Central Nervous Disorders Research Articles

Complete and Durable Responses in Primary Central Nervous System Posttransplant Lymphoproliferative Disorder with Zidovudine, Ganciclovir, Rituximab, and Dexamethasone

Purpose: Primary central nervous system posttransplant lymphoproliferative disorder (PCNS-PTLD) is a complication of solid organ transplantation with a poor prognosis and typically associated with Epstein-Barr virus (EBV). We hypothesized EBV lytic-phase protein expression would allow successful treatment with antiviral therapy.Patients and Methods: Thirteen patients were treated with zidovudine (AZT), ganciclovir (GCV), dexamethasone, and rituximab in EBV+ PCNS-PTLD. Twice-daily, intravenous AZT 1,500 mg, GCV 5 mg/kg, and dexamethasone 10 mg were given for 14 days. Weekly rituximab 375 mg/m2 was delivered for the first 4 weeks. Twice-daily valganciclovir 450 mg and AZT 300 mg started day 15. Lytic and latent protein expression was assessed using in situ hybridization and immunohistochemistry. Immunoblot assay assessed lytic gene activation. Cells transfected with lytic kinase vectors were assessed for sensitivity to our therapy using MTS tetrazolium and flow cytometry.Results: The median time to response was 2 months. Median therapy duration was 26.5 months. Median follow-up was 52 months. The estimated 2-year overall survival (OS) was 76.9% (95% CI, 44.2%-91.9%). Overall response rate (ORR) was 92% (95% CI, 64%-100%). BXLF1/vTK and BGLF4 expression was found in the seven tumor biopsies evaluated. Lytic gene expression was induced in vitro using the four-drug regimen. Transfection with viral kinase cDNA increased cellular sensitivity to antiviral therapy.Conclusions: EBV+ PCNS-PTLD expressed lytic kinases and therapy with AZT, GCV, rituximab and dexamethasone provided durable responses. Induction of the lytic protein expression and increased cellular sensitivity to antiviral therapy after transfection with viral kinase cDNA provides a mechanistic rationale for our approach. Clin Cancer Res; 24(14); 3273-81. ©2018 AACR.

Intracerebral lymphoproliferative disorder in an MS patient treated with fingolimod.

Fingolimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, is an effective oral immune therapy for treatment of relapsing-remitting MS (RRMS).1 Development of solid malignancies was observed in large randomized phase-3 trials examining the efficacy and safety of fingolimod in patients with RRMS.1 In this article, we present a patient who developed a primary central nervous system T-cell lymphoproliferative disorder during fingolimod treatment. The authors thank May H. Han for her critical reading of the article.

Effect of intrathecal botulinum toxin A injection on sheep's cystomanometric parameters: A comparative study

Detrusor overactivity is a public health issue in patients with central neurological disorders, in particular spinal cord injury. Sheep are valuable animal models because the bladder and urethral pressure measures are similar to humans’. Intrathecal botulinum toxin A (IT BoNT-A) injections have already proved efficacy on radicular pain, without motor nor postural adverse effect in rat and mice. But the possible effects on the urinary tract functioning are not yet known. To evaluate the effect of an IT BoNT-A injection on sheep urodynamic parameters and to evaluate the potentially motor adverse effects. Five 2-year old sheep were used in this experiment. After a familiarizing procedure, a first urodynamic exam was done at T0. A unique IT injection of BoNT-A (100 Units-Xeomin ® ) was done 3 weeks later. Cystomanometric parameters were again recorded 5 (T1) and 12 weeks (T2) after the IT injection. A control group of 7 sheep with no IT BoNT-A injection were used to compare the results. Maximum cystometric capacity (MCC) and post-void residual urine (PVRU) increased significantly in the group receiving IT BoNT-A at T1 (MCC at T0 = 35.0 mL ± 16.4; MCC at T1 = 105.6 mL ± 16.10; P < 0.05) (PVRU at T0 = 2.8 mL ± 4.1; PVRU at T1 = 93.5 ± 12.6; P < 0.01). Bladder contractions appeared during the filling phase between T1 and T2 in the IT BoNT-A group. No motor problems induced by IT BoNT-A injection have been recorded. IT BoNT-A injections influence the urinary tract functioning, and particularly increase the bladder capacity at T1, but induce small bladder contractions at T1 and T2. If it is confirmed by larger studies, this result should be taken into consideration for further use of IT BoNT-A in patients with detrusor overactivity after a spinal cord injury.

Cases of bed blockage in Northern Spain during 2010–2014: Delayed discharge from acute hospitalization to long-term care

Background The term ‘bed blocking’ is used in a situation where “patients who no longer require acute care are occupying acute care beds while awaiting lower-level placement”. This term is related with delayed discharge and represent an inefficient use of acute hospital beds. Evidence about this topic describes characteristics associated with a higher likelihood of became a bed-blocking: older age, lack of functional ability, emergency case and hospital's weighting. Our aim is to determinate in our region, which characteristics may influence the problem and to quantify inadequate hospitalization's days. Methods A descriptive retrospective study of patients with delayed discharge from acute hospitalization to long-term care was conducted. This study involved three public hospitals from the region of northern of Spain (Cantabria), during 2010–2014. The variables collected includes: age, gender, planned or emergency admission, level of hospital, diagnosis-related group (DRG) and inadequate hospitalization's days. Mean and standard deviation were estimated to continuous variables. Proportions were estimated with confidence intervals at 95% (95% CI) to discrete variables. Means were compared with t de Student and Anova. Results In the period between 2010 to 2014, it is found 1415 bed-blocking's cases in hospitals from Cantabria, waiting to be admitted in a to long-term care. Spent a total of 19,183 inadequate hospitalization's days. Mean of delayed discharge: 13.56 days [SD 14.34], range 1 to 131; 66.7% are delayed less than two weeks; 53.1% male and 46.9% female. Gender were not found to be significantly associated with delayed discharges but women [mean age 80.70] are significantly older than men [mean age 75.99]. The mean age of our population was 78.49 years [SD 10.48], range 27 of 102; 74.6% are older than 75 years but younger inpatients had delayed significantly longer; 94.1% of cases were emergency patients. Diagnosis-related group (DRG) more frequents were hip fracture (8.0%), stroke (7.5%), other central nervous system's disorder (5.6%) and simple pneumonia (4.0%). Compared with local hospital, the university hospital had delayed significantly longer. Conclusion Inpatient's characteristics related with bed blocking risk: older than 75, emergency admission in a university hospital and diagnosis that suppose unexpected lack of functional ability. Relation between gender and age could be related with gender role of caregiver. These results may reflect that university hospitals treat the more complex patients. Known the inpatient's characteristics, an early detection since the emergency admission could solve the delayed and prevent this inefficient use of acute hospital beds.

Efficacy of Repositioning Therapy in Patients With Benign Paroxysmal Positional Vertigo and Preexisting Central Neurologic Disorders.

With the exception of migraines, benign paroxysmal positional vertigo (BPPV) in patients with preexisting central neurologic disorders (CND) is rarely discussed in the literature. Demographic features of this patient group and the efficacy of repositioning therapy are still unknown. We hypothesized that a CND may alter the function of the central vestibular pathway, thus changing the pattern of BPPV and outcomes of repositioning. In this study, we enrolled 93 consecutive idiopathic BPPV patients and categorized them into two groups according to the presence or absence of a CND. In our series, 31.2% of BPPV cases had a CND. The most common associated CNDs were cerebrovascular disease and migraines. The two groups showed similar age distributions, canal involvement, success rates of repositioning, and cycles of treatment used to achieve complete resolution. The major differences were the proportion of females (89.7%) and a right-side predominance (75.9%) in the CND group. There was a trend of more residual dizziness (RD) after successful repositioning in the CND group, but the difference was not significant. The reason for the female and right-side predominance in the CND group is unclear. We concluded that the efficacy of repositioning therapy was excellent (with a success rate of 80.6% with one cycle and 93.5% within two cycles of treatment) for BPPV with or without a preexisting CND. Clinicians are encouraged to diagnose and treat BPPV in patients with a preexisting CND as early as possible to improve patients' quality of life, avoid complications, and reduce medical costs.

Aquaporin-4 Autoantibodies From Neuromyelitis Optica Spectrum Disorder Patients Induce Complement-Independent Immunopathologies in Mice

Neuromyelitis optica spectrum disorders (NMOSD) are central nervous system inflammatory disorders causing significant morbidities and mortality. The majority of NMOSD patients have autoimmunity against aquaporin-4 (AQP4), evidenced by seropositivity for autoantibodies against aquaporin-4 (AQP4–IgG). AQP4–IgG is pathogenic with neuroinflammation initiated upon binding of AQP4–IgG to astrocytic AQP4. Complement activation contributes to astrocytic cytotoxicity, neuroinflammation, and tissue necrosis in NMOSD, but the role of complement-independent mechanisms is uncertain. We studied the complement-independent pathogenic effects of AQP4–IgG by passive transfer of IgG from NMOSD patients to mice with breached blood–brain barrier (BBB). Mice, pretreated with bacterial proteins, received daily intraperitoneal injections of IgG purified from AQP4–IgG-seropositive NMOSD patients [IgG(AQP4+)], or IgG from AQP4–IgG-seronegative patients [IgG(AQP4−)] or healthy subjects [IgG(Healthy)] for 8 days. Motor function was tested by walking across narrow beams, and spinal cords were collected for immunofluorescent analysis. We found that human IgG infiltrated into cord parenchyma of mice with breached BBB without deposition of complement activation products. Spinal cord of mice that received IgG(AQP4+) demonstrated loss of AQP4 and glial fibrillary acidic protein (suggestive of astrocyte loss), decrease in excitatory amino acid transporter 2, microglial/macrophage activation, neutrophil infiltration, patchy demyelination, and loss in axonal integrity. Mice that received IgG(AQP4+) required longer time with more paw slips to walk across narrow beams indicative of motor slowing and incoordination. Our findings suggest that AQP4–IgG induces complement-independent cord pathologies, including astrocytopathy, neuroinflammation, demyelination, and axonal injuries/loss, which are associated with subtle motor impairments. These complement-independent pathophysiologies likely contribute to early NMOSD lesion development.

Fetal growth restriction: features of somatomental development in infancy

Aim. To determine the features of physical and somatic health of full-term infants with fetal growth restriction during the first year. Methods. A retrospective analysis of 100 neonatal medical records of full-term infants was performed. All children were divided into 2 groups: group 1 - full-term infants, who were diagnosed with fetal growth restriction at birth (n=50), group 2 - full term infants born with normal body weight (n=50). Control points of comparison were neonatal period, months of life 1, 3, 6 and 12. Overall anthropometric data (length, weight, head and chest circumference), incidence and structure of morbidity and child's key system involvement were assessed. Results. Full-term newborns with fetal growth restriction present a risk group of growth and weight gain retardation during infancy, perinatal disorders of central nervous system persistent in 28±12% of cases by year 1 and, consequently, restriction of psychomotor (16±10%) and pre-verbal development (16±10%). Full-term low birth-weight newborns are characterized by short period of breast feeding and are included into the group of frequently ill children. The most vulnerable system, except for central nervous system, is the respiratory system. Conclusion. Children born with fetal growth restriction by the full term of gestation require special approach: diagnosis of and degree of central nervous system perinatal disorders at the first minutes of life, dynamic monitoring and personalized rehabilitation and preventive measures during the first year of life.

Flora from Fărăgău Area (Mureş County) as Potential Source of Medicinal Plants

Abstract The aim of this study was to identify a potential source of medicinal plant from Transylvanian Plain. Also, the paper provides information about the hayfields floral richness, a great scientific value for Romania and Europe. The study of the flora was carried out in several stages: 2005-2008, 2013, 2017-2018. In the studied area, 397 taxa were identified, distributed in 82 families with therapeutic potential, represented by 164 medical taxa, 37 of them being in the European Pharmacopoeia 8.5. The study reveals that most plants contain: volatile oils (13.41%), tannins (12.19%), flavonoids (9.75%), mucilages (8.53%) etc. This plants can be used in the treatment of various human disorders: disorders of the digestive system, respiratory system, skin disorders, muscular and skeletal systems, genitourinary system, in gynaecological disorders, cardiovascular, and central nervous sistem disorders. In the study plants protected by law at European and national level were identified: Echium maculatum, Cephalaria radiata, Crambe tataria, Narcissus poeticus ssp. radiiflorus, Salvia nutans, Iris aphylla, Orchis morio, Orchis tridentata, Adonis vernalis, Dictamnus albus, Hammarbya paludosa etc.

Revealing the Inhibitory Effect of Ginseng on Mitochondrial Respiration through Synaptosomal Proteomics.

Ginseng, the active ingredients of which are ginsenosides, is the most popular herbal medicine and has potential merit in the treatment of cerebral disorders. To better understand the function of Ginseng in the cerebral system, we examined changes in the protein expression profiles of synaptosomes extracted from the cerebral cortical and hippocampal tissues of rats administered a high or low dose of Ginseng for 2 weeks. More than 5000 proteins belonging to synaptosomes were simultaneously identified and quantitated by an approach combining tandem mass tags with 2D liquid chromatography-mass spectrometry (LC-MS). Regarding differentially expressed proteins, downregulated proteins were much more highly induced than upregulators in the cerebral cortical and hippocampal synaptosomes, regardless of the dose of Ginseng. Bioinformatic analysis indicated the majority of the altered proteins to be located in the mitochondria, directly or indirectly affecting mitochondrial oxidative respiration. Further functional experiments using the substrate-uncoupler inhibitor titration approach confirmed that three representative ginsenosides were able to inhibit oxidative phosphorylation in mitochondria. Our results demonstrate that Ginseng can regulate the function of mitochondria and alter the energy metabolism of cells, which may be useful for the treatment of central nervous disorders.

Structural studies and drug discovery of G protein-coupled receptors

G protein-coupled receptors (GPCRs) constitute the largest membrane protein family in human body. Over 800 kinds of GPCRs have been characterized in human and are divided into Rhodopsin, Adhesion, Secretin, Glutamate and Frizzled/Taste 2 families. GPCRs can be stimulated by a variety of cell signal molecules, including hormones, neurotransmitters, ions, light etc. As the most widely distributed membrane proteins, GPCRs play important roles in almost all of the physiological activities and serve as drug targets for many diseases, such as cardiovascular diseases, central nervous disorders, inflammation, metabolic diseases and cancer. Despite their pivotal roles in the physiological and pharmaceutical fields, structure determination of GPCRs remains to be extremely challenging due to low protein yield when expressed in vitro , poor protein stability and multiple conformational states. To date, structures of 48 GPCRs have been determined, accounting for ~5% of characterized GPCRs. The most important developments of technique include fusion partner insertion and lipidic cubic phase (LCP) crystallization. Fusion partners, such as T4 lysozyme, thermo-stabilized apocytochrome b562RIL and flavodoxin etc, are inserted into the N terminus or intracellular loops to replace the unstable regions and provide hydrophilic contact for crystal packing. LCP is essential for crystallization as it mimics native environment of membrane proteins and is used to solve most of GPCR structures. Besides, stabilization mutations and disulfide-bond engineering are also widely used for GPCR structure determination. The X-ray free-electron laser (XFEL) and cryo-electron microscopy (EM) pave the way for obtaining high-resolution protein structure information from small size crystals or without the need for crystallization. According to the solved structures, GPCRs share a canonical seven transmembrane architecture despite their sequence diversity. However, the ligand binding pockets of different GPCRs vary in shape, size, location and electrostatics. The binding sites of orthostreric and allosteric ligands locate at extracellular, middle, intracellular and even outside of the transmembrane region. The diversity of the binding pockets provides structural basis for recognizing various ligands. Upon activation, GPCRs undergo conformational changes including a large outward movement of TM6 on the intracellular side, which exposes a pocket and engages downstream signal proteins. Three classes of downstream signal proteins have been reported, namely G proteins, G protein-coupled receptor kinases (GRKs) and arrestins. Approximate 34% of the US Food and Drug Administration approved drugs act at GPCRs. During 2011−2015, drugs targeting GPCRs accounted for about 27% of the global therapeutic drugs market share. Biologics, allosteric modulators and biased ligands are increasing in clinical trials targeting GPCRs, while major disease indications for GPCRs-targeted drugs show a shift from traditional popular areas such as allergy and hypertension toward diabetes, oncology and central nerves system disorders etc. Recent breakthroughs on GPCR structural determination provide insights into the mechanisms of ligand recognition and signal transduction, and facilitate structure-based drug design. However, more structural information is needed, including the interaction patterns of GPCR with other G proteins and basis of biased ligand signaling, to fully understand the superfamily membrane proteins. Here, we summarize the recent progresses on GPCR structural studies and drug discovery, and give suggestions for future research directions.

Pierwotne i wtórne zapalenia naczyń układu nerwowego

ABSTRAKTZapalenia naczyń ośrodkowego i obwodowego układu nerwowego stanowią heterogenną grupę chorób. Dzieli się je na zapalenia pierwotne i wtórne. W pierwotnych zapaleniach naczyń zmiany ograniczają się do układu nerwowego, bez zmian zapalnych w naczyniach innych narządów. Jako wtórne natomiast określa się zapalenia naczyń, w których zajęcie układu nerwowego towarzyszy chorobom ogólnoustrojowym. W przebiegu zapalenia naczyń układu nerwowego występuje różnorodność objawów neurologicznych i ich kombinacje, co sprawia, że są trudne do rozpoznania.Celem niniejszej publikacji był przegląd aktualnej symptomatologii neurologicznej oraz możliwości diagnostycznych i terapeutycznych w przebiegu zapalenia naczyń układu nerwowego.

Pyogenic brain abscess caused by Serratia marcescens in a Brazilian premature neonate

Bacterial brain abscess remain a serious central nervous system infectious disorder despite advances in neurosurgical, neuroimaging, clinical support on intensive care units, microbiological techniques and availability of new antibiotics. The successful treatment of brain abscess usually requires surgery, appropriate antibiotic therapy and eradication of the primary source. Although uncommon, brain abscesses are particularly important in the pediatric population due to its devastating potential to cause severe neurologic deficits, especially in preterm newborns. The purpose of the present report is to describe the case of a Brazilian premature neonate with pyogenic brain abscesses caused by Serratia marcescens and to discuss therapeutic and diagnostic approaches. The early suspicion, proper diagnostic measures and immediate neurosurgical consultation associated with aggressive antibiotic therapy seem to be the essentials steps on themanagement for those high-risk pediatric patients.

Variant of EOMES Associated with Increasing Risk in Chinese Patients with Relapsing-remitting Multiple Sclerosis.

Background:Multiple sclerosis (MS) is a common central nervous system autoimmune disorder. Increasing number of genome-wide association study (GWAS) analyses hint that MS is strongly associated with genetics. Unfortunately, almost all the GWAS analyses were Caucasian population based. Numbers of risk loci might not be replicated in Chinese MS patients. Hence, we performed a MassArray Assay to genotype the previously reported variants located in the transcription regulation genes in order to elucidate their role in the Chinese MS patients.Methods:One hundred and forty-two relapsing-remitting MS (RRMS) patients and 301 healthy controls were consecutively collected from September 2, 2008, to June 7, 2013, as stage 1 subjects. Eight reported transcription regulation-related single-nucleotide polymorphisms (SNPs) were genotyped using the Sequenom MassArray system. In stage 2, another 44 RRMS patients and 200 healthy controls were consecutively collected and Sanger sequenced from April 7, 2015, to June 29, 2017, for the validation of positive results in stage 1. Differences in allele and genotype frequencies between patients and healthy controls, odds ratios, and 95% confidence intervals were calculated with the Chi-square test or Fisher's exact test. Hardy-Weinberg equilibrium was tested also using the Chi-square test.Results:In stage 1 analysis, we confirmed only one previously reported risk variant, rs11129295 in EOMES gene. We found that the frequency of T/T genotype was much higher in MS group (χ2 = 10.251, P = 0.005) and the T allele of rs11129295 increased the risk of MS (χ2 = 10.022, P = 0.002). In stage 2 and combined analyses, the T allele of rs11129295 still increased the risk of MS (χ2 = 4.586, P = 0.030 and χ2 = 16.378, P = 5.19 × 10−5, respectively).Conclusions:This study enhances the knowledge that the variant of EOMES is associated with increasing risk in Chinese RRMS patients and provides a potential therapeutic target in RRMS.

Enhanced release of acid sphingomyelinase-enriched exosomes generates a lipidomics signature in CSF of Multiple Sclerosis patients

Multiple Sclerosis (MuS) is a complex multifactorial neuropathology, resulting in heterogeneous clinical presentation. A very active MuS research field concerns the discovery of biomarkers helpful to make an early and definite diagnosis. The sphingomyelin pathway has emerged as a molecular mechanism involved in MuS, since high levels of ceramides in cerebrospinal fluid (CSF) were related to axonal damage and neuronal dysfunction. Ceramides are the hydrolysis products of sphingomyelins through a reaction catalyzed by a family of enzymes named sphingomyelinases, which were recently related to myelin repair in MuS. Here, using a lipidomic approach, we observed low levels of several sphingomyelins in CSF of MuS patients compared to other inflammatory and non-inflammatory, central or peripheral neurological diseases. Starting by this result, we investigated the sphingomyelinase activity in CSF, showing a significantly higher enzyme activity in MuS. In support of these results we found high number of total exosomes in CSF of MuS patients and a high number of acid sphingomyelinase-enriched exosomes correlated to enzymatic activity and to disease severity. These data are of diagnostic relevance and show, for the first time, high number of acid sphingomyelinase-enriched exosomes in MuS, opening a new window for therapeutic approaches/targets in the treatment of MuS.

Symptoms of menopause - global prevalence, physiology and implications.

The symptoms of menopause can be distressing, particularly as they occur at a time when women have important roles in society, within the family and at the workplace. Hormonal changes that begin during the menopausal transition affect many biological systems. Accordingly, the signs and symptoms of menopause include central nervous system-related disorders; metabolic, weight, cardiovascular and musculoskeletal changes; urogenital and skin atrophy; and sexual dysfunction. The physiological basis of these manifestations is emerging as complex and related, but not limited to, oestrogen deprivation. Findings generated mainly from longitudinal population studies have shown that ethnic, geographical and individual factors affect symptom prevalence and severity. Moreover, and of great importance to clinical practice, the latest research has highlighted how certain menopausal symptoms can be associated with the onset of other disorders and might therefore serve as predictors of future health risks in postmenopausal women. The goal of this Review is to describe in a timely manner new research findings on the global prevalence and physiology of menopausal symptoms and their impact on future health.

Male and female opinions about orthotic devices of the lower limb: A multicentre, observational study in patients with central neurological movement disorders.

Because user-satisfaction and acceptance may partly determine the grade of compliance to an orthotic device (OD), the aim of this multicentre observational study was to inquire the reasons for acceptance and the user-satisfaction of an OD of the lower limb in male and female central neurological movement disorders (CNMD) patients. Persons with CNMD having at least one prescribed OD of the lower limb were included. Two questionnaires were used: the MIRAD-ACCORT-II (reasons for acceptance) and a modified version of the D-QUEST 2.0 (user-satisfaction). Descriptive analyses were performed and to analyse the differences between the males' and females' answers Chi2- and Mann-Whitney U tests were used. Twenty-six stroke and 23 multiple sclerosis patients participated (53% males). "Comfort", "safety", "effectiveness" and "ease of use" were reported as most important aspects. 86% of the patients were (very) satisfied about their OD. Only for the aspect safety, compared to males, significant more females reported that if the OD is not safe enough they will not use it. For both, males and females, aspects related to comfort and functionality were reported as much more important than the esthetical aspects, and in general they are quite satisfied with the OD and the process of providing the OD. Orthopaedic technicians and health care providers can take these aspects into account when developing, constructing and providing OD's.

The Effect of Toluene Exposure on Central Nervous Disorder among Printing Workers

Background : The use of toluene in printing dominates the use of metal chemicals. Toluene is used in 75% of printing work activities. Accumulation of toluene concentrations in printing can cause health problems to workers. The purpose of this study was to analyze the effect of toluene exposure on central nervous system disorders in printing industry workers. Subjects and Method: This study was cross-sectional in the printing industry in Medan, North Sumatra. The population consists of 50 people with consecutive sampling technique sampling. Data on subjective symptoms of central nervous system disorders were measured by the German version of the Q18 questionnaire. The data were analyzed using multiple logistic regression tests. Results: Subjective symptoms of central nervous system disorders increased with tenure ≥2 years (OR = 4.19; p = 0.018) and smoking (OR = 8.91; p = 0.001). Subjective symptoms of central nervous system disorders decreased with age ≤30 years (OR = 0.17; p = 0.004), female sex (OR = 0.50; p = 0.002). Conclusions: The most dominant variable affecting the subjective symptoms of central nervous system disorders is the smoking habit variable with a probability value of 0.92 or 92%. Keywords: subjective symptoms, central nervous system disorders, workers, a printing industry Correspondence: Samuel Marganda. Department of Environmental Health, Faculty of Public Health, Universitas Sumatera Utara, Medan, North Sumatera. Email: samuelmarganda@yahoo.co.id. Mobile: 085362985340. Indonesian Journal of Medicine (2018), 3(3): 125-133 https://doi.org/10.26911/theijmed.2018.03.03.01

Establishment for big data base of Microbiota closely related to diseases - Showa U bank -

The emergence of the next generation sequencer (NGS) and its technological progress have caused a major change in genetic analysis. Technological innovation by NGS had an enormous influence on the study of classification and analysis of intestinal bacteria inhabiting the intestine. It has been reported that in the intestines of humans, approximately 1,000 species, 100 trillion bacteria may coexist, and the intestinal bacteria could be about three times more than the number of cells constituting a human being. Following development of NGS, novel areas have been discovered in microbiota; however, in oncology, the relationships between microbiota and cancer have not been fully clarified. In recent literature, surprisingly, detection of gut microbiota in tumor issue itself has been reported. Microbiota might play a significant role in carcinogenesis. However, this phenomenon is not well understood, and research in this area has just begun. Gut microbiota and human beings are co-evolutionary, in a win-win symbiosis. Recently, there have been many studies and much research on the relationships between the gut microbiota and human disease. Gut microbiota seem to be strongly correlated with various kinds of disease, such as inflammatory bowel disease, diabetes mellitus, central nervous disorder, allergic diseases, and infectious diseases. On the other hand, the relationship between tumor and microbiota is not well clarified, and there has been yet clarified the relationship between Japanese patients and diseases. To clarify those, we have attempted to establish the big data base of Microbiota, we call, Showa U bank. We have sequenced V1 and V2 of 16s rRNA to determine the bacteria from specimen by NGS. In Showa University, we have 3,200 beds in the affiliated 8 hospitals. Our collaborations in Showa University makes possible accelerate the amounts of data of Microbiota related to clinical data from patients. From one of these data, microbiota from healthy subjects and cancer patients is much different. In this presentation, we will demonstrate the present data from Showa U bank.

Association between Sun Exposure, Vitamin D Intake, Serum Vitamin D Level, and Immunoglobulin G Level in Patients with Neuromyelitis Optica Spectrum Disorder.

Background:Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system inflammatory disorder in which immunoglobulin G (IgG) autoantibodies possibly play a pathogenic role against the aquaporin-4 water channel protein. Vitamin D may modulate B-cell function and decrease the IgG synthesis and may play a role in NMOSD as a crucial factor. The aim of this study was to investigate the relation between Vitamin D intakes from food, Vitamin D intake from sunlight exposure, blood Vitamin D levels, and IgG-neuromyelitis optica (NMO) level in serum of patients with NMOSD and NMO.Method:In this cross-sectional study, food Frequency Questionnaires (FFQ) and Sun Exposure Questionnaire (SEQ) were completed to evaluate of vitamin D intakes from food and sun light exposure. Moreover, serum levels of 25(OH) vitamin D3 and IgG-NMO were assessed in patients with NMOSD and NMO.Results:We assessed IgG-NMO levels in 29 patients with NMOSD that nine patients (n = 31%) were positive and for the rest it was negative. Sunlight exposure scale (P = 0.01) and 25(OH) D3 (P = 0.04) in IgG-NMO-negative patients were significantly more than patients with positive IgG-NMO. Age, gender, and latitude were not confounder variables. A positive significant correlation was observed between the sun exposure scale and serum levels of 25(OH) D3 in all participants (r = 0.747, P ≤ 0.001).Conclusions:Physiological variation in Vitamin D may apply a significant effect on IgG-NMO synthesis in patients with NMO. Vitamin D may have significant role in pathogenesis of NMOSD and NMO.

Isolated central nervous system post-transplant lymphoproliferative disorder in a pediatric patient: a case report with pathobiological perspective

Isolated central nervous system post-transplant lymphoproliferative disorder (ICNS-PTLD) in pediatric patients is a distinctly rare entity without accepted diagnostic criteria or treatment recommendations. We present a case of an 8-year-old male with a prior history of a kidney transplant who developed and ICNS-PTLD. We highlight the pathobiology and diagnostic features with a brief review of the literature on these rare cases. There is a complex interplay between CD30, Epstein Barr Virus and MYC as part of lymphocyte transformation leading to PTLD. In the appropriate clinical setting, CD30 and EBV positivity along with normal MYC expression are highly predictive of CNS-PTLD over a Primary CNS lymphoma. ICNS-PTLD has only been rarely reported in children. The faithful diagnosis is necessary for prognostication and to accrue data for treatment recommendations.