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Biomedical subjects

P Rosel

Publications and source records attributed to P Rosel.

At least 19 recordsLinked to original sources
PubMed2005

Cerebrospinal fluid: postmortem biochemical study.

UNLABELLED: Postmortem phenomena can change and alter biochemical components in body fluids such as blood and as cerebrospinal fluid (CSF). AIMS OF THE STUDY WERE: (a) to analyse urea, glucose, potassium, chloride, protein, creatinine, calcium, alkaline phosphatase and cortisol in CSF fluid and (b) to compare results between two age groups, between groups with or without mental or degenerative neurological illness and between a group reported as dying from natural causes and a group that had a violent death. MATERIALS AND METHODS: The study was carried out in Hospitalet de Llobregat (Barcelona) of 55 corpses. Samples were obtained following section of the corpus callosus, through the lateral ventricles and frozen to -80 degrees C until processed. RESULTS: Significant differences were found in urea levels between the two age groups, in protein between natural and violent death groups and in alkaline phosphatase between the two age groups and between the natural and violent death group. Cortisol levels revealed significant difference between the two age groups and is those supplying natural and violent death. CONCLUSIONS: The study indicates to the need for further studies designed to include groups with defined diagnose of mental or degenerative disorders as well as different age groups.

Age Factors↗
PubMed2002

Loss of the circadian variation of platelet [3H]imipramine binding in delusional compared with non-delusional endogenously depressed patients.

BACKGROUND: The circadian variations of the serotonin reuptake sites were studied in 16 patients meeting DSM-IV criteria for major depression with melancholia, either with (n=8) or without (n=8) psychotic symptomatology. METHOD: The [3H]imipramine binding sites were measured in platelet samples. RESULTS: While no statistically significant difference was found between the morning (09:00 h) and evening (21:00 h) [3H]imipramine B(max) values in the control group, both the non-delusional and delusional melancholic patients showed higher evening than morning B(max) values, which were only statistically significant in the former. When both diagnostic groups were compared, the delusional patients showed significantly lower [3H]imipramine binding values than the non-delusional patients both in the morning and evening samples. Within the non-delusional depressed patients, those individuals with mood circadian variation, assessed by the 18th item of the HDRS, showed significantly lower B(max) values than those without mood variation. Lowest morning and evening B(max) values were noted in the delusional depressed group without mood variations. CONCLUSIONS: These results suggest that delusional depressions might have a different neurobiological substrate with loss of chronobiological rhythms.

Antidepressive Agents, Tricyclic↗
PubMed2001

Water metabolism disturbances at different stages of primary thyroid failure.

The aim of the present study was to study salt and water metabolism in thyroid deficiency. We performed an oral water loading test (OWL) and a hypertonic 5% saline infusion test (HSI) in 16 patients with overt primary hypothyroidism before replacement treatment (PRE group) and after, in eight patients with subclinical hypothyroidism (SUB group) and in 16 normal individuals (CG group). In the PRE group, a lower free water clearance was detected in the OWL (P < 0.022), with lower plasma osmolality (OWL: P < 0.005; HSI: P < 0.001) and arginine vasopressin (AVP) (OWL: P < 0.001; HSI: P < 0.001) than the CG group, across both tests; they normalized with the replacement treatment. The same plasma abnormalities were detected in the SUB group with the HSI. Although the AVP and thirst thresholds did not differ between the groups, the lag between them was lower in the PRE (4.1+/-3.2 mOsm/kg) and SUB group (2.6+/-2.1 mOsm/kg) than in the CG group (13.3+/-9.2 mOsm/kg) (P < 0.05). There were no differences in atrial natriuretic hormone (ANH), plasma renin activity (PRA) and plasma aldosterone among the groups. These results indicate that plasma hypo-osmolality and low levels of AVP are present in primary hypothyroidism, and indeed are already present in the subclinical phase of the disease. An overlap between the thresholds of thirst and AVP seem to play a role in these abnormalities, but ANH, PRA and plasma aldosterone do not appear to contribute.

Adolescent↗
PubMed2000

Altered 5-HT(2A) binding sites and second messenger inositol trisphosphate (IP(3)) levels in hippocampus but not in frontal cortex from depressed suicide victims.

The binding parameters of 5-HT(2A) and levels of its second messenger, 1,4,5-trisphosphate (IP(3)), were simultaneously studied in frontal cortex and hippocampus from the brains of 18 control subjects and 18 depressed suicide victims. All suicides met DSM-III-R criteria for depressive symptoms, suffered a violent death and had not taken any antidepressant drugs for at least 6 months prior to death. A significant decrease in the number of 5-HT(2A) binding sites (154+/-22 vs. 254+/-36 fmol/mg), together with a significantly lower apparent affinity constant (1.02+/- 0.08 vs. 1. 36+/-0.09 nM), was detected in hippocampus but not in frontal cortex from the depressed suicides compared to the control subjects. Furthermore, IP(3) concentrations were significantly increased in hippocampus (3.2+/-0.3 vs. 2.1+/-0.3 pmol/g) but not in frontal cortex (1.3+/-0.3 vs. 2.7+/-0.5 pmol/g) from the suicide victims. The reported results may indicate a significant hypersensitivity of the 5-HT(2A) postsynaptic receptor located in the hippocampus from depressed suicide victims, giving rise to an enhancement of its intracellular signaling system with higher IP(3) production.

Adolescent↗
PubMed2000

Weak androgen levels, glucocorticoid therapy, and bone mineral density in postmenopausal women with rheumatoid arthritis.

OBJECTIVE: To study dehydroepiandrosterone sulfate (DHEAS) and androstenedione (AND) status in postmenopausal women with rheumatoid arthritis (RA), the effects of glucocorticoid therapy on DHEAS and AND levels, and their relationship with bone mineral density (BMD). METHODS: Forty-six postmenopausal women with RA were separated into two groups based on whether they had a negative history for glucocorticoid therapy (n = 24) or were currently on glucocorticoid therapy (n = 22). The control group was composed of 39 postmenopausal women who had never received hormone replacement therapy. Serum DHEAS and AND levels were measured using a radioimmunoassay. BMD was determined at the lumbar spine (L2-L4) and femoral neck using a DEXA Hologic QDR-1000 densitometer. Results. RA patients and controls were similar in age, weight, body mass index, and years since menopause. DHEAS and AND levels were lower in the glucocorticoid-treated RA group than in the other two groups. The glucocorticoid-treated RA group also had a significantly lower femoral BMD value than the nonglucocorticoid-treated RA group. Lumbar BMD was similar in the two RA groups and in the controls. CONCLUSION: Decreases in DHEAS and AND levels in postmenopausal women with RA are probably related to glucocorticoid therapy rather than to the disease itself.

Androgens↗
PubMed1999

Secretion and dual regulation between epidermal growth factor and transforming growth factor-beta1 in MDA-MB-231 cell line in 42-hour-long cultures.

MDA-MB-231 is a breast cancer cell line which possesses large quantities of epidermal growth factor (EGF) receptors and specific high-affinity transforming growth factor-beta1 (TGF-beta1) receptors. We have established that these cells secrete constitutively measurable levels of EGF and TGF-beta1 in conditioned medium. The constitutive secretion of EGF decreased over time in culture (42 h), while the constitutive secretion of TGF-beta1 remained constant. TGF-beta1 secretion in EGF-treated cells was lower than in controls (P < 0.0001), but EGF concentrations were not modified after TGF-beta1 supplement. We postulate that in MDA-MB-231 cell line there is a dual regulation between both growth factors.

Breast Neoplasms↗
PubMed1999

Constitutive and regulated secretion of epidermal growth factor and transforming growth factor-beta1 in MDA-MB-231 breast cancer cell line in 11-day cultures.

Epidermal growth factor (EGF) and transforming growth factor type beta1 (TGF-beta1) exert opposite effects in most cells. A potential regulation between the two factors has been studied at a transcriptional level, but never at a protein level. MDA-MB-231 is a breast carcinoma cell line which possesses large quantities of membrane receptors and expresses high activities for both factors. In this study, conditioned mediums (CM) of 11-day cultures of these cells were collected to measure EGF and TGF-beta1 by immunochemical assays. Four types of cultures were tested: (1) controls; (2) after treatment with 17-beta-estradiol; (3) treated with EGF; and (4) treated with TGF-beta1. These cells secreted constitutively quantifiable concentrations of both factors to the CM. EGF treatment inhibited TGF-beta1 levels in CM throughout the study period (P = 0.002), while EGF levels diminished after TGF-beta1 treatment (P = 0.05). This finding suggests a dual regulation between EGF and TGF-beta1, at a protein level, in this cell line.

Breast Neoplasms↗
PubMed1998

Variations in [3H]imipramine and 5-HT2A but not [3H]paroxetine binding sites in suicide brains.

Both the [3H]imipramine and [3H]paroxetine binding sites and the 5-HT2A receptor were simultaneously determined in frontal cortex, cingulate cortex, hippocampus and amygdala from 17 control subjects and 17 depressed suicide victims. A significant decrease in the maximum binding (Bmax) of [3H]imipramine was observed in the hippocampus of suicide victims as compared to control subjects (160 +/- 25 vs. 328 +/- 52 fmol/mg protein; P = 0.007) without changes in the apparent affinity constant (Kd). Furthermore, a significant decrease in the number of 5-HT2A binding sites, together with a significantly lower Kd, was also observed in the hippocampus of suicides as compared to control subjects (129 +/- 18 vs. 225 +/- 32 fmol/mg protein; P = 0.02 and 0.91 +/- 0.07 vs. 1.38 +/- 0.08 nM, respectively; P = 0.006). [3H]Paroxetine binding did not display modifications between the two groups in either Bmax or Kd from any of the brain regions studied. When all four brain regions were taken together, a down-regulation was noted between presynaptic [3H]imipramine binding and the postsynaptic 5-HT2A receptor (r = -0.40; P = 0.0013) in the control group. This correlation did not appear in the suicide group. No correlation was observed between [3H]paroxetine binding and the 5-HT2A receptor in either control subjects or suicides. Taken together, these results suggest that the 5-HT uptake site measured with [3H]imipramine and the 5-HT2A receptors are reliable markers of serotonergic dysfunction.

Adult↗
PubMed1998

Growth of MDA-MB-231 cell line: different effects of TGF-beta(1), EGF and estradiol depending on the length of exposure.

The human cell line MDA-MB-231 is a prototype for the study of hormone-independent breast cancer. Modification of cell growth behaviour has been observed after treating these cells with growth factors. EGF is a typical stimulatory growth factor for many cell types, whereas transforming growth factor beta(1)(TGF-beta(1)) acts with inhibitory character. Here we observed cell growth inhibition after EGF as well as after TGF-beta(1)treatments. Nevertheless, in the 42-h experiments, EGF-treated cultures grew before (18 hours) respect to the TGF-beta(1)and E(2)-treated cultures (24 h), and in the 11-day experiments, EGF-treated cultures started growing (7 days) after TGF-beta(1)-treated cultures (5 days). Estradiol inhibited the proliferation of these cells only after several days of treatment.

Breast Neoplasms↗
PubMed1998

Characterization of the 5-HT4 binding site in human brain.

In this study, drug inhibition and saturation experiments on the binding of the highly selective 5-HT4 antagonist [3H]GR 113808 were performed in human brain membranes so as to better characterize this binding site. Drug competition studies were carried out by incubating 0.2 nM [3H]GR 113808 in the presence of increasing concentrations of six different drugs, i.e. 5-HT, 5-CT, ondansetron, tropisetron, BIMU 1 and BIMU 8 (mixed 5-HT3 and 5-HT4 agonists). The binding displaced by 5-HT showed a drug inhibition constant (Ki) value of 197nM. The use of 5-CT or ondansetron also showed the existence of single-site models albeit with Ki values in the micromolar range (11,5 microM). Tropisetron, BIMU 1 and BIMU 8 displaced bound [3H]GR 113808 according to a two-site binding model, with the high affinity component in the nanomolar range and the low affinity site in the micro or milimolar range. Saturation experiments revealed high binding densities in basal ganglia (187 fmol/mg in putamen, and 149 fmol/mg in caudate nucleus), while lower densities were observed in cortical regions (49 fmol/mg in temporal cortex, 45 fmol/mg in parietal cortex and 71 fmol/mg in cingulate cortex). The apparent affinity (Kd) was similar in the brain regions studied, ranging from 0.13 to 0.34 nmol/l. Despite the enrichment of 5-HT receptors in human brain, their functional correlate in brain diseases remains to be clarified.

Adult↗
PubMed1998

Immunological quantitation of nuclear steroid receptors to optimize the biological classification of breast tumors.

We used immunological methods to determine cytosolic and nuclear steroid receptors to evaluate the advantages of nuclear receptor measurement in the selection of breast cancer patients for treatment. Around 75% of tumors showed coincidence between nuclear and cytosolic receptors (+/+ or -/-) for estrogen receptor (ER) and for progesterone receptor (PgR). Only cytosolic receptors were detected in around 20% of tumors. Distributed in the ER/PgR phenotypes according to the nuclear or cytosolic receptors, 64% of tumors remained in the same subgroup, whereas 16% of tumors were classified as hormone dependent according to cytosolic and independent according to nuclear receptors, which could be considered as 'false-positive' results. 6% of tumors would be classified as negative according to cytosolic receptors but positive according to nuclear receptors and would correspond to 'false-negative' results by conventional methods. Cytosolic receptor results may overrate the hormone dependence and cause some 'misclassifications' of patients. This could partially explain the lack of response to therapy in some cases.

Adult↗
PubMed1997

Regional distribution of specific high affinity binding sites for 3H-imipramine and 3H-paroxetine in human brain.

The binding of 3H-paroxetine and 3H-imipramine has been compared in 17 different regions of 12 human control brains. Our findings reveal that the regional distribution is similar for both radioligands and their bindings tend to be parallel in the brain. The highest binding site density was found in basal ganglia (hypothalamus Bmax 780 +/- 102 fmol/mg protein for 3H-imipramine binding and Bmax 515 approximately 83 for 3H-paroxetine binding). The lowest values were found in cortical areas (cingulate cortex 191 +/- 18.5 fmol/mg for 3H-imipramine binding and 88 +/- 7.5 fmol/mg for 3H-paroxetine binding). The Kd values for 3H-paroxetine binding to neuronal membranes were similar in all brain regions (mean +/- s.d. Kd 0.07 +/- 0.007 nM) and also for 3H-imipramine binding (mean +/- s.d. Kd 1.05 +/- 0.12 nM). As these values are the same as in platelet membrane, the results obtained indicate that both binding sites are identical in neuronal and in platelet membranes. These findings suggest that both ligands are good markers of the 5HT transporter. However, the higher affinity of 3H-paroxetine confirms that this compound is a better radioligand for the 5HT uptake site.

Adult↗
PubMed1997

High affinity [3H]imipramine and [3H]paroxetine binding sites in suicide brains.

Specific binding of [3H]imipramine and [3H]paroxetine was simultaneously examined in human brains (frontal cortex, temporal cortex, cingulate cortex, hypothalamus, hippocampus and amygdala) from 11 controls and 11 depressed suicide victims. A single saturable high affinity site was obtained for both radioligands. Age was not related to significant changes in [3H]imipramine and [3H]paroxetine binding parameters, which indicates the stability of the brain serotonergic system with increasing age. A major finding of the present study concerns the existence of a significant decrease in the maximum number (Bmax) of [3H]imipramine binding sites in hippocampus from depressed suicides as compared with the control group, without changes in the binding affinity (Kd). In contrast, when [3H]paroxetine was used as radioligand, no changes in either Bmax or Kd were detected in any of the brain regions studied. These findings suggest that [3H]imipramine may be a better marker than [3H]paroxetine when alterations in the presynaptic serotonergic uptake site are to be detected.

Adolescent↗
PubMed1997

Platelet [3H]imipramine and [3H]paroxetine binding in depressed patients.

[3H]Paroxetine and [3H]imipramine binding to blood platelet membranes was simultaneously measured in 63 control subjects and 18 patients with DSM-III-R criteria for major depression with melancholia. Both binding sites showed significantly different (p < 0.001) maximum binding (Bmax) and equilibrium dissociation constant (Kd) values. Age was not correlated with either [3H]imipramine Bmax or Kd values, but a negative correlation was found between [3H]paroxetine Bmax and age in healthy controls. Furthermore, depressed patients showed significantly lower [3H]imipramine Bmax values (p < 0.001) and higher Kd values (p < 0.001) in comparison to the control group. No differences were observed in [3H]paroxetine Bmax and Kd values between the two groups.

Adult↗
PubMed1996

[Expression of pS2 protein in breast cancer and its relationship with estrogen and progesterone receptors].

BACKGROUND: We studied pS2 protein in breast tumors and its relation with estrogen and progesterone receptors and with anatomopathological characteristics of the tumors. MATERIAL AND METHODS: We measured the pS2 content (by IRMA) and steroid receptors content (by EIA) in 151 breast tumors. Results were compared and correlated with tumoral characteristics. RESULTS: 53% of tumors were pS2+. Among them, 91% were estrogen receptors +.86% of estrogen receptors negative tumors were pS2-. We observed correlation between pS2 and estrogen receptors values (r = 0.56; p < 0.0001) and between pS2 and progesterone receptors values (r = 0.53; p < 0.0001). Distributing the tumors in pS2+ and pS2-, we observed association between pS2+ and estrogen receptors + (chi 2 = 45.6; p < 0.0001) and pS2+ and progesterone receptors + (chi 2 = 43.1; p < 0.0001). However, we found a 18.5% of estrogen receptors + pS2- tumors. We observed a significant difference between GII and GIII tumoral grades (chi 2 = 5.51; p < 0.019), with a majority of pS2+ tumors in GII and pS2- tumors in GIII. CONCLUSIONS: The estrogen receptors in estrogen receptors + ps2- tumors may be non functional. The presence of pS2 protein alternative to that of progesterone receptors may indicate a functional heterogeneity of the estrogen receptors system, which is of interest in evaluating prognosis and response to the hormonal therapy.

Adult↗
PubMed1996

Growth hormone response to growth hormone releasing hormone in non-delusional and delusional depression and healthy controls.

Growth hormone (GH) responses to growth hormone releasing hormone (GHRH) of 53 in-patients meeting DSM-III-R criteria for major depressive episode with melancholia (24 non-delusional and 23 delusional depression) were compared with those of 19 healthy controls. No significant differences in basal GH were found between the control and either the non-delusional or the delusional groups. The whole group of depressed patients showed a significantly lower response than the control patients at all points of the GH response to GHRH curve as well as a lower area under curve. When the three groups (control, delusional, and non-delusional depressed) were compared, it was found that only the non-delusional depressed patients had a significantly lower area under curve and lower values at +60, +90 and +120 min than the controls. The only significant difference between the two groups of depressed patients was that the delusional group showed a delayed appearance of the maximum response peak and a more prolonged response.

Adult↗