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PubMed1981

"Thalamic" dementia in herpes encephalitis: clinico-pathological report.

Herpes zoster (HZ) primary affections of the CNS are rare and, in most of the reported patients, are representing variously extended forms of ascending myelitis. Our examination concerns a man who at the age of 37 developed apathy after a feverish episode with iridocyclitis. Six months later an ophthalmic HZ was diagnosed and thenceforth the patient showed a dementia with Korsakow's syndrome, apathy and a right hemipalsy, and diplopia appeared; the later symptoms remitted after steroid therapy. Post-mortem examination revealed a slowly progressive encephalitis with symmetrical impairment of the anterior ventral, medial, and centrum medianum of the thalamus. The HZ origin of the lesions and the relation between their site and the peculiar form of dementia, to be ascribed to the "thalamic" ones, are discussed. A vasculitis process can be hypothesized considering both the symmetrical localisation and the microscopical aspects of the lesions.

Adult↗
PubMed1982

Do urinary MHPG and plasma drug levels correlate with response to amitriptyline therapy?

Twenty-nine inpatients with primary affective disorder were treated with 150 mg amitriptyline (AT) daily for 28 days. Pretreatment urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) was measured in two or three 24-h urine samples. Plasma levels of AT and nortriptyline (NT) were determined after 14, 21, and 28 days of treatment. MHPG excretion was significantly correlated with clinical response to treatment. Responders defined by two different methods showed higher pretreatment MHPG excretion than nonresponders. Correspondingly, high MHPG excretors (median split) showed significantly more improvement than low excretors. These relationships were even more apparent when possibly incomplete urine samples (creatinine excretion below 1000 mg/24h) were excluded. The high and low MHPG subgroups did not significantly differ from each other in their plasma levels of AT, NT, or AT plus NT. A significant rank correlation between clinical response and plasma levels of AT and/or NT did not exist, but there was a trend towards lower levels in responders.

Adult↗
PubMed1982

Antidepressive effect and pharmacokinetics of amitriptyline with consideration of unbound drug and 10-hydroxynortriptyline plasma levels.

In 27 inpatients with primary affective disorder the urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) was measured prior to a 4-week treatment with 150 mg amitriptyline (AT)/day. Ratings according to the Hamilton depression scale were performed before therapy and repeated after 2 and 4 weeks. Plasma levels of AT, nortriptyline (NT), and E-10-hydroxynortriptyline (OHNT) were assayed weekly, and binding of AT to plasma proteins was determined in one sample. Better therapeutic results were obtained at intermediate, as compared to low and high concentrations of AT or AT plus NT. Independent evaluation of AT and metabolite levels revealed that patients with AT of 50--125 ng/ml responded particularly well when NT did not exceed 95 ng/ml or when NT plus OHNT was below 150 ng/ml. Outside this "therapeutic window' the outcome was markedly poorer. Interindividual variation of AT binding was much smaller than variation of total concentrations. Evaluation of free, instead of total levels did not help to clarify the relationship between clinical and pharmacokinetic variables. Plasma levels within the optimal ranges were found in more patients with high than with low MHPG excretion. The free fraction of OHNT in plasma of healthy subjects was about 35%.

Adult↗
PubMed1994

Nerve growth factor enhances the dendritic arborization of sympathetic ganglion cells undergoing atrophy in aged rats.

We have investigated whether dendritic growth can be induced from sympathetic neurons of aged rats by the application of exogenous nerve growth factor to their target tissues. A previous study showed that significant dendritic atrophy (19%) occurs during aging in the sympathetic neurons innervating the middle cerebral artery and that dendritic atrophy correlated with loss of axon collaterals in the same population of neurons. Using retrograde tracing in conjunction with intracellular injection of fixed tissue and confocal microscopy, we now demonstrate that infusion of nerve growth factor over the peripheral processes of the same neurons from aged rats induces significant dendritic (45%) and cell body (60%) growth. However, not all aspects of the dendritic arborization were affected. Primary dendrites and branch points were not altered by nerve growth factor. In contrast, nerve growth factor induced a significant increase in the number of primary dendrites and branch points (100%) of neurons from young adults. Our results demonstrate that sympathetic neurons undergoing dendritic atrophy during aging can exhibit significant dendritic growth in response to the in vivo infusion of nerve growth factor, although the lack of regenerative response displayed by some parts of the dendritic tree leads us to believe that these neurons also show signs of reduced plasticity.

Aging↗
PubMed1981

Antibodies to Epstein-Barr virus, herpes simplex type 1, cytomegalovirus and measles virus in psychiatric patients.

Distribution of antibodies to herpes simplex type 1 (HSV1), Epstein-Barr virus (EBV), cytomegalovirus (CMV) and measles virus (MV) was studied in sera and cerebrospinal fluids (CSF) of 41 patients with schizophrenia, 27 patients with primary affective disorders and 25 control patients with neurological diseases. No significant differences in distribution and mean geometric titers (GMT) of antibodies to HSV1 between the psychiatric and control groups were found. Distribution and GMT of antibodies to EBV were highly significant in psychiatric patients as compared to controls with highest titers in the affective disorder group. Antibodies to HSV1 were present in 15 CSF specimens of psychiatric patients with reduced CSF/serum ratio in 4, and low levels of antibodies were detected in 8 control patients. Antibodies to EBV-VCA were detected in 4 CSFs of psychiatric patients. Total protein levels were determined in CSF specimens and no correlation with antibodies was found. No significant differences in distribution of antibodies to CMV or MV in the three study groups were found. No antibodies to CMV were demonstrated in CSFs and in one specimen from a patient and two controls antibodies to MV were detected.

Affective Disorders, Psychotic↗
PubMed1979

Acquired hydrocephalus. III. A pathophysiological study correlated with neuropathological findings and clinical manifestations.

On the basis of the laws of Pascal and Laplace, it is shown that the ventricular dilatation in acquired hydrocephalus is due to a primary increase in the intraventricular pressure (IVP), and that a new steady state can be reached, whether the IVP is increased or normal. The pressure increase is due to a disproportion between the production and reabsorption of cerebrospinal fluid (CSF). As water and salts pass freely across the ependyma and the choroid plexus in hydrocephalus, the pressure increase is caused by an increased protein concentration in the ventricular CSF, leading to increased fluid contents according to the Gibbs-Donnan equilibrium. During the ventricular dilatation, the ependyma is destroyed, and the protein molecules penetrate into the subependymal part of the white matter. This results in a reduction in the colloid osmotic pressure of the ventricular CSF, and a new steady state can be reached, with a normal protein concentration in an increased volume. The attendant microscopic changes in the ventricular wall were demonstrated in a patient with acquired hydrocephalus, and the observations made were in conformity with the results of a number of animal experiments. The symptomatology of acquired hydrocephalus is in agreement with a primary affection of the axons running in the juxtaventricular part of the white matter.

Biophysical Phenomena↗
PubMed1985

Endocrinological differentiation of primary hypothalamic and pituitary disease.

The paper reviews approaches that can be applied to separating the endocrinological central nervous system (CNS) from pituitary components of neuroendocrine disorders. Major reasons which hamper the differentiation of primary hypothalamic from pituitary diseases are considered. Finally, future strategies suitable for a better accomplishment of this task are mentioned. Theoretically, the combined application of CNS-active compounds and hypothalamic regulatory hormones (RHs) should unravel the hypothalamic or pituitary etiology of the disorder. Until now, the most useful diagnostic application of RHs deals with their use in disease states due to isolated or multiple RH deficiency. Thus, the recent isolation of GRF molecules from human pancreatic tumors holds promise of a better functional characterization of GH deficiency states. The differentiation of the hypothalamic or pituitary origin of the disease in states of pituitary hyperfunction, e.g., acromegaly, or prolactinomas, is influenced by factors such as the development or expression of aberrant pituitary receptors for neurotransmitters and neuropeptides, the persistence of the responsiveness of tumorous pituitary cells to the respective RH, the disrupting effect of the excessively produced pituitary or target gland hormone on hypothalamic function. Future strategies of research in this area may include: 1. the development of sensitive and specific assays for RHs, e.g., GRF, CRF, etc. and RH determinations in biological fluids; 2. the search for non-hypophysiotropic peptides in the cerebrospinal fluid and their evaluation after appropriate stimulation; 3. better functional and clinical characterization of ectopic hormone-producing syndromes, or of psychiatric disorders mimicking neuroendocrine abnormalities from an endocrinological viewpoint (e.g., primary affective disorders v. Cushing's disease; 4. use of neuroactive compounds probing selective aspects of neurotransmitter function and, finally, 5. long-term follow-up studies after adenomectomy.

Adrenocorticotropic Hormone↗
PubMed1983

Neuroimmunology in multiple sclerosis.

A review of latest immunological interpretations regarding the pathogenesis of Multiple the Sclerosis. Data on a new immunoenzymatic method for the identification of blood lymphocyte populations are presented together with preliminary results relating to an immunogenetic correlation between primary affective disorders and Multiple Sclerosis.

Antibody Formation↗
PubMedDate not supplied

Soluble metals in the atmosphere and their biological implications. A study to identify important aerosol components by statistical analysis of PIXE data.

Multivariate statistical analysis has been applied to time series measurements of aerosol elemental composition from PIXE analysis of filter samples, and principal components have been resolved that represent distinct particle types in an external mixture in the atmosphere. In this study, it is argued that a combination of chemical and statistical analyses of the data may be more powerful in determining chemical species in atmospheric aerosols than studied that employ mainly direct chemical analysis of chemical species in unresolved mixtures of aerosol particle samples. Sulfur is generally associated with mineral dust elements. It is reasoned that the association may represent sulfuric acid coatings on particles that can lead to mineral dissolution and solubilization of significant amounts of aluminum, iron, and other metals. Upon wet or dry deposition to the surface, the fluxes of these metals in biologically-available form may be sufficient to affect primary productivity in the world ocean and cause ecological damage in lakes. As a consequence, the fluxes of biogenic trace gases to the atmosphere may be changed, possibly leading to changes in the tropospheric concentration of ozone. The inputs to lakes of soluble aluminum, which is toxic to fish, may be partly by deposition directly from the atmosphere, thus not limited to leaching of soils by acid deposition. Human inhalation of soluble aluminum and other solubilized mineral metals may account, in part, for the observed geographic pattern of deaths attributed to chronic obstructive pulmonary disease (COPD) that show high rates in cities of the Western US and the southeast region, but low in most of the midwest and northeast.

Aerosols↗
PubMed1999

Anxiety, depression, hunger and body composition: III. Their relationships in obese patients.

The present paper explores the relationships between anxiety, depression, hunger sensation and body composition in obese patients (OP). The aim is to detect whether or not there are abnormalities in these relationships in OP as compared to clinically healthy subjects (CHS). The study was performed on 22 CHS (2 M, 20 W; mean age = 24 +/- 2 years; mean body mass index = 21 +/- 2 kg/m2) and 48 OP (4 M, 44 W; mean age = 40 +/- 17 years; mean body mass index = 32 +/- 7 kg/m2). Anxiety and depression were found to be correlated, negatively, with the relative lean body mass, and, positively, with the fat body mass in OP but not in CHS. These findings corroborate the idea that anxiety and depression can reach an abnormal expression when obesity shows its worst loss in lean body mass and its highest expansion in adipocyte mass. As hunger sensation was found not to correlate with either anxiety or depression in OP, the opinion is expressed that the impairment of anxio-depressive integrity is a corollary of obesity rather than a primary affective disorder leading to obesity via an enhanced food intake.

Adult↗
PubMed2006

Dietary fat, genes and insulin sensitivity.

Both insulin resistance and dyslipidaemia are determined by genetic and environmental factors. Depending on their expression and their function, gene variants may influence either insulin action or dyslipidaemia. The purpose of this review was to give some examples from recent studies of gene variants that influence insulin signalling and the interaction between gene and diet to predispose insulin resistance. Recent findings indicate a major role for genetic susceptibility to the insulin resistance syndrome. Nutrition also plays an important role in the development and progression of the condition. Genetic background may interact with habitual dietary fat composition, affecting predisposition to the insulin resistance syndrome and individual responsiveness to changes in dietary fat intake. Due to the complex nature of gene-environment interactions, therefore, therapeutic dietary therapy may require a 'personalized' nutrition approach in the future. Although results have not always been consistent, gene variants that affect primary insulin action or dyslipidaemia, and particularly their interaction with the environment, are important modulators of glucose metabolism and insulin resistance syndrome.

Animals↗
PubMed2005

Somatotopy and movement representation sites following cortical stroke.

Stroke has been associated with many changes in motor system function, but there has been limited study of changes in somatotopic organization. This was examined in a group of patients with cortical stroke affecting primary sensorimotor cortex. In 17 patients with good outcome after cortical stroke involving precentral and/or postcentral gyri, plus 14 controls, four functional MRI evaluations of brain activity were obtained: finger, shoulder, and face motor tasks plus a sensory task, passive finger motion. For each, coordinates for contralateral primary sensorimotor cortex activation site were determined, as was a measure of inter-hemispheric balance. The normal motor somatotopy measured in controls was largely preserved after stroke. The main difference found between controls and patients was that the face was lateral to finger motor activation in all controls, but face was centered medial to finger in 43% of patients. Among patients, smaller infarct volume was associated with more ventral, and larger infarct with more dorsal, contralateral primary sensorimotor cortex activation. On the other hand, better behavioral outcome was associated with a more posterior, and poorer outcome with more anterior, activation. Larger infarct and poorer behavioral outcome were each associated with a change in inter-hemispheric balance towards the non-stroke hemisphere. Shifts in contralateral movement representation site did not correlate with changes in inter-hemispheric balance. Motor somatotopy is generally preserved after injury to primary sensorimotor cortex. Greater injury and larger behavioral deficits are associated with distinct effects on movement representation sites. Changes in motor organization within and between hemispheres arise independently after stroke.

Adult↗
PubMed2006

Multiple sclerosis associated with systemic sclerosis.

Multiple sclerosis (MS) has been increasingly reported in association with other autoimmune diseases not primary affected the nervous system. The coexistence of MS and systemic sclerosis (SSc) has been rarely described. We report here the case of a 46-year-old female patient with longstanding MS since the age of 26, who developed SSc 12 years later. Her MS was of the relapsing-remitting type, but the definite diagnosis was not made until the age of 33. MS diagnosis was based on medical history, magnetic resonance imaging (MRI) studies and positive cerebrospinal fluid analysis. One year after the diagnosis of MS, she developed Raynaud's phenomenon, skin tightness and hypopigmented patches, suggestive of scleroderma. Further investigation with laboratory studies, including serology, hand and chest X-rays, and chest computerized tomography scan confirmed the SSc diagnosis. Our report highlights the interesting association between MS and SSc that may be due to an overlapping pathogenetic mechanism for both processes.

Adult↗
PubMed2005

Inhibitory effect of fluoranthene on photosynthetic processes in lichens detected by chlorophyll fluorescence.

The effect of increasing concentration (0.01, 1 and 5 mg l(-1)) of fluoranthene (FLT) and the duration of exposure (12, 24, 36, 48 and 60 h) on the chlorophyll fluorescence parameters (F0, F(V)/F(M), Phi II and (F(M) - F(S))/F (S)) of symbiotic algae in thalli of two foliose lichens Lasallia pustulata and Umbilicaria hirsuta was investigated. Also the FLT concentration in thalli of both lichen species and the proportion of symbiotic algae (photobionts) in thalli was studied. The results obtained demonstrated that the applied concentration of FLT (1 and 5 mg l(-1)) affected primary photochemical processes of photosynthesis of algae in both lichen species. The F0 values increased and the F(V)/F(M) and Phi II values decreased. The fluoranthene content in thallus of both lichen species was increased with increasing FLT concentration in the environment. Chlorophyll fluorescence parameters showed different sensitivity to the content of FLT in Lasallia pustulata and Umbilicaria hirsuta, respectively. Higher sensitivity, detected in U. hirsuta, can be related to its diverse anatomical structure (higher portion of symbiotic algae in thalli) and to the different (nearly 2.5 times higher) content of FLT after exposure.

Chlorophyll↗
PubMed2006

Translational approaches using metastasis suppressor genes.

Cancer metastasis is a significant contributor to breast cancer patient morbidity and mortality. In order to develop new anti-metastatic therapies, we need to understand the biological and biochemical mechanisms of metastasis. Toward these efforts, we and others have studied metastasis suppressor genes, which halt metastasis in vivo without affecting primary tumor growth. The first metastasis suppressor gene identified was nm23, also known as NDP kinase. Nm23 represents the most widely validated metastasis suppressor gene, based on transfection and knock-out mouse strategies. The biochemical mechanism of metastasis suppression via Nm23 is unknown and likely complex. Two potential mechanisms include binding proteins and a histidine kinase activity. Elevation of Nm23 expression in micrometastatic tumor cells may constitute a translational strategy for the limitation of metastatic colonization in high risk cancer patients. To date, medroxyprogesterone acetate (MPA) has been identified as a candidate compound for clinical testing.

Animals↗
PubMed1987

8-Cyclopentyl 1,3-dimethylxanthine prolongs epileptic seizures in rats.

We tested the effects of 8-cyclopentyl-1,3 dimethylxanthine (8-CPT) on electrically induced seizures in rats. 8-CPT prolonged secondary seizures and converted partial seizures into generalized motor seizures, but did not affect primary seizure duration. Because 8-CPT is a potent and specific adenosine antagonist, these results add further support to the hypothesis that endogenous adenosine prevents the spread of epileptic seizures.

Animals↗
PubMed1985

Inhibition of thromboxane and 12-HPETE formation by dazoxiben and its two thiophenic acid-substituted derivatives.

LG 82-4-00 (5-(2-(1-imidazolyl)-ethoxy)-thiophene-2-carboxylate) and LG 82-4-01 (4-chloro-thiophenic-substituted derivative) were examined for specific inhibition of thromboxane (TX) synthetase. Thromboxane formation was measured by a radioimmunoassay specific for TXB2. In thrombin (0.6 IU/ml)-stimulated, washed human platelet suspensions (WPS) the IC50 (microM) for inhibition of TX formation were 1.1 (LG 82-4-00), 1.3 (LG 82-4-01) and 0.7 (dazoxiben). LG 82-4-00, LG 82-4-01 and dazoxiben also inhibited collagen (0.6-2.5 micrograms/ml)-induced TXB2 formation and platelet aggregation in human platelet-rich plasma. Neither LG 82-4-00 nor LG 82-4-01 had vasoconstrictor, proaggregatory or TX antagonistic activity or affected primary wave ADP aggregation. There was less than 10% inhibition of PGI2 formation from bovine coronary artery slices with concentrations up to 100 microM. At 100 microM, dazoxiben inhibited thrombin-induced 12-HPETE formation in WPS by 81 +/- 10% whereas LG 82-4-00 and LG 82-4-01 were much less active. These data indicate that LG 82-4-00 and LG 82-4-01 are specific inhibitors of thromboxane synthetase in human platelets.

Animals↗
PubMed1979

Further studies on cell-mediated immunity to myelin basic protein in schizophrenic patients.

Cell-mediated immunity (CMI) toward myelin human basic protein (HBP) was studied in 19 chronic drug-free schizophrenic patients and in 30 patients with primary affective disorders receiving psychoactive drugs, 74% of the schizophrenics showed an inhibition of macrophage migration, whereas only one patient from the affective group showed such a response. These results indicate that drugs are not responsible for the appearance of CMI to HBP in schizophrenics. One out of 9 ECT-treated patients developed a CMI to HBP.

Adult↗