Parts Of Central Nervous System Research Articles

Beyond the division of multiple sclerosis into different subgroups: The Concept of Connectomopathy.

Multiple Sclerosis (MS) pathophysiologically is a dynamic and progressive disease that involves all parts of central nervous system. This widespread involvement of the CNS has paved the way for proposing a new theory in MS in which MS is considered as a connectomopathy. Connectomopathy is a new concept describing the diseases in which not only the brain connectome is completely and extensively damaged, but the defective connectome itself can also become a breeding ground for the disease's progression. Connectomopathy provides a dynamic picture of MS. Since each person's connectome is unique to him/herself, so MS patients' connectomopathy varies from one to another. This variety not only challenges the classification of MS into different phenotypes, but also emphasizes the need for providing a personalized approach for the treatment of these patients.

Interrogation of human microglial phagocytosis by CRISPR genome editing.

Microglia are an integral part of central nervous system, but our understanding of microglial biology is limited due to the challenges in obtaining and culturing primary human microglia. HMC3 is an important cell line for studying human microglia because it is readily accessible and straightforward to maintain in standard laboratories. Although HMC3 is widely used for microglial research, a robust genetic method has not been described. Here, we report a CRISPR genome editing platform, by the electroporation of Cas9 ribonucleoproteins (Cas9 RNP) and synthetic DNA repair templates, to enable rapid and precise genetic modifications of HMC3. For proof-of-concept demonstrations, we targeted the genes implicated in the regulation of amyloid beta (Aβ) and glioblastoma phagocytosis in microglia. We showed that CRISPR genome editing could enhance the phagocytic activities of HMC3. We performed CRISPR gene knockout (KO) in HMC3 by the electroporation of pre-assembled Cas9 RNP. Co-introduction of DNA repair templates allowed site-specific knock-in (KI) of an epitope tag, a synthetic promoter and a fluorescent reporter gene. The editing efficiencies were determined genotypically by DNA sequencing and phenotypically by immunofluorescent staining and flow cytometry. The gene-edited HMC3 cells were examined in vitro by fluorescent Aβ and glioblastoma phagocytosis assays. Our platform enabled robust single (>90%) and double (>70%) KO without detectable off-target editing by high throughput DNA sequencing. We also inserted a synthetic SFFV promoter to efficiently upregulate the expression of endogenous CD14 and TREM2 genes associated with microglial phagocytosis. The CRISPR-edited HMC3 showed stable phenotypes and enhanced phagocytosis of fluorescence-labeled Aβ1-42 peptides. Confocal microscopy further confirmed the localization of Aβ1-42 aggregates in the acidified lysosomes. HMC3 mutants also changed the phagocytic characteristic toward apoptotic glioblastoma cells. CRISPR genome editing by Cas9 RNP electroporation is a robust approach to genetically modify HMC3 for functional studies such as the interrogation of Aβ and tumor phagocytosis, and is readily adoptable to investigate other aspects of microglial biology.

Diferencijalna dijagnoza vertiga - prikazi slučajeva

Introduction: Vertigo represents illusion or hallucination of movement caused by disturbance of perception of own movements or movements of observed object. It is caused by dysfunction of the inner ear vestibular apparatus (peripheral vertigo) or parts of central nervous system (central vertigo). Making distinction between these two types is very important for the making of rational decision by emergency medicine physician. Case report I: Female, 69 years of age is referred to neurologist in Emergency Center for attacks of acute onset rotatory vertigo, horizontal nystagmus and severe autonomic disturbances provoked by movement. Anamnesis, clinical, neuroultrasound examinations and CT scan showed no signs of acute neurologic disease. Treatment of peripheral type vertigo with vasodilators was indicated and further continued with otolaryngologist follow up. Case report II: Male, 72 years of age was treated on Clinic of Neurology for infarction of left cerebellar hemisphere. Symptoms at onset were vertigo, headache, diplopia, nausea and vomiting. Neurological examination revealed right sided horizontalrotatory nystagmus with fine vertical nystagmus, astasia/abasia and right sided hemiparesis. Treatment included thrombolytic, antithrombotic and anticoagulant therapy, as well as established vascular risk treatment. Conclusion: Role of emergency physician in establishing of etiology of vertigo at the place of onset is very important. Detailed anamnesis about onset of symptoms and their duration, clinical examination, diagnostic (ABCD2) score, and therapeutic repositioning (Epley) maneuver ensure fast triage and shorter transport delays if necessary.

Trends in the incidence of malignant central nervous system tumors in Brazil, 2000-2015.

In Brazil, 5870 new cases of malignant central nervous system tumors (MCNST) were estimated for men and 5220 for women for each year of the 2020-2022 triennium. The objective of this study was to analyze incidence rate trends and compare demographic characteristics of new MCNST cases according to tumor topographies in Brazil from 2000 to 2015. This study comprises an analytical cross-sectional assessment of secondary databases extracted from the Brazilian National Cancer Institute (INCA) website. Data comprised new neoplasm cases of meninges (C70), brain (C71), spinal cord, cranial nerves, and other central nervous system parts (C72) retrieved from 23 population-based cancer registries. A descriptive analysis was performed. Crude and age-adjusted incidence rates were calculated. Linear trends were calculated using a linear least squares regression for adjusted incidence rates versus time. A total of 24 986 new MCNST cases were recorded. The main topography was the brain (91.5%). Except for meninges tumors, where 62.4% of the cases were observed in women, MCNST cases were more frequent among men concerning the other evaluated topographies. All 3 topographies occurred predominantly in adult patients aged from 40- to 64-year-old. Between 2000 and 2015, incidence rates ranged from 5.12 to 4.95 (a 1.4% increase of per year; 95% CI -4.0 to 6.8; P = .584) in men and from 4.35 to 3.61 (a 3.1% increase per year; 95% CI -1.7 to 8.0; P = .189). The most frequent topography was the brain. Incidence rates of MCNST remained relatively stable over time in both sexes.

Field-programmable gate arrays-based Morris-Lecar implementation using multiplierless digital approach and new divider-exponential modules

Simulation, modeling, and hardware implementation of different parts of central nervous system (CNS) are very attractive research areas in terms of neuromorphic engineering aspects. Considering the neuronal parts of the human brain, the hardware implementation of neural models of spiking neural networks should be evaluated from preparing a simple efficient model and optimal hardware implementation. In this paper, Morris-Lecar (ML) model as a biological neuronal model with nonlinear differential equations and hyperbolic functions is discussed. This original model with non-linear complex functions needs high-computational high-cost hardware implementation on Field-Programmable Gate Arrays (FPGA). This paper presents a new divider module and exponential term (2X) to provide low-cost and high-speed implementation of original ML called Division-Based ML (DBML). DBML model suggests simpler equations using division-based exponential terms, logical shifts and simple arithmetic operations. Thus, high-performance neuronal design is presented following original ML model in terms of time domain and different dynamic behaviors.

Genome-wide characterization of RNA editing highlights roles of high editing events of glutamatergic synapse during mouse retinal development

Adenosine-to-inosine (A-to-I) RNA editing leads to functional change of neurotransmitter receptor which is essential for neurotransmission and normal neuronal development. As a highly accessible part of central nervous system, retina has been extensively studied, however, it remains largely unknown how RNA editing regulates its development. Here, a genome-wide screening of high-confidence RNA editing events were performed to decipher the dynamic transcriptome regulation by RNA editing during mouse retinal development. 2000 high-confidence editing sites across eight developmental stages of retina were called. Three unique patterns (RNA-editinghigh pattern, RNA-editingmedium pattern and RNA-editinglow pattern) were identified by clustering these editing sites based on their editing level during retinal development. Editing events from RNA-editinghigh pattern were significantly associated with glutamate receptors and regulated synaptic transmission. Interestingly, most non-synonymous high-editing sites were mapped to ion channel genes of glutamatergic synapse which were associated with neurotransmission by controlling ion channel permeability and affecting exocytosis. Meanwhile, these non-synonymous editing sites were evolutionarily conserved and exhibited a consistently increasing editing levels between mouse and human retinal development. Single-cell RNA-seq data analysis revealed that RNA editing events prefer to occur in two main cell types including bipolar and amacrine cells. Genes with non-synonymous high-editing sites were enriched in both bipolar cells and retina ganglion cells, which may mediate retina ganglion cell differentiation by altering channel ion permeability. Together, our results provide novel insights into mechanism of post-transcriptional regulation during retinal development and help to develop novel RNA editing-guided therapeutic strategies for retinal disorders.

GlioCova: Treatment and hospital admissions for patients with GBM in England

Abstract Aims Data on the treatment and outcomes of patients with primary brain tumours in England is sparse. The GlioCova project uses linked national data from England to explore the incidence, treatment, outcomes, and treatment costs of all adult brain tumour patients in all 50,000 patients in England from 2013 – 2018. Here we present initial results from patients with glioblastoma (GBM). Method We used a linked dataset from the national cancer registration system in England including all adult patients diagnosed with a malignant or benign brain tumour between 2013 and 2018 (51,775 patients in total). Glioblastoma patients were selected based on ICD-10 codes (C70, C71, C72), morphology codes (9440, 9441, 9442), and grade (G4, G3, GX and NA) from the national cancer registry. We extracted data on treatment (radiotherapy, chemotherapy, brain surgery or biopsy) and measured how many patients who had adjuvant Temozolomide completed 6 cycles. Results We identified 15,294 glioblastoma patients. Most had glioblastoma morphology (14,924), followed by gliosarcoma (264) and giant cell glioblastoma (106). Almost all had a cranial tumour (C71) while 17 had a tumour originating in the spinal cord, cranial nerves or other part of central nervous system (C72). Median age was 66 (IQR=17) and 60% were male. 51.9% (7,935) underwent surgery; an additional 18.2% (2,784) had a biopsy; 3,701 (24.2%) out of 15,294 patients received radiotherapy (only) and 316 (2.1%) received chemotherapy (only). 5,520 (36.1%) received both radiotherapy and chemo. Out of 4,101 GBM patients receiving temozolomide after radiotherapy, only 1,535 (37.4%) completed 6 cycles. The 7,935 GBM patients who had surgery had a median length of stay in hospital of 5 days (IQR=6) while those that had a biopsy had a median of 3 days (IQR=6). Conclusion We have presented a description of treatment of all GBM patients in England over a five-year period. This is the first time we have been able to understand detailed treatment patterns at a national scale, and significantly extends previous analyses. Further work will look at patient safety indicators, variation across centres and costs of treatment. Acknowledgements We would like to thank the GlioCova Expert Advisory Group for their input and discussion. This work uses data provided by patients and collected by the NHS as part of their care and support.

Froin syndrome - A rare mimic of spinocerebellar ataxia

Spinocerebellar ataxias are degenerative heritable disorders affecting cerebellum accompanied by changes in brainstem and other parts of central nervous system. This case highlights the same and emphasizes on the importance of recognizing clinical and radiological clues for identification of secondary causes of cerebellar degeneration for timely intervenetion and management of patient.

P14.27 Exploring end-of-life care in the GlioCova national brain tumour patient cohort

Abstract BACKGROUND Brain tumours are the leading cause of cancer deaths in the under-40s. Research on end-of-life care, especially in brain tumour patients is rare, yet important to patients and carers. The GlioCova project holds data on all adult brain tumour patients in England diagnosed between 2013 and 2018. Using this linked data set, we performed preliminary analysis on end-of-life care, focusing on treatment close to death and place of death. MATERIAL AND METHODS We used data from the English National Cancer Registry and identified all patients with a primary CNS tumour (ICD-10: C70, C71, C72) who were diagnosed between 2013 - 2018. We examined demographics, tumour morphology and grade, primary cause of death, treatment received within the last 3 and 1 month of life, and the location of death. For patients with unclear location of death (‘unknown’, ‘other’, ‘NA’), we looked at their final destination of discharge recorded in their last inpatient admission. RESULTS We identified 26,239 brain tumour patients of whom 20,715 had died. 41.7% were female and median age was 68 (IQR=19). Most patients had a malignant neoplasm of brain (98.6%), followed by meninges (0.7%) and spinal cord, cranial nerves and other parts of central nervous system (0.7%). The most common primary cause of death was malignant neoplasm (70%). Of the 10,021(48.4%) patients who received radiotherapy at any time between diagnosis and death, 1,341 (6.5%) received it within the last three months of life and 254 (1.3%) received it within the last month of life. Of the 5,957 (28.8%) patients who received chemotherapy, 1,358 (6.6%) started a chemotherapy regimen 3 months and 200 (0.97%) 1 month before death. 36.0% of all patients died at home, 23.8% at hospital, 14.7% in a hospice and 8.8% in a nursing home. For 16.7% of patients with an unclear location of death, the most common destination of discharge during their last hospital admission was usual place of residence (54.5%), non-NHS run Care Home (13.9%), NHS run Care Home (11.2%). CONCLUSION To the best of our knowledge, this is the first national analysis of end-of-life care in brain tumour patients. Active treatment towards the end of life and in a hospital deaths appear lower in brain tumour patients than in studies of other cancer groups.

Effectiveness of vitamin D supplements in the patients suffering from Alzheimer disease

Introduction: Vitamin D is a steroid hormone. It crosses the blood brain barrier and binds with receptors present in neurons and glial cells of various parts of central nervous system like hippocampus, cortex, sub-cortex etc. Due to its antioxidant property and regulating intra-neuronal calcium homeostasis, it can be hypothesized that vitamin D has a role to play in preventing age related cognitive decline. Materials and Methods: Total of 160 patients were included in the study. MMSE is useful for evaluating the subjects having dementia syndrome because these subjects cooperate well only for short duration. Mini Mental state examination score was used for the assessment of dementia. They were included in the study on the basis of serum vitamin D level and MMSE score. Results: The collected data showed that mean serum vitamin D levels were found to be lower in group A when compared to group B. After 3 months of treatment with supplements, the score of post treatment MMSE was found to be higher in group A as compared to group B. After 6 months of treatment with supplements, the score of post treatment MMSE was found to be higher in group A as compared to group B. Discussion & Conclusion: Vitamin D acts like a neurosteroid hormone in areas of neurotransmission and neuro-immunomodulation. Patients on medical therapy for dementia has also shown improve results with regulation of vitamin D. It has also exhibited neuro-protective properties against glutamate toxicity through antioxidant effects thus preventing apoptosis. The present study is one of on-going steps in the direction of establishing role of Vitamin D in prevention and treatment of senile dementia.

Evaluation of Molecular and Cellular Alterations Induced by Neuropathic Pain in Rat Brain Glial cells.

Neuropathic pain originates from illness or damage of the nervous system and affects the somatosensory system. Recently, many efforts have been made to illuminate the influences of neuropathic pain in different parts of central nervous system (CNS). However, the toxic consequences of neuropathic pain in glial cells, which involve in the control of pain is poorly understood. Therefore, the present study aimed to assess the molecular and cellular effects of neuropathic pain in the glial cells of rat brain. Induction of neuropathic pain in rats was associated with oxidative stress as evident by elevated reactive oxygen species (ROS) formation as well as reversible glutathione (GSH) depletion in the glial cells. Moreover, neuropathic pain caused mitochondrial membrane potential collapse (∆Ψm%), lysosomal membrane rapture, and proteolysis, probably due to ROS-induced MPT pore opening. These toxic events could cause cytochrome c release from intermembrane space into the cytosole and trigger caspase activation pathway. Our finding confirmed that the activity of caspase-3 was significantly increased in the glial cells as a core component of the apoptotic machinery. In conclusion, the neuropathic pain induces ROS generation as the major cause of GSH depletion along with mutual mitochondrial/lysosomal potentiation (cross-talk) of oxidative stress in the glial cells. Subsequently, this toxic cross-talk can induce proteolysis and trigger apoptosis by caspase-3 activation in the glial cells of rat brain.

Impact of P-Glycoprotein-Mediated Active Efflux on Drug Distribution into Lumbar Cerebrospinal Fluid in Nonhuman Primates.

Estimation of unbound drug concentration in the brain (Cu,brain) is an essential part of central nervous system (CNS) drug development. As a surrogate for Cu,brain in humans and nonhuman primates, drug concentration in cerebrospinal fluid (CCSF) collected by lumbar puncture is often used; however, the predictability of Cu,brain by lumbar CCSF is unclear, particularly for substrates of the active efflux transporter P-glycoprotein (P-gp). Here, we measured lumbar CCSF in cynomolgus monkey after single intravenous administration of 10 test compounds with varying P-gp transport activities. The in vivo lumbar cerebrospinal fluid (CSF)-to-plasma unbound drug concentration ratios (Kp,uu,lumbar CSF) of nonsubstrates or weak substrates of P-gp were in the range 0.885-1.34, whereas those of good substrates of P-gp were in the range 0.195-0.458 and were strongly negatively correlated with in vitro P-gp transport activity. Moreover, concomitant treatment with a P-gp inhibitor, zosuquidar, increased the Kp,uu,lumbar CSF values of the good P-gp substrates, indicating that P-gp-mediated active efflux contributed to the low Kp,uu,lumbar CSF values of these compounds. Compared with the drug concentrations in the cisternal CSF and interstitial fluid (ISF) that we previously determined in cynomolgus monkeys, the lumbar CCSF were more than triple for two and all of the good P-gp substrates examined, respectively. Although lumbar CCSF may overestimate cisternal CSF and ISF concentrations of good P-gp substrates, lumbar CCSF allowed discrimination of good P-gp substrates from the weak and nonsubstrates and can be used to estimate the impact of P-gp-mediated active efflux on drug CNS penetration. SIGNIFICANCE STATEMENT: This is the first study to systematically evaluate the penetration of various P-glycoprotein (P-gp) substrates into lumbar cerebrospinal fluid (CSF) in nonhuman primates. Lumbar CSF may contain >3-fold higher concentrations of good P-gp substrates than interstitial fluid (ISF) and cisternal CSF but was able to discriminate the good substrates from the weak or nonsubstrates. Because lumbar CSF is more accessible than ISF and cisternal CSF in nonhuman primates, these findings will help increase our understanding of drug central nervous system penetration at the nonclinical stage.

A study of neurological problems in HIV infection

Background: Knowledge of central nervous system manifestation (CS) is crucial for clinical practitioners, which is why this study was conducted to identify the neurological manifestations in HIV patient is crucial problems with HIV and the difficulties in managing these patients.Methods: The present study was conducted on patients of HIV infection who were either admitted or being treated in OPD during study period. The cases were selected based seropositivity for HIV on two consecutive occasions by ELISA and presence of WHO surveillance definition criteria. Based on a detailed history account including high risk behaviour to HIV infection was obtained from patients or relatives. Then each patient was subjected to thorough physical examination with specific attention to any clinical evidence of immunosuppression viz oral thrush. Thorough neurological examination was done to localize the part of central nervous system affected. Patients were then categorized into various clinical neurological syndromes.Results: Commonest finding was single or multiple ring enhancing lesions seen in 21(35%) patients followed by basal exudates (21.6%). Hydrocephalus was seen in 5 patients (8.3%) and infarct due to vascular lesion in 4(7%) patients. Oral thrush was more commonly seen in patients with cryptococcal meningitis. CSF analysis was useful and revealed abnormalities in most of the patients with infective disorders.Conclusions: In conclusion, variety of neurologic manifestations occur and any part of nervous system can be affected in HIV infection and high index of euspicion is required to pick up the cases early in the course which may help to improve the quality and life span of these suspicion patients.

Do the Dento-Thalamic Connections of Genetic Absence Epilepsy Rats from Strasbourg Differ from Those of Control Wistar Rats?

The thalamo-cortical circuit is important in the genesis of absence epilepsy. This circuit can be influenced by connecting pathways from various parts of central nervous system. The aim of the present study is to define the dento-thalamic connections in Wistar animals and compare the results with genetic absence epilepsy rats from Strasbourg (GAERS) using the biotinylated dextran amine (BDA) tracer. We injected BDA into the dentate nucleus of 13 (n = 6 Wistar and n = 7 GAERS) animals. The dento-thalamic connections in the Wistar animals were denser and were connected to a wider range of thalamic nuclei compared with GAERS. The dentate nucleus was bilaterally connected to the central (central medial [CM], paracentral [PC]), ventral (ventral medial [VM], ventral lateral [VL], and ventral posterior lateral [VPL]), and posterior (Po) thalamic nuclei in Wistar animals. The majority of these connections were dense contralaterally and scarce ipsilaterally. Contralateral connections were present with the parafascicular (PF), ventral posterior medial, ventral anterior (VA), and central lateral (CL) thalamic nuclei in Wistar animals. Whereas in GAERS, bilateral connections were observed with the VL and CM. Contralateral connections were present with the PC, VM, VA, and PF thalamic nuclei in GAERS. The CL, VPL, and Po thalamic nucleus connections were not observed in GAERS. The present study showed weak/deficit dento-thalamic connections in GAERS compared with control Wistar animals. The scarce information flow from the dentate nucleus to thalamus in GAERS may have a deficient modulatory role on the thalamus and thus may affect modulation of the thalamo-cortical circuit.

Mouse models for retinal degeneration

Retina is a part of central nervous system. Retinal degeneration is characterized by the death of photoreceptor cells, causing partial vision loss or even blindness. Retinal degeneration includes inherited retinal degeneration such as retinitis pigmentosa (RP) and complex retinal degeneration such as diabetic retinopathy. In this talk, I will discuss the disease mechanisms and current treatment of inherited retinal degeneration. I will also discuss techniques for retinal degeneration in mouse models.  I will demonstrate how to dissect mouse retina and retinal pigment epithelial (RPE) cells.   

Multiple secondary cauda equina non-Hodgkin\u2019s lymphoma: a case report and literature review

BackgroundSecondary central nervous system involvement of non-Hodgkin’s lymphoma (NHL) is rare and with poor prognosis, the most common pathological type is diffuse large B cell lymphoma (DLBCL). Although it can occur in any part of central nervous system, it rarely directly infiltrates the spinal cord or cauda equina.Case presentationWe present the case of 64-year-old immunocompetent man with a worsening pain of waist and left lower extremity, accompanied by numbness and paresis of bilateral lower extremity for 20 days. His previous medical history included a resection of painless mass in the left groin in another hospital 7 months ago, and the pathological diagnosis was non-Hodgkin small B cell lymphoma. Gd-enhanced MRI and F-18 FDG PET-CT scan demonstrated multiple infiltrations in the cauda equina. During the operation, we removed as many as 11 subdural-extramedullary bean-size lesions involving multiple nerve roots. The paralysis of his left leg recovered rapidly after the operation. During the follow-up period of more than one year, he underwent standard R-CHOP chemical therapy, no evidence of recurrence was noted until the 13th month, the patient died because of intracranial relapse.ConclusionsImaging examination is important in the diagnosis of multiple secondary cauda equina non-Hodgkin’s lymphoma, and we highlight the significance of gadolinium-enhanced MRI and F-18 FDG-PET/CT in preoperative diagnosis as well as the previous history.

Do Inhalational Anesthetic Agents Still Hold Their Place in Modern Anesthesia Practice?

Inhalational anesthetic agents are chemi-cal substances that are administered into the body via lungs and distributed to or-gans and tissues by blood circulation.The main site of their action is the brain, but they also affect other parts of central nervous system. Volatile and intravenous anesthetics alike have nearly reached the characteristics of an ideal anesthetic, but at a first glance, the increase in use of in-travenous anesthetics could likely push out their volatile counterparts. Looking at the situation more thoroughly, positive side effects of volatile anesthetics that are not found in their intravenous counterparts, still give them a place in modern anesthe-sia practice. It is also possible to combine both techniques to reduce negative adverse effects, while making use of the positive ones.opioids, nitrogenous oxide, muscle relax-ants). Most often, we use them in so called “balanced anesthesia”. This way, safety is increased, while negative adverse effects are decreased.Recently, TCI (target-controlled anesthe-sia) with intravenous anesthetics is being used more and more. It would appear that intravenous anesthetics are going to com-pletely push out the volatile anesthetics that had been used a lot in the past. But is this really going to happen?

Study of Diameter of Inferior Cerebellar Peduncle in Bangladeshi Cadaver

Background: The cerebellum is a very important part of central nervous system. It is involved in the maintenance of balance and posture, coordination of voluntary movements, motor learning and cognitive functions such as language. Inferior cerebellar peduncle connects the spinal cord and medulla oblongata with the cerebellum and carries unconsciousness proprioceptive information from body and limb. The mean diameter of inferior cerebellar peduncle at birth is only a fraction of the adult diameter then diameter increases up to certain age and decreases in old age.Objectives: The present study was done to observe the diameter of the inferior cerebellar peduncle in different age groups of Bangladeshi cadaver which will serve as a baseline data for clinician about the neurological disorders in our country.Materials and Methods: A cross sectional, analytical type of study was carried out in the department of anatomy, Mymensingh Medical College, Mymensingh from April'2009 to September'2009. A total of 63 cerebellums were collected of which 40 (male 25 and female 15) were from during postmortem of unclaimed Bangladeshi cadaver aged between 5 to 60 years and 23 (male 14 and female 9) were from caesarian section of dead fetuses aged between 34 wks to 42 wks. of gestation. The collected sample was grouped into three age groups like Group A (34 to 42 weeks of gestation), Group B (5 to 30 years) and Group C (31 to 60 years). The diameters of the inferior cerebellar peduncles were measured by using slide calipers and expressed in millimeter (mm).Result: The mean (±SD) diameter of right inferior cerebellar peduncle was in Group A 5.40±1.13, B 7.72±1.18 and C 6.77±1.68 mm respectively and the mean (±SD) diameter of left inferior cerebellar peduncle was in Group A 5.20±1.09, B 7.59±1.23 and C 6.66±1.58 mm respectively.Conclusion: From the present study it is observed that the mean diameter of the inferior cerebellar peduncle increased with age upto certain level then slightly decreased in the late age. The result of the present study will enrich the information pool on diameter of the inferior cerebellar peduncle of Bangladeshi people.KYAMC Journal Vol. 8, No.-1, Jul 2017, Page 27-32

Investigation of the effects of systemic isotretinoin treatment on retinal nerve fiber layer and macula

Purpose: To investigate the effects of systemic isotretinoin therapy on retina by measuring retinal nerve fiber layer (RNFL) and macular thicknesses.Method: This prospective, cross-sectional study was conducted in patients prescribed systemic isotretinoin therapy. Seventy-two eyes of 36 patients were included in the study. The patients were followed during three months. Detailed ophthalmologic examination including anterior and posterior segment examination, best corrected visual acuity and intraocular pressure measurement, RNFL and macular thicknesses measurement by Spectral Domain Cirrus Optical Coherence Tomography Model 400 (Carl Zeiss Meditech, Jena, Germany) were performed at baseline, first, second and third months after the beginning of systemic isotretinoin therapy in ophthalmology clinic.Result: Thirty (83.3%) of the 36 patients were women and six (16.7%) of them were men. Mean age was 21.17 years. Mean RNFL thickness in the temporal quadrant at first, second, third months after beginning of treatment were found as significantly lower compared to baseline (p = .001). Mean macular thicknesses in superior outer, nasal outer and temporal outer quadrants at second and third months after beginning of treatment were found to be significantly lower compared to baseline and first month after beginning of treatment (p ≤ .001, .002 and .001, respectively). Macular thicknesses in superior inner quadrant at first, second and third months were found to be significantly lower than baseline values (p< .01). No significant difference was detected between groups in other quadrants (p> .05).Conclusion: The effect of oral isotretinoin therapy may cause regional thinning in RNFL and macula, directly visible part of central nervous system.

P-Hydroxy benzoic acid-conjugated dendrimer nanotherapeutics as potential carriers for targeted drug delivery to brain: an in vitro and in vivo evaluation

Dendrimers which are discrete nanostructures/nanoparticles are emerging as promising candidates for many nanomedicine applications. Ligand-conjugated dendrimer facilitate the delivery of therapeutics in a targeted manner. Small molecules such as p-hydroxyl benzoic acid (pHBA) were found to have high affinity for sigma receptors which are prominent in most parts of central nervous system and tumors. The aim of this study was to synthesize pHBA-dendrimer conjugates as colloidal carrier for site-specific delivery of practically water insoluble drug, docetaxel (DTX) to brain tumors and to determine its targeting efficiency. pHBA, a small molecule ligand was coupled to the surface amine groups of generation 4-PAMAM dendrimer via a carbodiimide reaction and loaded with DTX. The conjugation was confirmed by 1HNMR and FT-IR spectroscopy. In vitro release of drug from DTX-loaded pHBA-conjugated dendrimer was found to be less as compared to unconjugated dendrimers. The prepared drug delivery system exhibited good physico-chemical stability and decrease in hemolytic toxicity. Cell viability and cell uptake studies were performed against U87MG human glioblastoma cells and formulations exerted considerable anticancer effect than plain drug. Conjugation of dendrimer with pHBA significantly enhanced the brain uptake of DTX which was shown by the recovery of a higher percentage of the dose from the brain following administration of pHBA-conjugated dendrimers compared with unconjugated dendrimer or formulation in clinical use (Taxotere®). Therefore, pHBA conjugated dendrimers could be an efficient delivery vehicle for the targeting of anticancer drugs to brain tumors.