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Biomedical subjects

J C Soares

Publications and source records attributed to J C Soares.

At least 55 records · Page 3Linked to original sources
PubMed1999

Platelet membrane phospholipids in euthymic bipolar disorder patients: are they affected by lithium treatment?

BACKGROUND: Abnormalities in cell membrane processes and intracellular signal transduction pathways may be implicated in the pathophysiology of bipolar disorder. In this study, we attempted to investigate, in euthymic bipolar patients: 1) in vivo signal transduction abnormalities of the phosphatidylinositol pathway in platelets; and 2) possible in vivo effects of lithium treatment on platelet membrane phospholipids. METHODS: We determined the relative absorbances of eight individual classes of platelet membrane phospholipids, using two-dimensional thin-layer chromatography in high-performance plates, followed by scanning laser densitometry, in a group of 10 lithium-treated euthymic bipolar patients and 11 normal controls. RESULTS: The mean relative absorbance of phosphatidyl-inositol-4,5-bisphosphate (PIP2) was lower in the patient group (0.29 +/- 0.08% vs. 0.39 +/- 0.12%; t = 2.35, df = 19, p = .03); no significant differences between patients and controls were found for the other phospholipids. CONCLUSIONS: This study provides in vivo evidence that bipolar patients on lithium treatment exhibit a decreased relative amount of PIP2 in the platelet cell membranes compared to normal controls.

Adult↗
PubMed1999

Adjunctive antipsychotic use in bipolar patients: an open 6-month prospective study following an acute episode.

BACKGROUND: We examined the use of adjunctive antipsychotics in the treatment of bipolar patients. METHODS: A total of 88 bipolar type I patients (DSM-IV diagnosis) were included. The patterns of adjunctive antipsychotic use in the first 6 months after an index episode were examined. RESULTS: A total of 34 patients (39%) received at least one antipsychotic during the follow-up period. At time 0, 23 subjects (26%) were on antipsychotics; at 3 months, 10 subjects (11%); and at the end of the 6 month period, 11 subjects (12%). Prolonged use of antipsychotics (more than 15 weeks) was found in eight patients (9%). No significant differences were found in demographic characteristics or baseline clinical variables between the patients who received or did not receive antipsychotics, except that the use of adjunct antipsychotics in the 6-month period was significantly more common after an index manic than depressive episode (68 versus 17%, respectively, P = 0.001; Fisher's exact test). LIMITATIONS: This report presents a secondary analysis of follow-up data from a prospective study, and therefore the hypotheses here examined were not originally part of the primary hypotheses that led to the design of the study. A larger sample size could eventually reveal small differences among the patient sub-groups not presently found. CONCLUSIONS: The use of adjunctive antipsychotics among bipolar patients was less extensive than previously reported, and mostly related to an index manic episode. Our findings suggest that in samples of carefully diagnosed bipolar type I patients the group that may need continued antipsychotic treatment is relatively small.

Acute Disease↗
PubMed1999

Histochemical study of the extensor digitorum longus and soleus muscles in alcoholic rats.

The extensor digitorum longus (EDL) and soleus (SOL) muscle fibres from albino rats submitted to experimental chronic alcoholism were evaluated in accordance with their metabolic and morphometric profiles. Twenty-seven male animals aged 4 months and weighing approximately 400 g were used. The animals were divided into three groups: control, isocaloric and alcoholic and sacrifices were carried out after 5, 10 and 15 months. The muscles were dissected, removed, cross-sectioned in a cryostat and submitted to the NADH (nicotinamide adenine dinucleotide) reaction. The SO (slow-twitch-oxidative), FG (fast-twitch-glycolytic) and FOG (fast-twitch-oxidative-glycolytic) muscle fibre types exhibited a polygonal, triangular or rounded shape and did not present noteworthy modifications in either muscles during the study. The cross-sectional areas of the fibres from the studied muscles did not present significant differences during the observations. Fibre area behaved similarly in the alcoholic animals up to the 10th month, i.e. it was decreased, as also observed in the other groups. At 15 months, however, all fibres were increased, with a predominance of FG fibres in the SOL muscle. Changes in fibre population were observed mainly in the SOL muscle of alcoholic animals: SO fibres were initially increased in number but decreased after the 10th month, and the opposite was observed for the population of FG fibres. FOG fibres increased linearly in number throughout the experiment. The statistical analysis showed nevertheless that the fibre population and cross-sectional area changes were not significant. In the alcoholic animals quantitative variations of muscle fibres were more evident in the SOL muscle, suggesting that the SOL muscle is more sensitive to the toxic action of ethanol. The results concerning the increased fibre diameter in alcoholic animals would be associated with muscle oedema induced directly or indirectly by the ethanol.

Alcoholism↗
PubMed1999

Ultrastructural aspects of the retractor ocular bulbi muscle in the opossum (Didelphis albiventris).

In the present study the different types of muscle fibers of the retractor ocular bulbi muscle of the South American opossum were classified according to their ultrastructural characteristics. The tridimensional characteristics of the neuromuscular junctions present in this muscle were also demonstrated by scanning electron microscopy (SEM). Five adult opossums, three males and two females, were perfused with fixative solution through the left ventricle and their right retractor ocular bulbi muscle was prepared for the ultrastructural study of muscle fibers. The contralateral muscle was used for the study of neuromuscular junctions by SEM. Three types of fibers were detected, denoted 1r, 2r and 3r. Only simple neuromuscular junctions of the plate type were visualized by SEM.

Animals↗
PubMed1998

The lithium ion: a foundation for psychopharmacological specificity.

The idea of lithium's specificity for bipolar disorder was proposed in Cade's original work in 1949. Since then, many controlled studies have been performed, examining lithium for treatment of bipolar disorder and other psychiatric conditions. This review was undertaken to determine if the suggestion of lithium's specificity has support in the controlled studies conducted after Cade's initial proposal. Studies were selected in a Medline search, dating back to 1966 and also identified from the bibliography of some of these papers. The controlled trials with lithium for the treatment of mania and bipolar depression, unipolar depression, schizophrenia, and schizoaffective disorder were reviewed. The published studies with lithium in other neuropsychiatric conditions were also considered. Additionally, we reviewed literature on other therapeutic agents proposed for bipolar disorder, looking at their comparative effectiveness to lithium. The data analyzed give strong support for lithium's being most effective in bipolar disorder, with minimal or no therapeutic effects in other neuropsychiatric disorders. The neurochemical underpinnings of this specificity are being investigated, without conclusive findings to date. The study of this paradigm of specificity in neuropsychopharmacology research may lead to meaningful contributions to understanding the pathophysiology of bipolar disorder and may help to develop newer treatments for this condition.

Animals↗
PubMed1998

Comparative structural analysis of neuromuscular junctions in mice at different ages.

The authors studied the histochemical and ultrastructural modifications that occur in the neuromuscular junctions (NMJ) of fibularis longus muscles of mice with an age range of 3 to 21 months. Twenty-four male and female animals were killed at 3, 5, 14 and 21 months of age: 7 of them at 3 months, 4 of them at 5 month, 9 at 14 months and 4 at 21 months. The fibularis longus muscles were processed and their NMJ examined with the transmission electron microscope. The most relevant changes were associated with the degeneration and retraction of terminal axons, i.e., axons poor in synaptic vesicles with degenerated mitochondria, and exhibiting multivesicular bodies and vacuoles; exposed and widened junctional folds and cytoplasmic processes of Schwann cells located in the synaptic gutter. The presence of lysosomes or lipofuchsin in the juxtajunctional sarcoplasm was also noted. These observations suggest that the phenomena of retraction and budding occur in the NMJ with advancing age, with a predominance of events associated with degeneration, leading to profound changes in NMJ shape.

Acetylcholinesterase↗
PubMed1997

Therapeutic targets in late-life psychoses: review of concepts and critical issues.

Psychoses in late life are a diagnostic challenge because of disagreement over how these entities should be classified. The main diagnostic categories of late-life psychoses include dementia with psychotic symptoms, late-onset schizophrenia, delusional disorder, early-onset psychotic disorders extending through late life, late-onset mood disorders, psychotic disorders caused by medical conditions or medications, and delirium. First onset of psychotic symptoms in late life is commonly associated with identifiable structural brain abnormalities and reflects underlying brain pathology. We reviewed the available literature on late-life psychotic manifestations, focusing on diagnostic classification and treatment approaches. Antipsychotics are the mainstay of treatment for these conditions, but should be used cautiously in elderly patients because of their increased sensitivity to side effects. Overall, appropriate research data on the effectiveness of various antipsychotic agents for late-life psychotic conditions are lacking. Non-antipsychotic psychotropic medications may be of value in managing some of these conditions.

Affective Disorders, Psychotic↗
PubMed1997

Platelet membrane phosphatidylinositol-4,5-bisphosphate alterations in bipolar disorder--evidence from a single case study.

Abnormalities in the cellular phosphatidylinositol (PI) pathway have been proposed to be implicated in the pathophysiology of bipolar disorder. A platelet model was used to study phosphatidylinositol-4,5-bisphosphate (PIP2) membrane values in a bipolar disorder patient in different mood states, in a single case study. The patient was studied unmedicated, initially in the euthymic and later in the manic states, and subsequently on lithium after remission of manic symptoms. The relative percentage of PIP2 in the platelet membranes increased with cycling from the euthymic into the manic state. After lithium treatment, PIP2 decreased, and was similar to the euthymic state. This study further demonstrates the feasibility of this method, as well as its applicability to longitudinal studies in bipolar disorder, and suggests promising directions for future research in this area.

Adult↗
PubMed1997

The anatomy of mood disorders--review of structural neuroimaging studies.

The structural neuroimaging findings in mood disorders were reviewed, to evaluate evidence for a neuroanatomic model of pathophysiology, involving the prefrontal cortex, the basal ganglia, the amygdala-hippocampus complex, thalamus, and connections among these structures. Global atrophy is not consistently found. The best replicated finding is an increased rate of white matter and periventricular hyperintensities. A smaller frontal lobe, cerebellum, caudate, and putamen appear present in unipolar depression. A larger third ventricle, and smaller cerebellum and perhaps temporal lobe appear present in bipolar disorder. These localized structural changes involve regions that may be critical in the pathogenesis of mood disorders. Generalized and localized anatomic alterations may be related to age or vascular disease. The clinical and biological correlates of these changes need to be investigated to allow development of a more complete model of pathophysiology of mood disorders.

Atrophy↗
PubMed1997

The role of antipsychotic agents in the treatment of bipolar disorder patients.

Antipsychotic agents have been an important adjunct in the acute and at times prophylactic management of bipolar disorder patients. As a result of safety considerations, particularly the risk of tardive dyskinesia, there are concerns about their long-term use as adjunctive treatment. Although alternative agents have been proposed, some treatment-refractory cases may not respond as well to other regimens. This sub-group of patients has not been well characterized, but may result from overinclusive criteria in defining bipolar disorder. A comprehensive Medline search dating back to 1966 was conducted to identify published studies on antipsychotic utilization in bipolar disorder patients. We investigated the support for their use, and their effectiveness in this population, and attempted to define the group of patients requiring antipsychotic treatment. Additionally, we reviewed specific safety considerations, and suggested standards for their use in bipolar patients.

Antipsychotic Agents↗
PubMed1997

Time-dependent sensitization--possible implications for clinical psychopharmacology.

Time-dependent sensitization (TDS) has been described in animal models over the past 20 years. It is a phenomenon that occurs in a variety of biological systems, and corresponds to the cellular and systems response to a foreign or stressful stimulus. The exposure to the stimulus triggers the responses typical of that particular biological system, which are progressively amplified with time. This phenomenon has potential major implications for clinical pharmacology. Some human studies have investigated this phenomenon to date. Antidepressant action, with its typical lag in the onset of effects, may be a fruitful paradigm to understand the relevance of TDS for psychopharmacological treatment. In this paper we review these emerging findings, and suggest that clinical pharmacology research should investigate this process further in expanded human studies.

Animals↗
PubMed1997

[Morphologic and histochemical aspects of the extraocular muscles of the opossum (Didelphis albiventris)].

The extraocular muscle fibres of the South-American opossum were determined according to their metabolic profiles using NADH-diaforase, and myofibrilar ATPase after pre-incubation in both acid (pH 4.3) and alkaline (pH 10.4) media. Three muscles were selected to study the arrangement of the fibres (obliquous dorsalis, rectus dorsalis and rectus lateralis muscles). It was demonstrated that they are organized in two layers: the orbital layer composed by small diameter fibres and the global layer with three-times thicker fibres than the former. The global layer has three fibre types: white, red and intermediate; while the orbital layer presents two fibre types, which react differently to the ATPase.

Adenosine Triphosphatases↗
PubMed1997

Intracellular phosphatidylinositol pathway abnormalities in bipolar disorder patients.

A dysfunction in the intracellular signal transduction pathways may be implicated in the pathophysiology of bipolar disorder. In particular, the phosphatidylinositol (PI) signal transduction pathway may be a possible site of dysfunction. Platelets, peripheral cells, and post-mortem brain samples have been used as models in preliminary studies aimed at investigating this hypothesis. Emerging findings from clinical studies are consistent with a hyperfunction in the PI pathway in the manic state, which could be state-related. Findings of increased protein kinase C (PKC) activity in the manic state, and increased intracellular Ca2+ responsiveness in the manic and possibly depressed states, are also consistent with a hyperactive PI pathway in this disorder. Future research should attempt to replicate and extend these preliminary findings further.

Bipolar Disorder↗
PubMed1996

Nuclear magnetic resonance spectroscopy: new insights into the pathophysiology of mood disorders.

Magnetic Resonance Spectroscopy (MRS) is a novel non-invasive approach for investigation of in vivo brain neurochemistry. In this paper, we review the initial studies conducted in mood disorders. 31P MRS studies have suggested membrane phospholipid and energy metabolism abnormalities in the frontal and temporal lobes of bipolar patients. 1H MRS studies have pointed to increase in choline resonance in the basal ganglia of patients with unipolar and bipolar disorders. Mood disorders are not associated with reductions in N-acetyl-aspartate, unlike schizophrenia and other neuropsychiatric disorders. Both 31P and 1H MRS have begun to be used to investigate the mechanisms of action of ECT. 19F and 7Li MRS offer therapeutically relevant new tools for psychopharmacological investigation, allowing the determination of brain concentrations of psychotropic drugs. Measurement of in vivo brain lithium concentrations may have clinical relevance. While several methodological limitations persist, the noninvasiveness and the unique neurochemical insights provided by MRS offer an excellent opportunity for in vivo investigation of the neurobiology of mood disorders.

Bipolar Disorder↗
PubMed1996

Prospects for the development of new treatments with a rapid onset of action in affective disorders.

Several compounds have been claimed to have a faster onset of antidepressant action. However, these trials suffered from lack of appropriate definitions and of standardised and comparable methodology, as far as measurement instruments, dosage strategies and statistical analyses were concerned. This article was undertaken to examine the data on the speed of onset of action with the available antidepressant compounds. To date, no compound has clearly been proven to act any faster than others. Electroconvulsive therapy is the modality that seems to produce faster onset of action compared with available medications. The major methodological issues in these studies are reviewed, and areas for future research are suggested.

Antidepressive Agents↗