ABSTRACT
Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hematological disorder characterized by uncontrolled activation of CD8+ T and natural killer cells, leading to a cytokine storm and severe organ dysfunction. Although secondary HLH related to autoimmune diseases usually demonstrates a good treatment response to immunosuppressive therapy for underlying conditions, there is no consensus regarding the treatment in case of unresponsiveness to the treatment. Herein, we present a case of HLH that was unresponsive to high-dose glucocorticoid and cyclosporine treatment in a patient with newly diagnosed systemic lupus erythematosus. The patient’s clinical features and laboratory abnormalities rapidly improved with ruxolitinib, an oral Janus kinase 1 and 2 (JAK1/2) inhibitor. This result suggests that blocking JAK-STAT pathway may be a potential treatment option in patients with refractory HLH secondary to autoimmune diseases.
ABSTRACT
Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties. Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development. We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse. Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse. We found that glycan expression profiles were dynamically regulated during postnatal developments. A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain were also identified. Interestingly, changes primarily attributed to sialylated and fucosylated glycans were extensively observed during PFC development. Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development. Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
Subject(s)
Carbohydrate Metabolism , Polysaccharides/biosynthesis , Prefrontal Cortex/metabolism , Adolescent , Adult , Animals , Child , Child, Preschool , Glycomics , Humans , Infant , Infant, Newborn , Male , Mice , Prefrontal Cortex/growth & development , Young AdultABSTRACT
BACKGROUND: Osteoporosis is a systemic skeletal disease characterized by reduced bone mineral density and skeletal microstructural abnormalities. We investigated the correlation between serum uric acid (SUA) levels and bone mineral content (BMC) values as a surrogate marker of bone health. Additionally, we assessed whether the correlation, if any, was evident even after classifying the study population into two groups based on a diagnosis of obesity in these individuals.METHODS: This study included 936 women who visited the healthcare centers that participated in this study. Fasting blood samples were obtained from all women to measure SUA, BMC of the lumbar spine was measured using dual-energy X-ray absorptiometry. We evaluated the correlation between SUA and BMC in obese and non-obese groups.RESULTS: SUA concentration and BMC were positively correlated (β=0.257, P=0.001); however, this correlation was significant only in the obese group (β=0.203, P=0.001).CONCLUSION: SUA concentration and BMC are positively correlated in women diagnosed obesity.
Subject(s)
Female , Humans , Absorptiometry, Photon , Biomarkers , Body Mass Index , Bone Density , Delivery of Health Care , Diagnosis , Fasting , Obesity , Osteoporosis , Spine , Uric AcidABSTRACT
Chinese hamster ovary (CHO) cells are the most widely used host cell lines for the commercial production of therapeutic proteins including Fc-fusion proteins. During the culture of recombinant CHO (rCHO) cells, host cell proteins (HCPs), secreted from viable cells and released from dead cells, accumulate extracellularly, potentially impairing product quality. In this study, the HCPs that accumulated extracellularly in batch and fed-batch cultures of Fc-fusion protein-producing rCHO cell lines (DG-Fc and DUKX-Fc) were identified and quantified using nanoflow liquid chromatography-tandem mass spectrometry (LC-MS/MS), followed by gene ontology and functional analysis. When the proteome database of Cricetulus griseus was used as a reference to identify the HCPs, more HCPs were identified for DG-Fc (1632 HCPs in batch culture and 1733 HCPs in fed-batch culture) than for DUKX-Fc (1114 HCPs in batch culture and 1002 HCPs in fed-batch culture). Clustering analysis of HCPs, which were classified into four clusters according to their concentration profiles during culture, showed that the concentration profiles of HCPs affecting the quality of Fc-fusion proteins correlated with changes in Fc-fusion protein quality. Taken together, the dataset of HCPs obtained in this study using the two different rCHO cell lines provides insights into the determination of appropriate target proteins to be removed during the culture and purification steps so as to ensure good Fc-fusion protein quality. Biotechnol. Bioeng. 2017;114: 2267-2278. © 2017 Wiley Periodicals, Inc.
Subject(s)
Batch Cell Culture Techniques/methods , CHO Cells/physiology , Gene Expression Profiling/methods , Immunoglobulin Fc Fragments/metabolism , Proteome/metabolism , Recombinant Fusion Proteins/biosynthesis , Animals , CHO Cells/classification , Cricetulus , Culture Media , Genetic Engineering/methods , Immunoglobulin Fc Fragments/chemistry , Peptide Mapping/methods , Proteome/chemistry , Recombinant Fusion Proteins/chemistryABSTRACT
The R47H coding variant of the triggering receptor expressed on myeloid cells-2 (TREM2) increases the risk of Alzheimer's disease (AD) similar to apolipoprotein E4. TREM2 R47H has recently been shown to have impaired binding to damage-associated lipid or apolipoprotein ligands. However, it is not known how this R47H variant affects the biochemical characteristics of TREM2 and alters the pathogenesis of AD. We previously reported that TREM2-R47H has a slightly different glycosylation pattern from wild-type. A more detailed characterization in our present study confirms that TREM2 R47H has an altered glycosylation pattern and reduced stability. TREM2 R47H shows different glycosylation profiles from analysis using monensin or kifunensine treatment which were confirmed by mass spectrometry. The solubility of TREM2 R47H and its cleaved products such as intracellular domain (ICD) is also decreased, increasing its proteasomal and lysosomal degradation. The different biochemical characteristics of TREM2 R47H, including glycosylation, solubility and processing, may offer insights into a future therapeutic strategy for AD.
ABSTRACT
OBJECTIVES: The aim of this study is to evaluate the effect of suburban community water fluoridation programs on preventing caries in permanent teeth. METHODS: In 2012, surveys were administered to children aged 8, 12, and 15 years residing in fluoridated Habcheon township area. Samples collected during the national survey in 2012 from children of the same age residing in non-fluoridated township areas were used as the control, and the caries prevalence data from this sample were used to estimate the caries preventive effect in the studied regions. This study included 457 subjects from the Habcheon township area and 1,792 in the control group. The data obtained from the survey were analyzed using the IBM SPSS statistical package version 21.0. The caries preventive effect exerted by fluoride in the community water supply was determined by calculating the differences in the DMFT and DMFS indices between the study and control groups. The cofounders of the mean number of fissure-sealed teeth and surfaces were controlled to estimate the effectiveness of caries prevention. RESULTS: The odds ratio of subjects with no dental caries in the fluoridated region was 0.75 compared to that in the control group. The mean DMFT scores or DMFS scores adjusted for the number of fissuresealed teeth or tooth surfaces were lower than those in the control group. The caries prevention fraction was estimated to be 23.4% based on the difference in the adjusted mean DMFT scores between the control and study groups. CONCLUSIONS: These results suggest that fluoridation of the community water in the suburban area was highly effective in preventing dental caries in permanent teeth, and therefore, this community water fluoridation program should be implemented in other regions in Korea.
Subject(s)
Child , Humans , Dental Caries , Dentition, Permanent , Fluoridation , Fluorides , Korea , Odds Ratio , Prevalence , Tooth , Water Supply , WaterABSTRACT
Tissue glyco-capture (TGC), a highly sensitive MS-compatible method for extraction of glycans from tissue, was combined with structure-specific nano-LC/MS for sensitive and detailed profiling of the mouse brain glycome. Hundreds of glycan structures were directly detected by accurate mass MS and structurally elucidated by MS/MS, revealing the presence of novel glycan motifs such as antennary fucosylation, sulfation, and glucuronidation that are potentially associated with cellular signaling and adhesion. Microgram-level sensitivity enabled glycomic analysis of specific regions of the brain, as demonstrated on not only brain sections (with a one-dimensional spatial resolution of 20 µm) but also isolated brain structures (e.g., the hippocampus). Reproducibility was extraordinarily high (R > 0.98) for both method and instrumental replicates. The pairing of TGC with structure-specific nano-LC/MS was found to be an exceptionally powerful platform for qualitative and quantitative exploration of the brain glycome.
Subject(s)
Brain/metabolism , Glycomics/methods , Polysaccharides/chemistry , Animals , Chromatography, Liquid/methods , Glycosylation , Male , Mice , Mice, Inbred C57BL , Nanotechnology/methods , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Tandem Mass Spectrometry/methodsABSTRACT
The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune-modulatory receptor involved in phagocytosis and inflammation. Mutations of Q33X, Y38C and T66M cause Nasu-Hakola disease (NHD) which is characterized by early onset of dementia and bone cysts. A recent, genome-wide association study also revealed that single nucleotide polymorphism of TREM2, such as R47H, increased the risk of Alzheimer's disease (AD) similar to ApoE4. However, how these mutations affect the trafficking of TREM2, which may affect the normal functions of TREM2, was not known. In this study, we show that TREM2 with NHD mutations are impaired in the glycosylation with complex oligosaccharides in the Golgi apparatus, in the trafficking to plasma membrane and further processing by γ-secretase. Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. Our results suggest that the impaired glycosylation and trafficking of TREM2 from endoplasmic reticulum/Golgi to plasma membrane by mutations may inhibit its normal functions in the plasma membrane, which may contribute to the disease.
Subject(s)
Alzheimer Disease/metabolism , Golgi Apparatus/metabolism , Lipodystrophy/metabolism , Membrane Glycoproteins/genetics , Mutation , Oligosaccharides/metabolism , Osteochondrodysplasias/metabolism , Receptors, Immunologic/genetics , Subacute Sclerosing Panencephalitis/metabolism , Alzheimer Disease/genetics , Cell Membrane/metabolism , Endoplasmic Reticulum/metabolism , Glycosylation , HeLa Cells , Humans , Lipodystrophy/genetics , Membrane Glycoproteins/metabolism , Osteochondrodysplasias/genetics , Polymorphism, Single Nucleotide , Protein Transport , Receptors, Immunologic/metabolism , Subacute Sclerosing Panencephalitis/geneticsABSTRACT
OBJECTIVES: The aim of this study was to estimate the economic costs and benefits of a water fluoridation program in the city of Jinju, Korea. METHODS: In 2009, dental surveys were conducted on 2,315 children aged 6-12 years in Jinju, which had been fluoridated for 11 years. The decayed/missing/filled teeth (DMFT) scores of children in Jinju were compared to the DMFT scores of same-aged children in non-fluoridated small- and medium-sized cities in the fourth Korean National Health and Nutrition Examination Survey conducted from 2007 to 2009 by the Korea Centers for Disease Control and Prevention. The reduced number of decayed permanent teeth by the water fluoridation program was estimated as the difference between the DMFT scores of children in Jinju and those in non-fluoridated small- and medium-sized cities. The economic benefits were estimated by the savings from reduced dental treatment costs by using the reduced number of decayed permanent teeth from the water fluoridation program. All annual costs and benefits were calculated from 1998 to 2009. The social rate and untreated rate of decayed teeth were applied as 3% and 20%, respectively. The annual benefit-cost ratio was estimated by using the annual benefits and cumulative program costs. RESULTS: The economic benefit in 2009 from a water fluoridation program was estimated as 57,496,000,000 Korean Won (KRW), and the cumulative cost in 2009 was estimated as 1,387,000,000 KRW. The net present value in 2009 from a water fluoridation program was 56,109,000,000 KRW. The benefit-cost ratio in 2009 was estimated as 41.4. CONCLUSIONS: The economic benefit of a water fluoridation program in Jinju city was evaluated as excellent.
Subject(s)
Child , Humans , Cost-Benefit Analysis , Dental Caries , Fluoridation , Health Care Costs , Income , Korea , Nutrition Surveys , ToothABSTRACT
OBJECTIVES: The aim of the study was to analyze the factors related to the illegal dental treatment experience (IDTX) among Korean adults. METHODS: The raw data for the analysis of IDTX among Korean adults were obtained from the dataset of the Fourth Korea National Health and Nutrition Examination Survey conducted in 2007-2009. Stratified weighted subjects aged > or =45 years were selected according to region by using clustered sampling methods. In total, the data of 9,254 subjects, who participated in the interview and dental examinations related to the experience of illegal dental treatments, were analyzed using chi-square test, general linear model, and logistic regression analysis with complex sampling design by considering demographic and socioeconomic variables (age, gender, region, educational level, household income, and medical and dental delivery system) as well as oral status variables (prosthesis and number of natural remaining teeth). RESULTS: IDTX rate was 30% among adults aged > or =65 years. The age group with a high IDTX rate coincided with the age group with a high number of lost teeth. Most of the IDTX cases were presumed to be prosthetic treatments. The model comprising demographic, socioeconomic, and oral status variables had the highest explanation power. Significant variables were educational level, household income, prosthesis status, and number of remaining teeth. Women and persons under the medicaid system were more likely to undergo illegal dental treatments. CONCLUSIONS: Comprehensive prosthetic treatments are suggested to be included in the care services of the national health insurance and medicaid system to reduce the number of illegal dental treatments.
Subject(s)
Adult , Female , Humans , Dataset , Dental Care , Family Characteristics , Korea , Linear Models , Logistic Models , Medicaid , National Health Programs , Nutrition Surveys , Prostheses and Implants , Socioeconomic Factors , ToothABSTRACT
Human chromosome 11 is the third gene-rich chromosome having 1304 protein-coding genes. According to the GeneCards, this chromosome contains 240 genes related to diseases, as it is well known as a disease-rich chromosome. Although there are many protein-coding genes, the proteomic identification ratio is rather low. As a model study, human hippocampal tissues from patients suffering from Alzheimer's disease and epilepsy were prepared to evaluate the gene-centric statistics related to the gene expression and disorders of chromosome 11. A total of 8828 protein coding genes from brain tissues were extensively off-gel fractionated and profiled by a high resolution mass spectrometer with collision induced dissociation and electron transfer dissociation. Five-hundred twenty-three of the proteins from brain tissues were determined to belong to chromosome 11, representing 37% of the proteins reported in the Global Proteome Machine Database. We extracted gene clusters from a specific biological process or molecular function in gene ontology, among which the olfactory receptor genes showed the largest cluster on chromosome 11. Analysis of the proteome data set from the hippocampus provides a significant network associated with genes and proteins and leads to new insights into the biological and genetic mechanisms of chromosome 11-specific diseases such as Alzheimer's disease.
Subject(s)
Alzheimer Disease , Chromosomes, Human, Pair 11 , Epilepsy , Hippocampus/metabolism , Adult , Aged , Aged, 80 and over , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Chromosomes, Human, Pair 11/genetics , Chromosomes, Human, Pair 11/metabolism , Databases, Protein , Epilepsy/genetics , Epilepsy/metabolism , Gene Expression , Humans , Middle Aged , Proteins/classification , Proteins/genetics , Proteins/metabolism , ProteomeABSTRACT
PURPOSE: Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a association of genetic, environmental, and immunologic factors in the development of AD. And AD can be classified into IgE mediated and non-IgE mediated. We investigated a difference of clinical characteristics and immune response between the two groups. METHODS: From January 2008 to December 2011, we enrolled 125 children who visited Dong-A University Medical Center and Busan Medical Center, and were diagnosed as AD with the Haniffin and Rajka's criteria. We checked the history of combined asthma and allergic rhinitis and allergic disease of family in patients. We measured serum total IgE, specific IgE by ImmunoCAP or skin prick test. We measured serum interleukin (IL) 4 (IL-4), interferon-gamma (IFN-gamma), IL-10, and IL-17, which are associated with chronic inflammatory disorder by flow cytometry method (Luminex). RESULTS: Eighty (64%) were included in the IgE mediated group, while forty-five (36%) were included in the non-IgE mediated group. The frequency of combined allergic disorder and serum total eosinophil count were relatively higher in IgE mediated group (P=0.023, P=0.032). The incidence of a family history in allergic disease and the mean of SCORing Atopic Dermatitis index had no difference between the two groups. Serum IL-4, IFN-gamma, IL-10, IL-17 were higher in the IgE mediated group, but there were no statistically significant differences between two groups (P>0.05). CONCLUSION: IgE mediated AD showed higher total eosinophil count and higher incidence of bronchial asthma and allergic rhinitis than non IgE mediated AD.
Subject(s)
Child , Humans , Academic Medical Centers , Asthma , Dermatitis, Atopic , Eosinophils , Flow Cytometry , Immunoglobulin E , Immunologic Factors , Incidence , Interferon-gamma , Interleukin-10 , Interleukin-17 , Interleukin-4 , Interleukins , Methods , Rhinitis , SkinABSTRACT
Dopamine(DA)rgic neurons are particularly vulnerable due to the presence of oxidative stress-inducing molecules such as DA, tetrahydrobiopterin, iron and tyrosine hydroxylase (TH). We have recently observed that matrix metalloproteinase-3 (MMP-3) is involved in degeneration of DArgic neurons. In the present study, we sought to explore the role of MMP-3 in DArgic neurons not exposed to apparent stress conditions. In 8-week-old male mice deficient of MMP-3 gene (MMP-3 KO), the total number of DArgic neurons in the substantia nigra was considerably higher than wild type (WT). Primary cultured mesencephalic neurons from MMP-3 KO showed higher [(3)H]DA uptake capability compared to that of WT. The number of TH-immunopositive neurons and the length of average dendritic branch were also greater. This appeared to be selective for the DArgic system, because [(3)H]GABA uptake and calbindin D-28K and MAP-2 immunoreactivities were unaltered. On the other hand, no differences were noted in the levels of the striatal DA, DOPAC and BH4 and TH protein between the KO and WT. Interestingly, TH immunodensity per cell was lower in the DArgic neurons of MMP-3 KO both in primary culture and in vivo, suggesting the presence of a compensatory mechanism. These results further indicate a role of MMP-3 in the demise of DArgic neurons and suggest MMP-3 as a candidate cellular target for neuroprotective therapy.
Subject(s)
Dopamine/metabolism , Matrix Metalloproteinase 3/genetics , Nerve Degeneration/enzymology , Neurons/enzymology , Substantia Nigra/enzymology , Animals , Cell Count , Cells, Cultured , Corpus Striatum/metabolism , Cytoprotection/drug effects , Cytoprotection/physiology , Dendrites/enzymology , Dendrites/pathology , Disease Models, Animal , Down-Regulation/genetics , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Nerve Degeneration/pathology , Nerve Degeneration/physiopathology , Neurons/pathology , Parkinson Disease/enzymology , Parkinson Disease/pathology , Parkinson Disease/physiopathology , Substantia Nigra/pathology , Substantia Nigra/physiopathology , Tyrosine 3-Monooxygenase/metabolism , gamma-Aminobutyric Acid/metabolismABSTRACT
Parkinson's disease (PD) is caused by selective degeneration of the nigral dopaminergic (DArgic) neurons and is accompanied by motor dysfunctions such as tremor, akinesia, and rigidity. Changes in the degree of motor deficit can be utilized as a noninvasive way of assessing alterations in the number of DArgic neurons and/or the amount of DA in animal models of PD, such as mice systemically administrated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this study, in order to develop sensitive methods to detect DA-associated motor deficits, we designed a new test called vertical grid test and modified the existing horizontal grid test. After acute MPTP treatment, decreases in the levels of striatal DA (17.4% of control), dihydroxyphenylacetic acid (33.3%), and homovanillic acid (40.5%) were observed. On the modified horizontal grid test, the MPTP-administered mice exhibited average forelimb step distance that was lower than control (82.58%) and correlated with the striatal DA levels. On the vertical grid test, the MPTP-treated mice took dramatically longer total time to climb down (220.94%) and time to make the turn (339.29%) compared to control, and this correlated well with the degree of striatal DA depletion. In comparison, the gait test produced only a small, albeit statistically significant, reduction in the mean stride length (94.55% of control). These results show that the vertical grid test can provide a sensitive measure of motor deficit in mice following administration of MPTP.
Subject(s)
Disability Evaluation , Dyskinesia, Drug-Induced/diagnosis , Parkinsonian Disorders/diagnosis , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Animals , Biomechanical Phenomena , Chromatography, High Pressure Liquid , Corpus Striatum/metabolism , Disease Models, Animal , Dopamine/metabolism , Dyskinesia, Drug-Induced/etiology , Dyskinesia, Drug-Induced/metabolism , Forelimb , Gait , Homovanillic Acid/metabolism , Male , Mice , Mice, Inbred C57BL , Motor Skills , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/complications , Phenylacetates/metabolism , Time FactorsABSTRACT
Heat shock proteins (HSPs) are specifically induced by various forms of stress. Hsp70.1, a member of the hsp70 family is known to play an important role in cytoprotection from stressful insults. However, the functional role of Hsp70 in motor function after spinal cord injury (SCI) is still unclear. To study the role of hsp70.1 in motor recovery following SCI, we assessed locomotor function in hsp70.1 knockout (KO) mice and their wild-type (WT) mice via the Basso, Beattie and Bresnahan (BBB) locomotor rating scale, before and after spinal hemisection at T13 level. We also examined lesion size in the spinal cord using Luxol fast blue/cresyl violet staining. One day after injury, KO and WT mice showed no significant difference in the motor function due to complete paralysis following spinal hemisection. However, when it compared to WT mice, KO mice had significantly delayed and decreased functional outcomes from 4 days up to 21 days after SCI. KO mice also showed significantly greater lesion size in the spinal cord than WT mice showed at 21 days after spinal hemisection. These results suggest that Hsp70 has a protective effect against traumatic SCI and the manipulation of the hsp70.1 gene may help improve the recovery of motor function, thereby enhancing neuroprotection after SCI.
Subject(s)
Animals , Humans , Mice , Cytoprotection , Heat-Shock Proteins , HSP70 Heat-Shock Proteins , Paralysis , Spinal Cord , Spinal Cord Injuries , ViolaABSTRACT
In Parkinson disease (PD), the dopaminergic (DAergic) neurons in the substantia nigra undergo degeneration. While the exact mechanism for the degeneration is still not completely understood, neuronal apoptosis and inflammation are thought to play roles. We have recently obtained evidence that matrix metalloproteinase (MMP)-3 plays a crucial role in the apoptotic signal in DAergic cells as well as activation of microglia. The present study tested whether doxycycline might modulate MMP-3 and provide neuroprotection of DAergic neurons. Doxycycline effectively suppressed the expression of MMP-3 induced in response to cellular stress in the DAergic CATH.a cells. This was accompanied by protection of CATH.a cells as well as primary cultured mesencephalic DAergic neurons via attenuation of apoptosis. The active form of MMP-3, released under the cell stress condition, was also decreased in the presence of doxycycline. In addition, doxycycline led to downregulation of MMP-3 in microglial BV-2 cells exposed to lipopolysaccharide (LPS). This was accompanied by suppression of production of nitric oxide and TNF-alpha, as well as gene expression of iNOS, TNF-alpha, IL-1beta, and COX-2. In vivo, doxycycline provided neuroprotection of the nigral DAergic neurons following MPTP treatment, as assessed by tyrosine hydroxylase immunocytochemistry and silver staining, and suppressed microglial activation and astrogliosis as assessed by Iba-1 and GFAP immunochemistry, respectively. Taken together, doxycycline showed neuroprotective effect on DAergic system both in vitro and in vivo and this appeared to derive from anti-apoptotic and anti-inflammatory mechanisms involving downregulation of MMP-3.
Subject(s)
Dopamine/metabolism , Doxycycline/pharmacology , Matrix Metalloproteinase 3/metabolism , Neurons/drug effects , Neuroprotective Agents/pharmacology , Substantia Nigra/cytology , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology , Animals , Cell Death/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Enzyme-Linked Immunosorbent Assay/methods , Female , Gene Expression Regulation, Enzymologic/drug effects , In Situ Nick-End Labeling/methods , L-Lactate Dehydrogenase/metabolism , Male , Matrix Metalloproteinase 3/genetics , Mice , Mice, Inbred C57BL , Nerve Tissue Proteins/metabolism , Neurons/ultrastructure , Nitrites/metabolism , Pregnancy , Rats , Rats, Sprague-Dawley , Silver Staining/methods , Statistics, Nonparametric , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Sometimes, spinal cord injury (SCI) results in various chronic neuropathic pain syndromes that occur diffusely below the level of the injury. It has been reported that behavioral signs of neuropathic pain are expressed in the animal models of contusive SCI. However, the observation period is relatively short considering the natural course of pain in human SCI patients. Therefore, this study was undertaken to examine the time course of mechanical and cold allodynia in the hindpaw after a spinal cord contusion in rats for a long period of time (30 weeks). The hindpaw withdrawal threshold to mechanical stimulation was applied to the plantar surface of the hindpaw, and the withdrawal frequency to the application of acetone was measured before and after a spinal contusion. The spinal cord contusion was produced by dropping a 10 g weight from a 6.25 and 12.5 mm height using a NYU impactor. After the injury, rats showed a decreased withdrawal threshold to von Frey stimulation, indicating the development of mechanical allodynia which persisted for 30 weeks. The withdrawal threshold between the two experimental groups was similar. The response frequencies to acetone increased after the SCI, but they were developed slowly. Cold allodynia persisted for 30 weeks in 12.5 mm group. The sham animals did not show any significant behavioral changes. These results provide behavioral evidence to indicate that the below-level pain was well developed and maintained in the contusion model for a long time, suggesting a model suitable for pain research, especially in the late stage of SCI or for long term effects of analgesic intervention.
Subject(s)
Animals , Humans , Rats , Acetone , Benzeneacetamides , Cold Temperature , Contusions , Follow-Up Studies , Hyperalgesia , Hypersensitivity , Models, Animal , Neuralgia , Piperidones , Salicylamides , Spinal Cord , Spinal Cord InjuriesABSTRACT
Vitamin D-dependent rickets(VDDR) is a rare autosomal disorder, characterized by hypocalcemia, hypophosphatemia, increased alkaline phosphatase, secondary hyperparathyroidism and many other clinical features. Type I VDDR is due to congenital defects of renal 1alpha-hydroxylase, the enzyme responsible for the conversion of 25-(OH)D3 to 1,25-(OH)2D3. Type II VDDR arise from target organ resistance to 1,25-(OH)2D3. Unilateral renal aplasia is generally thought to result from a lack of induction of the metanephric blastema from the ureteral bud, which may be secondary to ureteral bud maldevelopment and/or to a problem with the formation of the mesonephric duct. The incidence of unilateral renal aplasia is approximately 1/500-3,200. Type 1 VDDR associated with unilateral renal aplasia has not been reported yet. Thus we report a case of a 3 month old female infant diagnosed as type 1 VDDR with unilateral aplasia of kidney.
Subject(s)
Female , Humans , Infant , Alkaline Phosphatase , Congenital Abnormalities , Hyperparathyroidism, Secondary , Hypocalcemia , Hypophosphatemia , Incidence , Kidney , Rickets , Ureter , Urogenital Abnormalities , Vitamins , Wolffian DuctsABSTRACT
PURPOSE: Urinary tract infections(UTIs) are not uncommon findings in febrile pediatric patients and approximately one third of patients with UTI may have renal scars. This research was intended to establish the relationship between duration of fever and renal scars. METHODS: The medical records of 143 patients were reviewed retrospectively. Inclusion criteria were as follows: 1) fever as defined by an axillary temperature > or =37.5degrees C, 2) accurate history of fever duration and the use of antibiotics 3) no previous history of UTI and 4) positive urine culture. We observed whether the longer fever duration could be associated with the development of initial renal defects and subsequent renal scars, increased C-reactive protein(CRP), leukocytosis and the presence of vesicoureteral reflux(VUR). RESULTS: 1) Patients with longer fever duration after antibiotics showed more frequent initial renal defects(P=0.014). However, fever duration before antibiotic use was not associated with the development of initial renal defects(P=0.244). 2)Incidence of renal scar increased with fever duration before antibiotic use(P=0.006) and fever duration after antibiotic use(P=0.015). 3) CRP correlated with the fever duration after antibiotic use(r=0.287, P=0.003). 4) There was no relationships between fever duration and VUR(P>0.05). CONCLUSIONS: Our data suggest that fever duration before/after antibiotic use is significantly associated with the increased development of renal scars in pediatric UTI.
Subject(s)
Humans , Anti-Bacterial Agents , C-Reactive Protein , Cicatrix , Fever , Leukocytes , Leukocytosis , Medical Records , Retrospective Studies , Urinary Tract , Urinary Tract Infections , Vesico-Ureteral RefluxABSTRACT
PURPOSE: We often have patients who acquired incorrect medical information from the mass media. The purpose of this study was to evaluate credibility of articles in newspapers and medical counseling on websites about renal diseases. METHODS: Kidney information was searched in 6 newspapers for the past 10 years, and 4 portal websites and 17 internet health counseling sites for the past 5 years. We classified them according to information providers and evaluated credibility by giving points 3, 2, 1 to correct, mostly correct but ambiguous, and incorrect contents, respectively. We compared the credibility of the groups with each other. RESULTS: Sixty four articles from newspapers, and 789 and 506 medical counselings from portal websites and internet health counseling sites were selected, respectively. The kidney information providers in newspapers were medical journalists(doctors)(31.2%), kidney specialists(doctors) (23.4%) and so on. The consultants in the portal sites were doctors(49.1%)and anonymous reporters(49.9%). In internet health counseling sites, 91% of the consultants were doctors. All articles in the newspapers were credible. Doctors' answers were more credible than nonphysicians'(P=0.005) and anonymous contributors(P<0.001) in portal sites. In health counseling sites, doctors answered more reliably than nonphysicians. CONCLUSIONS: The kidney information in newspapers was credible. It is important for questioners to confirm the type of consultants in websites. We suggest that doctors, especially kidney specialists need to increase their roles in offering information to mass media.