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1.
Phys Chem Chem Phys ; 24(23): 14440-14451, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35662295

RESUMO

We report a computational study of the structural and energetic properties of water clusters and singly-charged water cluster anions containing from 20 to 573 water molecules. We have used both a classical and a quantum description of the molecular degrees of freedom. Water intra and inter-molecular interactions have been modelled through the SPC/F model, while the water-excess electron interaction has been described via the well-known Turi-Borgis potential. We find that in general the quantum effects of the water degrees of freedom are small, but they do influence the cluster-size at which the excess electron stabilises inside the cluster, which occurs at smaller cluster sizes when quantum effects are taken into consideration.

2.
Phys Rev Lett ; 126(17): 175502, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33988423

RESUMO

We report the first study on the thermal behavior of the stiffness of individual carbon nanotubes, which is achieved by measuring the resonance frequency of their fundamental mechanical bending modes. We observe a reduction of the Young's modulus over a large temperature range with a slope -(173±65) ppm/K in its relative shift. These findings are reproduced by two different theoretical models based on the thermal dynamics of the lattice. These results reveal how the measured fundamental bending modes depend on the phonons in the nanotube via the Young's modulus. An alternative description based on the coupling between the measured mechanical modes and the phonon thermal bath in the Akhiezer limit is discussed.

3.
Rev Gastroenterol Mex ; 82(2): 106-114, 2017.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28283313

RESUMO

BACKGROUND: There are no studies on the factors associated with gastroesophageal reflux disease (GERD) relapse in primary care patients. AIM: To identify the risk factors associated with GERD relapse in primary care patients that responded adequately to short-term treatment with a proton pump inhibitor. PATIENTS AND METHODS: A cohort study was conducted that included GERD incident cases. The patients received treatment with omeprazole for 4 weeks. The ReQuest questionnaire and a risk factor questionnaire were applied. The therapeutic success rate and relapse rate were determined at 4 and 12 weeks after treatment suspension. A logistic regression analysis of the possible risk factors for GERD relapse was carried out. RESULTS: Of the 83 patient total, 74 (89.16%) responded to treatment. Symptoms recurred in 36 patients (48.64%) at 4 weeks and in 13 patients (17.57%) at 12 weeks, with an overall relapse rate of 66.21%. The OR multivariate analysis (95% CI) showed the increases in the possibility of GERD relapse for the following factors at 12 weeks after treatment suspension: basic educational level or lower, 24.95 (1.92-323.79); overweight, 1.76 (0.22-13.64); obesity, 0.25 (0.01-3.46); smoking, 0.51 (0.06-3.88); and the consumption of 4-12 cups of coffee per month, 1.00 (0.12-7.84); citrus fruits, 14.76 (1.90-114.57); NSAIDs, 27.77 (1.12-686.11); chocolate, 0.86 (0.18-4.06); ASA 1.63 (0.12-21.63); carbonated beverages, 4.24 (0.32-55.05); spicy food 7-16 times/month, 1.39 (0.17-11.17); and spicy food ≥ 20 times/month, 4.06 (0.47-34.59). CONCLUSIONS: The relapse rate after short-term treatment with omeprazole was high. The consumption of citrus fruits and NSAIDs increased the possibility of GERD relapse.


Assuntos
Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/epidemiologia , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Estudos de Coortes , Dieta , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Omeprazol/uso terapêutico , Atenção Primária à Saúde , Recidiva , Fatores de Risco , Resultado do Tratamento
4.
J Chem Phys ; 143(18): 184104, 2015 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-26567643

RESUMO

We describe a robust and efficient chain-of-states method for computing Minimum Energy Paths (MEPs) associated to barrier-crossing events in poly-atomic systems, which we call the acceleration method. The path is parametrized in terms of a continuous variable t ∈ [0, 1] that plays the role of time. In contrast to previous chain-of-states algorithms such as the nudged elastic band or string methods, where the positions of the states in the chain are taken as variational parameters in the search for the MEP, our strategy is to formulate the problem in terms of the second derivatives of the coordinates with respect to t, i.e., the state accelerations. We show this to result in a very simple and efficient method for determining the MEP. We describe the application of the method to a series of test cases, including two low-dimensional problems and the Stone-Wales transformation in C60.

5.
Int J Food Sci Nutr ; 64(5): 575-86, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23360131

RESUMO

Saturated and trans fatty acids have been associated with the risk to develop cardiovascular diseases. However, health-promoting effects are associated with consumption of anhydrous milk fat (AMF) and ruminant trans fatty acids, such as conjugated linoleic acid (CLA) and vaccenic acid (VA) contained in the lipid fraction of milk and dairy products. The purpose of this study was to evaluate the effect of AMF naturally enriched with CLA and VA in spontaneously hypertensive rats (SHR), using sterculic oil to inhibit the conversion of VA into CLA. The administration of AMF to SHR during 7 weeks exerted beneficial effects on cardiovascular risk biomarkers (reduction of insulin, blood lipids, increase of adiponectin). When sterculic oil was included, some parameters were further ameliorated (reduction of insulin, increase of adiponectin). Sterculic oil alone reduced body weight and adiposity, and improved blood pressure, adiponectin and triglyceride levels.


Assuntos
Doenças Cardiovasculares/sangue , Gorduras na Dieta/uso terapêutico , Hipertensão/tratamento farmacológico , Ácido Linoleico/uso terapêutico , Ácidos Linoleicos Conjugados/uso terapêutico , Leite/química , Ácidos Oleicos/uso terapêutico , Adiponectina/sangue , Adiposidade/efeitos dos fármacos , Animais , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Ciclopropanos/farmacologia , Ciclopropanos/uso terapêutico , Dieta , Gorduras na Dieta/farmacologia , Ácidos Graxos Monoinsaturados/farmacologia , Ácidos Graxos Monoinsaturados/uso terapêutico , Hipertensão/sangue , Insulina/sangue , Ácido Linoleico/farmacologia , Ácidos Linoleicos Conjugados/farmacologia , Lipídeos/sangue , Masculino , Ácidos Oleicos/farmacologia , Ratos , Ratos Endogâmicos SHR , Ruminantes , Triglicerídeos/sangue , Redução de Peso/efeitos dos fármacos
6.
Phys Rev Lett ; 104(18): 185701, 2010 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-20482189

RESUMO

We report large-scale first-principles simulations of melting of four different phases of Li at pressures ranging from 0 to 50 GPa. We find excellent agreement with existing experimental data at low pressures, and confirm that above 10 GPa the melting line develops a negative slope, in parallel to what occurs for Na at 30 GPa. Surprisingly, our results indicate that the melting temperature of the bcc phase is always higher than that of fcc Li, suggesting the intriguing possibility of the existence of a narrow field of bcc stability separating the fcc and liquid phases, as predicted by Alexander and McTague [Phys. Rev. Lett. 41, 702 (1978)].

7.
J Am Chem Soc ; 131(49): 17853-9, 2009 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-19916555

RESUMO

The amphiphillic character, that is, the capacity to simultaneously attract and repel water, has been traditionally reserved to organic molecules such as phospholipids and surfactants, containing both hydrophilic and hydrophobic groups within the same molecule. However, this general concept can be extended to artificial structures such as micrometer-sized particles, the so-called Janus particles, and patterned surfaces. Here we provide an example of an amphiphillic crystalline solid, l-alanine, by combining atomic force microscopy measurements performed on two different cleavage surfaces showing contrasting behaviors when exposed to water vapor, with computer simulations that allow us to clarify the dipolar origin of this behavior. Although we take l-alanine as an example, our results should apply quite generally to dipolar molecular crystals.


Assuntos
Alanina/química , Simulação por Computador , Cristalização , Microscopia de Força Atômica , Tamanho da Partícula , Propriedades de Superfície , Água/química
8.
Phys Rev E ; 100(3-1): 032103, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31639902

RESUMO

We consider the problem of how a condensed molecular system approaches equilibrium, focusing on the particular case of water. We show, by means of extensive molecular dynamics simulations, that the existence of different types of degrees of freedom affects the dynamics of equilibration, and this influence is made most obvious in the system's temperature. When equipartition of energy does not hold in the initial, nonequilibrium state, the instantaneous temperature can be up to a few degrees lower than that observed under equipartition conditions, resulting in a Mpemba-like effect. Though our study considers water in particular, our findings apply more generally to condensed molecular systems.

9.
Rev Gastroenterol Mex (Engl Ed) ; 84(4): 442-448, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30318401

RESUMO

INTRODUCTION AND AIMS: An inlet patch (IP) is the presence of gastric columnar epithelium outside of the stomach. No studies have been conducted in Mexico on that pathology. The aim of the present study was to determine the prevalence of esophageal IP and the clinical characteristics of the patients that present it. MATERIALS AND METHODS: A cross-sectional study was conducted that included consecutive patients referred for endoscopy within the time frame of September 2015 to May 2016. The patients answered a questionnaire, and high-definition endoscopy with digital chromoendoscopy was performed. The prevalence of IP was identified. The chi-square test was used to compare the clinical characteristics between patients that presented with esophageal IP and those without it. RESULTS: A total of 239 patients were included in the study. Their mean age was 53 years, and 130 (54.4%) were women. IP was found in 26 patients (10.9%), 15 of whom were men (57.7%). The main reason for referral to endoscopy was gastroesophageal reflux disease, present in 69.2% of the patients with IP and in 55.9% without IP (p=.19). The most common symptoms were heartburn and regurgitation. The former was present in 69.2% of the patients with IP and in 59.1% without IP (p=.32), and the latter was present in 65.4% of the patients with IP and 69.1% without IP (p=.7). Extraesophageal manifestation distribution was: cough in 46.2% of the patients with IP and 38% without IP (p=.45) and dysphonia in 54% with IP and 47% without IP (p=.53). Twenty-three percent of the patients with IP had Barrett's esophagus, as did 23% without IP (p=.99). CONCLUSIONS: The prevalence of IP was high. The primary referral diagnosis was gastroesophageal reflux disease. No differences were found in relation to symptoms or the presence of Barrett's esophagus between the patients with and without IP.


Assuntos
Coristoma/diagnóstico , Coristoma/epidemiologia , Doenças do Esôfago/diagnóstico , Doenças do Esôfago/epidemiologia , Mucosa Gástrica , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
10.
J Chem Phys ; 129(6): 064110, 2008 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-18715054

RESUMO

The path integral formulation has been combined with several methods to determine free energies of quantum many-body systems, such as adiabatic switching and reversible scaling. These techniques are alternatives to the standard thermodynamic integration method. A quantum Einstein crystal is used as a model to demonstrate the accuracy and reliability of these free energy methods in quantum simulations. Our main interest focuses on the calculation of the melting temperature of Ne at ambient pressure, taking into account quantum effects in the atomic dynamics. The free energy of the solid was calculated by considering a quantum Einstein crystal as reference state, while for the liquid, the reference state was defined by the classical limit of the fluid. Our findings indicate that, while quantum effects in the melting temperature of this system are small, they still amount to about 6% of the melting temperature, and are therefore not negligible. The particle density as well as the melting enthalpy and entropy of the solid and liquid phases at coexistence is compared to results obtained in the classical limit and also to available experimental data.

11.
J Clin Invest ; 90(4): 1593-9, 1992 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1383276

RESUMO

An increasing body of information now suggests that insulin-like growth factor (IGF) binding proteins (BPs) may serve as antigonadotropins at the level of the ovary. It is the objective of the present communication to evaluate the functional role of endogenous (granulosa cell-derived) IGFBPs by exploiting the unique properties of des(1-3)IGF-I, a naturally occurring IGF-I analogue characterized as a weak ligand of IGFBPs but not of type I IGF receptors. Given IGFBP-replete circumstances, des(1-3)IGF-I proved more potent (10-fold) than its intact counterpart in promoting the follicle stimulating hormone (FSH)-stimulated accumulation of progesterone by cultured rat granulosa cells. In contrast, des(1-3)IGF-I proved virtually equipotent to the unmodified principle under IGFBP-deplete circumstances. Taken together, these findings are in keeping with the notion and that the apparently enhanced potency of des(1-3)IGF-I (under IGFBP-replete conditions) is due to its diminished affinity for endogenously generated IGFBPs and that rat granulosa cell-derived IGFBPs are inhibitory to IGF (and thus inevitably to gonadotropin) hormonal action. Accordingly, the reported ability of gonadotropins to attenuate IGFBP release by granulosa cells may be designed to enhance the bioavailability of endogenously generated IGFs in the best interest of ovarian steroidogenesis.


Assuntos
Proteínas de Transporte/fisiologia , Células da Granulosa/fisiologia , Fator de Crescimento Insulin-Like I/antagonistas & inibidores , Fator de Crescimento Insulin-Like I/farmacologia , Fragmentos de Peptídeos/farmacologia , Animais , Ligação Competitiva , Células Cultivadas , Feminino , Hormônio Foliculoestimulante/farmacologia , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Fragmentos de Peptídeos/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Somatomedina/metabolismo
12.
J Clin Invest ; 89(6): 1746-54, 1992 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-1534816

RESUMO

To delineate the scope of the human intraovarian IL-1 system we used a solution hybridization/RNase protection assay to test for expression of the genes encoding IL-1, its type I receptor (IL-1R), and its receptor antagonist (IL-1RA). IL-1 transcripts were not detected in whole ovarian material from days 4 or 12 of an unstimulated menstrual cycle but transcripts (IL-1 beta much greater than IL-11 alpha) were detected in preovulatory follicular aspirates from gonadotropin-stimulated cycles. Concurrently obtained peripheral monocytes did not contain IL-1 beta transcripts but macrophage-depleted follicular aspirates did, thus implicating the granulosa cells as the site of IL-1 expression. IL-1R transcripts were detected in RNA from whole ovaries and follicular aspirates but not in RNA from peripheral monocytes. IL-1RA transcripts were detected in whole ovarian material as well as in macrophage-free follicular aspirates. Cultured human granulosa and theca cells did not contain mRNA for IL-1 beta or IL-1RA but did contain mRNA for IL-1R. Treatment of cell cultures with forskolin (25 microM) induced IL-1 beta transcripts in granulosa but not theca cells. Forskolin also increased the basal levels of IL-1R transcripts in both granulosa and theca cells but did not induce IL-RA transcripts in either cell type. Taken together, these findings reveal the existence of a complete, highly compartmentalized, hormonally dependent intraovarian IL-1 system replete with ligands, receptor, and receptor antagonist.


Assuntos
Gonadotropinas/fisiologia , Interleucina-1/genética , Ovário/metabolismo , Receptores Imunológicos/genética , Adulto , Células Cultivadas , Técnicas de Cultura , Feminino , Citometria de Fluxo , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Interleucina-1/metabolismo , Receptores Imunológicos/antagonistas & inibidores , Receptores Imunológicos/metabolismo , Receptores de Interleucina-1
13.
Mol Endocrinol ; 5(12): 1799-805, 1991 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1724286

RESUMO

The intraovarian insulin-like growth factor (IGF) system constitutes a triad composed of ligands, receptors, and binding proteins. Although conventional radioligand receptor assays have documented the presence of specific receptors for insulin and insulin-like peptides in some rat somatic ovarian cell types, the exact cellular localization and hormonal regulation of the receptors in question remain matters of inquiry. To reevaluate the very presence, cellular localization, and hormonal regulation of the IGF receptor gene family in the rat ovary, solution hybridization/RNase protection assays were used wherein ovarian total RNA (20 micrograms) from immature (21-23 days old) rats was hybridized with 32P-labeled type I IGF receptor, type II IGF/mannose-6-phosphate receptor, and insulin receptor riboprobes. Single protected fragments 261 (type I IGF receptor), 500 (type II IGF/mannose-6-phosphate receptor), and 478 (insulin receptor) bases long were evident in whole ovary, granulosa, and theca-interstitial cells. Hypophysectomy of immature rats led to significant (P less than 0.05) albeit variable decrements in the relative (densitometrically quantified) ovarian abundance of transcripts corresponding to the type I IGF (but not insulin or type II IGF/mannose-6-phosphate) receptor. Treatment of immature hypophysectomized rats with FSH (10 micrograms/rat.day x 2.5 days) resulted in a significant (P less than 0.05) increase (4-fold) in transcripts corresponding to the type I IGF receptor in both whole ovarian material and freshly isolated granulosa cells. Similar (3.7-fold) increments (P less than 0.05) were noted after treatment with a diethylstilbestrol-containing sc silastic implant applied for a total of 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Regulação da Expressão Gênica/genética , Ovário/ultraestrutura , Receptores de Superfície Celular/genética , Animais , Dietilestilbestrol/farmacologia , Feminino , Hormônio Foliculoestimulante/farmacologia , Manosefosfatos/genética , Manosefosfatos/metabolismo , Ovário/química , Ovário/metabolismo , RNA/análise , RNA/genética , Ratos , Ratos Endogâmicos , Receptor de Insulina/análise , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Receptores de Superfície Celular/análise , Receptores de Superfície Celular/metabolismo , Receptores de Somatomedina , Transcrição Gênica/efeitos dos fármacos
14.
J Bone Miner Res ; 7(3): 317-9, 1992 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1585833

RESUMO

Osteoporosis is a very important age-related health problem. The body's composition changes with age, and these changes are a true reflection of aging and of the individuals's nutritional status. Mineral content changes have been reported in vertebral osteoporosis. Interestingly, enough, there have not been reports on concomitant water, fat, and fat-free mass changes associated with this condition. In this report, changes in the latter parameters are compared between patients with osteoporosis and controls. The four components (water, mineral, fat, and fat-free mass) were found significantly reduced (p less than 0.001) in osteoporosis. Serum albumin and protein mass were also reduced (p less than 0.001).


Assuntos
Envelhecimento/fisiologia , Deficiências Nutricionais/complicações , Osteoporose/complicações , Fraturas da Coluna Vertebral/etiologia , Idoso , Feminino , Humanos , Osteoporose/fisiopatologia , Síndrome
15.
J Bone Miner Res ; 13(3): 508-12, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9525352

RESUMO

The hypothesis that a zinc (Zn) deficit may cause osteopenia in athletes is well founded. In rats exposed to strenuous exercise, we evaluated the effect of a zinc supplement on femoral and vertebral bone mass determined by dual-energy X-ray absorptiometry. Four lots of 93-day-old female Wistar rats were studied. A control group of 30 rats were not manipulated (Zn- Ex- group). The experimental group of 40 rats was fed a diet supplemented with an additional 20% of Zn/kg of feed; this group was divided into two groups of 20 rats each, one that did not exercise (Zn+ Ex-) and one that did (Zn+ Ex+). A group of 15 rats exercised but did not receive a zinc supplement (Zn- Ex+ group). Training consisted of treadmill running for 5 out of 7 days over an 11-week period. Initial speed, running time, and treadmill speed were increased gradually. Analysis of variance with the Bonferroni/Dunn test showed that the length, weight, bone mineral content (BMC), and bone mineral density (BMD) of the femur were less in the Zn- Ex+ group than in the others (p < 0.008), and the weight, BMC, and BMD of the fifth lumbar vertebra also were lower in the Zn- Ex+ group than in the others (p < 0.008). These findings confirm the adverse effects of strenuous exercise (treadmill running) on bone tissue in rats and the effectiveness of zinc supplementation in preventing it.


Assuntos
Densidade Óssea , Suplementos Nutricionais , Zinco/administração & dosagem , Absorciometria de Fóton , Animais , Doenças Ósseas Metabólicas/etiologia , Feminino , Membro Posterior/diagnóstico por imagem , Condicionamento Físico Animal/efeitos adversos , Ratos , Ratos Wistar , Coluna Vertebral/diagnóstico por imagem
16.
Endocrinology ; 128(6): 3130-7, 1991 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-1645262

RESUMO

The putative endogenous occupant(s) of the ovarian GnRH receptor may play a role as an intraovarian regulator. In this communication we explore the possibility that in vivo activation of the ovarian GnRH receptor may prove heteroregulatory to the murine granulosa type I insulin-like growth factor (IGF) receptor complement. To eliminate potentially confounding pituitary involvement, exclusive use was made of hypophysectomized rats, thereby allowing study of the direct ovarian effect(s) of GnRH receptor ligands. Treatment of immature hypophysectomized rats, thereby allowing study of the direct ovarian effect(s) of GnRH receptor ligands. Treatment of immature hypophysectomized diethylstilbestrol-primed rats with a GnRH agonist (25 micrograms/rat, twice daily) for 2.5 days resulted in a 2.1-fold decrease in FSH (10 micrograms/rat, twice daily)-inducible (but not basal) specific [125I]IGF-I binding to isolated granulosa cells. Scatchard analysis of the binding data revealed this effect to be due in large measure to decreased binding capacity (46% inhibition) rather than affinity (2.5 x 10(-9) M). Although in vivo treatment with a GnRH antagonist (25 micrograms/rat, twice daily) by itself proved without significant effect on the specific binding of IGF-I to isolated granulosa cells, the concurrent provision of a minimally effective dose of FSH (1 microgram/rat, twice daily) resulted in a 2.8-fold amplification of the FSH effect consequent to enhanced binding capacity (110%), but not affinity (2.2 x 10(-9) M). Significantly, this level of binding proved comparable to that induced by a maximally effective dose of FSH when used by itself. Combined pretreatment with identical doses of both peptide analogs had little or no effect on granulosa cell IGF-I binding, suggesting stereospecificity of action and mutual neutralization by the opposing actions of the GnRH receptor ligands employed. The ability of ligands of the GnRH receptor to alter the granulosa cell type I IGF receptor complement proved functionally significant, as assessed by corresponding alterations in IGF-I hormonal action. Indeed, pretreatment with a GnRH antagonist resulted in a 2.1-fold enhancement of IGF-I (50 ng/ml)-supported proteoglycan biosynthesis, with the agonistic analog producing a diametrically opposite effect. Moreover, the ovarian effects of GnRH receptor ligands were not limited to type I IGF receptor binding; comparable effects were noted on basal and hCG-stimulated accumulation of progesterone by cultured granulosa cells, ovarian weight, ovarian protein content, as well as size and number of antral follicles.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Células da Granulosa/metabolismo , Ovário/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores LHRH/metabolismo , Adulto , Animais , Separação Celular , Feminino , Hormônio Liberador de Hormônio do Crescimento/antagonistas & inibidores , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Ligantes , Tamanho do Órgão , Ovário/anatomia & histologia , Progesterona/metabolismo , Proteínas/metabolismo , Proteoglicanas/biossíntese , Ratos , Ratos Endogâmicos , Receptores de Somatomedina , Somatomedinas/metabolismo
17.
Endocrinology ; 125(1): 572-4, 1989 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2737167

RESUMO

We, and others, have recently reported that the ovary is a site of insulin-like growth factor (IGF)I gene expression. It was the objective of the present studies to assess the relative ovarian abundance of IGF-I transcripts with alternative 5'-untranslated (UT) regions, their cellular localization, and hormonal regulation. To this end, a solution hybridization/RNase protection assay was employed wherein total rat ovarian RNA was hybridized with a 404-base 32P-labelled rat IGF-I riboprobe corresponding to the Class A 5'UT variant. As in liver, three protected bands [322 (Class A), 297 (Class B), and 242 (Class C) bases long] were noted, in keeping with established alternative 5' UT transcripts. The ovarian (as the hepatic) Class C variant proved the most abundant. The ovarian Class B variant was barely detectable. Cellular localization studies revealed these ovarian IGF-I transcripts to be primarily, if not exclusively, of granulosa but not theca-interstitial cell origin. Treatment of immature (21-23 days old) hypophysectomized rats with a diethylstilbestrol (DES)-containing subcutaneous silastic implant for a total of 5 days resulted in a 2-fold increase in the (densitometrically quantified) abundance of ovarian IGF-I transcripts, a diametrically-opposed effect (2.6-fold decrease) being noted at the level of the liver. Whereas treatment of hypophysectomized rats with oGH by itself (150 micrograms, qd, sc x5 days) resulted in a 5-fold increase in hepatic IGF-I gene expression, a limited, albeit distinct inhibitory effect was observed on the steady-state levels of ovarian IGF-I mRNA. In contrast, combined treatment with oGH and DES yielded a 3-fold increase in the abundance of ovarian IGF-I transcripts, there being no net alteration in hepatic IGF-I gene expression. Taken together, these findings reveal ovarian expression of the 3 known 5'-UT IGF-I mRNA variants, document the granulosa cell as the main somatic ovarian cell of IGF-I mRNA generation, and indicate that hepatic and ovarian IGF-I gene expression are differentially regulated in diametrically opposed directions.


Assuntos
Regulação da Expressão Gênica , Variação Genética , Células da Granulosa/fisiologia , Hormônios/fisiologia , Fator de Crescimento Insulin-Like I/genética , RNA Mensageiro/genética , Somatomedinas/genética , Animais , Feminino , Hormônio do Crescimento/farmacologia , Hipofisectomia , Ratos , Transcrição Gênica
18.
Endocrinology ; 128(2): 754-60, 1991 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1703483

RESUMO

Recent observations disclosed the multiplicity of granulosa cell-derived high affinity insulin-like growth factor binding proteins (IGFBPs) and revealed the striking ability of high doses of FSH to suppress their constitutive release under both in vitro and in vivo circumstances. It is the objective of this communication to characterize in greater detail the modulatory effect(s) exerted by FSH on the elaboration of IGFBPs by granulosa cells from immature, estrogen-primed rats. The ability of FSH to regulate the elaboration of granulosa cell-derived IGFBPs proved dose-dependent but biphasic in nature. Specifically, FSH concentrations in the range of 1-3 ng/ml applied for 72 h produced a significant (P less than 0.05) increase in polyethylene glycol-precipitable [125I]IGF-I binding activity corresponding to all IGFBP species detectable by ligand blotting. In contrast, treatment with higher concentrations (greater than or equal to 10 ng/ml) of FSH resulted in progressive dose-dependent inhibition of the constitutive release of IGF-I binding activity (80% inhibition at the 100 ng/ml dose level) and the virtual elimination of all detectable IGFBP species. Time-course studies disclosed a significant (P less than 0.05) initial (apparent at the 24-h time point) stimulatory effect of a high dose of FSH (100 ng/ml) corresponding mostly (but not solely) to the single minor (23K) IGFBP band. In contrast, more prolonged exposure to FSH (greater than or equal to 48 h) produced progressive time-dependent decrements in IGF-I binding activity, an effect associated with a decrease in the relative representation of the major band doublet (28-29K), the 23K species being all but eliminated under these experimental circumstances. Hypophysectomy produced significant (P less than 0.05) inhibition of the subsequent in vitro release of granulosa cell-derived precipitable IGF-I binding activity strongly suggesting that (presumptively stimulatory) pituitary principles other than FSH are likely involved in the regulation of granulosa cell IGFBP release and that the trophic influence of these putative agents appears to outweight the potential disinhibition of FSH hormonal action. Taken together, these findings indicate that the pituitary regulation of granulosa cell-derived IGFBPs is complex and is not FSH-exclusive. Our findings further indicate that the ability of FSH to regulate granulosa cell-derived IGFBPs is dose- and time-dependent but biphasic in nature, an effect characterized by an early low-dose stimulatory effect and a late high-dose inhibitory effect.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Proteínas de Transporte/metabolismo , Hormônio Foliculoestimulante/fisiologia , Células da Granulosa/metabolismo , Ovário/metabolismo , Animais , Proteínas de Transporte/antagonistas & inibidores , Precipitação Química , Relação Dose-Resposta a Droga , Feminino , Hormônio Foliculoestimulante/farmacologia , Hipofisectomia , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Ovário/citologia , Polietilenoglicóis , Ratos , Ratos Endogâmicos , Somatomedinas/metabolismo
19.
Endocrinology ; 129(6): 3427-9, 1991 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1954917

RESUMO

We, and others have recently demonstrated the ovary to be a site of interleukin-1 (IL-1) reception and action. Since IL-1 is an established mediator of inflammation and since ovulation may constitute an inflammatory-like reaction, consideration was given to the possibility that IL-1 may play an intermediary role in the ovulatory process. To begin to evaluate the above hypothesis, we have set out to evaluate rat ovarian IL-1 beta gene expression, to determine its cellular localization, and to study its modulation by key endocrine and autocrine regulatory signals. To this end, use was made of a solution hybridization/RNase protection assay in which rat ovarian total RNA (20 micrograms) was hybridized with a [32P]-labeled 272 base rat IL-1 beta antisense riboprobe. To assess rat ovarian IL-1 beta gene expression under in vivo circumstances, use was made of an established experimental model capable of simulating naturally-occurring follicular maturation, ovulation, and corpus luteum formation. Specifically, a single subcutaneous injection of PMSG (15IU/rat) was followed (48h) later by an ovulatory dose (15IU) of human chorionic gonadotropin (hCG). A faint protected fragment 222 bases long corresponding to the IL-1 beta message was detectable in whole ovarian material prior to gonadotropic stimulation. Treatment with PMSG for 48h resulted in a modest, albeit measurable increase in the densitometrically-quantified steady state levels of the ovarian IL-1 beta message. Most striking, however, were the increments noted in the relative abundance of ovarian IL-1 beta transcripts following a 6h exposure to hCG producing a 4 to 5-fold increase (P less than 0.05) over the untreated state at a time point approximately 6h prior to projected follicular rupture. Subsequent evaluation of ovarian IL-1 beta transcripts, 24 and 48h following hCG administration, revealed significant (P less than 0.05) decrements (relative to the 6h peak) to a level comparable to that seen at the conclusion of 48h of treatment with PMSG. Cellular localization studies revealed the gonadotropin-dependent IL-1 beta mRNA to be theca-interstitial cell-exclusive. To assess rat ovarian IL-1 beta gene expression under in vitro circumstances, we have set out to determine whether IL-1 itself may influence the relative level of its own message. Treatment of whole ovarian dispersates with rhIL-1 beta (10ng/ml) for 4 and 24h resulted in a marked (P less than 0.05) time-dependent increase (up to 12-fold) in the relative abundance of IL-1 beta transcripts when compared with untreated controls.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Gonadotropina Coriônica/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Gonadotropinas Equinas/farmacologia , Interleucina-1/genética , Ovário/metabolismo , Células Tecais/metabolismo , Animais , Células Cultivadas , Feminino , Hibridização de Ácido Nucleico , Ovário/química , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos , Células Tecais/química
20.
Endocrinology ; 130(5): 2865-70, 1992 May.
Artigo em Inglês | MEDLINE | ID: mdl-1315260

RESUMO

Circulating levels of insulin-like growth factor-I (IGF-I) increase during puberty, concurrent with an increase in the levels of GH and the gonadal steroids. The relationship between the changes observed in IGF-I and testosterone (T) levels are not understood. This study was designed to determine whether T has a direct effect on IGF-I serum levels, liver IGF-I gene expression, and epiphyseal growth plate IGF-I and IGF-I receptor gene expression. Hypophysectomized castrated rats were divided into four groups of six animals. The T group was treated with sc T for 5 days. The GH group was treated with a single dose of GH. The GH plus T group was treated with T for 5 days and with GH on the last day of treatment. The control group was injected for 5 days with vehicle alone. Serum IGF-I levels in the T group were not significantly different from those in the control group, and the levels in the GH plus T group were not significantly different from those in the GH group. There was an 11-fold increase in liver IGF-I mRNA abundance in the GH group compared to the control group (P less than 0.01). Liver IGF-I mRNA levels in the T group were not significantly different from those in the control group. When liver IGF-I mRNA levels in the GH plus T group were compared to those in the GH-treated group, no significant differences were found. In the epiphyseal growth plate region, there was a 12-fold increase in IGF-I mRNA levels in the GH group compared to those in the control group, but there was no statistical difference between the control and T groups. IGF-I mRNA levels in the GH plus T group were not significantly different from those in the GH-treated group. IGF-I receptor mRNA abundance was not significantly different in the T group compared to that in the control group. GH decreased IGF-I receptor mRNA by 2.3-fold, but T treatment before GH injection did not change this effect. We conclude that in castrated hypophysectomized rats, T does not stimulate IGF-I gene expression in the liver, nor does it increase IGF-I serum levels. T alone also does not have a stimulatory effect on IGF-I or IGF-I receptor gene expression in the epiphyseal growth plate region.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Hipofisectomia , Fator de Crescimento Insulin-Like I/genética , Fígado/fisiologia , Receptores de Superfície Celular/genética , Testosterona/farmacologia , Animais , Elementos Antissenso (Genética) , Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento/farmacologia , Lâmina de Crescimento/efeitos dos fármacos , Lâmina de Crescimento/fisiologia , Fator de Crescimento Insulin-Like I/metabolismo , Fígado/efeitos dos fármacos , Masculino , Sondas RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos , Receptores de Somatomedina , Valores de Referência
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