Contribution of microglial reactivity to olfactory ensheathing cell migration in vivo

Olfactory ensheathing cells (OECs) are glial cells that are an attractive candidate for neural repair after spinal cord injury and for remyelination of axons in diseases such as multiple sclerosis. OECs appear to migrate within the adult mammalian central nervous system (CNS) in animal models of spinal cord injury, but until recently there has been no systematic examination of the factors inducing or guiding this migration. Previous work in our lab (V.Skihar) implicated microglial reactivity in the generation of a migratory signal(s) inducing OECs to migrate towards an ethidium bromide-induced focal demyelination in the adult rat spinal cord. The long-term objective of this research project was to test the hypothesis that reactive microglial provide a migratory signal(s) driving the migration of OECs within the spinal cord of adult rats.The first set of experiments determined the time-frame in which Wallerian degeneration (WD) induced microglial reactivity occurs in the right dorsal corticospinal tract (dCST) of adult rats at the level of T11 following aspiration of the contralateral sensorimotor cortex. This timing data from this study demonstrated a prominent microglial activation in the right dCST of T11 eight weeks after sensorimotor cortex injury indicating the microglial response to WD of dCST axons was very slow to appear. The second set of experiments determined whether OECs were induced to migrate in response to WD-induced microglial reactivity in the dCST, which based on the first set of experiments was known to occur within 8 weeks of lesioning the left sensorimotor cortex. This second set of experiments also examined the migratory path taken by OECs with respect to the location of reactive microglia (i.e. inside vs outside the right dCST). For these experiments, the left sensorimotor cortex was damaged 8 weeks prior to grafting the OECs at T12. The next group of experiments examined the contribution of TNF-á induced microglial reactivity to generation of a migratory signal. First we identified concentrations of TNF-á that when injected into the DF of the T11 spinal cord segment of an adult rat induced microglial reactivity either along at least a 5 mm distance from the injection site or confined to the immediate vicinity of the injection site. The result of this experiment identified a concentration of 1 ng/µl and 0.01 ng/µl TNF-á as appropriate concentrations to induce the appropriate amount of microglial reactivity, respectively. The final set of experiments used these two concentrations to determine whether TNF-á induced microglial reactivity that is initiated 5 mm rostral to a DiI+ve OEC graft generates a migratory signal(s) inducing OECs to migrate towards the rostral part of T11 and whether the migratory signal(s) was present only if the microglial reactivity extended the full 5 mm distance between the TNF-á injection and the OEC graft. The major findings were: i) there was a significantly higher density of DiI+ve OECs within the right dCST of rats in which there was WD-induced microglial reactivity as compared to the right dCST of rats in which there was no microglial reactivity; ii) the migratory path taken by DiI+ve OECs was preferentially within areas containing reactive microglia (i.e. dCST) and towards the site of TNF-á induced microglial reactivity (i.e. rostral to cell graft as opposed to caudal); iii) significantly more DiI+ve OECs migrated towards the site of a TNF-á injection when the microglia were reactive along the entire length of the migratory path between the cytokine injection and cell graft; and iv) minocycline treatment both dampened microglial reactivity and significantly reduced the number of migrating DiI+ve OECs. The major conclusions are that the migration of OECs within the adult rat spinal cord occurs in response to migratory signal(s) arising as a result of microglial activation and that this migration occurs preferentially along the path of microglial reactivity

Rzadki przypadek ropnia mózgu wywołanego przez Trichosporon, skutecznie leczony wycięciem chirurgicznym i lekami przeciwgrzybiczymi

Trichosporonosis is an acute, sometimes fatal infection with the potential capability of disseminating to multiple deep organs. More than 100 cases of trichosporonosis have been described, particularly in patients with neutropenia or haematological malignancies. In 1970, Watson et al. described the first case of brain trichosporonosis; the patient died 4 weeks after admission. Herein, we describe a 34-year-old man with a history of autoimmune hepatitis, hypothyroidism, and alopecia totalis, treated with corticosteroids, who was admitted with left lower limb weakness. Brain MRI revealed a diffuse brain lesion in the right frontoparietal area mimicking a brain abscess. After resection of the lesion, Trichosporon asahii was isolated from the abscess. Further treatment with antifungal agents resulted in improvement in clinical status. To the best of our knowledge, this is the second case of Trichosporon brain abscess since the first description in 1970 and the first case of successful treatment of Trichosporon brain abscess.Trichosporonoza to ostre, niekiedy śmiertelne w skutkach zakażenie, w przebiegu którego może dochodzić do wielonarządowego rozsiewu. Dotąd opisano ponad 100 przypadków chorych na trichosporonozę, zwłaszcza pacjentów z neutropenią lub nowotworami krwi. W 1970 r. Watson i wsp. opisali po raz pierwszy przypadek ropnia mózgu spowodowanego przez Trichosporon; chory zmarł po 4 tygodniach. W niniejszej pracy przedstawiono przypadek 34-letniego mężczyzny obciążonego autoimmunologicznym zapaleniem wątroby, niedoczynnością tarczycy i łysieniem całkowitym, leczonego kortykosteroidem, który został przyjęty do szpitala z powodu niedowładu lewej kończyny dolnej. W badaniu mózgu za pomocą rezonansu magnetycznego (RM) stwierdzono rozlane ognisko uszkodzenia okolicy czołowo-ciemieniowej prawej, przypominające ropień mózgu. Po chirurgicznym wycięciu zmiany z ropnia wyizolowano Trichosporon asahii. Leczenie przeciwgrzybicze przyniosło poprawę stanu klinicznego. Zgodnie z naszą wiedzą jest to drugi opisany przypadek ropnia mózgu spowodowanego przez Trichosporon i pierwszy, w którym leczenie zakończyło się powodzeniem

The role of stem cells in tumor targeting and growth suppression of gliomas

Glioma remains the most challenging solid organ tumor to treat successfully. Based on the capacity of stem cells to migrate extensively and target invading glioma cells, the transplantation of stem cells as a cell-based delivery system may provide additional tools for the treatment of gliomas. In addition to the use of modified stem cells for the delivery of therapeutic agents, unmodified stem cells have been shown to have growth-suppressing effects on tumors in vitro and in vivo. This review outlines the probable factors involved in tumor tropism and tumor growth suppression, with a specific focus on the use of unmodified stem cells in the treatment of gliomas. Based on these and further future data, clinical trials may be justified

Immunohistochemistry Study on Androgen and Estrogen Receptors of Rat Seminal Vesicle Submitted to Simultaneous Alcohol-Nicotine Treatment

Objective: Alcohol consumption is habitually accompanied by the use of other psychoactive substances, mostly tobacco. Nicotine and alcohol affect male accessory reproductive glands function. Most studies have been done on pathologic features of prostate, but there has been no systematic study on the seminal vesicle. Therefore, the aim of current study was to investigate the distribution of androgen receptor (AR) and estrogen receptors-beta (ER-β) immune reactivities following long-term treatment of alcohol, nicotine or a combination of both substances. Materials and Methods: In this experimental study, a total of 40 adult Wistar rats, nine weeks of age, were used. Animals were randomly divided into four groups, including: i. Control group receiving normal saline 0.09%, ii. Ethanol group receiving ethanol 20% (2 ml/kg, via gavage), iii. Nicotine group receiving nicotine (0.1 mg/kg, subcutaneous injection), and iv. Ethanol-nicotine group receiving simultaneous ethanol 20% (2 ml/kg) and nicotine (0.1 mg/kg) treatment. All treatment lasted for eight weeks. Prior to intracardiac perfusion, blood sample was collected from left ventricle. The seminal vesicles were isolated and processed for paraffin blocking. The sample tissues were then studied for distribution of AR and ER-β immunereactivities using immunohistochemical (IHC) staining method. One way analysis of variance (ANOVA) and Tukey’s test were performed for data analysis. A value of P<0.05 was considered significant. Results: Our results revealed that the lowest mean number of positive cells belonged to the animals of ethanol-nicotine group that was followed by the ethanol, nicotine, and control groups, respectively. However, there was no significant difference regarding serum testosterone level among experimental groups. Conclusion: It was concluded that combination of both ethanol and nicotine may be a crucial factor in the expression levels of AR and ER-β

Immediate Results of Percutaneous Trans-Luminal Mitral Commissurotomy in Pregnant Women with Severe Mitral Stenosis

Background Valvular heart diseases and mainly rheumatic heart diseases complicate about 1% of pregnancies. During pregnancy physiological hemodynamic changes of the circulation are the main cause of mitral stenosis (MS) decompensation. Prior to introduction of percutaneous mitral balloon commissuroplasty (PTMC), surgical comissurotomy was the preferred method of treatment in patients with refractory symptoms. PTMC is an established non-surgical treatment of rheumatic mitral stenosis. The study aimed to assess the safety and efficacy of PTMC in pregnant women with severs mitral stenosis. Material and Method Thirty three consecutive patients undergoing PTMC during pregnancy enrolled in this prospective study. Mitral valve area (MVA), transmitral valve gradient (MVG), and severity of mitral regurgitation (MR) were assessed before and 24 hour after the procedure by transthoracic and transesophageal echocardiography. Mitral valve morphology was evaluated before the procedure using Wilkin's criteria. Patient followed for one month and neonates monitored for weight and height and adverse effect of radiation. Result Mitral valve area increased from 0.83 ± 0.13 cm 2 to 1.38 ± 0.29 cm 2 ( P = 0.007). Mean gradient of mitral valve decreased from 15.5 ± 7.4 mmHg to 2.3 ± 2.3 mmHg ( P = <0.001). Pulmonary artery pressure decreased from 65.24 ± 17.9 to 50.45 ± 15.33 ( P = 0.012). No maternal death, abortion, intrauterine growth restriction was observed and only one stillbirth occurred. Conclusion PTMC in pregnant women has favorable outcome and no harmful effect on children noted

Enhanced characterization of beta cell mass in a Tg(Pdx1-GFP) mouse model

Introduction: Measurement of pancreatic beta cell mass in animal models is a common assay in diabetes researches. Novel whole-organ clearance methods in conjunction with transgenic mouse models hold tremendous promise to improve beta cell mass measurement methods. Here, we proposed a refined method to estimate the beta cell mass using a new transgenic Tg(Pdx1-GFP) mouse model and a recently developed free-of-acrylamide clearing tissue (FACT) protocol. Methods: First, we generated and evaluated a Tg(Pdx1-GFP) transgenic mouse model. Using the FACT protocol in our model, we could quantify the beta cell mass and alloxan-induced beta cell destruction in whole pancreas specimens. Results: Compiled fluorescent images of pancreas resulted in enhanced beta cell mass characterization in FACT-cleared sections (2928869±120215 AU) compared to No-FACT cleared sections (1292372±325632 AU). Additionally, the total number of detected islets with this method was significantly higher than the other clearance methods (155.7 and 109, respectively). Using this method, we showed green fluorescent protein (GFP) expression confined to beta cells in Tg(Pdx1-GFP) transgenic. This enhanced GFP expression enabled us to accurately measure beta cell loss in a beta cell destruction model. The results suggest that our proposed method can be used as a simple, and rapid assay for beta cell mass measurement in islet biology and diabetes studies. Conclusion: The Tg(Pdx1-GFP) transgenic mouse in conjunction with the FACT protocol can enhance large-scale screening studies in the field of diabetes

Neurologic complications in percutaneous nephrolithotomy

Percutaneous nephrolithotomy (PCNL) has been the preferred procedure for the removal of large renal stones in Iran since 1990. Recently, we encountered a series of devastating neurologic complications during PCNL, including paraplegia and hemiplegia. There are several reports of neurologic complications following PCNL owing to paradoxical air emboli, but there are no reports of paraplegia following PCNL. Materials and Methods: We retrospectively reviewed the medical records of patients who had undergone PCNL in 13 different endourologic centers and retrieved data related to neurologic complications after PCNL, including coma, paraplegia, hemiplegia, and quadriplegia. Results: The total number of PCNL procedures in these 13 centers was 30,666. Among these procedures, 11 cases were complicated by neurologic events, and four of these cases experienced paraplegia. All events happened with the patient in the prone position with the use of general anesthesia and in the presence of air injection. There were no reports of neurologic complications in PCNL procedures performed with the patient under general anesthesia and in the prone position and with contrast injection. Conclusions: It can be assumed that using room air to opacify the collecting system played a major role in the occurrence of these complications. Likewise, the prone position and general anesthesia may predispose to these events in the presence of air injectio

Solo Sonographically Guided PCNL under Spinal Anesthesia: Defining Predictors of Success

Aim. Sonography has been brought in percutaneous nephrolithotripsy (PCNL) as an adjunct to or substitute for X-ray to restrict radiation exposure. Tis study was designed to investigate the possible predictors for the success of the solo sonographically guided PCNL. Methods. 148 consecutive cases were prospectively enrolled. All steps of PCNL were performed solely with sonography guidance under spinal anesthesia. Residual stones were evaluated the day afer surgery using sonography and plain radiography. Results. Te mean age was 46 ± 15 years; 40% of kidneys had hydronephrosis. Te mean stone burden was 504 ± 350 mm2. Te mean duration of surgery was 43 ± 21 minutes. Te early stone-free rate was 92% in inferior or middle calyceal stones, 89.5% in single pelvic stones, 81.5% in partial staghorn stones, and 61.9% in staghorn stones. Te mean residual stone size was 13 ± 8 mm. Logistic regression showed that a lower age and a larger stone burden signifcantly predicted positive residual stones. Fifeen percent of patients presented with grade I or II and six percent showed grade III complication based on Clavien classifcation. Tere was no cases of organ injury or death. Conclusion. Solo ultrasonographically guided PCNL under spinal anesthesia is feasible with an acceptable stone-free rate and complication rate