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No description available.

Fibrillary glomerulonephritis (FGN) is a rare disease identified in less than one percent of native kidney biopsy. FGN is characterized by hematuria, edema, renal insufficiency, and high-grade proteinuria. Renal biopsy results typically demonstrate deposition of randomly-arranged fibrils within the capillary wall or mesangium. Positive staining with DnaJ Heat Shock Protein Family Member B9 (DNAJB9) is considered diagnostic. Associations include malignancy, hepatitis C, dysproteinemia, autoimmune disorders, and diabetes mellitus. To our knowledge, this is the first case demonstrating association between fibrillary glomerulonephritis and vulvar squamous cell carcinoma. A 66-year-old year old Caucasian female presented to the emergency department for worsening renal injury. She was diagnosed with vulvar squamous cell carcinoma 5 years prior and underwent radical excision with inguinal lymphadenectomy and CO2 laser treatment. Over the years, she had multiple relapses and received wide local excision and adjuvant radiation, with the last treatment involving radiation being 2.5 years before admission. The patient had a recently identified non-malignant vulvar lesion at the time of admission, which was found to be lichen sclerosus et atrophicus. She was found to have renal dysfunction and nephrotic range proteinuria; her creatinine was 2.84 mg/dL (normal range 0.60–1.10 mg/dL), BUN 33 mg/dL (normal range 6–20 mg/dL), urine protein:creatinine ratio 3.9 mg/g (normal range < 0.15 mg/g). She was started on pulse dose methylprednisolone of 500 mg daily, but her creatinine worsened, necessitating renal biopsy. Renal biopsy findings indicated mesangial expansion and randomly-arranged non-branching fibril deposition. Glomerular immunofluorescence indicated positive staining for IgA, IgG, and DNAJB9. These findings confirmed the diagnosis of fibrillary glomerulonephritis. Screening for associations – coexistent malignancies, hepatitis C, multiple myeloma, and autoimmune disorders – was negative. The patient was started on rituximab and prednisone therapy after confirming the absence of underlying infection. One month after initial hospitalization, she was re-hospitalized for worsening kidney function and required initiation of dialysis, on which she remains dependent. FGN is rapidly progressing and results in end-stage-renal-disease within two years in 50% of individuals. It should be considered as a differential diagnosis in patients with a history of malignancy, especially vulvar squamous cell carcinoma. There is no definitive treatment for FGN. Rituximab can be used in conjunction with steroid therapy, but further research is needed to determine the proper treatment for FGN at various stages of disease manifestation. The original case is published in Cureus, and permission has been received to present this case.

Background Multiple sclerosis (MS) is an autoimmune disease characterised by inflammatory damage to the central nervous system (CNS). Accumulated CNS injury can be quantified as brain atrophy, definable as a reduction in brain parenchymal fraction (BPF). BPF correlate with disability in MS and is used routinely as an endpoint in clinical trials. In 2009/2010, a new MS clinical care program, that includes follow-up of BPF, was introduced at Umeå University Hospital (NUS). Levels of neurofilament light polypetide (NFL) and glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF) are markers of axonal and astrocytic injury, respectively, and also potential surrogate biomarkers for BPF decline. The goals of this thesis were to establish age-adjusted values of BPF in healthy individuals and to relate these to the BPF values from individuals with MS as well as to the levels of NFL and GFAP in CSF. Another goal was to investigate if expanded disability status scale (EDSS)-worsening could be predicted in a clinical MS cohort and if BPF measurements could contribute to such predictions. Methods A group of 111 healthy individuals volunteered to participate in the studies. A total of 106 of these underwent MRI with BPF measurements, 53 underwent lumbar puncture (LP) with measurement of NFL and GFAP and 48 underwent both MRI and LP. Three different automatic and one manual method were utilised to determine BPF. A literature search on BPF in healthy individuals was performed for the purpose of a systematic review. For studying disability progression in MS, all individuals with MS followed at NUS and included in the Swedish MS registry were included if they had matched data on BPF, EDSS and lesion load as part of clinical follow-up (n=278). Results BPF as well as NFL and GFAP levels in CSF were all associated with age. NFL was associated with BPF and GFAP, but only the association with GFAP was retained when adjusting for age. Significant differences were found between different methods for BPF determination. In the MS population, BPF was associated with EDSS. Only progressive disease course could predict EDSS worsening. Conclusion The data on BPF and levels of NFL and GFAP in CSF of healthy individuals can aid in the interpretation of these variables in the setting of MS. Knowledge on differences in BPF data from different methods for BPF determination can be useful in comparing data across studies, but also highlights the need for a commonly accepted gold standard. The correlation between GFAP and NFL levels in CSF may indicate an association between glial and axonal turnover that is independent of the aging effect on the brain. However, the low number of volunteers for LP precluded clear conclusions. An association between BPF and EDSS was seen in the MS group. The ability to predict EDSS worsening in the clinical MS cohort was limited.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2007. / Härtill 4 uppsatser.

This thesis assessed the suitability of unilateral, electrolytic lesions as a model of spinal cord damage and repair in the adult rat. This type of lesion resulted acutely in localized damage in the upper motor neuron at the L2-L3 level of the spinal cord. Minimal acute damage to ascending sensory pathways was indicated by preserved somatosensory evoked potentials elicited by stimulation of the tibial nerve. Immediately after lesion generation one of several substrates was injected into the lesion cavity. These substrates were saline buffer, liquid collagen solution, foetal spinal cord cells from 14 day old rat embryos, and a mixture of collagen and E 14 foetal spinal cord cells. The 4 groups were compared for functional recovery over 3 months using the inclined plane test and a Tarlov movement scale. After sacrifice, the tibialis anterior muscles were dissected and weighed to assess atrophy due to lower motor neuron injury. After removing and embedding the spinal cords in paraffin, transverse and longitudinal sections were taken for cytoarchitectural investigation. Cresyl violet was used to indicate Nissl substance, Luxol fast blue stained for myelin and anti - glial fibrillary acidic protein (GFAP) antibody revealed the expression of GFAP in the cord sections. Chronic electrolytic lesions were characterized by the highly variable degree of cavitation, demyelination and macrophage infiltration that was present. There was no significant performance deficit on the inclined plane test in any of the lesioned groups when compared to unoperated animals. The tibialis muscles from all groups were of normal weight, indicating that the lower motor neurons were not significantly damaged by the lesions used. There was, however, a marked decrease in the number of GFAP reactive astrocytes in the lesioned animals when compared to unlesioned controls (P < 0.01, Wilcoxon test). Moreover, this reduction of GFAP - like immunoreactivity was not prevented by implants of foetal neurons, collagen or foetal neurons suspended in collagen. Possible explanations for the reduced GFAP - like immunoreactivity seen in all electrolytically lesioned cords are discussed. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

Mesmo a isquemia sendo a terceira causa de morte em países industrializados, os mecanismos relacionados a esta doença ainda continuam polêmicos e obscuros. Utilizou-se a técnica de privação de oxigênio e glicose (OGD) em fatias do hipocampo de rato para investigar parâmetros mitocondriais, neurais, astrogliais e metabólicos no período de isquemia e durante o período de reoxigenação. Os resultados mostraram uma diminuição na atividade mitocondrial durante o período isquêmico que foi mantido durante todo o período de reoxigenação. Analisando o sobrenadante destas fatias submetidas à OGD, foi observado que os níveis de LDH, NSE e GFAP se elevaram. Com relação aos níveis de lactato, verificou-se sua diminuição durante todos os períodos. Os níveis de S100B estavam elevados somente durante o período de reoxigenação. Este aumento pode ser tanto um mecanismo de neuroproteção desta proteína frente ao insulto ou ainda uma liberação por dano celular astrocitário. Além disso, foi observado um grande aumento nos níveis de glutamato durante a isquemia e este aumento retornou no período de reoxigenação. Por fim, houve uma diminuição na captação de glutamato somente no período de reoxigenação. Todos estes resultados podem ser conseqüência de uma hiper-estimulação dos receptores glutamatérgicos devido ao insulto isquêmico. Em resumo, nosso estudo mostrou alterações em diversos parâmetros neuroquímicos específicos tanto no período isquêmico quanto na reoxigenação, mostrando que cada tipo celular, reage diferentemente frente ao insulto isquêmico na técnica de OGD in vitro. / Stroke is the third cause of mortality in industrialized countries, and the mechanisms related to this disease are polemic and unclear. Oxygen and glucose deprivation (OGD) in acute rat hippocampal slices was performed to investigate mitochondrial, neural, astroglial and metabolic neurochemical parameters at different ischemic and reoxygenation periods. Results showed the mitochondrial activity decrease due energy failure during ischemic insult and reoxygenation time. In the supernatant medium, LDH, NSE and glutamate levels were increased and the lactate decrease by the lack of energy observed in the ischemic period. Parameters such as GFAP, S100B and glutamate uptake suffered alterations only at the reoxygenation period. These results have shown the vulnerability of neurons facing ischemic insult. Meanwhile, it was also observed a delayed injure of astrocytes only at reoxygenation time, which demonstrate the difference between cell types at OGD. In summary, our finding has shown altered at specific neurochemical parameters in OGD in vitro which features the ischemic episodes and reoxygenation periods.

Thesis (Ph.D.)--University of Florida, 2004. / Typescript. Title from title page of source document. Document formatted into pages; contains 87 pages. Includes Vita. Includes bibliographical references.

Mesmo a isquemia sendo a terceira causa de morte em países industrializados, os mecanismos relacionados a esta doença ainda continuam polêmicos e obscuros. Utilizou-se a técnica de privação de oxigênio e glicose (OGD) em fatias do hipocampo de rato para investigar parâmetros mitocondriais, neurais, astrogliais e metabólicos no período de isquemia e durante o período de reoxigenação. Os resultados mostraram uma diminuição na atividade mitocondrial durante o período isquêmico que foi mantido durante todo o período de reoxigenação. Analisando o sobrenadante destas fatias submetidas à OGD, foi observado que os níveis de LDH, NSE e GFAP se elevaram. Com relação aos níveis de lactato, verificou-se sua diminuição durante todos os períodos. Os níveis de S100B estavam elevados somente durante o período de reoxigenação. Este aumento pode ser tanto um mecanismo de neuroproteção desta proteína frente ao insulto ou ainda uma liberação por dano celular astrocitário. Além disso, foi observado um grande aumento nos níveis de glutamato durante a isquemia e este aumento retornou no período de reoxigenação. Por fim, houve uma diminuição na captação de glutamato somente no período de reoxigenação. Todos estes resultados podem ser conseqüência de uma hiper-estimulação dos receptores glutamatérgicos devido ao insulto isquêmico. Em resumo, nosso estudo mostrou alterações em diversos parâmetros neuroquímicos específicos tanto no período isquêmico quanto na reoxigenação, mostrando que cada tipo celular, reage diferentemente frente ao insulto isquêmico na técnica de OGD in vitro. / Stroke is the third cause of mortality in industrialized countries, and the mechanisms related to this disease are polemic and unclear. Oxygen and glucose deprivation (OGD) in acute rat hippocampal slices was performed to investigate mitochondrial, neural, astroglial and metabolic neurochemical parameters at different ischemic and reoxygenation periods. Results showed the mitochondrial activity decrease due energy failure during ischemic insult and reoxygenation time. In the supernatant medium, LDH, NSE and glutamate levels were increased and the lactate decrease by the lack of energy observed in the ischemic period. Parameters such as GFAP, S100B and glutamate uptake suffered alterations only at the reoxygenation period. These results have shown the vulnerability of neurons facing ischemic insult. Meanwhile, it was also observed a delayed injure of astrocytes only at reoxygenation time, which demonstrate the difference between cell types at OGD. In summary, our finding has shown altered at specific neurochemical parameters in OGD in vitro which features the ischemic episodes and reoxygenation periods.

Mesmo a isquemia sendo a terceira causa de morte em países industrializados, os mecanismos relacionados a esta doença ainda continuam polêmicos e obscuros. Utilizou-se a técnica de privação de oxigênio e glicose (OGD) em fatias do hipocampo de rato para investigar parâmetros mitocondriais, neurais, astrogliais e metabólicos no período de isquemia e durante o período de reoxigenação. Os resultados mostraram uma diminuição na atividade mitocondrial durante o período isquêmico que foi mantido durante todo o período de reoxigenação. Analisando o sobrenadante destas fatias submetidas à OGD, foi observado que os níveis de LDH, NSE e GFAP se elevaram. Com relação aos níveis de lactato, verificou-se sua diminuição durante todos os períodos. Os níveis de S100B estavam elevados somente durante o período de reoxigenação. Este aumento pode ser tanto um mecanismo de neuroproteção desta proteína frente ao insulto ou ainda uma liberação por dano celular astrocitário. Além disso, foi observado um grande aumento nos níveis de glutamato durante a isquemia e este aumento retornou no período de reoxigenação. Por fim, houve uma diminuição na captação de glutamato somente no período de reoxigenação. Todos estes resultados podem ser conseqüência de uma hiper-estimulação dos receptores glutamatérgicos devido ao insulto isquêmico. Em resumo, nosso estudo mostrou alterações em diversos parâmetros neuroquímicos específicos tanto no período isquêmico quanto na reoxigenação, mostrando que cada tipo celular, reage diferentemente frente ao insulto isquêmico na técnica de OGD in vitro. / Stroke is the third cause of mortality in industrialized countries, and the mechanisms related to this disease are polemic and unclear. Oxygen and glucose deprivation (OGD) in acute rat hippocampal slices was performed to investigate mitochondrial, neural, astroglial and metabolic neurochemical parameters at different ischemic and reoxygenation periods. Results showed the mitochondrial activity decrease due energy failure during ischemic insult and reoxygenation time. In the supernatant medium, LDH, NSE and glutamate levels were increased and the lactate decrease by the lack of energy observed in the ischemic period. Parameters such as GFAP, S100B and glutamate uptake suffered alterations only at the reoxygenation period. These results have shown the vulnerability of neurons facing ischemic insult. Meanwhile, it was also observed a delayed injure of astrocytes only at reoxygenation time, which demonstrate the difference between cell types at OGD. In summary, our finding has shown altered at specific neurochemical parameters in OGD in vitro which features the ischemic episodes and reoxygenation periods.