to ED.     

Perioperative outcomes of goal-directed versus conventional fluid therapy in radical cystectomy with enhanced recovery protocol

International Urology and Nephrology - The aim of this study is to evaluate the intra/perioperative fluid management and early postoperative outcomes of patients who underwent radical cystectomy...     

Quality of hospital services during New Year holiday (Nowruz) in Iran

Journal of Public Health - Iranian New Year, with long consecutive holidays, although it is celebrated and enjoyed, might influence the quality of services provided by hospitals. The present study...     

Social Contact Patterns Associated With Tuberculosis: A Case-control Study in Southwest Iran

ObjectivesTuberculosis (TB) is a major public health concern worldwide. Social contact patterns can affect the epidemiology and risk of airborne diseases such as TB. This study was designed to investigate the social contact patterns associated with TB.MethodsIn this case-control study, groups of participants with and without TB were matched by age and sex. Participants reported the nature, location, frequency, and average duration of social contacts over 1 month. The duration and number of social and spatial contacts were compared between groups using the chi-square test and the t-test. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to quantify the relationship between social contact time and TB status. Data were analyzed using Stata version 11 statistical software. A p-value of <0.05 was considered to indicate statistical significance.ResultsIn this study, 80 patients with TB and 172 control participants were included, and a total of 3545 social contacts were registered. Social contact with family members (OR, 1.72; 95% CI, 1.10 to 2.40), contact with a person with TB (OR, 1.53; 95% CI, 1.16 to 2.01), and contact at the participant’s home (OR, 1.42; 95% CI, 1.19 to 1.82) were significantly associated with TB status.ConclusionsThe duration of long-term social contact, rather than the number of contacts, may be the main contact-related factor associated with TB transmission in this population. The focus of contact-tracing efforts should be on finding and treating both family members and long-term contacts in non-household settings.     

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.