Immunomodulatory and Anti-Inflammatory Effects of Scrophularia megalantha Ethanol Extract on an Experimental Model of Multiple Sclerosis

Background and objectives: Scrophularia megalantha is a native Iranian plant. In folk remedies, the species of the genus are used to treat stomach ulcers, goiter, eczema, cancer, psoriasis, and gall; however, there is not much research about S. megalantha. The current study aimed at evaluating the therapeutic effect of Scrophularia megalantha, a medicinal plant of Iran, on myelin oligodendrocyte glycoprotein 35-55 (MOG)-induced experimental autoimmune encephalomyelitis (EAE) as a model of multiple sclerosis (MS). Methods: The ethanol 80% extract of S. megalantha aerial parts was prepared by maceration method. The extract (100 mg/kg/day) was administered to C57BL/6 mice immunized with MOG (35-55) for 7 days, 3 weeks after EAE induction. The mice brain was removed and Hematoxylin-Eosin (H&E) was used to stain the sections. Moreover, spleen mononuclear cells from extract-treated or non-treated of EAE model mice were stimulated with MOG peptide and then culture supernatants were evaluated for IFN-ɣ, IL-17 and IL-10 cytokines using Enzyme-Linked Immuno Sorbent Assay (ELISA) kits. Results: Based on the obtained results, treatment with Scrophularia megalantha areal part extract significantly reduced inflammatory cells infiltration in the central nervous system (CNS) and also the disease severity in the experimental model of MS. Also, findings of the current study indicated that treatment with this medicinal plant in EAE mice model significantly decreased inflammatory cytokines including IFN-ɣ and IL-17 and vice versa significantly increased IL-10 as anti-inflammatory cytokine compared with non-treated of EAE model mice group. Conclusion: Scrophularia megalantha attenuated EAE by suppressing IFN-ɣ and IL-17 production and also increasing IL-10 cytokine. These findings suggested that this medicinal plant has the anti-inflammatory and immunomodulatory effects

Nano Drug Delivery Systems and Liposomes

Progressive development of nanotechnology during the last decades and its increasing involvement in new fields represents its great importance in science and technology. One of its major parts is nanomedicine that is focused in this review. First general principles of medicinal nanotechnology, its history, application and classification are explained. Then Abraxane (a protein conjugated nano drug) design will be addressed. Liposomes as one of the best nano drug delivery systems with a platform for passive targeting are discussed next. Two examples of approved liposomal nanomedicines are described from the state-of-the-art design emphasizing physiologic barriers and formulation strategies to overcome these imposed limitations. Passive targeting to tumors is provided by "Enhanced Permeation and Retention" effect (EPR). Liposomes can be removed from circulation by the mononuclear phagocyte system (MPS) clearance in no time. This effect is also used to passively target liposomes in MPS to treat localized infections for example. Pegylation of liposomes which means attachment of polyethylene glycol chains to the surface of liposomes is one of the methods used to enhance liposome residence time in blood circulation in order to give the vesicles more chance to accumulate at the target site by EPR effect. Liposomal medicines have shown significant decrease in toxicity in comparison with free drugs. Their accumulation in target tissue by passive targeting is the main reason for reduction in drug toxicity.   Liposomes are being used for treating different diseases such as infection, hepatitis, cardiovascular diseases and immune system disorders. However, the vast majority of investigational liposomes are anticancer drugs

Vitamin D3 mediates spatial memory improvement through nitric oxide mechanism in demyelinated hippocampus of rat

Studies have revealed beneficial role of vitamin D3 in neuro-cognitive function. There is also supporting evidence on the involvement of nitric oxide (NO) in the neuro-protective action. However, its over production could contribute to brain disorders. In this study, demyelination was induced by ethidium bromide (EB) injection into the right side of the hippocampus area of male rats. Vitamin D3 was administered to rats for 7 and 28 days prior to behavioral experiments using Morris water maze (MWM). Travelled distance, time spent to reach the platform, and time spent in target zone, were considered for learning and spatial memory evaluation. Nitrite oxide (NO2-) concentration was measured as an indicator for nitric oxide production. The time spent to reach the platform and the travelled distance were decreased significantly by 28 days of vitamin D3 administration (compared to 7 days experiment). Time spent in target quadrant was significantly lowered by administered vitamin on day 28. Therefore, considering a number of studies that have shown the effect of vitamin D3 on cognition, these findings could support their potential effect. Besides, nitric oxide concentration significantly differed in 28 days of vitamin D3 treated group compared with the groups treated with EB or 7 days of vitamin D3

Patient Experiences of Hospital Stay in Alborz Governmental Hospitals

Background and Aims: Attaining the patients' viewpoints and evaluating their experiences are reliable and important resources for determining the problems and appraising healthcare improvement. This study aimed to investigate the experiences of patients who hospitalized in hospitals of Alborz province. Materials and Methods: In this descriptive cross-sectional study 955 patients discharged from nine governmental hospitals were selected by stratified random sampling method and participated in this study. The questionnaire that its validity and reliability had been confirmed was used to assess patients' experiences of hospital stay. Results: More than half of the participants (56.4%) were female. The most frequent age group (34.3%) was the age group of 20 to 30 years. 45.4% of patients experienced a perfect organization in reception sector in emergency ward, and 42.5% of patients experienced a perfect organization in reception sector of non-emergency wards. In sum, 79.4% of patients assessed the hospital healthcare services in good level (or higher) and 35.9% stated that they would recommend the hospital to others. Conclusion: The results indicates the need for designing and implementing the programs to improve patients' experiences in the areas of reception and discharge sectors organization, physical environment and facilities, communication with doctors and nurses, respectfulness, through training and empowerment of staff of hospitals and improving the existing infrastructure in the hospital

No horizontal numerical mapping in a culture with mixed-reading habits

Reading habits are thought to play an important role in the emergence of cultural differences in visuo-spatial and numerical tasks. Left-to-right readers show a slight visuo-spatial bias to the left side of space, and automatically associate small numbers to the left and larger numbers to the right side of space, respectively. A paradigm that demonstrated an automatic spatial-numerical association involved the generation of random numbers while participants performed lateral head turns. That is, Westerners have been shown to produce more small numbers when the head was turned to the left compared to the right side. We here employed the head turning/random number generation (RNG) paradigm and a line bisection (LB) task with a group of 34 Iranians in their home country. In the participants' native language (Farsi) text is read from right-to-left, but numbers are read from left-to-right. If the reading direction for text determines the layout of spatial-numerical mappings we expected to find more small numbers after right than left head turns. Yet, the generation of small or large numbers was not modulated by lateral head turns and the Iranians showed therefore no association of numbers with space. There was, however, a significant rightward shift in the LB task. Thus, while the current results are congruent with the idea that text reading habits play an important role in the cultural differences observed in visuo-spatial tasks, our data also imply that these habits on their own are not strong enough to induce significant horizontal spatial-numerical associations. In agreement with previous suggestions, we assume that for the emergence of horizontal numerical mappings a congruency between reading habits for words and numbers is required

Unilateral Hypothalamus Inactivation Prevents PTZ Kindling Development through Hippocampal Orexin Receptor 1 Modulation

Introduction: Epilepsy is a neural disorder in which abnormal plastic changes during short and long term periods lead to increased excitability of brain tissue. Kindling is an animal model of epileptogenesis which results in changes of synaptic plasticity due to repetitive electrical or chemical sub-convulsive stimulations of the brain. Lateral hypothalamus, as the main niche of orexin neurons with extensive projections, is involved in sleep and wakefulness and so it affects the excitability of the brain. Therefore, we investigated whether lateral hypothalamic area (LHA) inactivation or orexin-A receptor blocking could change convulsive behavior of acute and kindled PTZ treated animals and if glutamate has a role in this regard.  Methods: Kindling was induced by 40 mg/kg PTZ, every 48 hours up to 13 injections to each rat. Three consecutive stages 4 or 5 of convulsive behavior were used to ensure kindling. Lidocaine was injected stereotaxically to inactivate LHA, unilaterally. SB334867 used for orexin receptor 1 (OX1R) blocking administered in CSF.  Results: We demonstrated that LHA inactivation prevented PTZ kindling and hence, excitability evolution. Hippocampal glutamate content was decreased due to LHA inactivation, OX1R antagonist infusion, lidocaine injection and kindled groups. In accordance, OX1R antagonist (SB334867) and lidocaine injection decreased PTZ single dose induced convulsive behavior. While orexin-A i.c.v. infusion increased hippocampal glutamate content, it did not change PTZ induced convulsive intensity.  Discussion: It is concluded that LHA inactivation prevented kindling development probably through orexin receptor antagonism. CSF orexin probably acts as an inhibitory step on convulsive intensity through another unknown process

Neurological complications after COVID-19: A narrative review

COVID-19 is primarily classified as a respiratory disorder; however, various neurological symptoms have been reported in COVID-19 patients. Neurological manifestations may be the initial signs of COVID-19 and can develop in patients of different age groups and with or without underlying disease. COVID-19 causes a broad range of complications in the central nervous system. These include headaches, altered mental status, dizziness, seizures, cerebrovascular events, encephalitis, and other encephalopathies. Moreover, a broad spectrum of peripheral nervous system symptoms such as olfactory and gustatory dysfunctions, neuropathy, visual impairments, neuralgia, cranial nerves palsy, and muscle involvement could manifest as symptoms. Despite various efforts, the exact pathogenesis of the COVID-19 neurological complications has not been clarified yet. Moreover, the reason for the development of neurological manifestation in only some COVID-19 patients has not been determined. This review focuses on the different neurological symptoms associated with COVID-19 and the possible pathological mechanisms hoping to provide new insights for diagnosis, therapies, or other forms of intervention

Focal Injection of Ethidium Bromide as a Simple Model to Study Cognitive Deficit and Its Improvement

Introduction: Memory and cognitive impairments are some of devastating outcomes of Multiple Sclerosis (MS) plaques in hippocampus, the gray matter part of the brain. The present study aimed to evaluate the intrahippocampal injection of Ethidium Bromide (EB) as a simple and focal model to assess cognition and gray matter demyelination. Methods: Thirty Wistar rats were divided into three groups: control group, which received saline, as solvent of EB, into the hippocampus and two experimental groups, which received 3 &muL of EB into the hippocampus, and then, were evaluated 7 and 28 days after EB injection (n=10 in each group), using a 5-day protocol of Morris Water Maze (MWM) task as well as Transmission Electron Microscopy (TEM) assay. Results: Seven days after EB injection, the behavioral study revealed a significance increase in travelled distance for platform finding in the experimental group compared to the control group. In addition, the nucleus of oligodendrocyte showed the typical clumped chromatin, probably attributed to apoptosis, and the myelin sheaths of some axons were unwrapped and disintegrated. Twentyeight days after EB injection, the traveled distance and the time spent in target quadrant significantly decreased and increased, respectively in experimental groups compared to the control group. Also, TEM micrographs revealed a thin layer of remyelination around the axons in 28 days lesion group. Discussion: While intracerebral or intraventricular injection of EB is disseminated in different parts of the brain and can affect the other motor and sensory systems, this model is confined locally and facilitates behavioral study. Also, this project could show improvement of memory function subsequent to the physiological repair of the gray matter of the hippocampus