Intranasal delivery of sunitinib: A new therapeutic approach for targeting angiogenesis of glioblastoma.

Glioblastoma multiforme (GBM) is one of the most vascular among solid tumors, and despite the use of multimodal therapies, the survival of these patients is poor. In order to target angiogenesis in GBM as a promising strategy, an antiangiogenic drug is required. This study was designed to evaluate the effects of sunitinib, a multityrosine kinase inhibitor with tumor proliferation and angiogenesis inhibitory properties, on GBM-bearing rats. Given the ineffective drug delivery to the brain due to the presence of the blood-brain barrier (BBB), intra-nasal (IN) drug delivery has recently been considered as a non-invasive method to bypass BBB. Therefore, in the current study, IN was used as an ideal method for the delivery of sunitinib to the brain, and the effects of this method were also compared to the OR administration of the sunitinib. GBM was induced in the brain of male Wistar rats, and they were randomly divided into 4 groups; IN-STB (sunitinib intranasal delivery), IN-sham (placebo intranasal delivery), OR-STB (sunitinib oral delivery) and OR-sham (placebo oral delivery). After the end of the treatment period, an MRI of animals' brains showed a reduction in tumor growth in the treatment groups. Immunohistochemistry revealed that sunitinib inhibits angiogenesis in GBM in both OR and IN delivery methods. Analysis of liver tissue and enzymes showed that IN delivery of sunitinib had less hepatotoxicity than the OR method. Overall, it was found that IN sunitinib delivery could be used as a potential non-hepatotoxic alternative for the treatment of GBM.

Withania coagulans extract attenuates oxidative stress-mediated apoptosis of cerebellar purkinje neurons after ischemia/reperfusion injury.

Cerebral ischemia/reperfusion (I/R) is known to increase reactive oxygen species (ROS) generation, consequences of oxidative stress (OS), and neuronal death in the susceptible brain areas including the cerebellum. Newly, remarkable attention has been paid to a natural diet with the capability to scavenge ROS. Withania coagulans root extract (WCE) is rich in components with antioxidants properties. Therefore, this study aimed to evaluate the effect of WCE on cerebellar Purkinje cells (PCs) against OS-mediated apoptosis after I/R injury. In this experimental study 64 male adult Wistar rats were randomly divided into 4 groups (n = 16) as follows: control, sham, I/R, and WCE 1000 + I/R. I/R animals were pretreated with daily administration of hydro-alcoholic WCE (1000 mg/kg) or distilled water as a vehicle for 30 days before I/R injury. After 72 h, the animals were sacrificed, the cerebellum tissue was removed and used for biochemical (CAT, SOD, GPx, and MDA levels) and histopathological (Nissl and TUNEL staining) assays. Findings showed that the MDA level and the number of apoptotic neurons significantly increased and viable Purkinje neurons decreased in I/R injury (p < 0.05). Administration of 1000 mg/kg WCE reduced MDA level and enhanced antioxidants activity including CAT, SOD, and GPx significantly. In addition, intact surviving PCs increased. At the same time, TUNEL-positive neurons decreased significantly in the WCE pre-treated group (p < 0.05). These findings suggest that WCE can counteract cerebral I/R-induced OS and associated neuronal death by enhancement of ROS scavenging and antioxidant capacity. It appears that pre-treatment with 1000 mg/kg WCE for thirty days can protect PCs against OS-mediated apoptosis after I/R injury.

Which neuroimaging and fluid biomarkers method is better in theranostic of Alzheimer's disease? An umbrella review.

Biomarkers are measured to evaluate physiological and pathological processes as well as responses to a therapeutic intervention. Biomarkers can be classified as diagnostic, prognostic, predictor, clinical, and therapeutic. In Alzheimer's disease (AD), multiple biomarkers have been reported so far. Nevertheless, finding a specific biomarker in AD remains a major challenge. Three databases, including PubMed, Web of Science, and Scopus were selected with the keywords of Alzheimer's disease, neuroimaging, biomarker, and blood. The results were finalized with 49 potential CSF/blood and 35 neuroimaging biomarkers. To distinguish normal from AD patients, amyloid-beta42 (Aß42), plasma glial fibrillary acidic protein (GFAP), and neurofilament light (NFL) as potential biomarkers in cerebrospinal fluid (CSF) as well as the serum could be detected. Nevertheless, most of the biomarkers fairly change in the CSF during AD, listed as kallikrein 6, virus-like particles (VLP-1), galectin-3 (Gal-3), and synaptotagmin-1 (Syt-1). From the neuroimaging aspect, atrophy is an accepted biomarker for the neuropathologic progression of AD. In addition, Magnetic resonance spectroscopy (MRS), diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), tractography (DTT), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI), can be used to detect AD. Using neuroimaging and CSF/blood biomarkers, in combination with artificial intelligence, it is possible to obtain information on prognosis and follow-up on the different stages of AD. Hence physicians could select the suitable therapy to attenuate disease symptoms and follow up on the efficiency of the prescribed drug.

Brain Structural Changes in Schizophrenia Patients Compared to the Control: An MRI-based Cavalieri's Method.

Introduction: Schizophrenia is a severe psychotic brain disorder. One of the potential mechanisms underlying this disease may be volumetric changes in some brain regions. The present study aimed to employ magnetic resonance imaging (MRI) to estimate and quantitatively analyze the brain of patients with schizophrenia compared to the controls. Methods: This case-control study was conducted on MRI scans of 20 patients with schizophrenia and 20 healthy controls in Zahedan City, Southeastern Iran. MRIs with 4 mm slice thickness and 5 mm intervals in coronal and sagittal planes were captured. Then, quantitative parameters, including volume and volume density of various brain regions, were estimated in both groups using Cavalieri's point counting method. Data analyses were performed using the Mann-Whitney U test. Results: The findings of this investigation revealed that volumes of gray matter, hippocampus, and gray/white matter in patients with schizophrenia were significantly lower than the controls (P<0.05). The volumes of lateral ventricles in patients with schizophrenia (36.60±4.32 mm3) were significantly higher than the healthy individuals (30.10±7.98 mm3). However, there were no statistically significant differences between the two groups regarding the changes in the brain's total volume, cerebral hemispheres, white matter, brain stem, cerebellum, and corpus callosum (P>0.05). Conclusion: Volumetric estimations on brain MRI-based stereological technique can be helpful for elucidation of structural changes, following up the treatment trends, and evaluating the therapeutic situations in schizophrenia patients. Volumetric alternations in specific brain areas might be linked to cognitive impairments and the severity of symptoms in patients with schizophrenia. Further research is needed in this regard. Highlights: Volumetric changes occur in certain regions of the brain of schizophrenia patients.Structural changes in the brain of schizophrenia patients are associated with the severity of clinical manifestations.A brain MRI-based stereological technique can clarify neuropathology and assess therapeutic efficiency in patients with schizophrenia. Plain Language Summary: Schizophrenia is a severe neuropsychiatric disorder with worldwide prevalence that disrupts a person's social life. It's characterized by progressive neuroanatomical alterations in both gray and white matter in different brain regions and associated with changes in the structural and functioning of some critical brain circuits. Several factors have been suggested to be involved in the development and progression of the disease including alternations and disconnection in myelin, genetic factors, neurodegenerative process, neuroinflammation, neurodevelopmental deficiencies, the number of dopaminergic neurons and volumetric changes in different areas of the brain. It has shown that quantitative volumetric brain measurements on magnetic resonance imaging (MRI) scans in patients with neurodegenerative disease owing to selective regional atrophy are beneficial for clinicians to ascertain disease progression and to evaluate volume alternations and response to treatment. Thus, we investigated structural changes of the brain in schizophrenia patients on MR images using accurate Cavalieri's estimation and compared to healthy controls. The findings demonstrated that some structural changes occurs in various brain areas which involved in many critical roles in normal brain's functionality and connectivity. On the other hand, these changes are associated with cognitive impairments and the severity of clinical symptoms in patients with schizophrenia. It's appears that elucidation of the different pathways of various structural abnormalities related to schizophrenia is required to recognize and determine the role of discrete pathophysiological phenomena in mental illness development and progress.

Long-term administration of metformin ameliorates age-dependent oxidative stress and cognitive function in rats.

BACKGROUND: Aging is an inevitable physiological process, associated with a decline in cognitive function. Recently, metformin, as the first-line treatment for type II diabetes, has been shown to increase the life expectancy of diabetic patients. Therefore, researchers are paying increasing attention to its anti-aging properties. Oxygen free radicals are responsible for oxidative stress, which is a prominent factor in age-associated diseases. This study aimed to evaluate the effects of long-term administration of metformin on age-dependent oxidative stress and cognitive function. METHODS: In this experimental study, 32 normal (nondiabetic) male Wistar rats were randomly assigned into control and metformin groups (n = 16 per group). The metformin group received 100 mg/kg of metformin in drinking water daily for six months. The shuttle box test was used for the passive avoidance task in 24-month-old rats. For the biochemical assay, the total antioxidant capacity (TAC) and malondialdehyde (MDA) level were measured. Nissl and TUNEL staining were also used for histopathological assessments. Data were analyzed using independent t-test. RESULTS: The present findings revealed that metformin significantly reduced the MDA level and increased the TAC in the hippocampus of the metformin group (p < 0.05). The survival of hippocampal CA1 neurons was significantly higher in the metformin group as compared to the control group, while the number of TUNEL-positive neurons decreased significantly (p < 0.05). On the other hand, metformin markedly improved the passive avoidance memory in the metformin group as compared to the control group (p < 0.05). CONCLUSION: It can be concluded that long-term metformin intake, by modulating the oxidant/antioxidant mechanisms, prevents the loss of hippocampal neurons caused by age-dependent oxidative stress and improves memory.

Structural changes in the brain of patients with relapsing-remitting multiple sclerosis compared to controls: a MRI-based stereological study.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system characterized by demyelination, inflammation, gliosis, and axonal loss. Nowadays, increasing scientific reports have focused on neurodegenerative processes and structural changes of the disease underlying pathogenesis. AIM: The aim of this study is a structural analysis of brain magnetic resonance images (MRIs) in patients with relapsing-remitting multiple sclerosis (RRMS) comparing with normal individuals. METHODS: This case-control study was carried out on MRIs of 20 patients with RRMS and 20 healthy controls in Zahedan, Iran. MR images with 4-mm slice thickness and 0.5-mm intervals in three anatomical planes (coronal, sagittal, axial) were acquired. Then, stereological parameters, including volume and volume density of different parts of the brain, based on Cavalries' point counting method were measured in both groups. Data analyses were performed using Mann-Whitney U and Pearson's correlation tests. RESULTS: The results of the study showed that there were no significant differences in total brain, hemispheres, gray matter, and basal nuclei volume and volume density between the two groups (p Ëƒ 0.05). However, the left hemisphere, cerebellum, lateral ventricles, brainstem, corpus callosum, and white matter volume in RRMS patients were significantly lower than those in controls (p Ë‚ 0.05). CONCLUSION: The findings showed that quantitative assessments based on stereological method on brain MRIs facilitate clarifying neuropathology of the disease. Also, it can be helpful as a simple index for following up the clinical situation and assessing therapeutic efficiency in MS patients. It may provide a precise treatment approach and justification of symptoms in patients with MS.

Investigating the Causes of Medication Errors and Strategies to Prevention of Them from Nurses and Nursing Student Viewpoint.

INTRODUCTION & AIM: Medication errors as a serious problem in world and one of the most common medical errors that threaten patient safety and may lead to even death of them. The purpose of this study was to investigate the causes of medication errors and strategies to prevention of them from nurses and nursing student viewpoint. MATERIALS & METHODS: This cross-sectional descriptive study was conducted on 327 nursing staff of khatam-al-anbia hospital and 62 intern nursing students in nursing and midwifery school of Zahedan, Iran, enrolled through the availability sampling in 2015. The data were collected by the valid and reliable questionnaire. To analyze the data, descriptive statistics, T-test and ANOVA were applied by use of SPSS16 software. FINDINGS: The results showed that the most common causes of medications errors in nursing were tiredness due increased workload (97.8%), and in nursing students were drug calculation, (77.4%). The most important way for prevention in nurses and nursing student opinion, was reducing the work pressure by increasing the personnel, proportional to the number and condition of patients and also creating a unit as medication calculation. Also there was a significant relationship between the type of ward and the mean of medication errors in two groups. CONCLUSION: Based on the results it is recommended that nurse-managers resolve the human resources problem, provide workshops and in-service education about preparing medications, side-effects of drugs and pharmacological knowledge. Using electronic medications cards is a measure which reduces medications errors.