Indications, response, and side effects of biologic treatment in Behçet's disease: an 8-year study with follow-up.

Introduction: The treatment of Behçet's disease has improved significantly with the introduction of biologic therapies. However, there is still a need for more information about their use. This study aimed to evaluate the indications, response, and side effects of biologic agents in patients with refractory or severe Behçet's disease in the south of Iran, their follow-up and reasons for changing the biologics. Material and methods: A retrospective analysis was conducted on 44 patients aged 16-65 years who were prescribed biologic agents for at least 6 months. The clinical history, partial and complete remission at 6 and 12 months, occurrence of side effects, and need for switching to a second or third biologic agent were recorded. Results: The most common indications for starting biologic agents were ophthalmic (68.2%), parenchymal brain involvement (15.9%), and arthritis (11.4%). Improvement was observed in various manifestations of Behçet's disease, with complete remission in 86, 51.6, 92.8, 66.7, 42.9, 33.3, and 80.0% of oral aphthous lesions, ophthalmic activity, genital aphthous lesions, skin activity, arthritis, brain parenchymal lesions, and vascular activity, respectively, 6 months after starting biologic agents. These rates were unchanged or increased at the 12-month follow-up. In 25.0% of patients, a switch to a second biologic agent was necessary due to severe disease, side effects, or refractory disease. Side effects occurred in 16.3% and 33.3% of patients on the first and second biologic agents, respectively. The majority of side effects were not serious. Conclusions: We found a promising improvement at 6-month and 12-month follow-ups with various biologic agents in treating Behçet's disease with an acceptable safety profile.

Combination Therapy with Platelet-Rich Plasma and Epidermal Neural Crest Stem Cells Increases Treatment Efficacy in Vascular Dementia.

This study aimed to evaluate the efficacy and treatment mechanism of platelet-rich plasma (PRP) and neural crest-derived epidermal stem cells (ESCs) in their administration alone and combination in vascular dementia (VaD) model by two-vessel occlusion (2VO). Methods. Sixty-six rats were divided into six groups: the control, sham, 2VO + vehicle, 2VO + PRP, 2VO + ESC, and 2VO + ESC + PRP. The treated groups received 1 million cells on days 4, 14, and 21 with or without 500 µl PRP (twice a week) after 2VO. The memory performance and anxiety were evaluated by behavioral tests including open field, passive avoidance, and Morris water maze. The basal-synaptic transmission (BST) and long-term potentiation (LTP) were assessed through field-potential recordings of the CA1. The mRNA expression levels of IGF-1, TGF-ß1, PSD-95, and GSk-3ß were measured in the rat hippocampus by quantitative reverse transcription polymerase chain reaction. Results. The results demonstrated impaired learning, memory, and synaptic plasticity in the 2VO rats, along with a significant decrease in the expression of IGF-1, TGF-ß1, PSD-95, and upregulation of GSK-3ß. Treatment with ESC alone and ESC + PRP showed similar improvements in spatial memory and LTP induction, with associated upregulation of PSD-95 and downregulation of GSK-3ß. However, only the ESC + PRP group showed recovery in BST. Furthermore, combination therapy was more effective than PRP monotherapy for LTP and memory. Conclusions. The transplantation of ESC showed better effects than PRP alone, and combination therapy increased the treatment efficacy with the recovery of BST. This finding may be a clue for the combination therapy of ESC and PRP for VaD.

Chronic exposure to 2.45 GHz microwave radiation improves cognition and synaptic plasticity impairment in vascular dementia model.

Purpose: In this study, we evaluated the effects of 2.45 GHz microwave radiation on cognitive dysfunction induced by vascular dementia (VaD).Methods: The VaD was induced by bilateral-common carotid occlusion (2-VO). The rats were divided into 4 groups including: control (n = 6), sham (n = 6), 2-VO (n = 8), and 2-VO + Wi-Fi (n = 10) groups. Wi-Fi modem centrally located at the distance of 25 cm from the animal's cages and the animals were continuously exposed to Wi-Fi signal while they freely moved in the cage (2 h/day for forty-five days). Therefore, the power density (PD) and specific absorption rate value (SAR) decreased at a distance of 25 to 60 cm (PD = 0.018 to 0.0032 mW/cm2, SAR = 0.0346 to 0.0060 W/Kg). The learning, memory, and hippocampal synaptic-plasticity were evaluated by radial arm maze (RAM), passive avoidance (PA), and field-potential recording respectively. The number of hippocampal CA1 cells was also assessed by giemsa staining.Results: Our results showed that VaD model led to impairment in the spatial learning and memory performance in RAM and PA that were associated with long-term potentiation (LTP) impairment, decrease of basal-synaptic transmission (BST), increase of GABA transmission, and decline of neurotransmitter release-probability as well as hippocampal cell loss. Notably, chronic Wi-Fi exposure significantly recovered the learning-memory performance, LTP induction, and cell loss without any effect on BST.Conclusions: The LTP recovery by Wi-Fi in the 2-VO rats was probably related to significant increases in the hippocampal CA1 neuronal density, partial recovery of neurotransmitter release probability, and reduction of GABA transmissiSon as evident by rescue of paired-pulse ratio 10 ms.

Neuroprotective effects of sodium valproate on hippocampal cell and volume, and cognitive function in a rat model of focal cerebral ischemia.

Valproate (VPA) as a histone deacetylase (HDAC) inhibitor has shown neuroprotective effects in neurodegenerative diseases. This study evaluated whether VPA treatment ameliorated the synaptic plasticity dysfunction, hippocampal neuronal loss, and spatial memory deficits induced by cerebral ischemia in the middle cerebral artery occlusion (MCAO) model. Thirty-two male Sprague-Dawley rats were randomly divided into 4 groups control, sham, cerebral ischemia+vehicle (MCAO+V), and MCAO+VPA. The right common carotid artery was occluded for 1 hour. VPA (300 mg/kg) or vehicles were injected intraperitoneally on days 0,1,2 and 3 of the reperfusion. After 7 days of reperfusion the Morris water maze, passive avoidance, and open field tests were performed. Hippocampal synaptic plasticity in the CA1 area was recorded by field potential recording. We used the term neuronal Input-Output (I/O) function and paired-pulse ratio (PPR) to refer to basal synaptic transmission and presynaptic neurotransmitter release probability respectively. After that, the brains were removed for assaying stereological parameters of the CA1 neurons. Our results showed the VPA administration significantly reduced the total infarct volume, improved MCAO-induced spatial learning -memory, fear memory, and anxiety compared to the MCAO+V group. In addition, the field potential recording showed that VPA significantly ameliorated the impaired the long- term potentiation (LTP) induced by MCAO, without any effects on basal synaptic transmission and neurotransmitter release probability. Therefore, it seems that a decrease in total infarct volume and induction of long-term potentiation via postsynaptic mechanisms is responsible for improving MCAO-induced cognitive impairment.

Co-treatment of vitamin D supplementation with enriched environment improves synaptic plasticity and spatial learning and memory in aged rats.

RATIONALE AND OBJECTIVE: Environmental enrichment (EE) has been shown in old rats to improve learning and memory. Vitamin D (VitD) has also been shown to modulate age-related, cognitive dysfunction. As both EE and VitD could work to improve cognition via enhancement of neurotrophic factors, their effects might occlude one another. Therefore, a clinically relevant question is whether noted cognition-promoting effects of EE and VitD can co-occur. METHODS: Aged rats were housed for 6 weeks in one of three housing conditions: environmentally enriched (EE), socially enriched (SE), or standard condition (SC). Further, a 4th group was co-treated with VitD supplementation (400 IU kg-1 daily, 6 weeks) under EE conditions (EE + VitD). RESULTS: Treatment with VitD and EE housing were associated with higher score on measures of learning and memory and exhibited lower anxiety scores compared to EE alone, SE or SC as assayed in the elevated plus maze, Morris water maze, passive avoidance, and open field tasks. Additionally, in the EE + VitD group, mRNA expression levels of NGF, TrkA, BDNF, Nrf2, and IGF-1 were significantly higher compared to expression seen in the EE group. Furthermore, field potential recordings showed that EE + VitD resulted in a greater enhancement of hippocampal LTP and neuronal excitability when compared to EE alone. CONCLUSIONS: These findings demonstrate that in aged rats exposure to EE and VitD results in effects on hippocampal cognitive dysfunction and molecular mechanisms which are greater than effects of EE alone, suggesting potential for synergistic therapeutic effects for management of age-related cognitive decline.

Clinical and radiological characteristics and predictors of outcome of cerebral venous sinus thrombosis, a hospital-based study.

Cerebral venous sinus thrombosis is an uncommon cause of stroke, which is more prevalent in Iran and the Middle East. We aimed to assess the etiology, radiologic, and clinical manifestations of cerebral venous sinus thrombosis, specifically the predictors of patients' outcome in Namazi hospital, Shiraz, Iran. In this retrospective study, we included all adult patients with the diagnosis of cerebral venous sinus thrombosis, who were admitted in hospital, from 2012 to 2016. Demographic data, radiologic findings, clinical presentation, risk factors, treatment, and outcome according to modified Rankin Scale (mRS) on discharge were assessed and the factors associated with hospital fatality and poor outcome (mRS > 2) were investigated through univariable and multivariable analyses. Adjusted odds ratio (OR), 95% confidence interval (CI), and p values were reported. Among 174 patients, 128 (73.6%) were female. The mean age was 37.8 ± 11.2. Total of 39 patients (22.4%) had poor discharge outcome and nine patients died in hospital. Older age (OR = 1.041, CI = 1.000-1.08), decreased level of consciousness (OR = 5.46, CI = 2.17-13.72), focal neurologic deficit (OR = 5.63, CI = 2.14-14.77), and expansion of intracranial hemorrhage (ICH) (OR = 9.13, CI = 1.96-42.64) were predictors of poor outcome according to the logistic regression model. Older age (p = 0.02), focal neurologic deficit (p = 0.005), deep venous system thrombosis (p = 0.002), early intracranial hemorrhage (p = 0.049), delayed hemorrhage (p = 0.007) and hemorrhage expansion (p = 0.002), infratentorial hemorrhagic lesions (p = 0.005), and higher CRP (p = 0.011) were associated with hospital fatality. The patients with gynecologic risk factors were at lower risk of hospital death (p = 0.005). Age, decreased consciousness and focal neurological deficit on admission, and expanded intracranial hemorrhage are predictors of poor outcome. The patients who are at higher risk of unfavorable outcome should be recognized and closely monitored.

Diagnosis and quantitative detection of HSV DNA in samples from patients with suspected herpes simplex encephalitis

Diagnosis of herpes simplex encephalitis (HSE) is based on the detection of herpes simplex virus (HSV) DNA in patients' CSF samples. HSV DNA quantitation has the potential for estimating the effects of antiviral therapy. The aim of this study was to diagnose HSV DNA in HSE suspected patients and the quantitative analysis of its genome using real-time PCR to assess the value of the viral load in the course of antiviral treatment. The CSF samples were collected from 236 consecutive HSE suspected patients from November 2004 to May 2008. Upon DNA extraction, the samples were analyzed by Real-Time PCR assay. A set of primers amplified a common sequence of HSV glycoprotein B gene. The copy numbers of unknown samples were expressed via a standard curve drawn with a known amount of amplified cloned plasmid. Of the 236 samples, 137 (58 percent) came from males and 99 (42 percent) from females. The HSV genome was detected in 22 (9.3 percent) patients by PCR, 13 males/ 9 females. Serial CSF samples were available from 10 of the 22 patients. The range of the HSV DNA copy numbers in the clinical samples ranged from 2.5 × 10² to 1.7 × 10(6) copies/mL of CSF. Quantitative PCR results can be helpful in evaluating the efficacy of antiviral therapy in the above-mentioned patients. There is an association between the initial viral load and the duration of treatment course.