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Pathological Alterations (pathological + alteration)
Selected AbstractsNeuropathic pain: symptoms, models, and mechanismsDRUG DEVELOPMENT RESEARCH, Issue 4 2006Simon Beggs Abstract Peripheral neuropathic pain is the most debilitating of all clinical pain syndromes and affects a large and growing number of people worldwide. There are diverse causes for peripheral neuropathic pain, which may be experienced after traumatic nerve injury or from diseases that affect peripheral nerves, such as diabetes, HIV/AIDS, and cancer, and it can also result from toxic chemicals, such as cancer chemotherapy agents. Despite these varying causes, it is clear that neuropathic pain is due to persistent pathological alterations resulting in hyperexcitability in the peripheral and central nervous systems, and it is the neuropathology that must be targeted for effective therapy of which there is none presently available. Mechanistically, neuropathic pain is distinct from acute pain and inflammatory pain, for which many effective therapies are known. In this review, we describe the relationships between clinical symptoms and experimental models of peripheral neuropathic pain, and we provide a framework for understanding the potential mechanisms that involve primary neuronal dysfunction as well as pathological changes in neuron-glial signaling. Drug Dev. Res. 67:289,301, 2006. © 2006 Wiley-Liss, Inc. [source] Increased glucose metabolism and ATP level in brain tissue of Huntington's disease transgenic miceFEBS JOURNAL, Issue 19 2008Judit Oláh Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by multifarious dysfunctional alterations including mitochondrial impairment. In the present study, the formation of inclusions caused by the mutation of huntingtin protein and its relationship with changes in energy metabolism and with pathological alterations were investigated both in transgenic and 3-nitropropionic acid-treated mouse models for HD. The HD and normal mice were characterized clinically; the affected brain regions were identified by immunohistochemistry and used for biochemical analysis of the ATP-producing systems in the cytosolic and the mitochondrial compartments. In both HD models, the activities of some glycolytic enzymes were somewhat higher. By contrast, the activity of glyceraldehyde-3-phosphate dehydrogenase was much lower in the affected region of the brain compared to that of the control. Paradoxically, at the system level, glucose conversion into lactate was enhanced in cytosolic extracts from the HD brain tissue, and the level of ATP was higher in the tissue itself. The paradox could be resolved by taking all the observed changes in glycolytic enzymes into account, ensuing an experiment-based detailed mathematical model of the glycolytic pathway. The mathematical modelling using the experimentally determined kinetic parameters of the individual enzymes and the well-established rate equations predicted the measured flux and concentrations in the case of the control. The same mathematical model with the experimentally determined altered Vmax values of the enzymes did account for an increase of glycolytic flux in the HD sample, although the extent of the increase was not predicted quantitatively. This suggested a somewhat altered regulation of this major metabolic pathway in HD tissue. We then used the mathematical model to develop a hypothesis for a new regulatory interaction that might account for the observed changes; in HD, glyceraldehyde-3-phosphate dehydrogenase may be in closer proximity (perhaps because of the binding of glyceraldehyde-3-phosphate dehydrogenase to huntingtin) with aldolase and engage in channelling for glyceraldehyde-3-phosphate. By contrast to most of the speculation in the literature, our results suggest that the neuronal damage in HD tissue may be associated with increased energy metabolism at the tissue level leading to modified levels of various intermediary metabolites with pathological consequences. [source] Human cytomegalovirus and natural killer-mediated surveillance of HLA class I expression: a paradigm of host,pathogen adaptationIMMUNOLOGICAL REVIEWS, Issue 1 2001Miguel López-Botet Summary: Among various strategies to evade the host immune response, some viruses like human cytomegalovirus (HCMV) interfere with surface MHC class I expression and antigen presentation to T lymphocytes. The ability of natural killer (NK) cells to detect MHC class I molecules through inhibitory receptors can be envisaged as an adaptation of the immune system for responding to such pathological alterations. To fulfil that role, rodents use members of the Ly49 C-type lectin superfamily, whereas primates employ killer immunoglobulin-like receptors and the immunoglobulin-like transcript 2/leucocyte immunoglobulin-like receptor-1 receptor. CD94/NKG2 lectin-like heterodimers represent the most conserved receptor system for MHC class I molecules; by interacting with human HLA-E or murine Qa-1b, CD94/NKG2A inhibitory receptors broadly probe the biosynthesis pathway of other class I molecules. Reciprocally, HCMV has developed mechanisms to evade the NK response while modulating HLA class Ia expression. The ability of HCMV to maintain surface levels of HLA-E and to express an HLA class I surrogate (UL18) are herein discussed in the context of the interplay with human NKR systems. This work was supported by grants FIS 00/0181 and SAF98-0006. We thank Dr A. Angulo for helpful discussion. [source] Residual rickets or osteomalacia: a case dating from the 16,18th centuries from Krosno Odrza,skie, PolandINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 5 2009E. Haduch Abstract A skeleton from a 16,18th century burial site in Krosno Odrza,skie, Poland, was examined using classical morphological, metric and macroscopic palaeopathological observations, as well as radiography and tomography of the skull and long bones. A wide variety of the observed bone deformations probably occurred as a consequence of past rickets and/or osteomalacia, whose primary cause may also have been chronic renal failure. Preservation of the bones enables a discussion of the cause of such pathological changes. The subject under study appears to be a very interesting example of an individual whose skeleton shows advanced pathological alterations associated with the subject's vitamin D deficiency, overall health conditions and relatively long lifespan. Copyright © 2008 John Wiley & Sons, Ltd. [source] Activation of MKK6, an upstream activator of p38, in Alzheimer's diseaseJOURNAL OF NEUROCHEMISTRY, Issue 2 2001Xiongwei Zhu Mitogen-activated protein kinase (MAPK) p38 has been implicated in the pathogenesis of Alzheimer's disease, but the upstream cascade leading to p38 activation has not been elucidated in the disease. In the present study, we focused on mitogen-activated protein kinase kinase 6 (MKK6), one of the upstream activators of p38 MAPK. We found that MKK6 was not only increased but also specifically associated with granular structures in the susceptible neurons in the hippocampus and cortex of Alzheimer's disease patients, but was only weakly diffuse in the cytoplasm in neurons in control cases. Immunoblot analysis demonstrated a significant increase of MKK6 level in Alzheimer's disease compared with age-matched controls. In this regard, in hippocampal and cortical regions of individuals with Alzheimer's disease, the activated phospho-MKK6 was localized exclusively in association with pathological alterations including neurofibrillary tangles, senile plaques, neuropil threads and granular structures, overlapping with activated p38 MAPK suggesting both a functional and mechanic link. By immunoblot analysis, phospho-MKK6 is also significantly increased in AD compared with control cases. Together, these findings lend further credence to the notion that the p38 MAPK pathway is dysregulated in Alzheimer's disease and also indicates an active role for this pathway in disease pathogenesis. [source] A review of morphological techniques for detection of peroxisomal (and mitochondrial) proteins and their corresponding mRNAs during ontogenesis in mice: Application to the PEX5-knockout mouse with Zellweger syndromeMICROSCOPY RESEARCH AND TECHNIQUE, Issue 2 2003Eveline Baumgart Abstract In the era of application of molecular biological gene-targeting technology for the generation of knockout mouse models to study human genetic diseases, the availability of highly sensitive and reliable methods for the morphological characterization of the specific phenotypes of these mice is of great importance. In the first part of this report, the role of morphological techniques for studying the biology and pathology of peroxisomes is reviewed, and the techniques established in our laboratories for the localization of peroxisomal proteins and corresponding mRNAs in fetal and newborn mice are presented and discussed in the context of the international literature. In the second part, the literature on the ontogenetic development of the peroxisomal compartment in mice, with special emphasis on liver and intestine is reviewed and compared with our own data reported recently. In addition, some recent data on the pathological alterations in the liver of the PEX5,/, mouse with a peroxisomal biogenesis defect are briefly discussed. Finally, the methods developed during these studies for the localization of mitochondrial proteins (respiratory chain complexes and MnSOD) are presented and their advantages and pitfalls discussed. With the help of these techniques, it is now possible to identify and distinguish unequivocally peroxisomes from mitochondria, two classes of cell organelles giving by light microscopy a punctate staining pattern in microscopical immunohistochemical preparations of paraffin-embedded mouse tissues. Microsc. Res. Tech. 61:121,138, 2003. © 2003 Wiley-Liss, Inc. [source] Extrapyramidal symptoms in Wilson's disease are associated with olfactory dysfunctionMOVEMENT DISORDERS, Issue 9 2006Antje Mueller MD Abstract Wilson's disease is a rare autosomal recessive disorder characterized by the accumulation of copper, mainly in the liver and the brain. As copper accumulation in the brain leads to disturbances in basal ganglia function, neurological-type patients typically present with hypo- and hyperkinetic extrapyramidal symptoms, with Parkinsonism being very common. Although there are numerous reports on olfactory deficits in primary neurodegenerative disorders, olfactory function has not been investigated in metabolic disorders presenting with extrapyramidal features. Twenty-four patients with Wilson's disease participated in the investigation. All patients were treated pharmacologically. They comprised patients with liver disease alone (including mild enzyme elevation in asymptomatic individuals; n = 11) and/or neurological symptoms (n = 13) at the time of testing. Twenty-one patients underwent both [18F]fluoro-2-deoxy-D-glucose positron emission tomography ([18F]FDG-PET) and magnetic resonance imaging (MRI). The severity of extrapyramidal symptoms was judged using a clinical score system ranging from 0 (no symptoms) to 3 (severe symptoms). In all patients, psychophysical testing was performed using the "Sniffin' Sticks," which involved tests for odor threshold, discrimination, and identification. Results from the present study revealed that Wilson's disease patients with neurological symptoms show a significant olfactory dysfunction compared to hepatic-type patients. Individuals who are more severely neurologically affected also present with a more pronounced olfactory deficit. Of interest, there was no significant effect of long-term treatment with penicillamine on olfactory function. Olfactory function did not correlate significantly with the presence of MRI visible lesions in the basal ganglia or with any regional glucose metabolism as measured by [18]F-FDG-PET. In conclusion, these findings indicate that the underlying pathological alterations with degeneration in the basal ganglia and neuronal loss in association with a marked increase of the copper content in this brain region play a role in the olfactory deficit. © 2006 Movement Disorder Society [source] Opportunities afforded by the study of unmyelinated nerves in skin and other organsMUSCLE AND NERVE, Issue 6 2004William R. Kennedy MS Abstract Neurological practice is mainly focused on signs and symptoms of disorders that involve functions governed by myelinated nerves. Functions controlled by unmyelinated nerve fibers have necessarily remained in the background because of the inability to consistently stain, image, or construct clinically applicable neurophysiological tests of these nerves. The situation has changed with the introduction of immunohistochemical methods and confocal microscopy into clinical medicine, as these provide clear images of thin unmyelinated nerves in most organs. One obvious sign of change is the increasing number of reports from several laboratories of the pathological alterations of cutaneous nerves in skin biopsies from patients with a variety of clinical conditions. This study reviews recent methods to stain and image unmyelinated nerves as well as the use of these methods for diagnosing peripheral neuropathy, for experimental studies of denervation and reinnervation in human subjects, and for demonstrating the vast array of unmyelinated nerves in internal organs. The new ability to examine the great variety of nerves in different organs opens opportunities and creates challenges and responsibilities for neurologists and neuroscientists. Muscle Nerve 756,767, 2004 [source] On the Structure of the Adrenal Gland of the Common Seal (Phoca vitulina vitulina)ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 5 2004H. Bragulla Summary The adrenal gland is a vitally important endocrine gland that occupies a central role in the regulatory mechanisms of the body metabolism. Environmental stress factors lead to permanent strain and overload of the body resulting in structural alterations of the adrenals that in turn are followed by hormonal imbalances. This leads to an increased susceptibility to bacterial and viral diseases. The recurrence of numerous fatalities in the different seal populations of the North Sea (during the years 1988, 1989 and 2002), of the Baikal Lake and Caspian Sea (during the years 2000 and 2001) were the motive for a morphological investigation of the species-specific structure of the adrenal gland of the common seal in order to differentiate environmental stress-induced pathological alterations from the physiological structure of this organ. The study was based on adrenals of 112 common seals (Phoca vitulina vitulina) using light microscopic and transmission and scanning electron microscopic methods. The phocine adrenal gland displays several structural characteristics. Originating from the connective tissue organ capsule, narrow and broad septa intersperse the adrenal cortex. These septa contain blastemata as a reserve for the regeneration of hormone-producing cortical cells. Such blastemata are also occurring in the form of an intermediate zone in between the zona glomerulosa and zona fasciculata in the phocine adrenal cortex. Another species-specific characteristic is an inverse part of the adrenal cortex encircling the central vein of the organ. These structural features have to be considered in assessment and definition of pathological alterations of the adrenals as observed in the form of exhausted blastema cell pools in the adrenocortex of seals perished in the mentioned phocine mass mortalities. [source] Is the Male Dog Comparable to Human?ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 4 2002A Histological Study of the Muscle Systems of the Lower Urinary Tract Because of their superficial anatomical resemblance, the male dog seems to be suitable for studying the physiologic and pathological alterations of the bladder neck of human males. The present study was carried out to compare and contrast the muscular anatomy of the male dog lower urinary tract with that of humans. The complete lower urinary tract, including the surrounding organs (bulb of penis, prostate, rectum and musculature of the pelvic floor) were removed from adult and newborn male dogs and histologically processed using serial section technique. Based on our own histological investigations, three-dimensional (3D)-models of the anatomy of the lower urinary tract were constructed to depict the corresponding structures and the differences between the species. The results of this study confirm that the lower urinary tract of the male dog bears some anatomical resemblance (musculus detrusor vesicae, prostate, prostatic and membranous urethra) to man. As with human males, the two parts of the musculus sphincter urethrae (glaber and transversostriatus) are evident in the canine bladder neck. Nevertheless, considerable differences in formation of individual muscles should be noted. In male dogs, no separate anatomic entity can be identified as vesical or internal sphincter. The individual course of the ventral and lateral longitudinal musculature and of the circularly arranged smooth musculature of the urethra is different to that of humans. Differences in the anatomy of individual muscles of the bladder neck in the male dog and man suggest that physiological interpretations of urethral functions obtained in one species cannot be attributed without qualification to the other. [source] A Novel Cyclic Squamosamide Analogue Compound FLZ Improves Memory Impairment in Artificial Senescence Mice Induced by Chronic Injection of D-Galactose and NaNO2BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2007Fang Fang Artificially senescent mouse model was induced by consecutive injection of D-galactose (120 mg/kg) and NaNO2 (90 mg/kg) once daily for 60 days. Compound FLZ (75 and 150 mg/kg) was orally administered once daily for 30 days after D-galactose and NaNO2 injection for 30 days. The water maze test was used to evaluate the learning and memory function of mice. The content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum were determined using different biochemical kits. The alterations in hippocampus morphology were assessed by light and electronic microscope. Immunoreactive cells of Bcl-2 in the hippocampus were counted by immunohistochemical staining, and Bcl-2 protein expression was analysed by Western blot method. The results indicate that injection of D-galactose and NaNO2 induces memory impairment and neuronal damage in hippocampus of mice. In addition, serum SOD and GSH-Px activities decreased, while MDA level increased. Bcl-2-positive neurons and Bcl-2 protein expression in the hippocampus decreased remarkably. Oral administration of FLZ for 30 days significantly improved the cognitive deficits and the biochemical markers mentioned above, and also reduced the pathological alterations in mouse hippocampus. The results suggest that FLZ ameliorates memory deficits and pathological injury in artificially senescent mice induced by chronic injection of D-galactose and NaNO2, indicating that FLZ is worth further studies for fighting antisenescence and dementia. [source] The protective and healing effects of a natural antioxidant formulation based on ubiquinol and Aloe vera against dextran sulfate-induced ulcerative colitis in ratsBIOFACTORS, Issue 1-4 2003Ludmila Korkina Abstract Oxygen/nitrogen reactive species (ROS/RNS) are currently implicated in the pathogenesis of ulcerative colitis, drawing attention on the potential prophylactic and healing properties of antioxidants, scavengers, chelators. We evaluated the possible protective/curative effects of a natural antioxidant preparation based on Aloe vera and ubiquinol, against intestinal inflammation, lesions, and pathological alterations of the intestinal electrophysiological activity and motility, in a rat model of DSS-induced colitis. 5% dextrane sulfate (DDS) (3 days), followed by 1% DSS (4 days) was administered in drinking water. The antioxidant formulation (25 mg/kg) was delivered with a pre-treatment protocol, or simultaneously or post-colitis induction. Spontaneous and acetylcholine-stimulated electrical activity were impaired in the small intestine and in distal colon, upon exposure to DSS only. Severe inflammation occurred, with increased myeloperoxidase activity, and significant alterations of the oxidant/antioxidant status in colonic tissue and peritoneal cells. Lipoperoxidation, superoxide production, glutathione peroxidase and glutathione-S-transferase activities, and reduced glutathione content increased, whilst superoxide dismutase and catalase activities were sharply suppressed in colon tissue. ROS/RNS formation in peritoneal cells was strongly inhibited. Inflammation, electrical/mechanical impairment in the gut, and a great majority of oxidative stress parameters were improved substantially by pre-treatment with the antioxidant preparation, but not by simultaneous administration or post-treatment. [source] 2432: Histological characteristics of the posterior lid marginACTA OPHTHALMOLOGICA, Issue 2010N KNOP Purpose The structure of the lid margin is insufficiently understood and defined although it is of obvious importance for ocular surface integrity. In particular the histological structure of the tissues of the normal lid margin and their zonal differentiation is partly unclear. Methods The structure and function of the different zones at the posterior lid margin are explained with a focus on dry eye disease, based on the available literature on the lid margin together with own findings on the histology of normal and pathological tissues from the human lid margin. Results The Meibomian glands (MG) that are of particular significance for the integrity of the ocular surface open still within the cornified epidermis. Their obstructive dysfunction (MGD) is a main cause for dry eye disease. The orifice is followed by the mucocutaneous junction (MCJ) that extends from the abrupt termination of the epidermis to the crest of the inner lid border. The physiological vital stainable line of Marx represents its surface and can be used as a diagnostic tool for the location and functionality of the MG orifices and lacrimal puncta. The marginal conjunctiva starts at the crest of the inner lid border and forms a thickened epithelial cushion. This is the point in closest apposition to the globe, represents the zone that wipes the bulbar surface and distributes the thin pre-ocular tear film. It is hence termed as the lid wiper and pathological alterations that result in a vital staining are a sensitive early indicator of dry eye disease. Conclusion The margin of the eyelid is an important but yet underestimated structure for the maintenance of the pre-ocular tear film and of utmost importance for the preservation of ocular surface integrity and for development of dry eye disease. Support DFG KN317/11 [source] Endothelial dysfunction in glaucomaACTA OPHTHALMOLOGICA, Issue 1 2009Hemma Resch Abstract. Glaucoma is a group of ocular diseases characterized by optic neuropathy associated with loss of the retinal nerve fibre layer and re-modelling of the optic nerve head, and a subsequent particular pattern of visual field loss. Increased intraocular pressure is the most important risk factor for the disease, but the pathogenesis of glaucoma is not monofactorial. Among other factors, ischaemia and vascular dysregulation have been implicated in the mechanisms underlying glaucoma. The vascular endothelium plays an important role in the regulation of ocular blood flow and pathological alterations of vascular endothelial cells may induce ischaemia and dysregulation. The present review summarizes our current evidence of endothelial dysfunction in glaucoma. This is of interest because endothelial dysfunction is a good prognostic factor for progression in several diseases. Although such data are lacking for glaucoma, endothelial dysfunction may provide an attractive target for therapeutic intervention in open-angle glaucoma and other vascular disorders of the eye. [source] | ||||||||||||||||||||||