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This study is based on a sample of 332 Argentinean teenagers in their last year of secondary school. In the context of the relational theory of motivation, an attempt is made to determine the motivational categories best predicting Future time Perspective (FTP) extension. The influence of the sex, locus of control, social class, and school ethos variables on FTP extension is also explored. A scale measuring locus of control and the Motivational Induction Method (MIM) have been employed to obtain the data. Through stepwise multiple regression, a predictive set is determined, made up of life-meaning values, self-fulfillment, academic achievement motivation, locus of control, sensual values, and social contact. Significant differences are found in FTP extension and locus of control in relation to school ethos. The Mann-Whitney and Kruskal-Wallis tests are used as statistical proof. A one-way ANOVA is run to examine the relationship between locus of control and school ethos levels. The possibility of a motivational profile common to Argentinean teenagers is considered and the pedagogical consequences of the findings are discussed. [ABSTRACT FROM AUTHOR]

Herein we present the update for the Mexican Guidelines for the Treatment of Systemic Lupus Erythematosus. It involves the participation of several experts along the country, following the GRADE system. We included aspects regarding vaccines, pregnancy and cardiovascular risk which were not presented in the previous guidelines in 2017., Competing Interests: Declaration of competing interest Deshire Alpizar-Rodriguez has undertaken previous work with GSK Mexico. Lilia Andrade-Ortega has been a speaker, or advisor, for Astra Zeneca and GSK. Sandra M. Carrillo-Vázquez has served as a lecturer for Abbvie, Asofarma, AstraZeneca, GSK, Novartis, and UCB. Sergio Durán-Barragán has been a speaker for Amgen, Janssen, Novartis, and Abbvie, as well as principal investigator in clinical trials with Lilly, Janssen, Novartis, Pfizer, Glaxo, Abbvie, Biogen, BMS, Astra Zeneca, Merck Serono, and UCB. Fedra Irazoque-Palazuelos has been a consultant and speaker for Abbvie, Lilly, and Janssen. Javier Merayo-Chalico has served as a speaker for Abbvie, Astra Zeneca, and Janssen. Sandra Sicsik-Ayala has been a speaker for Abbvie, Lilly, UCB, Janssen, and Roche. Luis H. Silveira has served as speaker for Johnson & Johnson, Teva, and Novartis. Daniel Xibillé-Friedmann has been a speaker and consultant for Astra Zeneca and Lilly, and conducted clinical trials with BMS and IDORSIA. The other authors have no conflict of interests to declare., (Copyright © 2024 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

The short half-life of existing prostate-specific membrane antigen (PSMA) tracers limits their time for internalization into tumor cells after injection, which is an essential prerequisite for robust detection of tumor lesions with low PSMA expression on PET/CT scans. Because of its longer half-life, the 89 Zr-labeled ligand 89 Zr-PSMA-DFO allows acquisition of PET scans up to 6 d after injection, thereby overcoming the above limitation. We investigated whether 89 Zr-PSMA-DFO allowed more sensitive detection of weak PSMA-positive prostate cancer lesions. Methods: We selected 14 prostate cancer patients with biochemical recurrence who exhibited no PSMA-positive lesions on a PET scan acquired with existing PSMA tracers ( 68 Ga-PSMA-11, 18 F-JK-PSMA-7). Within 5 wk after the negative scan result, we obtained a second PSMA PET scan using 89 Zr-PSMA-DFO (117 ± 16 MBq, PET acquisition within 6 d of injection). Results: 89 Zr-PSMA-DFO detected 15 PSMA-positive lesions in 8 of 14 patients, who had a PET-negative reading of their initial PET scans with existing tracers. In these 8 patients, the new scans revealed localized recurrence of disease (3/8), metastases in lymph nodes (3/8), or lesions at distant sites (2/8). On the basis of these results, patients received lesion-targeted radiotherapies (5/8), androgen deprivation therapies (2/8), or no therapy (1/8). The plausibility of 14 of 15 lesions was supported by histology, clinical follow-up after radiotherapy, or subsequent imaging. Furthermore, comparison of the 15 89 Zr-PSMA-DFO-positive lesions with their correlates on the original PET scan revealed that established tracers exhibited mild accumulation in 7 of 15 lesions; however, contrast-to-noise ratios were too low for robust detection of these lesions (contrast-to-noise ratios, 2.4 ± 3.7 for established tracers vs. 10.2 ± 8.5 for 89 Zr-PSMA-DFO, P = 0.0014). The SUV max of the 15 89 Zr-PSMA-DFO-positive lesions (11.5 ± 5.8) was significantly higher than the SUV max on the original PET scans (4.7 ± 2.8, P = 0.0001). Kidneys were the most exposed organ, with doses of 3.3 ± 0.7 mGy/MBq. The effective dose was 0.15 ± 0.04 mSv/MBq. Conclusion: In patients with weak PSMA expression, a longer period of time might be needed for ligand internalization than that offered by existing PSMA tracers to make lesions visible on PET/CT scans. Hence, 89 Zr-PSMA-DFO might be of significant benefit to patients in whom the search for weak PSMA-positive lesions is challenging. Radiation exposure should be weighed against the potential benefit of metastasis-directed therapy or salvage radiotherapy, which we initiated in 36% (5/14) of our patients based on their 89 Zr-PSMA-DFO PET scans., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: We present here a Zr-89-labeled inhibitor of prostate-specific membrane antigen (PSMA) as a complement to the already established F-18- or Ga-68-ligands., Procedures: The precursor PSMA-DFO (ABX) was used for Zr-89-labeling. This is not an antibody, but a peptide analogue of the precursor for the production of [ 177 Lu]Lu-PSMA-617. The ligand [ 89 Zr]Zr-PSMA-DFO was compared with [ 68 Ga]Ga-PSMA-11 and [ 18 F]F-JK-PSMA-7 in vitro by determination of the K d value, cellular uptake, internalization in LNCaP cells, biodistribution studies with LNCaP prostate tumor xenografts in mice, and in vivo by small-animal PET imaging in LNCaP tumor mouse models. A first-in-human PET was performed with [ 89 Zr]Zr-PSMA-DFO on a patient presenting with a biochemical recurrence after brachytherapy and an ambiguous intraprostatic finding with [ 18 F]F-JK-PSMA-7 but histologically benign cells in a prostate biopsy 7 months previously., Results: [ 89 Zr]Zr-PSMA-DFO was prepared with a radiochemical purity ≥ 99.9% and a very high in vitro stability for up to 7 days at 37 °C. All radiotracers showed similar specific cellular binding and internalization, in vitro and comparable tumor uptake in biodistribution experiments during the first 5 h. The [ 89 Zr]Zr-PSMA-DFO achieved significantly higher tumor/background ratios in LNCaP tumor xenografts (tumor/blood: 309 ± 89, tumor/muscle: 450 ± 38) after 24 h than [ 68 Ga]Ga-PSMA-11 (tumor/blood: 112 ± 57, tumor/muscle: 58 ± 36) or [ 18 F]F-JK-PSMA-7 (tumor/blood: 175 ± 30, tumor/muscle: 114 ± 14) after 4 h (p < 0.01). Small-animal PET imaging demonstrated in vivo that tumor visualization with [ 89 Zr]Zr-PSMA-DFO is comparable to [ 68 Ga]Ga-PSMA-11 or [ 18 F]F-JK-PSMA-7 at early time points (1 h p.i.) and that PET scans up to 48 h p.i. clearly visualized the tumor at late time points. A late [ 89 Zr]Zr-PSMA-DFO PET scan on a patient with biochemical recurrence (BCR) had demonstrated intensive tracer accumulation in the right (SUV max 13.25, 48 h p.i.) and in the left prostate lobe (SUV max 9.47), a repeat biopsy revealed cancer cells on both sides., Conclusion: [ 89 Zr]Zr-PSMA-DFO is a promising PSMA PET tracer for detection of tumor areas with lower PSMA expression and thus warrants further clinical evaluation., (© 2021. The Author(s).)

Bloodstream infections (BI) are relevant in neutropenic patients because they are associated with an increased number of complications and death. The objective was determinate the epidemiologic and microbiologic features of the BI in neutropenic patients with solid neoplasm (SN) and hematologic neoplasm (HN). Retrospective study in two third level hospitals between 2009 and 2016. They were included all the patients older than 18 years-old with active oncologic disease and neutropenia, who had BI. Patients with dermatologic cancer other than melanoma where excluded. A total of 143 BI in neutropenic were observed, of which 80.4% occurred in HN. Around 97.9% of the patients had a high-risk neutropenia without differences between both groups. The most frequent site of BI was primary bacteremia (46.9%) and catheter-associated infection (21%), without significant differences between the two groups. The gram negatives bacilli (GNB) predominated over the gram positive cocci (GPC) and they represented 74.1% of the isolated bacteria, being Escherichia coli the most frequent (32.8%). Among the gram positive cocci, Staphylococcus aureus (28.1%) was the most frequent isolated, followed by coagulase-negative Staphylococci (CNS). There were no differences in microbiological isolates between both groups. With regard to the antimicrobial susceptibility 67.5% of the CNS, 17.6% of the E. coli and 27.6% of the Klebsiella pneumoniae were multiresistant with no differences between both groups. Only 11.1% of S. aureus isolates were methicillin resistant. In conclusion BI of the neutropenic patients where most frequents within patients with HN, GNB were the main microbiological isolates. High mortality was observed in neutropenic patients with BI., (Copyright © 2020 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Urinary Tract Infections (UTI) are an important cause of morbidity in the community, constituting one of the main reasons for hospitalization, and the fourth cause of healthcare-associated infection. The objectives of this study were to determine the frequency of community-acquired UTI (CA-UTI) with need of hospitalization and healthcare-associated UTI (HA-UTI), their risk factors, etiologic agents and their antimicrobial susceptibility spectrum., Methods: A prospective and analytic study was conducted, in which all admissions regarding CA-UTI with need of hospitalization and HA-UTI were evaluated during the period between 2016 and 2017 in two university hospitals., Results: A total of 279 episodes of UTI in hospitalized patients were identified and, among those, 178 episodes corresponded to CA-UTI and 101 to HA-UTI. On average, patients were 60 years old in both groups. HA-UTI were more frequently associated with kidney transplant, recurrent UTI and chronic kidney disease compared with CA-UTI. The instrumentation of urinary tract within the previous month was more frequent in HA-UTI (75.2% vs 32.6%, p<0.001). Escherichia coli was the most frequent isolated microorganism (62.9% in CA-UTI and 56.4% in HA-UTI), followed by Klebsiella pneumoniae and Pseudomonas aeruginosa. A total of 101 multidrug resistant microorganisms were isolated, of which 53.5% were CA-UTI, and were associated with male patients, use of antimicrobials within the previous three months, chronic kidney disease and recurrent UTI., Conclusion: It is of great importance for the institutions to identify the local antimicrobial susceptibility spectrum of UTI in order to stablish adequate empiric treatments., (Universidad Nacional de Córdoba.)

Introduction: Uncomplicated urinary tract infections(UC-UTI) represent a frequent reason for consultation. Most cases are empirically treated, but the antimicrobial susceptibility of the causative microorganisms has changed over the past years. The objectives of this study where to determine UC-UTI causative microorganism and their antimicrobial susceptibility profiles in adult women., Methods: A prospective analytic study was conducted in two hospital in Córdoba, Argentina, between November/2016 and October/2017. From the identification of positive urine cultures, urinary tract infections (UTI) in women ≥18 years without risk factors for complicated UTIs were included, excluding asymptomatic bacteriurias., Results: A total of 610 UC-UTI were identified and 62.6% of them in patients younger than 50 years; 73.3% of cases were cystitis, being more frequent in older women. Escherichia coli was isolated in 89.2% of UTI and negative coagulase Staphylococcus in 4.2%. As regards Escherichia coli, its resistance against ciprofloxacin was 18.8%; 4.4% against ceftriaxone and 1.8% against nitrofurantoin. There was an elevated resistance against ampicillin, trimethoprim–sulfamethoxazole and ampicillin–sulbactam., Main Conclusion: The most frequent isolated microorganism was Escherichia coli, consistent with global epidemiology. This microorganism showed less than 20% total resistance against ciprofloxacin, ceftriaxone and nitrofurantoin., (Universidad Nacional de Córdoba)

Bloodstream infections (BI) are an important cause of morbidity and mortality in cancer patients. A retrospective study was performed in two hospitals aimed to evaluate characteristics of BI episodes occurred in adult patients with hematologic (HN) and solid (SN) neoplasia other than non-melanoma skin cancers in the period 2009-2016. A total of 467 episodes of bacteremia and 16 of fungemia were identified. A total of 200 (41.4%) bacteremias occurred in patients with HN and 283 (58.6%) in patients with SN. The most frequent SN and HN were colon cancer (18.7%) and non-Hodgkin lymphoma (27%), respectively. The main risk factors for BI were a previous surgical procedure in SN and chemotherapy in the previous 30 days and use of central venous catheter in HN. Infections were mainly acquired in the hospital environment and the most frequent presentation was bacteremia without focus, mostly in HN (38% vs. 20.8%, p < 0.001). Gram negative bacilli (GNB) were isolated in 336 (69.5%) episodes and predominated over Gram positive cocci (GPC) in both groups. Escherichia coli was the most frequent GNB isolated in both SN (24.7%) and HN patients (20.5%). The most frequent GPC was Staphylococcus aureus. Multidrug-resistance was found in 15% of the isolates in SN and 18% in HN. The overall mortality was 40.5% in patients with HN and 37.5% in patients with SN, with the majority of deaths occurring in the first 30 days.

The aim of this paper is to evaluate the relationship of salivary ammonium levels and the presence of bacteria with rheumatoid arthritis (RA) clinical disease activity in a cross-sectional study of Mexican patients. From a periodontal and disease activity standpoint, 132 consecutive RA patients fulfilling clinical criteria were evaluated. Ammonia levels (including peptidyl arginine deiminase activity) were evaluated by colorimetric assay and the presence of Porphyromonas gingivalis , Tannerella forsythia , and Prevotella intermedia was evaluated by polymerase chain reaction (PCR) technique. After a multivariate analysis, adjusting for clinical and serological parameters, a significant association was only observed between severe periodontitis and probing depth with high RA disease activity. Additionally, in contrast to P. gingivalis , the presence of T. forsythia was significantly associated with high disease RA activity even after multivariable adjustment analysis. There was also a significant increase in ammonium levels in the high RA activity group and a significant correlation between salivary ammonia and RA disease activity but not with autoantibody titers. Similarly, we observed a significant increase in the ammonium levels derived from the cultures of P. gingivalis and T. forsythia , with respect to P. intermedia and S. gordonii cultures, or even healthy donors. These results suggest that RA activity is associated with severe periodontitis, high salivary ammonium levels and the presence of T. forsythia .

Objective: To evaluate the association between the clinical activity of RA patients and serum adipocytokines (Leptin, Adiponectin and Resistin) and inflammatory cytokines., Methods: All RA patients fulfilled ACR 1987 criteria and were treated with DMARDs. Adipocytokine and inflammatory cytokine levels were evaluated using ELISA., Results: 121 patients were included in the study. Stratifying according to DAS28 (low, moderate and high activity), there were significant differences for Leptin, Resistin, IL-6 and IL-17, however, no differences were seen for Adiponectin, TNFα or IL-1β. Clinical activity positively correlated with Leptin, Resistin, IL-17 and IL-6 levels, but not with Adiponectin, TNFα or IL-1β. Adiponectin levels negatively correlated with TNFα and positively correlated with IL-1β. IL-1β positively correlated with IL-6 and negatively correlated with TNFα and IL-17., Conclusion: Circulating Leptin, Resistin, IL-6 and IL-17 levels positively correlate with RA clinical activity in a manner independent of the subject's BMI. Complex relationships between inflammatory cytokines were observed in RA patients suggesting that other metabolic or inflammatory factors could be involved., (Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

In this work we present, to our knowledge for the first time, the results of a transient infrared spectroscopic study of the photoinduced valence tautomerism process in cobalt-dioxolene complexes with sub-picosecond time resolution. The molecular systems investigated were [Co(tpa)(diox)]PF(6) (1) and [Co(Me(3)tpa)(diox)]PF(6) (2), where diox = 3,5-di-tert-butyl-1,2-dioxolene; tpa = tris(2-pyridylmethyl)amine and Me(3)tpa its 6-methylated analogue. Complex (1) is present in solution as ls-Co(III)(catecholate) (1-CAT), while (2) as hs-Co(II)(semiquinonate) (2-SQ). DFT calculation of the harmonic frequencies for (1) and (2) allowed us to identify the vibrational markers of catecholate and semiquinonate redox isomers. Irradiation with 405 and 810 nm pulses (~35 fs) of (1-CAT) induces the formation of an intermediate excited species from which the ground state population is recovered with a time constant of 1.5 ± 0.3 ns. Comparing the 1 ns transient infrared spectrum with the experimental difference spectrum FTIR(2-SQ)-FTIR(1-CAT) and with the calculated difference spectrum IR(c)(1-SQ)-IR(c)(1-CAT) we are able to unequivocally identify the long lived species as the semiquinonate redox isomer of (1). On the other hand, no evidence of photoconversion is observed upon irradiation of (2) with 405 nm. Temporal evolution of transient spectra was analyzed with the combined approach consisting of singular values decomposition and global fitting (global analysis). After 405 and 810 nm excitation of (1-CAT), the semiquinonate excited species is formed on an ultrafast time scale (<200 fs) and cools down within the first 50 ps. Excitation of (2-SQ) with 405 nm wavelength produces a short lived excited state in which the semiquinonate nature of dioxolene is preserved and the ground state recovery is completed within 30 ps.

Introduction. The present study examined the relationship between metacognition (i.e., "thinking about thinking") and depression. More specifically, the depressive realism hypothesis (Alloy & Abramson, 1979), which posits that depressed people have a more accurate view of reality than nondepressed people, was tested. Methods. Nondepressed, mildly depressed, and moderately depressed individuals predicted their memory performance by making judgements of learning after each studied item. These predictions were then compared with actual performance on a free recall task to assess calibration, an index of metacognitive accuracy. Results and conclusions. Consistent with the depressive realism hypothesis, mild depression was associated with better calibration than nondepression. However, this "sadder but wiser" phenomenon appears to only exist to point, as moderate depression and nondepression showed no calibration differences. Thus, the level-of-depression account of depressive realism is supported.

This report aims to study architectural Auerbach plexus structure with NADH histochemistry (nicotinamide adenine dinucleotide, reduced form), along ages and their modifications with restricted diet in obese beta line rats. Experimental groups were: 1) After weaning, male rats were fed ad libitum (ALD) with standard rat chow. Autopsies were done at 2, 4, 8, 12, and 18 months old. 2) After weaning, one group was fed ad libitum, another group of rats were maintained on a restricted diet (RD). Autopsy was performed at 8 months of age. 3) After weaning, male rats were fed ad libitum (ALD) with standard rat chow. At 60 days old one group was continued with standard rat chow. Another group was fed with a restricted diet (RD). Autopsy was performed at 120 days old. After autopsy, segments of small intestine, proximal and distal colon were processed for NADH histochemistry. 1) At 2 months of age some empty spaces ("neuronal ghosts") were seen between neurons. Later on partial to total disruption of reticular structures was seen along ages. 2) In RD rats of 8 months of age, a mesh-like structure similar to normal control rats was observed. In ALD rats, partial to total disruption of mesh-like structures was seen. 3) In RD rats of 4 months of age, disruption intermingled with normal mesh-like zones was seen, more severe in ALD rats. Changes in Auerbach plexus structure (disruption of mesh-like appearance) in this line of rats were quite different from normal control rats suggesting dismetabolism effects. Dietary restriction delayed alterations in Auerbach plexus structures in obese rats.

Epinephrine and Norepinephrine, typically released during stress bind to nine different adrenoceptors (AR) which classically control the cardiovascular and respiratory systems. New targets were described for the many agonists and antagonists developed for these AR, as the central nervous system. During the last three decades, AR expression and action on the mammary gland/breast were extensively investigated. In the cow mammary gland, good milkability was associated with low density of beta(2)-AR and high density of alpha(2)-AR. In the rat normal mammary gland, beta-AR are expressed in the epithelial cells, alveoli, ducts, and adipocytes showing an exquisite regulation by steroid hormones and prolactin. In rat dimethylbenz(a)anthracene (DMBA) tumors, a close correlation was observed between tumor growth and beta-AR concentration. beta(2)-AR were described in numerous human cell lines and breast tumors. The action of beta-adrenergic compounds on cell proliferation is contradictory. While some authors found that beta-agonists significantly inhibit cancer cell proliferation and tumor growth in mice, others described a significant reduction in DNA synthesis by beta-blockers. Also, positive effects of beta-AR on human carcinoma cell migration have been described. alpha(2)-AR are expressed in human breast cancer and non-cancer cell lines, their stimulation being associated with increased cell proliferation. In vivo clonidine increased tumor growth and alpha (2)-adrenergic antagonists completely reversed this effect. When administered alone, rauwolscine inhibited tumor growth behaving as an inverse agonist. Therefore, the numerous adrenergic beta- and alpha-AR agonists or antagonists could prove to be unexpected therapeutic options for mammary gland/ breast and mainly breast cancer.

Raynaud's phenomenon is characterized by repeated daily attacks of ischemia followed by reperfusion at the acrallevel. It is a frequent syndrome found in medical practice; and it can be considered as primary or secondary to other conditions, including rheumatic autoimmune diseases. Current classification had clinical and therapeutic implications. Careful clinical evaluation is the most reliable and reproducible method in the diagnosis of Raynaud's phenomenon. Several risk factors had been associated in the genesis of Raynaud's phenomenon; however, its pathogenesis remains elusive although recently, considerable progress in disease mechanism had been described. Such advances are directing new lines of therapy., (Copyright © 2006 Elsevier España S.L. Barcelona. Published by Elsevier Espana. All rights reserved.)

Adrenergic compounds (epinephrine and norepinephrine) are the most important hormones released during stress. Several different receptors are associated with their action in different tissues. However, alpha(2)-adrenoceptors have not yet been described in either normal or tumour human breast tissue. The aim of this work was to describe and characterize these receptors in several tumour and non-tumour human cell lines. The expression of alpha(2)-adrenoceptors was analyzed at the RNA (RT-PCR) and protein ([(3)H]-rauwolscine binding and immunocytochemistry) levels in different human breast cell lines, and the biological activity assessed by [(3)H]-thymidine incorporation. The cancer IBH-6, IBH-7 and MCF-7 and the non-tumour HBL-100 cells line, expressed both alpha(2B)- and alpha(2C)-adrenoceptor-subtypes. A single subtype was expressed in malignant HS-578T (alpha(2A)) and MDA-MB-231 and non-tumour MCF-10A cells (alpha(2B)). All cell lines exhibited significant binding for the specific antagonist [(3)H]-rauwolscine. The alpha-, alpha(2)-, and the alpha(1)-compounds with known affinity for alpha(2)-adrenoceptors, including epinephrine, norepinephrine, yohimbine, clonidine, rauwolscine and prazosin, competed significantly with binding in MCF-7 cells. In addition, IBH-6, IBH-7 and MCF-7 cells showed significant staining with specific antibodies against alpha(2B)- and alpha(2C)-adrenoceptor-subtypes, when tested by immunocytochemistry. In all cell lines, the specific agonist clonidine or oxymetazoline stimulated [(3)H]-thymidine incorporation. EC(50) values were in the range of 20-50 fM for IBH-6, IBH-7, and HS-578T; 0.14 pM for MCF-7; 2-82 pM for HBL-100 and MCF-10A cells, and a biphasic behaviour with a maximum value at 38.0 pM, was observed for MDA-MB-231 cells. The specific alpha(2)-adrenergic antagonist rauwolscine always reversed this stimulation at 0.1 nM. In conclusion, this study describes for the first time, the presence of alpha(2)-adrenoceptors in human epithelial breast cell lines. Moreover, activation of these receptors was associated with an enhancement of cell proliferation.

Objective and Design: Gross cystic disease (GCD) of the breast is reported to occur in 7% of women in the developed world and, although not premalignant, is thought to be associated with an increased risk of breast cancer. Hormone and growth factor concentration levels were measured in breast cyst fluid (BCF) to correlate them with their mitogenic activity in tumour (MCF-7) or nontransformed (MCF-10A) cells., Results: Oestradiol (E2), oestrone (E1), E2-sulfate (E2-S), E1-sulfate (E1-S) and epidermal growth factor (EGF) concentrations were, as expected, significantly higher in type I than in type II cysts, while transforming growth factor-beta 2 (TGF-beta2) showed higher levels in type II cysts. Fifty per cent of the BCF samples stimulated [3H]-thymidine incorporation into MCF-7 cells while 34.5% inhibited this parameter. In MCF-10A cells, most BCF samples were stimulatory (85%). E2, E1 and EGF concentrations in BCF samples correlated significantly and positively with cell proliferation in MCF-7 cells, whereas a significant negative correlation was found for TGF-beta2. In MCF-10A cells, only E2-S and E1-S exhibited significant positive correlation, whereas a significant negative correlation was found for TGF-beta2. Progesterone (Pg), E2 and EGF incubated under the same conditions had a stimulatory effect on [3H]-thymidine incorporation into MCF-7 cells, whereas TGF-beta2 inhibited this parameter. Pg, E2, E1 and EGF significantly stimulated this parameter in MCF-10A cells., Conclusions: The stimulatory action of BCF on cell proliferation in a model of human breast epithelial cells could partly explain the increased incidence of breast cancer in cyst-bearing women.

Human breast cancer primary cultures are useful tools for the study of several aspects of cancer biology, including the effects of chemotherapy and acute gene expression in response to different hormonal/chemotherapy treatments. The present study reports the conditions for primary culture of breast cancer samples from untreated patients and the most effective collagenization method to dissociate human samples consisting in an overnight incubation with 1 mg/ml types II or IV collagenase and further incubation in DMEM:F12 (1:1) medium supplemented with glutamine, bovine insulin, penicillin-streptomycin, HEPES, estradiol, cortisol (F), tri-iodothyronine (T(3)), transferrine (TR), and 10% fetal calf serum (FCS). These conditions proved to be appropriate for both primary culture and the development of stable cell lines. Of the seven cell lines obtained, three fast growing and estrogen receptor (ER)+/progesterone receptor (PgR)+/EGF receptor (EGFR)+ have been characterized. The cells are able to grow both in soft agar and in nude mice, and express cytokeratins, all parameters characteristic of malignant epithelial cell lines. The cells also exhibit an increased proliferation rate in the presence of estradiol, progesterone, and EGF, suggesting the presence of the corresponding receptors. The mRNA expression of type alpha- and beta-ER as well as EGFR, was confirmed by RT-PCR. In conclusion, the novel cell lines described, arose from primary tumors and are sensitive to estradiol, progesterone, and EGF. This not only expands the repertoire of breast cancer cells available as potentially useful tools for examining most parameters in breast cancer "in vitro", but also provides unique new models to explore the complex regulation by steroids as well as growth factors in such cells., (Copyright 2003 Wiley-Liss, Inc.)

(-)Epinephrine (Epi) and (-)Norepinephrine (NEpi) significantly stimulated tritiated Thymidine incorporation in MCF-7 cells at concentrations 10-30pM to 10nM, with an EC50 of 10pM for Epi and 14.2pM for NEpi. To characterize this action, cells were incubated in the presence of NEpi or Epi and different antagonists. The beta-adrenergic antagonist Propanolol showed no effect on the agonist's stimulation, whereas the alpha-adrenergic antagonist Phentolamine, reverted it completely at high concentrations (100 microM). The alpha1-adrenergic antagonist Prazosin (Pra) acted only at high concentrations, while the alpha2-adrenergic antagonist Yohimbine (Yo) reverted the stimulation at an EC50 of 0.11 microM. Likewise, when the cells were incubated in the presence of the specific alpha2-adrenergic agonist Clonidine (Clo), Thymidine incorporation was significantly stimulated at an EC50 of 0.298 pM. Again, the incubation of the cells in the presence of the alpha1-adrenergic antagonist Pra exerted its action at high concentrations, whereas the alpha2-adrenergic antagonist Yo showed a clear reversal of the agonist's enhancement at an EC50 of 0.136 microM. Moreover, Clo caused a clear and significant inhibition of stimulated cAMP levels both in the intracellular and the extracellular fractions. Yo showed a complete reversion of cAMP levels to control values in the presence of Clo, while Pra had the opposite effect. These data suggest that the stimulation provoked in Thymidine incorporation by the agonists Epi, NEpi, and Clo is, at least in part, due to an alpha2-adrenergic mechanism directly on tumoral cells, and that the effect is coupled with inhibition of cAMP levels, as described for this kind of receptors.

Scatchard analysis of prolactin binding sites (PRL-BS) from ejaculated spermatozoa showed a single population of binding sites (apparent association constant: 2.51+/-0.186 nmol/l[-1]) with 0.317+/-0.0743 fmol/10(6) sperm binding sites. Different pools of spermatozoa were incubated with increasing concentrations of several hormones. There was a decrease in [125I]-oPRL binding with purified ovine prolactin (oPRL) and human growth hormone (hGH) which was not observed in the presence of synthetic ACTH and recombinant FSH, suggesting that binding was hormone specific. When the patient's samples were analyzed using the single point assay at saturation concentration, asthenospermic patients showed a significantly higher concentration of binding sites compared to normospermic ones. Both groups of patients displayed similar PRL levels in seminal plasma measured by DELFIA. Moreover, individual values of PRL levels in seminal plasma did not correlate with PRL-BS concentrations. We thus conclude that [125I]-oPRL binding to ejaculated spermatozoa was hormone specific and with similar parameters as seen in other target tissues. PRL-BS concentration in asthenospermic patients was significantly higher than in normospermic but this was not due to different levels of PRL in seminal plasma.

Repeated isolation stress and prazosin effect were evaluated in 7,12-dimetylbenz[A]anthracene (DMBA) mammary tumors. Tumor volume was significantly lower in stressed than in control animals from 10 to 52 days considering day 1 the moment when tumors became palpable and treatment began. Control Prazosin (0.5 mg/kg) rats showed diminished tumor volume after 40 days. Stress Prazosin curve was similar to stress alone. The proportion of progressing tumors in control was significantly higher than in stressed groups, regardless of Prazosin administration. Body weight gain was similar in every group throughout the experiment. Behavioral studies were performed when stress effect was no longer evident. Grooming and the number of fecal boli were similar in all groups, as well as prolactin serum levels, suggesting that habituation took place. No significant differences were observed between groups for estrogen receptors. However, a greater concentration of progesterone receptors was found in Stressed rats, compared to all other groups. We conclude that the decrease of tumor volume provoked by stress could not be reversed by the alpha 1-adrenergic antagonist prazosin. Then, it appears that the main effect of stress is not mediated by the alpha 1-adrenergic receptors. Higher progesterone receptors in stressed rats could explain the differences observed.