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Biomedical subjects

V Charles

Publications and source records attributed to V Charles.

At least 19 recordsLinked to original sources
PubMed2006

[Wernicke's encephalopathy associated with chronic disulfiram intoxication].

INTRODUCTION: We report the case of a patient with an unusual association of Wernicke encephalopathy and chronic disulfiram intoxication. CASE REPORT: A 41-year-old man presented with progressive frontal decline and akineto-rigid parkinsonism under chronic disulfiram therapy. He also developed acute confusion with ataxia, blepharospasm, and supranuclear ophthalmoplegia following a severe malnutrition due to refusal of food intake. Brain MRI revealed symmetrical and reversible hyperintense lesions on T2 and FLAIR in the posterior putaminal regions, dorso-medial thalamic and subthalamic nuclei, the periaqueducal gray matter, the cerebellar peduncles, and the pontine tegmentum. A slow partial clinical recovery with persistent frontal syndrome was observed after discontinuation of disulfiram and parenteral administration of thiamine. DISCUSSION: The symmetry and reversibility of the MRI lesions in the basal ganglia and brain stem were suggestive of a deficiency, a toxic or a metabolic neurological disease. The dorso-medial thalamo-subthalamic and brainstem localizations, as well as their occurrence in a state of malnutrition, were consistent with Wernicke encephalopathy. Moreover, chronic disulfiram intoxication might explain the frontal syndrome and the akineto-rigid parkinsonism, associated with MRI putaminal lesions. Similar MRI lesions have been described in the so-called "energy deprivation syndromes", which are toxic, genetic or nutritional disorders that disrupt enzymes involved in energy generating metabolic pathways such as glycolysis and pyruvate oxidation.

Adult↗
PubMed2006

Retrospective study of 156 atrial septal defects in dogs and cats (2001-2005).

Atrial septal defect (ASD) is a common congenital heart disease (CHD) in humans, but considered relatively rare in veterinary medicine. However, modern echocardiographic and Doppler techniques currently offer a good view of the morphology of the interatrial septum, thus facilitating earlier detection of ASD in awake animals. In this context, we carried out a retrospective study of cases of recently diagnosed ASD in dogs and cats at the Cardiology Unit of Alfort (2001-2005) using echocardiography combined with colour Doppler mode. ASD was diagnosed in 156 animals and represented 37.7% of all canine and feline CHDs (n = 414). ASD was the most common CHD after mitral dysplasia in both species. Boxer and Domestic shorthair were the most common canine and feline breeds affected. Most defects (98.7%) were secundum-type ASD, without clinical signs in 73.7% of cases. The most common clinical signs included systolic murmur heard over the left heart base (20.2%), exercise intolerance (7.0%), syncope (5.3%), dyspnoea (2.6%) and cough (2.6%). Animals that presented a systolic heart murmur over the left base had a significantly larger ASD than others (P < 0.05). These data suggest that the incidence of ASD is higher than previously assumed. ASD should be suspected, for example, in instances of left basal systolic heart murmur, although its clinical and haemodynamic consequences are usually minor.

Animals↗
PubMed2003

Comorbidity of substance misuse and mental illness in community mental health and substance misuse services.

BACKGROUND: Improved management of mental illness and substance misuse comorbidity is a National Health Service priority, but little is known about its prevalence and current management. AIMS: To measure the prevalence of comorbidity among patients of community mental health teams (CMHTs) and substance misuse services, and to assess the potential for joint management. METHOD: Cross-sectional prevalence survey in four urban UK centres. RESULTS: Of CMHT patients, 44% (95% CI 38.1-49.9) reported past-year problem drug use and/or harmful alcohol use; 75% (95% CI 68.2-80.2) of drug service and 85% of alcohol service patients (95% CI 74.2-93.1) had a past-year psychiatric disorder. Most comorbidity patients appear ineligible for cross-referral between services. Large proportions are not identified by services and receive no specialist intervention. CONCLUSIONS: Comorbidity is highly prevalent in CMHT, drug and alcohol treatment populations, but may be difficult to manage by cross-referral psychiatric and substance misuse services as currently configured and resourced.

Adult↗
PubMed2001

Early degenerative changes in transgenic mice expressing mutant huntingtin involve dendritic abnormalities but no impairment of mitochondrial energy production.

Mitochondrial defects, which occur in the brain of late-stage Huntington's disease (HD) patients, have been proposed to underlie the selective neuronal loss in the disease. To shed light on the possible role of mitochondrial energy impairment in the early phases of HD pathophysiology, we carried out Golgi impregnation and quantitative histochemical/biochemical studies in HD full-length cDNA transgenic mice that were symptomatic but had not developed to a stage in which neuronal loss could be documented. Golgi staining showed morphologic abnormalities that included a significant decrease in the number of dendritic spines and a thickening of proximal dendrites in striatal and cortical neurons. In contrast, measurements of mitochondrial electron transport Complexes I-IV did not reveal changes in the striatum and cerebral cortex in these mice. Examination of the neostriatum and cerebral cortex in human presymptomatic and pathological Grade 1 HD cases also showed no change in the activity of mitochondrial Complexes I-IV. These data suggest that dendritic alterations precede irreversible cell loss in HD, and that mitochondrial energy impairment is a consequence, rather than a cause, of early neuropathological changes.

Animals↗
PubMed2000

Alpha-synuclein immunoreactivity of huntingtin polyglutamine aggregates in striatum and cortex of Huntington's disease patients and transgenic mouse models.

Polyglutamine expansions in proteins are implicated in at least eight inherited neurodegenerative disorders, including Huntington's disease. These mutant proteins can form aggregates within the nucleus and processes of neurons possibly due to misfolding of the proteins. Polyglutamine aggregates are ubiquitinated and sequester molecular chaperone proteins and proteasome components. To investigate other protein components of polyglutamine aggregates, cerebral cortex and striata from patients with Huntington's disease and full-length cDNA transgenic mouse models for this disease were examined immunohistochemically for alpha-synuclein reactivity. Our findings demonstrate that alpha-synuclein can be used as a marker for huntingtin polyglutamine aggregates in both human and mice. Moreover in the HD transgenic mice, the intensity of immunoreactivity increases with age. The significance of recruitment of alpha-synuclein into huntingtin aggregates and its translocation away from the synapses remains to be determined. We propose that aberrant interaction of mutant huntingtin with other proteins, including alpha-synuclein, may influence disease progression.

Amino Acid Motifs↗
PubMed1999

Transgenic mice expressing mutated full-length HD cDNA: a paradigm for locomotor changes and selective neuronal loss in Huntington's disease.

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized clinically by motor and psychiatric disturbances and pathologically by neuronal loss and gliosis (reactive astrocytosis) particularly in the striatum and cerebral cortex. We have recently created HD full-length cDNA transgenic mouse models that may serve as a paradigm for HD. A more detailed characterization of these models is presented here. The transgene encoding normal huntingtin consists of 9417 bp of the huntingtin coding sequences including 16 tandem CAGs coding for polyglutamines as part of exon 1. The transgene is driven by a heterologous cytomegalovirus promoter. Five independent transgenic mouse lines were obtained using this construct. An additional six transgenic lines were obtained using full-length HD constructs that have been modified to include either 48 or 89 CAG repeat expansions. Southern blot and densitometric analyses indicated unique integration sites for the transgene in each of the lines with a copy number ranging from two to 22 copies. Widespread expression of the transgene in brain, heart, spleen, kidney, lung, liver and gonads from each line was determined by Western blot analyses. In the brain, transgene expression was found in cerebral cortex, striatum, hippocampus and cerebellum. Expression of the transgene was as much as five times the endogenous mouse huntingtin level. Phenotypically, only mice expressing 48 or 89 CAG repeats manifested progressive behavioural and motor dysfunction. Early behavioural abnormalities were characterized by trunk curling and clasping of both fore- and hindlimbs when the animals were suspended by their tails. Subsequently, these mice exhibited hyperkinetic movements, including heightened exploratory activities, unidirectional rotational behaviour, backflipping and excessive grooming that lasted for several weeks. Eventually, the animals progressed to a hypokinetic phase consisting of slowed movements and lack of response to sensory stimuli. Urine retention or incontinence was also a prominent feature of the hypokinetic phase. At the end stage of the disease process, HD48(B,D) and HD89(A-C) mice became akinetic just prior to death. Neuropathological examination of mice at various stages indicated that it was only during the hypokinetic phase and thereafter when selective neuronal loss was most apparent. Regions of neurodegeneration and loss included the striatum, cerebral cortex, thalamus and hippocampus. TUNEL staining indicated an apoptotic mode of cell death in these brain regions. Comparative neuronal counts after Nissl staining showed as much as 20% loss of small and medium neurons in the striatum in mice at the hypokinetic and akinetic stages. Reactive astrocytosis accompanied the areas of neurodegeneration and loss. Polyglutamine aggregates in the form of neuronal intranuclear inclusions and diffuse nuclear and perinuclear aggregations were found in a small percentage of neurons, including those in brain regions that are typically spared in HD. This observation suggests that polyglutamine aggregates may not be sufficient to cause neuronal loss in HD. In both behavioural and neuropathological analyses, wild-type and transgenic animals with 16 CAG repeats were indistinguishable from each other and do not exhibit the changes observed for mice carrying the 48 and 89 CAG repeat mutations. Thus, animals expressing the CAG repeat expansions appear to represent clinically analogous models for HD pathogenesis, and may also provide insights into the underlying pathophysiological mechanisms of other triplet repeat disorders.

Animals↗
PubMed1998

Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA.

Huntington disease (HD) is an adult-onset, autosomal dominant inherited human neurodegenerative disorder characterized by hyperkinetic involuntary movements, including motor restlessness and chorea, slowing of voluntary movements and cognitive impairment. Selective regional neuron loss and gliosis in striatum, cerebral cortex, thalamus, subthalamus and hippocampus are well recognized as neuropathological correlates for the clinical manifestations of HD. The underlying genetic mutation is the expansion of CAG trinucleotide repeats (coding for polyglutamines) to 36-121 copies in exon 1 of the HD gene. The HD mRNA and protein product (huntingtin) show widespread distribution, and thus much remains to be understood about the selective and progressive neurodegeneration in HD. To create an experimental animal model for HD, transgenic mice were generated showing widespread expression of full-length human HD cDNA with either 16, 48 or 89 CAG repeats. Only mice with 48 or 89 CAG repeats manifested progressive behavioural and motor dysfunction with neuron loss and gliosis in striatum, cerebral cortex, thalamus and hippocampus. These animals represent clinically relevant models for HD pathogenesis, and may provide insights into the underlying pathophysiological mechanisms of other triplet repeat disorders.

Animals↗
PubMed1997

Grafts of EGF-responsive neural stem cells derived from GFAP-hNGF transgenic mice: trophic and tropic effects in a rodent model of Huntington's disease.

The present study examined whether implants of epidermal growth factor (EGF)-responsive stems cells derived from transgenic mice in which the glial fibrillary acid protein (GFAP) promoter directs the expression of human nerve growth factor (hNGF) could prevent the degeneration of striatal neurons in a rodent model of Huntington's disease (HD). Rats received intrastriatal transplants of GFAP-hNGF stem cells or control stem cells followed 9 days later by an intrastriatal injection of quinolinic acid (QA). Nissl stains revealed large striatal lesions in rats receiving control grafts, which, on average, encompassed 12.78 mm3. The size of the lesion was significantly reduced (1.92 mm3) in rats receiving lesions and GFAP-hNGF transplants. Rats receiving QA lesions and GFAP-hNGF-secreting grafts stem cell grafts displayed a sparing of striatal neurons immunoreactive (ir) for glutamic acid decarboxylase, choline acetyltransferase, and neurons histochemically positive for nicotinamide adenosine diphosphate. Intrastriatal GFAP-hNGF-secreting implants also induced a robust sprouting of cholinergic fibers from subjacent basal forebrain neurons. The lesioned striatum in control-grafted animals displayed numerous p75 neurotrophin-ir (p75NTR) astrocytes, which enveloped host vasculature. In rats receiving GFAP-hNGF-secreting stem cell grafts, the astroglial staining pattern was absent. By using a mouse-specific probe, stem cells were identified in all animals. These data indicate that cellular delivery of hNGF by genetic modification of stem cells can prevent the degeneration of vulnerable striatal neural populations, including those destined to die in a rodent model of HD, and supports the emerging concept that this technology may be a valuable therapeutic strategy for patients suffering from this disease.

Animals↗
PubMed1996

Atrophy of cholinergic basal forebrain neurons following excitotoxic cortical lesions is reversed by intravenous administration of an NGF conjugate.

Nerve growth factor (NGF) has been shown to sustain the viability and modulate the function of cholinergic basal forebrain neurons. However, under normal circumstances, NGF does not cross the blood-brain barrier (BBB) following systemic administration making this neurotrophin unavailable to NGF-responsive neurons within the central nervous system (CNS). Recently, a non-invasive method for delivering NGF to the brain was established in which NGF was conjugated to an antibody directed against the transferrin receptor (OX-26) [15, 16]. This conjugation facilitates the transfer of NGF from the systemic circulation to the CNS via the transferrin transport system. In the present study, we tested whether intravenous administration of an OX-26-NGF conjugate could reverse the atrophy of cholinergic basal forebrain neurons following removal of the target sites. Lesions of the left cerebral cortex were created by epidural application of N-methyl-D-aspartic acid (NMDA). Seventy-five days later, cholinergic nucleus basalis neurons were atrophic ipsilateral to the lesion relative to the contralateral side in control rats receiving intravenous injections of vehicle or a non-conjugated mixture of OX-26 and NGF. In contrast, intravenous injections of the OX-26-NGF conjugate restored the size of nucleus basalis perikarya to within normal limits relative to the unlesioned contralateral side. Immunohistochemical studies using rat serum albumen antisera indicated that the BBB was closed at the time of treatment indicating that this trophic effect did not result from NGF crossing through a compromised BBB at the site of the lesion. These data demonstrate that systemic administration of a neurotrophic factor-antibody conjugate, intended to circumvent the BBB, can provide trophic influences to degenerating cholinergic basal forebrain neurons. These data support the emerging concept that the conjugate method can facilitate the transfer of impermeable therapeutic compounds across the BBB.

Animals↗
PubMed1994

Intravenous administration of a transferrin receptor antibody-nerve growth factor conjugate prevents the degeneration of cholinergic striatal neurons in a model of Huntington disease.

Intrastriatal injections of quinolinic acid induce a pattern of neuronal degeneration similar to that seen in Huntington disease. In the present study, nerve growth factor (NGF) crossed the blood-brain barrier in a dose-dependent fashion following intravenous infusion when conjugated to an antibody directed against the transferrin receptor (OX-26). Intravenous injections of the OX-26-NGF conjugate selectively prevented the loss of striatal choline acetyltransferase-immunoreactive neurons which normally occurs following quinolinic acid administration relative to control rats receiving vehicle or a nonconjugated mixture of OX-26 and NGF. These data demonstrate that a neurotrophic factor-antibody conjugate can prevent the degeneration of central NGF-responsive neurons following systemic administration.

Animals↗
PubMed1993

Development of local circuits in human visual cortex.

How we see the world largely depends on the organization of neuronal circuits in visual cortex. Physiological recordings in mammals indicate that circuits develop over a period that extends well into early postnatal ages (LeVay et al., 1980; Albus and Wolf, 1984). Our understanding of how these circuits are assembled during development is still fragmentary (Katz and Callaway, 1992). Here we describe the development of local connections within visual cortex, using the fluorescent dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate to trace axonal projections in post-mortem human brains. Vertical (intracolumnar) connections between layers 2/3 and 5, which link neurons representing the same point in the visual field, develop prenatally at 26-29 weeks gestation. In contrast, horizontal (intercolumnar) connections between different points in the visual field develop later. They first emerge prenatally at approximately 37 weeks gestation within layers 4B and 5. After birth (> 40 weeks gestation) the fiber density increases rapidly, showing a uniform plexus of connections at 7 weeks postnatal. The more adult-like patchiness of the projection, however, emerges after 8 weeks postnatal. Long-range horizontal connections within layer 2/3 develop after the connections within layers 4B, 5, and 6. These connections emerge after 16 weeks postnatal, long after cytochrome oxidase blobs have developed, and reach mature from sometime before 15 months of age. Unlike the patchy horizontal projections within layers 4B and 5, which seem to develop through a process of collateral elimination, long-range projections within layer 2/3 are patchy from the outset and seem to develop with greater topographical precision. The finding that intracolumnar connections develop before intercolumnar projections suggests that circuits that process local features of a visual scene develop before circuits necessary to integrate these features into a continuous and coherent neural representation of an image. In addition, the sequential development of horizontal connections within layer 4B before those within layer 2/3 suggests that circuits that may be related to the processing channel for visual motion develop in advance of those that may be more intimately related to the processing of form, color, and precise stereoscopic depth.

Aging↗
PubMed1992

The use and efficacy of Azadirachta indica ADR ('Neem') and Curcuma longa ('Turmeric') in scabies. A pilot study.

In the Ayurvedha and Sidha system of medicine (Indian system of medicine) Azadirachta indica ADR ('Neem') and Curcuma longa ('Turmeric') has been used for healing chronic ulcers and scabies. The 'Neem' and 'Turmeric' was used as a paste for the treatment of scabies in 814 people. In 97% of cases cure was obtained within 3 to 15 days of treatment. We find that this is a very cheap, easily available, effective and acceptable mode of treatment for the villagers in the developing countries. We have noticed no toxic or adverse reaction so far. However, further research is needed.

Administration, Topical↗
PubMed1990

Organization of local axon collaterals of efferent projection neurons in rat visual cortex.

We have studied the laminar origins of local long-range connections within rat primary visual cortex (area 17), by using retrograde tracing of nerve cell bodies with fluorescent markers. Injections throughout the thickness of cortex produce distinct laminar labeling patterns which indicate that a substantial number of cells in layers 2/3, 5, and 6 have wide local axon collateral arbors, while the local arbors of layer 4 cells are much narrower. Double labeling experiments which combined area 17 injections with injections into different projection targets of area 17 (opposite area 17, area 18a, and area 18b) show that many cortico-cortically projecting cells make widespread projections within area 17. In contrast, the overwhelming majority of subcortically projecting cells have narrow collateral arbors within area 17. Anterograde tracing of local projections within areas 17 with the lectin Phaseolus vulgaris leucoagglutinin shows an extensive system of horizontally running fibers which terminate in distinct 0.15-0.25 mm wide clusters up to 1.8 mm from the injection site. On horizontal sections the termination pattern resembles a closely spaced lattice. The results indicate that cortico-cortically projecting cells provide for long-range interactions between distant points of the visuotopic map, while subcortically projecting cells mediate information within a cortical column. Interestingly, subcortically projecting cells differ functionally from cortico-cortically projecting cells in that they are not orientation selective (Klein et al., Neurosci. 17:57-78, '86; Mangini and Pearlman, J. Comp. Neurol. 193:203-222, '80; Simmons and Pearlman, J. Neurophysiol. 50:838-848, '83). We therefore suggest that cortico-cortically projecting cells with wide collateral arbors are orientation selective and that clustered long-range projections within area 17 connect columns with similar functional specificity.

Animals↗
PubMed1979

Developing world. Child rearing practices in an Indian slum.

Our study has revealed the strong influence of tradition on child rearing practices in an Indian slum community. It is made clear that health education is essential to correct malpractices. Though the mothers were knowledgeable about the supplementary feeding they did not put the ideas into practice.

Breast Feeding↗