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Biomedical subjects

J C Soares

Publications and source records attributed to J C Soares.

At least 19 recordsLinked to original sources
PubMed2003

Determination of the composition of light thin films with artificial neural network analysis of Rutherford backscattering experiments.

AlO(x)N(y) ultrathin films are used as insulating layers in advanced microelectronic devices. Structural characterization of these films is often done by the Rutherford backscattering (RBS) analysis. The RBS analysis of these oxinitrides is a difficult task since the relevant signals of the spectrum are washed out by the large substrate background and a considerable time is required for an analyst to characterize the sample. In this work we developed specialized artificial neural networks that are able to perform a fast and efficient analysis of the data. The results are in good agreement with traditional methods.

Journal Article↗
PubMed2003

GABAergic dysfunction in mood disorders.

The authors review the available literature on the preclinical and clinical studies involving GABAergic neurotransmission in mood disorders. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter present almost exclusively in the central nervous system (CNS), distributed across almost all brain regions, and expressed in interneurons modulating local circuits. The role of GABAergic dysfunction in mood disorders was first proposed 20 years ago. Preclinical studies have suggested that GABA levels may be decreased in animal models of depression, and clinical studies reported low plasma and CSF GABA levels in mood disorder patients. Also, antidepressants, mood stabilizers, electroconvulsive therapy, and GABA agonists have been shown to reverse the depression-like behavior in animal models and to be effective in unipolar and bipolar patients by increasing brain GABAergic activity. The hypothesis of reduced GABAergic activity in mood disorders may complement the monoaminergic and serotonergic theories, proposing that the balance between multiple neurotransmitter systems may be altered in these disorders. However, low GABAergic cortical function may probably be a feature of a subset of mood disorder patients, representing a genetic susceptibility. In this paper, we discuss the status of GABAergic hypothesis of mood disorders and suggest possible directions for future preclinical and clinical research in this area.

Brain Chemistry↗
PubMed2002

Histochemical and SEM evaluation of the neuromuscular junctions from alcoholic rats.

In the present study morphological changes occurring in the neuromuscular junctions (NMJ) of the extensor digitorum longus (EDL) and soleus muscles from albino rats (Rattus norvegicus) submitted to experimental chronic alcoholism were evaluated. Seventy two male animals aged 4 months and weighing on average 400g were divided into three groups: control, alcoholic and isocaloric. Six rats from each group were anesthetized and sacrificed after 5, 10, 15 and 18 months. The NMJ did not show detectable morphological changes in either muscle after treatment when examined by light microscopy. With respect to the dimensions, statistical analysis demonstrated a tendency to a statistically significant treatment x time interaction for the length of soleus muscle NMJ. The ultrastructural study, however, revealed that the NMJ of the soleus muscle of animals submitted to 18 months of experimental alcoholism presented important morphological alterations. Characteristically, the NMJ of these muscles is located on an elevation on the surface of the muscle fiber, presenting a regular round, oval or elliptical shape and continuous and not very deep synaptic grooves. Approximately 30% of the NMJ of alcoholic rats are irregular in shape, with the sarcolemmal elevations typical of the synapse region being flattened on at least one side, with discontinuous synaptic grooves, and deep and punctiform contacts of the synaptic buds. These data suggest that, although skeletal muscle has a greater natural resistance against the direct or indirect effects of alcohol, some submicroscopic morphological alterations are detectable in the NMJ, especially in muscles with oxidative metabolism (soleus) following long periods of ingestion of alcohol.

Alcoholism↗
PubMed2002

Elevated serum S100B protein in drug-free bipolar patients during first manic episode: a pilot study.

S100B protein is a calcium-binding protein mostly derived from glial cells, which exerts trophic or toxic effects on neural cells depending on its concentration. Since serum S100B levels has been tested as a potential marker in neuropsychiatric disorders, and structural abnormalities on glial cells have been recently associated with bipolar disorder patients, we conducted this preliminary study to examine if S100B serum levels are altered during first manic episode. We quantitated S100B in serum of 40 subjects (20 unmedicated patients during manic episode and 20 healthy matched controls). The mean+/-S.D. values for S100B for bipolar subjects were 0.065+/-0.068 microg/l and 0.018+/-0.029 microg/l for healthy controls. Increased levels of S100B in bipolar mania was statistically significant (Wilcoxon signed ranks test, Z=-2.45, P=0.01). These preliminary findings suggest that mania may increase the levels of S100B in serum of bipolar disorder patients, which could be related to adaptative neural mechanisms in bipolar mania.

Adult↗
PubMed2002

Can brain-imaging studies provide a 'mood stabilizer signature?'.

Brain-imaging investigations have attempted to characterize the neurobiological basis of bipolar disorder. Preliminary studies have also focused on in vivo brain correlates of treatment response with antidepressants, mood stabilizers and other psychotropic medications. A MEDLINE literature search was conducted dating back to 1966. Selected in vivo brain-imaging studies that examined neurobiological correlates of treatment response in mood disorder patients were identified. Discrete anatomical abnormalities in subregions of the prefrontal cortex, medial temporal lobe and cerebellum have been identified in bipolar patients. Functional imaging studies suggested abnormalities in particular brain circuits encompassing these same brain regions and the striatum. However, functional imaging correlates of treatment response with lithium or other mood stabilizers have not yet been characterized. Neurochemical studies suggested a reduction in N-acetyl aspartate levels in prefrontal cortex and abnormalities in membrane phospholipids in frontal and temporal lobes. Preliminary findings suggest that lithium may increase the gray matter content and N-acetyl aspartate levels in various cortical regions, which could reflect its putative neurotrophic effects. Few in vivo receptor-imaging studies have examined brain correlates of treatment response in bipolar patients. The available studies suggest anatomical, neurochemical and functional brain abnormalities in bipolar patients. However, in vivo brain correlates of treatment response with mood stabilizers in bipolar patients have not yet been well characterized.

Antidepressive Agents↗
PubMed2002

Anatomical study of the diaphragm of the opossum (Didelphis albiventris).

The anatomical characteristics of the South American opossum diaphragm were described. Five male and seven female adult opossums, weighing between 700 and 1110 g, were used. Animals were killed by ether inhalation saturation. The abdominal and thoracic walls were dissected and opened, the viscerae were removed and the diaphragm anatomy was described and photographed in situ. After diaphragm removal, some dimensional data were taken and tabled. Primary branches of the phrenic nerves were dissected under a surgical microscope. The secondary branches were studied and described by transillumination after clarification in acetic acid. The opossum diaphragm is domed and has a mean area of 54.33 +/- 3.8 cm2. Well-identified costal, sternal and lumbar parts form the peripheral muscular region. The central tendinous region presents with a V-like form. Three folioles comprise the phrenic centre and present different dimensions. The caudal vena cava passes through its foramen between the ventral and right dorsal folioles. Both right and left phrenic nerves present one ventral branch and one dorsolateral trunk in 50.0% and 66.67% of the cases, respectively.

Animals↗
PubMed2001

MRI study of thalamic volumes in bipolar and unipolar patients and healthy individuals.

The thalamus is a key structure in brain anatomic circuits potentially involved in the pathophysiology of mood disorders. Available findings from studies that examined this brain region in mood disorder patients have been conflicting. To examine the hypothesis of anatomical abnormalities in the thalamus in patients with mood disorders, we conducted a magnetic resonance imaging (MRI) study in 25 bipolar patients (mean age+/-S.D.=34.4+/-9.8 years), 17 unipolar patients (mean age+/-S.D.=42.8+/-9.2 years), and 39 healthy control subjects (mean age+/-S.D.=36.6+/-9.7 years). Thalamic volumes Gray Matter were measured blindly with a semi-automated technique. Multivariate analysis of variance, with age and gender as covariates, revealed no significant differences in left or right thalamic volumes among bipolar patients, unipolar patients and healthy individuals. There were no significant effects of gender, age at illness onset, episode type, number of episodes, length of illness, or family history of mood disorders on thalamic measurements. Although functional abnormalities in the thalamus are likely to be implicated in the pathophysiology of mood disorders, no abnormalities in thalamic size appear present in bipolar or unipolar individuals.

Adult↗
PubMed2001

Decreased pituitary volume in patients with bipolar disorder.

BACKGROUND: Neuroendocrinologic investigations in bipolar disorder have suggested abnormalities in pituitary function. However, few imaging studies have evaluated possible anatomical differences in this brain structure in mood disorder patients. Our aim was to examine potential abnormalities in pituitary volume in patients with bipolar and in a comparison group of patients with unipolar disorder. METHODS: We measured the volumes of the pituitary gland in 23 patients with bipolar disorder (mean +/- s.d. = 34.3 +/- 9.9 years) and 13 patients with unipolar disorder (41.2 +/- 9.6 years), and 34 healthy control subjects (36.6 +/- 9.6 years) using 1.5 mm thick T1-weighted coronal 1.5 T MRI images. All measurements were done blindly by a trained rater. RESULTS: Patients with bipolar disorder had significantly smaller pituitary volumes than healthy control subjects (mean volume +/- s.d. = 0.55 +/- 0.15 ml and 0.68 +/- 0.20 ml, respectively; ANCOVA, F = 8.66, p = 0.005), and than patients with unipolar disorder (0.70 +/- 0.12 ml, F = 5.98, p = 0.02). No differences were found between patients with unipolar disorder and healthy control subjects (F = 0.01, p = 0.91). CONCLUSIONS: To our knowledge, this is the first study that reports smaller pituitary volumes in bipolar disorder. Our findings suggest that detectable abnormalities in pituitary size are present in patients with bipolar disorder, which may reflect a dysfunctional HPA axis.

Adult↗
PubMed2001

Reproducibility of in vivo brain measures of 5-HT2A receptors with PET and.

The test/retest reproducibility of brain measures of 5-HT2A receptors with positron emission tomography (PET) and [18F]deuteroaltanserin was examined in a group of eight healthy human subjects. PET measures of 5-HT2A receptors were obtained under an equilibrium paradigm, with a 40-min PET acquisition starting approximately at 300 min (308+/-11 min) after bolus plus constant infusion of the radiotracer. Three brain outcome measures were obtained at equilibrium, V(3) (ratio of specific brain uptake to free parent plasma concentration of radiotracer), V(3)' (ratio of specific brain uptake to total parent plasma concentration) and RT (ratio of specific to non-displaceable brain uptakes). V(3)' and RT had high test/retest reproducibility, as measured by mean intra-subject% change for cortical brain areas of 14.1 and 11.0%, respectively. They also had high reliability, as measured by mean intra-class correlation coefficients (ICC) for cortical brain areas of 0.86 and 0.88, respectively. V(3) had low test/retest reproducibility, due to high variability in the measures of free parent tracer in plasma. This study supports the feasibility of equilibrium imaging of 5-HT2A receptors with PET and [18F]deuteroaltanserin. The equilibrium imaging method with [18F]deuteroaltanserin allows a single acquisition and blood measurement to provide an image whose pixel values equal a receptor volume of distribution. Since the single image pixel values are proportional to receptor densities, the images can be used in pixel-by-pixel statistical methods, such as SPM, to assess the distribution and density of 5-HT2A receptors in neuropsychiatric disorders.

Adult↗
PubMed2001

Anatomical MRI study of basal ganglia in bipolar disorder patients.

This study examined possible anatomical abnormalities in basal ganglia structures in bipolar disorder patients. Caudate and putamen gray matter volumes, and globus pallidus total volume were measured with magnetic resonance imaging (MRI) in 22 DSM-IV bipolar patients (age+/-S.D.=36+/-10 years; eight drug-free and 14 lithium monotherapy patients) and 22 matched healthy control subjects (age+/-S.D.=38+/-10 years). No significant differences were found between bipolar patients and healthy control subjects for any of the basal ganglia measures (t-tests, P>0.05). Age was inversely correlated with left putamen volumes in patients (R=-0.44, P=0.04), but not in healthy control subjects (R=-0.33, P=0.14). Older patients (>36 years old) had a significantly larger left globus pallidus than younger ones (< or =36 years old) (ANOVA, P=0.01). In a multiple regression analysis, after entering age as independent variable, the length of illness predicted smaller left putamen volumes, explaining 10.4% of the variance (F=4.07, d.f.=2, P=0.03). No significant effects of episode type, number of prior episodes, or gender were found in any basal ganglia measurements (ANOVA, P>0.05). In conclusion, our findings indicate that the basal ganglia may be anatomically preserved in bipolar patients. This is in contrast to available findings for unipolar disorder. However, our findings also suggest that age and length of illness may have significant effects on basal ganglia structures in bipolar patients, which may be more pronounced among bipolar I patients, and of relevance for the pathophysiology of the disorder.

Adult↗
PubMed2001

Brain lithium concentrations in bipolar disorder patients: preliminary (7)Li magnetic resonance studies at 3 T.

BACKGROUND: This study was conducted to investigate the feasibility of human brain (7)Li MRS investigations at a high magnetic field (3 T), and to further explore the relationship between brain and serum lithium measures in lithium-treated bipolar patients. METHODS: Eight bipolar disorder type I patients (5 males, 3 females; mean age +/- SD = 33 +/- 9 years) were studied. A 3-T scanner, using a dual-tuned ((1)H and (7)Li) echoplanar imaging (EPI) compatible radiofrequency (RF) birdcage coil was used. (7)Li magnetic resonance spectroscopy (MRS) signal was acquired at the frequency of 49.64 MHz using an imaging selective in vivo spectroscopy (ISIS) sequence (TR = 15 sec, 128 averages), and quantitation was obtained in reference to an external standard. RESULTS: The mean +/- SD oral lithium dose was 1265 +/- 442 mg/day, and the mean +/- SD 12-hour serum level was 0.69 +/- 0.19 mEq/L. The measured brain lithium concentrations varied from 0.23 to 0.55 mEq/L (mean +/- SD = 0.35 +/- 0.11 mEq/L). The brain-serum ratios varied from 0.30 to 0.80 (mean +/- SD = 0.52 +/- 0.16). Subjects on single daily doses of lithium at bedtime (n = 5) had higher brain-serum lithium ratios compared with those on twice-a-day schedules (n = 3) (0.61 +/- 0.12 and 0.37 +/- 0.07, respectively; Mann--Whitney U test, Z = -2.24, p =.03). CONCLUSIONS: This study demonstrated for the first time the feasibility of (7)Li MRS human studies at 3 T. Future studies should examine a possible role for this methodology in investigations of lithium refractoriness and prediction of treatment outcome in bipolar patients.

Adult↗
PubMed2001

Increased platelet membrane phosphatidylinositol-4,5-bisphosphate in drug-free depressed bipolar patients.

Prior investigations in bipolar disorder patients have suggested abnormalities in the cellular phosphoinositide second messenger system. This study was conducted to examine the levels of platelet membrane phosphoinositides in drug-free bipolar patients in the depressed state (n=9) and healthy controls (n=19). Bipolar patients had significantly increased levels of platelet membrane phosphatidylinositol-4,5-bisphosphate (PIP(2)) compared to healthy individuals (0.67+/-0.14 and 0.44+/-0.17%, respectively, t-test=3.71, d.f.=26, P=0.001). No significant differences in the levels of phosphatidylinositol-4-phosphate (PIP) (0.65+/-0.17 and 0.58+/-0.20%, respectively, t-test=1.02; d.f.=26; P=0.32) or phosphatidylinositol (PI) (5.92+/-1.23 and 5.56+/-1.45%, respectively, t-test=0.68; d.f.=26; P=0.51) were found. These findings provide the first demonstration of increased PIP(2) platelet levels in bipolar patients in the depressed state, and provide additional evidence that the phosphoinositide second messenger system may be a site of abnormality in bipolar disorder.

Adult↗
PubMed2001

Perspectives on the use of anticonvulsants in the treatment of bipolar disorder.

The authors reviewed the available literature on the efficacy of carbamazepine, valproate, and other newer anticonvulsants for the treatment of bipolar disorder. A comprehensive Medline search was conducted, and all uncontrolled and controlled reports on anticonvulsants used for the treatment of bipolar patients were identified. Carbamazepine and valproate have been shown to be effective in the acute treatment of bipolar disorder, and are the first-choice treatments for lithium-refractory patients. While the efficacy of these drugs in the acute treatment of the illness has been satisfactorily documented, double-blind randomized studies are still necessary to evaluate the long-term effectiveness of both anticonvulsants. Patients on a mixed state and rapid cyclers seem to respond better to valproate and carbamazepine than to lithium. The preliminary data evaluating the efficacy of newer anticonvulsants, such as gabapentin, lamotrigine, and topiramate in bipolar patients is still limited, but some of the available findings are promising, and these new agents may represent appropriate third choices for refractory bipolar individuals. Double-blind, controlled studies with the newer anticonvulsants are still largely unavailable, and it will be necessary to evaluate their acute and prophylactic mood-stabilizing effects. The prospects for future therapeutic advances in this area are also discussed.

Anticonvulsants↗
PubMed2001

Differential effects of age on brain gray matter in bipolar patients and healthy individuals.

This study examined possible differences in total gray and white matter brain content in bipolar patients and healthy individuals, and their relationship with age. 22 DSM-IV bipolar patients and 22 healthy controls underwent a 1.5-tesla Spoiled Gradient Recalled Acquisition (SPGR) MRI. Evaluators blind to patients' identities measured total brain, gray and white matter volumes using a semi-automated software. No differences were found for total brain volume, gray matter or white matter volumes between bipolar patients and healthy controls (MANCOVA, age as covariate, p > 0.05). Age was inversely correlated with total gray matter volume in patients (r = -0.576, p = 0.005), but not in controls (r = -0.193, p = 0.388). Our findings suggest that any existing gray matter deficits in bipolar disorder are likely to be localized to specific brain regions, rather than generalized. The inverse correlation between age and brain gray matter volumes in bipolar patients, not present in healthy controls, in this sample of mostly middle-aged adults, could possibly indicate more pronounced age-related gray matter decline in bipolar patients, and may be of potential relevance for the pathophysiology of the disorder.

Adolescent↗
PubMed2000

Concurrent measures of protein kinase C and phosphoinositides in lithium-treated bipolar patients and healthy individuals: a preliminary study.

This study examined the hypothesis that lithium inhibits the PI signaling pathway in humans during in vivo administration by concurrently measuring PKC isozymes and platelet membrane phosphoinositides in lithium-treated patients and healthy individuals. The platelet membrane and cytosolic levels of PKC alpha, beta I, beta II, delta, and epsilon were measured using Western blotting. The relative platelet membrane contents of phosphatidylinositol (PI), phosphatidylinositol-4-phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP(2)) were measured with two-dimensional thin-layer chromatography. Nine euthymic lithium-treated bipolar subjects and 11 healthy control subjects were studied. Compared to control subjects, lithium-treated bipolar patients had significantly lower levels of cytosolic PKC alpha isozyme (t-test=-3.24, d.f.=17, P=0.01) and PIP(2) platelet membrane levels (t-test=-2.51, d.f.=18, P=0.02), and a trend toward reduced levels of cytosolic PKC beta II isozyme (t=-2.17, d.f.=17, P=0.05). There was no significant correlation between PIP(2) and any of the PKC isozymes. These preliminary findings suggest that chronic lithium treatment may decrease the levels of both cytosolic PKC alpha isozyme and membrane PIP(2) in platelets of bipolar disorder patients.

Adult↗
PubMed2000

Effects of lithium on platelet membrane phosphoinositides in bipolar disorder patients: a pilot study.

RATIONALE: In vitro and in vivo animal studies suggest that the intracellular phosphatidylinositol (PI) pathway is an important target for the effects of lithium. OBJECTIVES: We conducted a preliminary study to examine the in vivo effects of lithium treatment on platelet membrane phosphoinositides in bipolar disorder subjects, in an attempt to examine further the hypothesis that lithium has significant in vivo effects on the PI pathway in these patients. METHODS: We quantitated PI, phosphatidylinositol-4-phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP2) in platelet membranes of seven subjects (five male, two female; mean age= 27.9+/-5.7 years), initially while they were unmedicated, and a second time after at least 21 days of lithium treatment (mean+/-SD=28.7+/-7.1 days). RESULTS: The mean+/-SD values for PI were 5.63+/-2.25% and 5.21+/-1.06%; for PIP 0.68+/-0.20% and 0.55+/-0.11%; and for PIP2 0.60+/-0.21% and 0.38+/-0.15%, before and after lithium treatment, respectively. The decrease in PIP2 values after lithium treatment was statistically significant (Wilcoxon signed ranks test, Z=-2.37, P=0.02). CONCLUSION: This longitudinal study suggests that therapeutic doses of lithium significantly decrease platelet membrane PIP2 levels in vivo in bipolar disorder subjects, which may be related to lithium's mechanism of action in bipolar disorder.

Adult↗
PubMed2000

Brain lithium measurements with (7)Li magnetic resonance spectroscopy (MRS): a literature review.

7Li magnetic resonance spectroscopy (MRS) has been successfully used in recent years as a new tool to measure brain tissue lithium concentrations in vivo. After demonstration of its feasibility in animal studies over a decade ago, human investigations have characterized the brain pharmacokinetics of lithium. Preliminary studies have investigated brain pharmacokinetic correlates of clinical response in the treatment of bipolar disorder patients, with indication of possible clinical relevance of 7Li MRS measures. In this paper we reviewed the accumulated literature in this area, and discuss possible directions for this research in the context of preliminary studies conducted by our group that demonstrated the feasibility of 7Li MRS at 3 T.

Animals↗