The course of anxiety and depression in surgical and non-surgical patients.

OBJECTIVE: The aim of this study was to compare the level of anxiety and depression in patients admitted to surgery or internal departments. METHODS: The study was carried out on 359 hospitalized patients over the age of 18 years and designed as a cross sectional survey. Participants were recruited from internal medicine and surgery departments of Khatam Ol Anbia hospital, Tehran, Iran. Information was collected using the Hospital Anxiety and Depression Scale. RESULTS: Ninety-four (26.18%) patients had no anxiety and depression, 96 (26.7%) were borderline cases of anxiety, 140 (39%) were very anxious, 89 (24.8%) were borderline cases of depression, and 106 (29.5%) had depressed mood. There was a significant correlation between anxious mood and sex and duration of background disease as well as between the level of depressive mood and age. Patients with anxiety are significantly more prone to depression. However there were no significant differences between the level of anxiety or depression between surgical or non-surgical patients. CONCLUSIONS: The prevalence of anxious and depressive moods was high in both surgical and non-surgical patients. However, non-surgical treatments were as stressful as surgical procedures for patients admitted to hospital in the first 24 h.

Diminution of the NMDA receptor NR2B subunit in cortical and subcortical areas of WAG/Rij rats.

Modulation of glutamatergic NMDA receptors affects the synchronization of spike discharges in in WAG/Rij rats, a valid genetic animal model of absence epilepsy. In this study, we describe the alteration of NR2B subunit of NMDA receptors expression in WAG/Rij rats in different somatosensory cortical layers and in hippocampal CA1 area. Experimental groups were divided into four groups of six rats of both WAG/Rij and Wistar strains with 2 and 6 months of age. The distribution of NR2B receptors was assessed by immunohistochemical staining in WAG/Rij and compared with age-matched Wistar rats. The expression of NR2B subunit was significantly decreased in different somatosensory cortical layers in 2- and 6-month-old WAG/Rij rats. In addition, the distribution of NR2B in hippocampal CA1 area was lower in 6-month-old WAG/Rij compared with age-matched Wistar rats. The reduction of NR2B receptors in different brain areas points to disturbance of glutamate receptors expression in cortical and subcortical areas in WAG/Rij rats. An altered subunit assembly of NMDA receptors may underlie cortical hyperexcitability in absence epilepsy.

Behavioural and histopathological assessment of the effects of periodic fasting on pentylenetetrazol-induced seizures in rats.

OBJECTIVES: Periodic fasting (PF) was suggested to display antiepileptic and neuroprotective effects, which is in stark contrast to severe fasting or starvation. However, these beneficial effects seem to depend on the type and duration of the used feeding protocol. There are discrepancies concerning both antiepileptic and neuroprotective effects of a PF-diet during repetitive seizures in different epilepsy models. This study was designed to evaluate the effects of different PF protocols on behavioural and histopathological consequences of epilepsy in adult rats. METHODS: Recurrent generalized seizures were caused by repetitive injection of pentylenetetrazol (PTZ) for a period of 4 weeks every other day. While control animals had free access to food and water, animals on a PF-diet were on intermittent fasting for 24 hours every 48 hours for 4 weeks before (T1), after (T2), or both before and after (T3) the injection of PTZ. Behavioural studies were carried out after PTZ injections and histological investigations were performed after the experiments were completed. RESULTS: Seizure assessment showed that the severity of seizures was significantly decreased in groups T1 and T3 when compared with control rats. Dark neuron densities in hippocampal CA1 and CA3 areas were decreased in PF groups, but never in the temporal cortex. The PF-diet also decreased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling-positive neurons in the hippocampus in both areas and all PF-diet protocols. DISCUSSION: These results support the idea that a PF-diet has anticonvulsive and neuroprotective effects on epileptic rats but underlines that different PF-diet protocols can have varying effects. Anticonvulsive effects were strongest when the PF-diet started before the onset of excitotoxic injuries, the number of dark neurons was decreased and apoptosis was prevented by all PF-diet protocols investigated in this work. Further evaluation of PF-diet protocols for possible clinical anticonvulsant and neuroprotective effects is suggested.

Sequential changes in neuronal activity in single neocortical neurons after spreading depression.

BACKGROUND: Cortical spreading depression (CSD) has an important role in migraine with aura. Prolonged neuronal depression is followed by a late excitatory synaptic plasticity after CSD. METHOD: Intra- and extracellular recordings were performed to investigate the effect of CSD on intracellular properties of mouse neocortical tissues in the late excitatory period. RESULTS: During CSD, changes in the membrane potentials usually began with a relatively short hyperpolarization followed by an abrupt depolarization. These changes occurred roughly at the same time point after CSD as the beginning of the negative extracellular deflection. Forty-five minutes after CSD, neurons showed significantly smaller amplitude of afterhyperpolarization and a reduced input resistance. Depolarization and hyperpolarization of the cells by constant intracellular current injections in this period significantly changed the frequency of the action potentials. CONCLUSION: These data indicate higher excitability of the neocortical neurons after CSD, which can be assumed to contribute to hyperexcitability of neocortical tissues in patients suffering from migraine.

Anticonvulsant and neuroprotective effects of Pimpinella anisum in rat brain.

BACKGROUND: Essential oil of Pimpinella anisum L. Apiaceae (anise oil) has been widely used in traditional Persian medicine to treat a variety of diseases, including some neurological disorders. This study was aimed to test the possible anti-seizure and anti-hypoxia effects of anise oil. METHODS: The effects of different concentrations of anise oil were tested on seizure attacks induced by pentylenetetrazol (PTZ) injection and neuronal hypoxia induced by oxygen withdrawal as well as on production of dark neurons and induction of long-term potentiation (LTP) in in vivo and in vitro experimental models of rat brain. RESULTS: Anise oil significantly prolonged the latency of seizure attacks and reduced the amplitude and duration of epileptiform burst discharges induced by injection of intraperitoneal PTZ. In addition, anise oil significantly inhibited production of dark neurons in different regions of the brain in epileptic rats. Anise oil also significantly enhanced the duration of the appearance of anoxic terminal negativity induced by oxygen withdrawal and inhibited induction of LTP in hippocampal slices. CONCLUSIONS: Our data indicate the anticonvulsant and neuroprotective effects of anise oil, likely via inhibition of synaptic plasticity. Further evaluation of anise oil to use in the treatment of neurological disorders is suggested.

In vitro differentiation of bone marrow stromal cells into oligodendrocyte-like cells using triiodothyronine as inducer.

An in vitro technique was devised to induced autologous adult stem cells into oligodendrocyte-like cells. In this study, a protocol was developed for the induction of bone marrow stromal cells (BMSCs) into oligodendrocyte-like cells. BMSCs were incubated in one of these three pre-inducers: dimethyl sulfoxide (DMSO), ß-mercaptoethanol (ßME) or biotylated hydroxyanisol (BHA), each followed by retinoic acid (RA) treatment. The percentage of viable cells in BHA-RA preinduced cells was significantly lower than the others. The results showed that the preinduced cells were immunoreactive for nestin and NF-68; among the mentioned protocols, the immunoreactivity yielded by following the DMSO-RA protocol was significantly higher than the others. Moreover, no significant immunoreactivity was observed for preinduced cells to O4, O1, MBP (myelin basic protein), S100, and GFAP (glial fibrillary acidic protein). The cells were immunoreactive to oligo-2. Two phases of induction were done: the first was a combination of basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) and heregulin (HRG), followed by either triiodothyronine (T3) or Forskolin (FSK) as the second phase. The conclusion is that the trans-differentiation of BMSCs by DMSO followed by RA (preinduction stage) then bFGF-PDGF-HRG followed by T3 (10 ng/ml) (induction stage) can be a potential source for oligodendrocyte-like cells preparation.

Epilepsy lifetime prevalence in Iran: a large population- based national survey.

Epilepsy has garnered increased public health focus because patients who suffer from epilepsy experience pronounced and persistent health and socioeconomic disparities despite treatment and care advances. The epidemiology of epilepsy is diverse in different countries and regions. This nationwide population-based cross-sectional study was conducted to determine the life time prevalence and health related factors of epilepsy for the first time in Iran through a two-phase door-to-door survey method. In phase I, a screening for epilepsy was performed on 68,035 people. Then in phase II, after the neurological evaluation of participants and reviewing medical records, 1130 subjects with epilepsy was confirmed. The life time prevalence of epilepsy was achieved to be 16.6 per 1000 people (95% CI 15.4-17.8) with the average age onset 19.1 ± 21.1 (active prevalence 9.5 per 1000 people). Focal seizure (59.3%), generalized epilepsy (38%) and unknown types of epilepsy (2.7%) were detected among participants. The overall life time prevalence of febrile convulsion was 4.1 per 1000 people. The frequency of attacks per year and per month were 3.0 ± 1.6 and 0.5 ± 0.1, respectively. Age-specific life time prevalence was highest among the age group of 15-19 years old [32.7 per 1000 persons (95% CI 29.1-36.8)] and it was higher in male (53.8%) than female (46.2%) participants. Our results showed that the life time prevalence of epilepsy in Iran is higher than worldwide average.

Comparison of Two Validation Nutrition Tools in Hospitalized Elderly: Full Mini Nutritional Assessment and Short-form Mini Nutritional Assessment.

BACKGROUND: The aim was to determine validity, reliability, and cutoff of full-mini nutritional assessment (MNA) and MNA-short form (SF) also which one was better for the screening of malnutrition in the Iranian hospitalized elderly. METHODS: In this cross-sectional validation study, 96 hospitalized elderly ≥60 years selected from two hospitals in Tehran. Anthropometric measures (body mass index [BMI], mid-arm circumference [MAC], calf circumference [CC], abdomen, and waist skinfold thickness) and laboratory tests (albumin and hemoglobin levels, and red blood cell count were performed. Nutrition tools (full-MNA and MNA-SF), cognition tool (mini-mental state examination, depression scale (Geriatric Depression Scale15 and activities of daily living (ADL) index (Modified Barthel-ADL) were administered. RESULTS: The full-MNA scores were significantly correlated to measures of MAC, BMI, waist, and CC. The MNS-SF scores were significantly related to measures of MAC, waist, and CC. Serum albumin showed a poor correlation with both tools. At cutoff 24 in full-MNA had a sensitivity 75% and specificity 77.8% and the MNA-SF considered 62.5% sensitivity and 65.3% specificity at cutoff 10.50 to detect well-nourished from malnourished subjects. The internal consistencies of both tools were >90%. In exploratory factor analysis, six components found for full-MNA and two components for MNA-SF. Known group validity of full-MNA was reflected significant differences between geriatric patients with expected higher full-MNA scores and patients with expected lower scores (BMI ≥24 vs. BMI <24 or bed ulcer or assisted food intake). CONCLUSIONS: It seems the Persian version of full-MNA is more appropriate in comparison to MNA-SF for screening malnutrition in the Iranian hospitalized elderly patients.

Double spinal dysraphism. Report of three cases.

The simultaneous presence of multiple spinal neural tube defects is unusual. There have been only a few of these cases reported in the literature. The authors report on three cases of double spina bifida cystica. One patient had two myelomeningoceles (MMCs) at the cervical and lumbosacral regions, one was noted to have both thoracolumbar and sacral defects, and the third presented with double MMCs at lumbar and lumbosacral levels. All three neonates in these cases underwent surgical treatment and ventriculoperitoneal (VP) shunt insertion for associated hydrocephalus. One child died at the age of 2 months despite a well-functioning VP shunt. The other two patients had no complications. Current models of neural tube closure do not thoroughly explain the mechanisms of multiple spinal dysraphism, but the multisite closure model provides a better understanding of caudal neural tube closure than other closure-site models.

Effect of shunt catheter on the systemic immune response: evaluation of neutrophil count, function, and rate of chemotaxis.

OBJECT: The localized impairment of the host defense mechanism due to the presence of a shunt apparatus has been suggested as a risk factor for shunt infection. The purpose of this study was to evaluate the probable systemic effect of a shunt catheter on neutrophil phagocytosis and chemotaxis in vivo. METHODS: Twenty-four children with hydrocephalus who were referred to the Children's Hospital Medical Center in Tehran for ventriculoperitoneal shunt placement were included in this study. Neutrophil count, chemotaxis, and nitroblue tetrazolium (NBT) tests were performed before and 2 months after the operation. In comparing the preoperative neutrophil count, NBT percentage, and chemotaxis (with and without the addition of a chemoattractant factor) with these same factors postoperatively, the authors found no statistically significant differences. In four children, shunt infections developed during the follow-up period. There were no significant differences between the aforementioned parameters in children with infected shunts and those with uninfected shunts. CONCLUSIONS: The results of this study do not support the idea of systemic impairment of neutrophils after shunt insertion. Further studies with more specific methods are required to elaborate on this issue.

Progesterone-induced transdifferentiation of bone marrow stromal cells into Schwann cells improves sciatic nerve transection outcome in a rat model.

BACKGROUND: Peripheral nerve injury is a common lesion in clinical practice and transplantation is one of the most common approaches to its treatment. While nerve graft is used for restoring the defected nerve using autologous or allogenic tissues, Schwann cells are considered as an alternative source. In this study, bone marrow stromal cells (BMSCs) were induced to transdifferentiate into Schwann-like cells (SLCs) using progesterone. METHODS: The BMSCs were collected from the long bones of rats and were transdifferentiated in vitro into SLCs by preinduction with ß-mercaptoethanol and retinoic acid, followed by induction with bFGF, PDGF, forskelin and progesterone. The SLCs were then transplanted in a rat model of sciatic nerve injury with 1-cm gaps. A sciatic function index (SFI), histological, immunohistochemical and ultrastructural studies were used in evaluating the improvement in the nerves regeneration. RESULTS: The results show significant differences in the SFI between the control and the treated groups (P<0.05). The transplant was immunoreactive to S100, and the electron microscopy showed myelination in the transplanted cells. CONCLUSIONS: There were functional and structural improvements in the progesterone-induced SLCs, which were not significantly different from the heregulin-treated ones (positive control) but still significantly different from negative controls.

Improvement of spinal contusion model by cotransplanting bone marrow stromal cells and induced BMSCs into oligodendrocytes-like cells.

BACKGROUND: Demyelination is a common lesion in spinal cord injury, cell therapy is one of the approaches for replacing the lost oligodendrocytes. In this study, bone marrow stromal cells (BMSCs) have been transdifferentiated into oligodendrocyte-like cells (OLCs) and used in cytotherapy of contused spinal cords in rats. METHODS: The BMSCs were collected from the rat long bones, and cultured and characterized by different markers, then they were preinduced with dimethyl sulfoxide followed by retinoic acid, and then the preinduced cells were induced with combination of basic fibroblast growth factor, platelet-derived growth factor and heregulin, followed by triiodothyronine. The OLCs were transplanted in the contused spinal cords of the rats, combined with undifferentiated BMSCs. Specific markers were used in order to characterize the cells by immunohistochemistry and real-time polymerase chain reaction. The BMSCs showed typical immnuoreactivity to the markers, and the OLCs were immunostained with specific markers. RESULTS: There was an improvement in the Basso, Beattie and Bresnahan score with reduction in the cavitation in the contused rats treated with OLCs combined with BMSCs. The transplanted cells were detected in the contused spinal cord. CONCLUSIONS: The combination of the transdifferentiated BMSCs into OLCs with the undifferentiated BMSCs improved the contused spinal cord.

Controlled release of an endostatin peptide using chitosan nanoparticles.

Whereas several anticancer peptides are in different stages of clinical development, their administration is limited by the fast elimination from the systemic circulation. Peptide loading on nano-carriers can pave the way for their future application. We have recently indicated that a disulfide loop rather than a Zn-binding loop improves the anti-angiogenic and antitumor activities of the N-terminal fragment of endostatin. In this study, chitosan nanoparticles (CS NPs) are used for the controlled release of the engineered peptide. Loading of the peptide into CS NPs using the ionic gelation method was confirmed by FTIR and resulted in final particle size, poly-dispersity index and surface charge of 186.5 ± 24.0 nm, 0.26 ± 0.02 and 20.1 ± 0.4 mV respectively. The SEM morphological analysis revealed spherical particles with an average size of 80 ± 5 nm. Peptide loading studies revealed that CS NPs are able to adsorb the peptide as ~70%. The release measurements indicated an initial burst release by 49% after 2 hr and complete release after 80 hr. According to in vitro studies, the loaded peptide was much more toxic for endothelial cells than different cancer cell lines. These results underscore the promise of CS NPs as therapeutics nanosystems and open a perspective for improving the clinical applications of peptide drugs.

Enhancement of Neural Stem Cell Survival, Proliferation, Migration, and Differentiation in a Novel Self-Assembly Peptide Nanofibber Scaffold.

Considerable efforts have been made to combine biologically active molecules into the self-assembling peptide in order to improve cells growth, survival, and differentiation. In this study, a novel three-dimensional scaffold (RADA4GGSIKVAV; R-GSIK) was designed by adding glycine and serine between RADA4 and IKVAV to promote the strength of the peptide. The cell adhesion, viability, proliferation, migration, and differentiation of rat embryonic neural stem cells (NSCs) in R-GSIK were investigated and compared to laminin-coated, two-dimensional, and Puramatrix cultures. The scanning electron microscopy studies of the R-GSIK showed an open porous structure and a suitable surface area available for cell interaction. R-GSIK promoted the cell adhesion, viability, proliferation, and migration compared to the other cultures. In addition, the R-GSIK enhanced NSCs differentiation into neuronal cells. The NSCs injected in R-GSIK had a lower glial differentiation rate than in the Puramatrix. The results suggest that R-GSIK holds great promise for cell therapies and neuronal tissue repair.

Survival, proliferation and differentiation enhancement of neural stem cells cultured in three-dimensional polyethylene glycol-RGD hydrogel with tenascin.

Polyethylene glycol hydrogel (PEG) conjugated with arginyl glycyl aspartic acid (RGD) (PEG-RGD) has been considered to be a scaffold in three-dimensional (3D) culture that improves neurite outgrowth; on the other hand, tenascin C controls neural growth and differentiation. In this study, the effect of a combined RGD and tenascin C mixture in 3D culture (3D-PEG-RGD-TnC) on the survival, growth and differentiation of neural stem cells. The viability of the culture has been evaluated by live/dead assay and the results show that the viability of NSCs in 3D-PEG-RGD-TnC is significantly higher than its value in 3D-PEG-RGD. The proliferation was evaluated by MTS test and was found to be slightly improved but statistically not significant. Accordingly, the differentiation was evaluated by immunoreactivity to nestin, neurofilament 68, neurofilament 160, neurofilament 200 and GFAP; and the expression of nestin, neuro D, musashi1, ß-tubulin III, GFAP, MBP and Oct4 was studied using RT-PCR. The results showed enhancement of the differentiation of NSCs into the neuronal phenotype in 3D-PEG-RGD-TnC. The morphology of NSCs cultured in 3D-PEG-RGD-TnC showed neurite outgrowths and increase in the contact between the differentiated cells' extensions. The conclusion of this study was that NSC survival, proliferation and differentiation are enhanced when the cells are cultured in 3D-PEG-RGD-TnC.

The prevalence of carpal tunnel syndrome among long-term manual wheelchair users with spinal cord injury: A cross-sectional study.

CONTEXT: Use of a handrim wheelchair could force the wrist into extreme excursions and encroachment of the median nerve. OBJECTIVE: We performed a study of the prevalence of carpal tunnel syndrome in prolonged wheelchair users. DESIGN AND SETTING: A cross-sectional study was conducted for one year in an outpatient clinic of spinal cord injury. PARTICIPANTS: Patients had traumatic injury at the first thoracic level and below, with time since injury of at least 5 years. OUTCOME MEASURE: The prevalence of carpal tunnel syndrome by history taking, clinical examinations and motor and sensory nerve conduction studies of median nerve performed for both hands. RESULTS: Participants (N = 297) were all male. Mean (SD) age and duration since injury were 48 (8.5) and 23 (6.6) years, respectively. A significant difference in median duration of injury based on the severity of the syndrome (P < 0.001), and a significant trend in time since injury for the severity (P (one tailed) < 0.001) were seen. There was a significant difference in the median age among the groups (P = 0.009), and the median increased with the severity (P (one tailed) = 0.001). CONCLUSIONS: Carpal tunnel syndrome is a common side effect of the long time use of wheelchair, and its severity is associated with duration of wheelchair use and age. Alternative methods for wheelchair propulsion should be developed to diminish the likelihood of the syndrome.

Survival, proliferation, and migration of human meningioma stem-like cells in a nanopeptide scaffold.

OBJECTIVES: In order to grow cells in a three-dimensional (3D) microenvironment, self-assembling peptides, such as PuraMatrix, have emerged with potential to mimic the extracellular matrix. The aim of the present study was to investigate the influence of the self-assembling peptide on the morphology, survival, proliferation rate, migration potential, and differentiation of human meningioma stem-like cells (hMgSCs). MATERIALS AND METHODS: The efficacy of a novel method for placing hMgSCs in PuraMatrix (the injection approach) was compared to the encapsulation and surface plating methods. In addition, we designed a new method for measurement of migration distance in 3D cultivation of hMgSCs in PuraMatrix. RESULTS: Our results revealed that hMgSCs have the ability to form spheres in stem cell culture condition. These meningioma cells expressed GFAP, CD133, vimentin, and nestin. Using the injection method, a higher proliferation rate of the hMgSCs was observed after seven days of culture. Furthermore, the novel migration assay was able to measure the migration of a single cell alone in 3D environment. CONCLUSION: The results indicate the injection method as an efficient technique for culturing hMgSCs in PuraMatrix. Furthermore, the novel migration assay enables us to evaluate the migration of hMgSCs.

Intraspinal delivery of bone marrow stromal cell-derived neural stem cells in patients with amyotrophic lateral sclerosis: A safety and feasibility study.

BACKGROUND: Stem cells have been used in several studies with different methodologies to treat patients with ALS. METHODS: In this safety and feasibility study, 11 patients with definite or probable ALS according to El Escorial criteria were selected. 3 patients were excluded due to inadequate bone marrow or safety measures after acquisition of bone marrow. Bone marrow stromal cell-derived neural stem cells were injected in C7-T1 spinal cord under general anesthesia. Patients were followed for 12months after injection with manual muscle testing, ALSFRS-R, quality of life changes, pulmonary function test and electromyography. RESULTS: None of the patients had perioperative mortality or major morbidity. One patient had temporary deterioration in lower extremities after injection which improved after a few weeks. In the 12months post-injection, only one patient died due to pulmonary embolism. From the remaining 7 patients, all had a stable course after 4months and 5 were stable for the first 8months post-injection and deteriorated afterwards. DISCUSSION: In this study, intraspinal injection of bone marrow derived neural stem cells appears to be safe. Patients experienced a temporary stabilization for the first few months post-injection and then gradually deteriorated.

Relationship between insulin resistance and subclinical atherosclerosis in individuals with and without type 2 diabetes mellitus.

BACKGROUND: Insulin resistance is of utmost importance as an underlying mechanism for increased risk of cardiovascular disease (CVD). We assessed the association between Homeostatic Model Assessment (HOMA-IR) and two surrogate subclinical atherosclerosis markers (SCA) among individuals with and without type 2 diabetes (DM), those who did not have any clinical presentation of the CVD. METHODS: In a cross-sectional study, 208 participants (105 diabetics and 103 non-diabetics) were enrolled from referred patients with diabetes to an academic outpatient clinic and their non-diabetic relatives in-law. Fasting serum levels of insulin, blood glucose and lipid profile, were measured. Anthropometric and blood pressure were measuremented standardly. Body Mass Index (BMI) and Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index were calculated. Coronary Artery Calcium Score(CACS) was measured using a Multi-Detctor CT scanner. Flow mediated dilation (FMD) was measured using bimode ultrasonography (with linear transducer 13,000 MHZ). Univariate and multivariate logistic regression models were used to evaluate the association between these SCA markers and HOMA index in adjusting models. RESULTS: CACS and HOMA-IR were higher and FMD was lower in diabetic participants than non-diabetic ones (P < 0.01) In a stepwise logistic regression model, CACS and FMD were associated with HOMA-IR (odds ratio = 1.778; 95 % confidence interval (CI): 1.211-2.726 and odds ratio = 1.557; 95 % CI: 1.601-2.275, respectively) in non-diabetics but not among diabetic participants. CONCLUSIONS: CACS and FMD are related to insulin resistance among non-diabetic individuals, but we could not find this relationship among diabetic patients.