Biomedical subjects

M A Navarro

Publications and source records attributed to M A Navarro.

At least 19 recordsLinked to original sources

PubMed2007

Inhibitory effect of TNF-alpha on the intestinal absorption of galactose.

Sepsis is a systemic response to infection in which toxins, such as bacterial lipopolysaccharide (LPS), stimulate the production of inflammatory mediators like the cytokine tumor necrosis factor alpha (TNF-alpha). Previous studies from our laboratory have revealed that LPS inhibits the intestinal absorption of L-leucine and D-fructose in rabbit when it was intravenously administered, and that TNF-alpha seems to mediate this effect on amino acid absorption. To extend this work, the present study was designed to evaluate the possible effect of TNF-alpha on D-galactose intestinal absorption, identify the intracellular mechanisms involved and establish whether this cytokine mediates possible LPS effects. Our findings indicate that TNF-alpha decreases D-galactose absorption both in rabbit intestinal tissue preparations and brush-border membrane vesicles. Western blot analysis revealed reduced amounts of the Na+/glucose cotransporter (SGLT1) protein in the plasma membrane attributable to the cytokine. On the contrary, TNF-alpha increased SGLT1 mRNA levels. Specific inhibitors of the secondary messengers PKC, PKA, the MAP kinases p38 MAP, JNK, MEK1/2 as well as the proteasome, diminished the TNF-alpha-evoked inhibitory effect. LPS inhibition of the uptake of the sugar was blocked by a TNF-alpha antagonist. In conclusion, TNF-alpha inhibits D-galactose intestinal absorption by decreasing the number of SGLT1 molecules at the enterocyte plasma membrane through a mechanism in which several protein-like kinases are involved.

Animals↗

PubMed2006

Profile, mean residence time of ACTH and cortisol responses after low and standard ACTH tests in healthy volunteers.

OBJECTIVE: No consensus exists until now about the suitable dose of tetracosactin in the ACTH stimulation test for detecting adrenal insufficiency. Our aim was to characterize both the ACTH(1-24) and the cortisol profiles after standard high-dose test (250 microg) (HDT) and low-dose test (1 microg) (LDT) in healthy subjects in order to provide a deeper knowledge about the relationship between stimulus and response. DESIGN AND PATIENTS: ACTH tests were performed in 10 healthy volunteers (five men, five women) with at least 1 week of difference. MEASUREMENTS: Plasma ACTH(1-24) and ACTH(1-39) and serum cortisol were measured before tetracosactin i.v. injection and at 5, 15, 30, 45, 60, 75 and 90 min after stimulus. Area under the curve (AUC) of ACTH(1-24) and cortisol, as well as mean residence time (MRT) for ACTH(1-24) were calculated in both tests. RESULTS: Elimination of ACTH(1-24) was faster in HDT than in LDT (MRTs of 0.14 vs 0.37, respectively, P = 0.008), but plasma concentrations were higher up to 60 min cortisol production in HDT reaching a higher maximum concentration (Cmax: 1144 vs 960 nmol/l) but delayed in time (75 vs 52.5 min). No significant relationship was observed between AUC or Cmax of ACTH(1-24) and AUC, Cmax and increment of cortisol in any of the tests. However, a negative correlation of basal cortisol values was observed with relative cortisol increment (HDT: r = 0.77 P = 0.009; LDT: r = 0.94 P < 0.0001), but not so with Cmax (HDT: r = 0.22 P = 0.55; LDT: r = 0.57 P = 0.09). CONCLUSIONS: The elimination rate of ACTH in healthy volunteers was significantly lower in LDT than in HDT, but cortisol production rate appears to be identical in both tests, so that a maximum adrenal stimulation seems to exist. The use of LDT may be more adequate, although data from patients need studying.

Adrenal Cortex Function Tests↗

PubMed2005

Divergent mechanisms of cis9, trans11-and trans10, cis12-conjugated linoleic acid affecting insulin resistance and inflammation in apolipoprotein E knockout mice: a proteomics approach.

Conjugated linoleic acids (CLA) affect atherogenesis, but mechanisms are not well understood. We explored how two isomers of CLA, cis9, trans11-CLA and trans10, cis12-CLA, affected lipid and glucose metabolism, as well as hepatic protein expression, in apolipoprotein E knockout mice. After 12 wk of intervention, plasma triglyceride, NEFA, and glucose concentrations were significantly higher in the trans10, cis12-CLA group, whereas plasma triglyceride, NEFA, glucose, and insulin concentrations were significantly lower in the cis9, trans11-CLA group, compared with control mice consuming linoleic acid. Proteomics identified significant up- or down-regulation of 113 liver cytosolic proteins by either CLA isomer. Principal component analysis revealed that the treatment effect of cis9, trans11-CLA was mainly explained by the up-regulation of different posttranslational forms of heat shock protein 70 kD. In contrast, the treatment effect of trans10, cis12-CLA was mainly explained by up-regulation of key enzymes in the gluconeogenic, beta-oxidation, and ketogenesic pathways. Correlation analysis again emphasized the divergent effects of both CLA isomers on different pathways, but also revealed a linkage between insulin resistance and increased levels of hepatic serotransferrin. Thus, our systems biology approach provided novel insights into the mechanisms by which individual CLA isomers differentially affect pathways related to atherogenesis, such as insulin resistance and inflammation.

Animal Feed↗

PubMed2005

Association between ACE gene I/D polymorphism and clinical presentation and prognosis of sarcoidosis.

Serum angiotensin converting enzyme (SACE) concentration is considered a marker of sarcoidosis activity. This concentration is influenced by an insertion/deletion (I/D) polymorphism of the ACE gene, such that SACE levels follow the pattern DD>ID>II. The aim of our work was to study the relationship between I/D polymorphism and susceptibility to sarcoidosis, as well as the relation between this polymorphism and the clinical presentation and evolution of the disease in 177 sarcoidosis patients. A group of 104 individuals without sarcoidosis was included as control. Genotyping was done by a polymerase chain reaction (PCR) method, and SACE concentration at diagnosis was determined by a kinetic method. No differences were observed in genotype or allele distributions between patients and controls, nor between patients considering the type of presentation (Löfgren versus non-Löfgren) and evolution of the disease (acute versus chronic). As reported for healthy populations, SACE concentrations followed the pattern DD>ID>II in sarcoidosis patients, but significant differences between genotypes existed only in the Löfgren group (p = 0.003) and in acute patients (p = 0.02). SACE concentrations at diagnosis were lower in acute patients (p = 0.05) and in Löfgren's syndrome (p = 0.04), but this seemed to occur only in ID individuals (p = 0.02 and p = 0.01, respectively). No relation was thus found between I/D polymorphism and susceptibility to sarcoidosis, but ACE I/D genotyping may improve the assessment of disease activity, both at diagnosis and during the follow-up of treated and untreated patients.

Female↗

PubMed2004

The effect of tumor necrosis factor-alpha on D-fructose intestinal transport in rabbits.

Tumor necrosis factor-alpha (TNF-alpha) is an important immunoregulatory cytokine involved in septic responses during bacterial infection. The aim of this study was to examine the effect of TNF-alpha on the transport of D-fructose across rabbit jejunum. A sepsis condition was evoked by intravenous administration of this cytokine and hematological and plasma parameters were analyzed and body temperature was recorded. D-Fructose transport was assayed in rabbit jejunum. Sugar absorption in TNF-alpha treated rabbits was lower than in control animals. TNF-alpha decreased both the mucosal-to-serosal transepithelial flux and the transport across brush border membrane vesicles of D-fructose. The number of D-fructose transporters (GLUT5) was analyzed by Western blot in an attempt to explain this inhibition. TNF-alpha treated animals had lower levels of GLUT5, indicating a reduction in the expression of GLUT5 protein and therefore in transport capacity. The inhibition could also be related with the secretagogue effect of TNF-alpha on the gut since the intracellular tissue water was affected and the absence of chloride ion in the incubation medium partly removed the cytokine inhibition on sugar intestinal transport in treated rabbits. Finally, in terms of possible mediators involved in the TNF-alpha effect, nitric oxide and prostaglandins appeared to play a role in the inhibition of D-fructose intestinal uptake.

Animals↗

PubMed2004

Relationship between 25-(OH) D3, the IGF-I system, leptin, anthropometric and body composition variables in a healthy, randomly selected population.

OBJECTIVE: This study prompted us to investigate the relationship between 25-(OH) D (3) and the IGF-I system, leptin, sex, age, anthropometric and body composition variables in healthy adults. We hypothesised that these variables would regulate 25-(OH) D (3) concentrations. DESIGN: We included 253 subjects--126 men and 127 women. Body mass index (BMI) and body composition was determined, along with serum leptin, total IGF-I, free IGF-I, IGFBP3 and plasma 25-(OH) D (3) concentrations. RESULTS: 25-(OH) D (3) deficiency was observed in 69 subjects. There was a difference between 25-(OH) D (3) values and season (summer vs. winter). We observed similar 25-(OH) D (3) concentrations in men to those in women. The differential characteristics in subjects without 25-(OH) D (3) deficiency were lower BMI, fat mass and body fat and higher free IGF-I. We observed that leptin increased in the last decades and IGF-I system decreased by decade in both men and women. In subjects without 25-(OH) D (3) deficiency, there was a correlation between free IGF-I and 25-(OH) D (3) in men, and a negative correlation between 25-(OH) D (3) and age, BMI, fat mass and leptin and a positive correlation with total IGF-I in women. The multivariate linear regression analysis explained 37.8 % of 25-(OH) D (3) variability in men and 39 % in women, and only season and free IGF-I made an independent contribution to 25-(OH) D (3) in men, and season and fat mass in women. CONCLUSION: These data suggest that free IGF-I in men and fat mass in women could regulate 25-(OH) D (3) concentrations.

Adolescent↗

PubMed2003

Serum insulin-like growth factor levels do not predict functional recovery after hospitalization in nonagenarian patients.

AIM: To analyze the insulin-like growth factor 1 (IGF-1) serum levels in nonagenarian patients and to investigate the predictive capacity of this measure to assess the functional recovery of this population following hospitalization. METHODS: We performed a prospective study in 60 consecutive nonagenarian patients admitted for medical or surgical diseases. We assessed IGF-1 serum levels and nutritional status. The functional status was assessed using the Barthel index. Thirty-four patients were reinvestigated 3 months after discharge from hospital. RESULTS: The mean levels of IGF-1 were lower in nonagenarians than in younger patients. No relationship was found between IGF-1 levels and nutritional status. The decline in Barthel index values 3 months after discharge from hospital did not correlate with serum levels of IGF-1 on admission. CONCLUSION: IGF-1 serum levels in nonagenarian patients do not predict functional recovery after hospitalization.

Aged↗

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

The enhancement of endogenous cAMP with pituitary adenylate cyclase-activating polypeptide protects rat kidney against ischemia through the modulation of inflammatory response.

BACKGROUND: Cyclic nucleotide analogue administration improves ischemia-reperfusion damage in several organs. The neuropeptide pituitary adenylate cyclase-activating polypeptide, PACAP-38, is a potent stimulus to enhance cellular cAMP levels. This study tested the protective effect of enhancing endogenous cAMP levels by PACAP-38 in a model of warm renal ischemia. METHODS: Sprague-Dawley rats underwent 40 min of bilateral warm renal ischemia. PACAP-38 continuous infusion began either before ischemia or at 6 hr or 18 hr after ischemia. A mini-osmotic pump infused PACAP-38 throughout 7 days of follow-up. Groups were constructed with sham, ischemic control, and dibutyryl cAMP treated animals, and four PACAP-38 treatment groups, using 16 pmol/hr or 160 pmol/hr of the compound, or delaying its administration by 6 hr or 18 hr after ischemia. Renal function was assessed by means of serum creatinine levels on days 1, 2, 3, and 7 after ischemia. Conventional histology was performed on day 7. Renal myeloperoxidase (MPO) activity, infiltrating CD45+ cells, plasma and tissue cAMP, and serum IL-6 were measured. RESULTS: Continuous administration of the high concentration of PACAP-38 ameliorated renal function and morphologic abnormalities induced by warm ischemia. Treatment with dibutyryl cAMP produced morphologic protection but only partial functional effect on the ischemic kidney. A 6-hour delay in the administration of the compound after ischemia offered similar protective effect, whereas an 18-hr delay did not. The neuropeptide clearly increased circulating cAMP after ischemia but not cAMP in renal tissue. PACAP-38 increased circulating IL-6, and minimized renal inflammatory cell infiltration induced by ischemia-reperfusion injury, as evidenced by a reduction of MPO activity and the number of CD45+ cells in ischemic renal tissue. CONCLUSIONS: Enhancement of endogenous circulating cAMP with PACAP-38 modulates postischemic inflammatory response and strongly protects from ischemic acute renal failure, even when administration is delayed for 6 hr after injury.

Acute Kidney Injury↗

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

[Prevention of thromboembolic disease in patients with heart disease].

OBJECTIVE: To evaluate the adequacy to thromboembolic disease prophylaxis protocol in patients with heart disease. DESIGN: Cross-sectional study. SUBJECTS: Patients older than 14 years affected of heart disease in a semi-urban health primary-care clinic with a population of 10,610 persons and 5582 clinical records. METHODS: Data about age, sex, cardiovascular risk factors, heart disease, prophylactic treatment and its adequacy to the protocol of the "thromboembolic disease commission" of the reference hospital were analysed. RESULTS: Age 67 +/- 13 years (mean +/- SD). Cardiovascular risk factors: hypertension 40%, diabetes 33%, dyslipemia 15%, smoking 21%. Heart disease: ischemic cardiopathy 48%, atrial fibrillation 15%, valvulopathy 19%, dilated myocardiopathy 4% and other 14%. In 20% of cases had two different affections (80% with atrial fibrillation). Prophylactic therapy: 52% of patients were under prophylactic treatment (35% antiaggregation, 18% anticoagulation). Among antiaggregants, drugs used were acetylsalicylic acid 73.5%, triflusal 14.7%, dipyridamole, 8.8% and ticlopidine 3%. In 53% of people without prophylactic treatment antiaggregation criteria were present. 15% of patient under antiaggregation therapy did not meet antiaggregation criteria, and 6% fulfilled anticoagulation criteria. 67% treatments accorded the reference protocol, without significant differences between kind of heart disease or sex. The only statistically significant difference was found in age: 46% of patients older than 80 year were correctly treated, in front 75% adequacy in younger people. CONCLUSION: Prophylactic antithrombotic therapy was according the reference protocol in 67% of cases. In older patients, with greater risk of thromboembolic disease, the adequacy is worse.

Age Factors↗

PubMed2000

Salivary testosterone is associated with higher lumbar bone mass in premenopausal healthy women with normal levels of serum testosterone.

The relationships among lumbar and femoral bone mineral density (BMD) and different forms of testosterone--total, salivary testosterone and free testosterone index (FTI) calculated with the sex hormone binding globulin (SHBG)--, body mass index (BMI) and body fat distribution (waist-to-hip ratio and breast-to-hip ratio) were analysed in a cross-sectional study with 66 Spanish premenopausal healthy women aged 42 years and with normal levels of serum testosterone. BMD was measured using dual-energy X-ray absorptiometry (Hologic QDR 1000), and salivary and blood samples were obtained during early follicular phase. In a multiple stepwise regression analysis, lumbar BMD was positively predicted by salivary testosterone and negatively by SHBG adjusted by BMI (R2 = 0.20; p < 0.02). The most femoral BMDs were negatively predicted by SHBG and positively by breast-to-hip ratio (R2 = 0.22-0.33, according to the site measured), but neck BMD was not predicted by any variable. When FTI was entered into the regression model instead of SHBG, it was not an independent predictor of BMD. The waist-to-hip ratio was positively correlated with several femoral BMD sites, but breast-to-hip ratio was better predictor. After adjusting by SHBG, the BMI was only predictor for intertrochanter BMD. All women with elevated salivary testosterone (n = 12) had higher lumbar BMD than those with normal value (1.120 +/- 0.112 vs. 1.026 +/- 0.118; p < 0.01) without differences in other confounding variables. As a conclusion, in premenopausal healthy women of the same age with normal levels of serum testosterone, low levels of SHBG and high levels of salivary testosterone are associated with higher lumbar BMD, whereas low levels of SHBG together with higher breast-to-hip ratio are associated with higher femoral BMD.

Absorptiometry, Photon↗

PubMed2000

Establishment of reference values for standard dose short synacthen test (250 microgram), low dose short synacthen test (1 microgram) and insulin tolerance test for assessment of the hypothalamo-pituitary-adrenal axis in normal subjects.

OBJECTIVE: To assess the integrity of the hypothalamo-pituitary-adrenal(HPA) axis, many authors have proposed the short synacthen test (ACTH1-24, Tetracosactrin) as a replacement for the insulin tolerance test (ITT). The aim of this study was to compare the plasma cortisol response obtained with both short synacthen tests (high dose (HDT, 250 microgram) and low dose (LDT, 1 microgram)) with the peak reached during the ITT in healthy volunteers, and to establish the plasma cortisol cut-off level in each test. SUBJECTS AND METHODS: Thirty healthy subjects (16 F, 14 M), mean age 34 years, underwent both short synacthen tests. Twenty healthy subjects, 15 of whom (11 F, nine M) belonged to the above group, mean age 30 years, underwent an ITT. Plasma cortisol was measured using a chemiluminiscence immunoassay. RESULTS: There were no differences between plasma cortisol 30 minutes after both short synacthen tests (HDT: 684 +/- 123, LDT: 669 +/- 119 nmol/l) and the peaks reached with the LDT (691 +/- 123 nmol/l) and the ITT (673 +/- 99 nmol/l). The only difference (P < 0.001) was found in the comparison of plasma cortisol peak reached with the HDT (802 +/- 142 nmol/l) with the other tests. Plasma cortisol levels obtained in the 5th percentile in each test were: at + 30 minutes: (HDT: 537, LDT: 489 nmol/l), peak: (HDT 649, LDT 498, ITT: 539 nmol/l). CONCLUSIONS: Comparison of the plasma cortisol response at + 30 minutes with both short ACTH tests and the peak in the insulin tolerance test did not reveal differences. Each test, for each time point and for each biochemical method, requires its own minimum threshold of normality to assess the hypothalamo-pituitary-adrenal axis.

Adult↗

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↗