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Biomedical subjects

C Morales

Publications and source records attributed to C Morales.

At least 91 records · Page 5Linked to original sources
PubMed1998

Dexamethasone rapidly regulates TRH mRNA levels in hypothalamic cell cultures: interaction with the cAMP pathway.

The biosynthesis of thyrotropin-releasing hormone (TRH) in the hypothalamic paraventricular nucleus (PVN) is subject to neural and hormonal regulations. To identify some of the potential effectors of this modulation, we incubated hypothalamic dispersed cells with dexamethasone for short periods of time (1-3 h) and studied the interaction of this hormone with protein kinase C (PKC) and PKA signaling pathways. TRH mRNA relative changes were determined by the RT-PCR technique. One hour incubation with 10(-10)-10(-4) M dexamethasone produced a concentration-dependent biphasic effect: an inhibition was observed on TRH mRNA levels at 10(-10) M, an increase above control at 10(-8)-10(-6) M and a reduction at higher concentrations (10(-5)- 10(-4) M). The stimulatory effect of 10(-8) M dexamethasone on TRH mRNA was essentially independent of new protein synthesis, as evidenced by cycloheximide pretreatment. Changes in TRH mRNA levels were reflected by enhanced TRH cell content. Incubation with a cAMP analogue (8-bromo-cAMP, 8Br-cAMP) or with a PKC activator (12-O-tetradecanoylphorbol-13-acetate, TPA) increased TRH mRNA levels after 1 and 2 h, respectively. An increase in TRH mRNA expression was observed by in situ hybridization of dexamethasone or 8Br-cAMP-treated cells. The interaction of dexamethasone, PKA and PKC signaling pathways was studied by combined treatment. The stimulatory effect of 10(-7) M TPA on TRH mRNA levels was additive to that of dexamethasone; in contrast, coincubation with 10(-3) M 8-Br-cAMP and dexamethasone diminished the stimulatory effect of both drugs. An inhibition was observed when the cAMP analogue was coincubated with TPA or TPA and dexamethasone. These results demonstrate that dexamethasone can rapidly regulate TRH biosynthesis and suggest a cross talk between cAMP, glucocorticoid receptors and PKC transducing pathways.

Animals↗
PubMed1998

Changes of the inducible heat shock protein 70 mRNA level in rat retina after ischemia and reperfusion.

The heat shock protein 70 (HSP-70) mRNA level was evaluated in Long Evans rat retinas after ischemia and after reperfusion following ischemia. Retinal ischemia was induced by ligation of the optic nerve and vessels. Rats were sacrificed after 90 min of ischemia or 120 min of reperfusion following ischemia. Retinas were dissected. Total mRNA was extracted and inducible HSP-70 (iHSP-70) gene expression was analyzed by quantification of transcripts using an RT-PCR assay. Results were expressed in arbitrary units as a ratio of the optical density of iHSP-70/beta-actin electrophoretic bands. iHSP-70 gene expression was 0.220 +/- 0.027 (n = 5), 0.502 +/- 0.045 (n = 5) and 0.468 +/- 0.032 (n = 5) for the sham-operated, ischemia only and ischemia and reperfusion groups, respectively. There was a statistically significant difference between the control and ischemia groups, and between the control and ischemia and reperfusion groups (p < 0.001), suggesting a rapid HSP-70 mRNA expression of the retina due to an ischemic injury.

Animals↗
PubMed1998

[Effect of enalaprilat on postischemic systolic and diastolic dysfunction (stunned myocardium) on the isolated rabbit heart].

The aim was to determine: 1) whether Enalaprilat (0.08 mg/kg/min) administration: a) before ischemia or b) at the beginning of reperfusion improved the postischemic systolic and diastolic dysfunction ("stunned myocardium") and attenuated the "hyperfunction" phase at the beginning of reperfusion; and 2) whether creatine kinase (CPK), and lactate dehydrogenase (LDH) activities, and lactate release are involved in the protective effects of Enalaprilat. An isolated isovolumic rabbit heart preparation was used as experimental model and subjected to 15 minutes of ischemia followed by 30 minutes of reperfusion, without (group 1), and with Enalaprilat before the ischemia (group 2) and at the beginning of reperfusion (group 3). Left ventricular developed pressure, and end diastolic pressure (diastolic stiffness) were measured and the time constant of isovolumic relaxation (t, Tau) and the ratio between +dP/dtmax and -dP/dtmax were calculated. For the determinations of lactate release and CPK and LDH activities in the perfusate, samples were taken from the coronary effluent for spectrophotometrical measurements. In comparison to the stunned group (group 1) both Enalaprilat preischemia (group 2) and postischemia (group 3) exerted a significant protective effect on the postischemic recovery of contractile state and diastolic stiffness, and attenuated the "hypercontractile" phase in both groups. However Enalaprilat failed to improve myocardial relaxation. Lactate release was also attenuated, but the enzyme activities were not modified.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Comparison of the effects of ACE inhibition with those of angiotensin II receptor antagonism on systolic and diastolic myocardial stunning in isolated rabbit heart.

The aim was to determine whether enalaprilat (0.08 mg/kg/min) or losartan (0.01 mg/kg/min) administration before ischemia can improve postischemic systolic and diastolic dysfunction ('stunned myocardium') and attenuate the 'hyperfunction' phase at the beginning of reperfusion. An isolated isovolumic rabbit heart preparation was subjected to 15 min of ischemia followed by 30 min of reperfusion without (group 1) or with pretreatment with enalaprilat (group 2) or losartan (group 3). Left ventricular developed pressure and end-diastolic pressure (diastolic stiffness) were measured and the time constant of isovolumic relaxation (T, Tau) and the ratio between +dP/dt and -dP/dt were calculated. In comparison to the stunned group (group 1) both enalaprilat (group 2) and losartan (group 3) exerted a significant protective effect on postischemic recovery of contractile state and diastolic stiffness. Only enalaprilat attenuated the 'hypercontractile' phase. However, both enalaprilat and losartan failed to improve myocardial relaxation. In summary, these data strongly suggest a direct deleterious action of the local renin-angiotensin system on ischemic myocardium and diminution of myocardial stunning with its successful blockade. Although, we can not exclude the possibility that bradykinin has some cardioprotective effect, these data suggest that angiotensin exacerbates myocardial injury.

Angiotensin II↗
PubMed1997

Expression of the proprotein convertases PC1 and PC2 mRNAs in thyrotropin releasing hormone neurons of the rat paraventricular nucleus of hypothalamus.

PC1 and PC2 are subtilisin-like processing enzymes capable of cleaving thyrotropin releasing hormone (TRH) precursor (pro-TRH) at paired basic residues in vitro. In the paraventricular nucleus of the hypothalamus (PVN), pro-TRH is synthesized to control adenohypophysial thyrotropin and prolactin release. Biochemical and immunological approaches have shown that in the hypothalamus, pro-TRH is extensively cleaved at pairs of basic amino acids. We quantified, by two different approaches, in situ hybridization (ISH) on consecutive cryostat sections or double label ISH, the proportion of PVN TRH neurons containing either PC1 or PC2 mRNAs. Both techniques gave similar results: PC2 mRNA was present in 60-70% of TRH neurons, and PC1 mRNA in 37-46%. Values were similar in the anterior and medial parts of the parvocellular PVN. TRH neurons containing either PC1 or PC2 mRNA were found throughout the areas containing TRH cells without any evidence of anatomical segregation. These results suggest a biochemical heterogeneity in PVN TRH biosynthetic machinery.

Animals↗
PubMed1997

Proliferative activity of preovulatory follicles and newly formed corpora lutea in cycling rats from late prooestrus to early oestrus.

Ovaries from adult cycling rats were studied from 1600 h on the day of prooestrus to 0700 h on the day of oestrus in order to relate the cyclic hormonal changes to the proliferative activity of preovulatory and postovulatory (i.e. newly-formed corpora lutea) follicles. Proliferative activity was studied by the immunohistochemical demonstration of DNA-incorporated 5-bromodeoxyuridine (BrdU). The proliferative activity of granulosa cells (GC) in large preovulatory follicles showed a centripetal pattern and decreased during prooestrus, reaching a minimum at 2100 h. However, a proliferative wave was found in the GC of preovulatory follicles at 0200 h on the day of oestrus and in those of newly-formed corpora lutea at 0700 h on the day of oestrus. These results suggest that the granulosa cells of preovulatory follicles show maturational changes that followed a different pattern, depending on their location within the follicle, and that the proliferative wave found from 0200 to 0700 h on oestrus is important for the establishment of the number of steroidogenic cells in the cyclic corpus luteum.

Animals↗
PubMed1997

Role of prolactin in the regulation of macrophages and in the proliferative activity of vascular cells in newly formed and regressing rat corpora lutea.

The proliferative activity of vascular cells and the number of macrophages were studied in corpora lutea of cycling and pregnant rats after prolactin (PRL) administration or depletion with the dopaminergic agonist CB154. Pregnant rats showed a higher proliferative activity of the vascular cells in newly formed corpora lutea than did cycling rats in metestrus. When cycling rats were treated with PRL, the proliferative activity was equivalent to that of pregnant rats. Treatment of pregnant rats with CB154 decreased the proliferative activity of vascular cells to the level in cycling rats. Otherwise, the proliferative activity was not modified in cycling rats after CB154 treatment. This indicates that the increase in the proliferative activity of vascular cells in the corpus luteum of pregnancy was due to the twice-daily PRL surges induced by mating. Treatment of cycling rats with CB154 decreased the number of macrophages in both newly formed and regressing corpora lutea, whereas PRL treatment increased the number of macrophages in regressing corpora lutea. In pregnant rats, treatment with CB154 decreased the number of macrophages in both newly formed and regressing corpora lutea. These results suggest that both the preovulatory and the twice-daily PRL surges regulate the macrophage population in newly formed and regressing corpora lutea.

Animals↗
PubMed1997

Reverse iontophoresis: monitoring prostaglandin E2 associated with cutaneous inflammation in vivo.

In response to topical application of irritants, increased concentrations of prostaglandin E2 (PGE2) are found in human skin exudate and in cultured dermal fibroblasts. In this study, PGE2 generated in response to transdermal delivery of irritant drug compounds was monitored in hairless guinea pig (HGP) by a non-invasive method, reverse iontophoresis. Reverse iontophoresis is the movement of molecules from the skin under the influence of an applied electric field. Irritant drug compounds were applied with iontophoresis (electrotransport), and reverse iontophoresis of PGE2 from skin was monitored by radioimmunoassay (RIA) after extraction from the delivery system. Chlorpromazine was used as a model drug irritant. When chlorpromazine and saline were applied over a range of current densities from 0 to 200 microA/cm2, visual scores of erythema and edema yielded a correlation with measured skin efflux of PGE2 (r = 0.86). Delivery of chlorpromazine resulted in greater efflux of PGE2 than delivery of non-irritant saline controls under the same delivery conditions. Five drug compounds, chloroquine, promazine, chlorpromazine, tetracaine, metoclopramide, and saline were applied to hairless guinea pig skin. The 6 agents were similarly rank ordered by visual erythema/edema scores and by PGE2 efflux, indicating that the quantity of PGE2 effluxed reflects the intensity of skin irritation. In contrast, vasoconstriction or vasodilation produced by the local delivery of vasoactive agents did not correlate with PGE2 skin efflux, indicating that this measurement is specific for an inflammatory response. In summary, PGE2 generated in response to transdermally applied drug irritants can be monitored non-invasively in vivo by reverse iontophoresis.

Amebicides↗
PubMed1997

Body proportionality in growth-retarded VLBW infants.

The aim of this study was to investigate how intrauterine growth retardation affects body proportions in VLBW infants. The cohort consisted of 135 surviving and 80 deceased preterm infants weighing less than 1250 grams at birth. Gestational age varied between 24 and 36 weeks (mean age 29.7 and 27.5 weeks, respectively). Birth weight was more than 2 SD below the mean birth standard values in 32% of the surviving, and in 27% of the deceased infants. Reduction of weight, length and head circumference at birth was analysed using Z scores based on Swedish birth standards. Z scores of weight, length and head circumference were highly correlated in the surviving and the deceased infants (r = 0.78 to 0.94 and 0.65 to 0.97, respectively). Length was significantly more affected by growth retardation than weight. Weight and head circumference were proportionately reduced. Intrauterine growth retardation influences body proportions in VLBW infants differently than in larger preterm and term infants.

Body Constitution↗
PubMed1997

Role of the testis in the response of the pituitary-testicular axis to nitric oxide-related agents.

Nitric oxide (NO) is generated from the guanidine group of L-arginine by NO synthases (NOS) in a wide variety of tissues, including endocrine organs. In order to discriminate between central and local effects of NO-related agents on the pituitary-testicular axis, adult rats were injected intraperitoneally with 1 g/kg body weight (bw) L-arginine methyl ester (L-AME, an exogenous substrate of NOS), 0.5 mg/kg bw sodium nitroprusside (SNP, an NO donor) or vehicle (0.9% NaCl) or intratesticularly with 2 mg/testis L-AME, 2 micrograms/testis SNP or 25 microliters vehicle, and killed at 60 or 120 min after treatment. Both intraperitoneal and intratesticular administration of L-AME had the same effects: a decrease in the serum concentrations of LH and testosterone and in those of testosterone in the testicular interstitial fluid. However, treatment with SNP was more effective when given intratesticularly, inducing a decrease in serum and interstitial fluid testosterone concentrations, without significant changes in LH concentrations. Furthermore, when rats were injected intraperitoneally with 4 mg L-AME (the same dose as that given intratesticularly), serum LH concentrations were not changed. In addition, L-AME administration was not effective in modifying serum LH concentrations in castrated rats. To test the possible role of Leydig cells, the effects of systemic administration of L-AME were studied in rats depleted of Leydig cells by treatment with ethylene dimethane sulphonate. In these animals L-AME significantly decreased serum LH concentrations. To study the role of macrophages in this system, rats depleted of testicular macrophages by the liposome-suicide approach were injected intraperitoneally (1 g/kg bw) or intratesticularly (2 mg/testis) with L-AME or vehicle, 10 days after macrophage depletion, and killed at 120 min after treatment. The effects of L-AME on serum LH concentrations were blocked when the drug was administered intratesticularly.

Animals↗
PubMed1997

Follicular growth pattern in cyclic rats from late pro-oestrus to early oestrus.

Adult cyclic rats were studied from 16:00 h on pro-oestrus to 07:00 h on oestrus to relate the cyclic hormonal changes to the proliferative activity and growth pattern of growing follicles. The proliferative activity was studied by 5-bromodeoxyuridine (BrdU) labelling and by the presence of mitoses. Small growing follicles (less than 275 microns in diameter) were divided into five classes: multilaminar classes a (Ma, up to 75 microns in diameter), b (Mb, 76-150 microns), c (Mc, 151-200 microns) and d (Md, 201-274 microns) and follicles measuring > or = 275 microns in diameter were considered as > or = class 1, following previous classifications. I.H concentrations were maximal at 18:30 h on pro-oestrus, and this was coincident with an increase in FSH, prolactin and progesterone concentrations, whereas oestradiol and testosterone concentrations were decreased. From 02:00 h on oestrus the concentrations of all hormones, except those of FSH, were decreased. The number of Ma, Mb and Mc follicles did not change during pro-oestrus-oestrus, whereas an increase in the number of follicles > or = class 1 was found at 07:00 h on oestrus. This appears to be a consequence of the increased proliferative activity of Md follicles, evidenced by the increase in the BrdU labelling and mitotic index of this follicle class, found from 02:00 to 07:00 h on oestrus, together with a decrease in the percentage of early atretic follicles > or = class 1 at 07:00 h on oestrus. This study provides an improved classification of small growing follicles into discrete classes and delineates a size class of follicles (Md follicles) that is responsive to the cyclic hormonal changes on early oestrus.

Animals↗
PubMed1997

Evidence for steroidogenic luteal cell hypertrophy and hyperplasia during pregnancy in the rat.

The proliferative activity of the rat corpus luteum was studied on days 2, 3, 6, 9, 12, 15, 17, 19 and 21 of pregnancy. Proliferating cells were detected by the immunohistochemical demonstration of DNA-incorporated 5-bromodeoxyuridine (BrdU) and by the presence of mitoses. Steroidogenic luteal cells showed two proliferative waves on days 12-15 and on day 21, when relatively abundant BrdU-labeled and mitotic cells were observed. These cells were clearly distinguishable from non-steroidogenic cells by their round nuclei and large polygonal cytoplasm. The proliferative activity on days 12-15 was coincident with an increase in the size of the cells and in progesterone concentrations. On the other hand, the proliferative activity of non-steroidogenic luteal cells (especially endothelial cells of the blood and lymphatic vessels) followed a different pattern. These cells intensely proliferated on days 2-3 of pregnancy and this proliferative activity was significantly higher than that observed in non-pregnant rats on metestrus and diestrus. A new proliferative wave was observed on days 12-15, in association with the increase in the proliferative activity of steroidogenic cells. The presence of both BrdU-labeled and mitotic steroidogenic luteal cells provides evidence that these cells do proliferate and that both hypertrophy and hyperplasia are involved in the increase in the parenchyma of the corpus luteum during pregnancy. Also, the results suggest that different mechanisms are involved in the regulation of the proliferative activity in the corpus luteum at different times during pregnancy.

Animals↗
PubMed1997

Release of reactive oxygen species by phagocytic cells in response to live parasites in mice infected with Trypanosoma cruzi.

The release of reactive oxygen intermediates (ROI), mediators of inflammatory reactions, was evaluated in murine Trypanosoma cruzi infection. In acutely infected BALB/c mice, spleen cells were stimulated, either with epimastigote or trypomastigote forms of the parasite, and the effect was enhanced by serum from infected mice. Only opsonized parasites triggered the release of ROI by normal mouse cells and this response was several times lower than in infected mice. This seems to indicate that cells from acutely infected mice reacted to T. cruzi and that neither parasites nor serum factors blocked the release of ROI. During the acute stage of the infection, both the parasitemia and the release of ROI by spleen cells were higher in BALB/c than in C3H mice (ROI generated in response to a phagocytic stimulation was 12 and 3 times the normal levels, respectively). In addition, in BALB/c mice infected with different numbers of parasites, the production of ROI was related to parasitemia. On the other hand, during the chronic stage of the infection, the inflammatory reaction in myocardium was greater in C3H than in BALB/c mice, and the increase in ROI production was 30% and 100% above the normal levels in BALB/c and C3H mice, respectively. This suggests that the increased ROI production paralleled the parasite burden in the acute phase, and could be related to inflammatory processes after the control of the parasitemia.

Acute Disease↗