Factors affecting improvement after intravenous administration of recombinant tissue plasminogen activator (rtPA) among patients with acute ischemic stroke: A historical cohort study.

Background: One of the most effective treatments for patients with acute ischemic stroke (AIS) is intravenous recombinant tissue plasminogen activator (rtPA) which can minimize mortality and morbidities. In this historical cohort study, we investigate the factors affecting clinical outcomes after IV thrombolysis for AIS. Methods: We included 87 patients with acute ischemic stroke who were treated with rtPA between 2015 and 2019. Demographic and clinical data were recorded. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the clinical outcomes. Results: 36 patients showed lack of improvement at discharge. In unadjusted model, hypercholesterolemia was the only predictor of lack of improvement (P= 0.043; OR=0.304; CI= 0.096-0.963). After adjusting, hypertension (P= 0.018; OR= 0.18; CI= 0.043-0.749) and hypercholesterolemia (P= 0.008; OR= 8.68; CI= 1.773-42.54) were independent determinants of lack of clinical response. To evaluate risk factors in association with the duration of hospitalization, we found variables which lengthened hospitalization span including; age over 60 years (HR= 0.42 P= 0.002), hypercholesterolemia (HR= 2.19 P= 0.031), Angiotensin-converting enzyme (ACE) Inhibitors consumption (HR= 1.87 P= 0.022), and type of infarction (non-lacunar) (HR= 0.51 P= 0.026). Results indicated no considerable relationship between dose of rtPA and the appropriate response to treatment (OR=8.686 P= 0.324). Conclusion: The closer dose of rtPA goes up to standard range, the more chance of improvement will gain without increasing the risk of symptomatic intra-cerebral hemorrhage (SICH). Determining factors involved in intravenous reperfusion outcomes help physicians to identify the patients who benefit the most from rtPA.

Verbal and oral apraxia in patients with acute stroke: Frequency, relationship, and some risk factors.

Verbal and oral apraxia are two possible consequences of stroke. It seems that there are not sufficient studies regarding the frequency of these disorders. This study aimed to evaluate the frequency of Verbal and oral apraxia. In addition, the relationship between apraxia and some variables such as age, gender, and education, as well as the relationship between types of apraxia with each other, and damaged areas of the brain in apraxia of the oral system in Persian-speaking patients with stroke were studied. In this descriptive-analytical study, 42 patients participated using the convenient sampling method. Verbal and oral apraxia were assessed using the oral and verbal apraxia tasks for adults test. Data were analyzed using independent t-test, Chi-square, and Fisher's exact test. The frequency of patients with oral apraxia was 35.7%, those with verbal apraxia was 2.3%, and the combination of both verbal and oral apraxia was 4.7%. People with apraxia were significantly older than those without apraxia. There was not any significant relationship between apraxia and gender, apraxia and education, and oral apraxia with verbal apraxia (p < 0.05). The present study's findings showed the high frequency of post-stroke apraxia and the high rate of its incidence with age.

The Interplay of Tau Protein and ß-Amyloid: While Tauopathy Spreads More Profoundly Than Amyloidopathy, Both Processes Are Almost Equally Pathogenic.

Alzheimer's disease (AD) is a neurodegenerative disorder, in which amyloid precursor protein (APP) misprocessing and tau protein hyperphosphorylation are well-established pathogenic cascades. Despite extensive considerations, the central mediator of neuronal cell death upon AD remains under debate. Therefore, we examined the direct interplay between tauopathy and amyloidopathy processes. We employed primary culture neurons and examined pathogenic P-tau and Aß oligomers upon hypoxia treatment by immunofluorescence and immunoblotting. We observed both tauopathy and amyloidopathy processes upon the hypoxia condition. We also applied Aß1-42 or P-tau onto primary cultured neurons. We overexpressed P-tau in SH-SY5Y cells and found Aß accumulation. Furthermore, adult male rats received Aß1-42 or pathogenic P-tau in the dorsal hippocampus and were examined for 8 weeks. Learning and memory performance, as well as anxiety behaviors, were assessed by Morris water maze and elevated plus-maze tests. Both Aß1-42 and pathogenic P-tau significantly induced learning and memory deficits and enhanced anxiety behavior after treatment 2 weeks. Aß administration induced robust tauopathy distribution in the cortex, striatum, and corpus callosum as well as CA1. On the other hand, P-tau treatment developed Aß oligomers in the cortex and CA1 only. Our findings indicate that Aß1-42 and pathogenic P-tau may induce each other and cause almost identical neurotoxicity in a time-dependent manner, while tauopathy seems to be more distributable than amyloidopathy.

Tau Pathology Triggered by Spinal Cord Injury Can Play a Critical Role in the Neurotrauma Development.

Traumatic spinal cord injury (SCI) can result in substantial neurological impairment along with significant emotional and psychological distress. It is clear that there is profound neurodegeneration upon SCI, gradually spread to other spinal cord regions and brain areas. Despite extensive considerations, it remains uncertain how pathogenicity diffuses in the cord. It has been reported that tau protein abnormal hyperphosphorylation plays a central role in neurodegeneration triggered by traumatic brain injury (TBI). Tau is a microtubule-associated protein, heavily implicated in neurodegenerative diseases. Importantly, tau pathology spreads in a traumatic brain in a timely manner. In particular, we have recently demonstrated that phosphorylated tau at Thr231 exists in two distinct cis and trans conformations, in which that cis P-tau is extremely neurotoxic, has a prion nature, and spreads to various brain areas and cerebrospinal fluid (CSF) upon trauma. On the other hand, tau pathology, in particular hyperphosphorylation at Thr231, has been observed upon SCI. Taken these together, we conclude that cis pT231-tau may accumulate and spread in the spinal cord as well as CSF and diffuse tau pathology in the central nervous system (CNS). Moreover, antibody against cis P-tau can target intracellular cis P-tau and protect pathology spreading. Thus, considering cis P-tau as a driver of tau pathology and neurodegeneration upon SCI would open new windows toward understanding the disease development and early biomarkers. Furthermore, it would help us develop effective therapies for SCI patients.

Dopamine-loaded poly (butyl cyanoacrylate) nanoparticles reverse behavioral deficits in Parkinson's animal models.

Aim: Parkinson's disease (PD) is a neurological disorder resulting from decreased dopamine (DA) secretion in the brain, which reflects impaired motor function. Thus, a drug-delivery system for releasing DA into the brain would be of crucial importance. Materials & methods: We herein examined the in vivo drug efficiency of novel poly-butyl-cyanoacrylate nanoparticles loaded with DA (DA-PBCA NPs). Results & conclusion: The NPs were able to pass through the blood-brain barrier and improve brain structure and function in the PD animal models. Moreover, we found a reduced α-synucleinopathy in the animal model brains after the NPs administration. Thus, the NPs seem to be a reliable DA delivery system for treating PD patients.

Silymarin-albumin nanoplex: Preparation and its potential application as an antioxidant in nervous system in vitro and in vivo.

In this study, we formulated silymarin-HSA nanoplex and assayed its ability to reduce LPS-induced toxicity in vitro and in vivo. Silymarin molecules were encapsulated into HSA nanoplex and the loading efficiency and characterization of fabricated nanoplex were performed by using HPLC, TEM, SEM, DLS, FTIR analysis, and theoretical studies. Afterwards, their protective effect against LPS (20 µg/ml) -induced toxicity in SH-SY5Y cells was investigated by MTT, ROS, and apoptosis assays. For in vivo experiments, rats were pre-treated with either silymarin or silymarin -HSA nanoplex (200 mg/kg) orally for 3 days and at third day received LPS by IP at a dose of 0.5 mg/kg, 150 min before scarification followed by SOD and CAT activity assay. The formulation of silymarin-HSA nanoplex showed a spherical shape with an average diameter between 50 nm and 150 nm, hydrodynamic radius of 188.3 nm, zeta potential of -26.6 mV, and a drug loading of 97.3%. In LPS-treated cells, pretreatments with silymarin-HSA noncomplex recovered the cell viability and decreased the ROS level and corresponding apoptosis more significantly than free silymarin. In rats, it was also depicted that, silymarin-HSA noncomplex can increase the SOD and CAT activity in brain tissue at LPS-triggered oxidative stress model more significantly than the free counterpart. Therefore, nanoformulation of silymarin improved its capability to reduce LPS-induced oxidative stress by restoring cell viability and elevation of SOD and CAT activity in vitro and in vivo, respectively. In conclusion, formulation of silymarin may hold a great promise in the development of antioxidant agents.

Development of rheumatoid arthritis during treatment of multiple sclerosis with interferon beta 1-a. Coincidence of two conditions or a complication of treatment: A case report.

Coexistence of multiple sclerosis (MS) with other autoimmune diseases has been attributed to common background genetic or environmental factors. This study presents development of rheumatoid arthritis (RA) during treatment of MS. The MS was confirmed by the Mc Donald criteria and the diagnosis of RA was confirmed by the ACR/EULAR criteria. A 35 years old women with 9 years of MS who was receiving interferon beta 1-a (INF) for 7 years and who did not respond to conventional therapy of RA over 8 months developed clinical manifestations of RA. But a rapid response was observed after discontinuation of INF. These findings suggest a possible contribution of INF in the development of RA.

Optic neuritis, the most common initial presenting manifestation of multiple sclerosis in northern Iran.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory and demyelinating disease of central nervous system (CNS). The aim of the present study was to determine the type and the frequency of initial presenting symptoms in patients with MS and their relation with demographic characteristics in Babol, northern Iran. METHODS: All patients of this study were recruited over a ten year period from 2002 to 2012 from single neurologic clinic. Diagnosis of MS was confirmed according to the McDonald criteria, demographic and clinical features Then, all the clinical findings and demographic variables including: age, sex, marital status, age at onset, education, place of residence, disease duration, initiation pattern of disease have been collected. Expanded Disability Status Scale (EDSS) was used for the evaluation of disability at the onset of disease. Data analysis was performed by chi-square test. RESULTS: A total of 263 consecutive MS patients with the age range of 17 to 61 yr were examined. Optic neuritis was the most prevalent initial presenting symptom in 123 (46.8%) patients followed by sensory disturbances as the second common presenting symptom of MS. Significant difference was found between patients with or without optic neuritis and the onset age of the disease and EDSS (p<0.001). The mean EDSS score at the time of initial presentation was 1.67±0.77. CONCLUSION: The findings of this study indicated that optic neuritis is the most prevalent initial presentation of MS in the geographic region of northern Iran. In patients less than 30 years, development of visual disturbances justifies neurologic examination.

Relation between EDSS and monosymptomatic or polysymptomatic onset in clinical manifestations of multiple sclerosis in Babol, northern Iran.

BACKGROUND: Polysymptomatic or monosymptomatic patients of multiple sclerosis (MS) at the onset of the disease may influence the natural course of the disease. The purpose of this study was to determine the prognostic effect of the expanded disability status scale (EDSS) of patients with MS with polysymptomatic or monosymptomatic onset of the disease. METHODS: From 2001 to 2011, 263 patients with definitive diagnosis of MS were investigated in Shahid Beheshti Teaching Hospital in Babol, Iran. These patients were assessed regarding mono-or poly symptoms at the beginning of their disease. MRI of brain and spinal cord was done for all cases. These cases were evaluated every three months interval. EDSS of each patient at the beginning of their disease and then yearly were evaluated and registered. RESULTS: One hundred sixty-one subjects (61.2%) were monosymptomatic and 102 (38.8%) were polysymptomatic at the onset of their disease. The mean age of patients with monosymptomatic onset was 26.81+84 while in polysymptomatic was 26.35+7.7 years (P=0.656). Sex, place of residence and marriage statusbetween these two groups were equal. The mean EDSS in monosymptomatic and polysymptomatic patients were 1.37±0.64 and 2.16±0.714, respectively (P=0.0001). After the initiation of treatment, reduction of EDSS was seen in both groups but after the reduction in the first year, an increase of EDSS was seen in both groups. But there was no significant difference in the increase of EDSS in both groups. CONCLUSION: The results showed that the mean EDSS in monosymptomatic was lower than the polysymptomatic patients before treatment, but after treatment, this value does not differ in the increase of EDSS.

Soil organic carbon sequestration as affected by afforestation: the Darab Kola forest (north of Iran) case study.

Following the ratification of the Kyoto Protocol, afforestation of formerly arable lands and/or degraded areas has been acknowledged as a land-use change contributing to the mitigation of increasing atmospheric CO(2) concentration in the atmosphere. In the present work, we study the soil organic carbon sequestration (SOCS) in 21 year old stands of maple (Acer velutinum Bioss.), oak (Quercus castaneifolia C.A. Mey.), and red pine (Pinus brutia Ten.) in the Darab Kola region, north of Iran. Soil samples were collected at four different depths (0-10, 10-20, 20-30, and 30-40 cm), and characterized with respect to bulk density, water content, electrical conductivity, pH, texture, lime content, total organic C, total N, and earthworm density and biomass. Data showed that afforested stands significantly affected soil characteristics, also raising SOCS phenomena, with values of 163.3, 120.6, and 102.1 Mg C ha(-1) for red pine, oak and maple stands, respectively, vs. 83.0 Mg C ha(-1) for the control region. Even if the dynamics of organic matter (OM) in soil is very complex and affected by several pedo-climatic factors, a stepwise regression method indicates that SOCS values in the studied area could be predicted using the following parameters, i.e., sand, clay, lime, and total N contents, and C/N ratio. In particular, although the chemical and physical stabilization capacity of organic C by soil is believed to be mainly governed by clay content, regression analysis showed a positive correlation between SOCS and sand (R = 0.86(**)), whereas a negative correlation with clay (R = -0.77(**)) was observed, thus suggesting that most of this organic C occurs as particulate OM instead of mineral-associated OM. Although the proposed models do not take into account possible changes due to natural and anthropogenic processes, they represent a simple way that could be used to evaluate and/or monitor the potential of each forest plantation in immobilizing organic C in soil (thus reducing atmospheric C concentration), as well as to select more appropriate species during forestation plan management at least in the north of Iran.