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C Morales

Publications and source records attributed to C Morales.

At least 37 records · Page 2Linked to original sources
PubMed2003

Immunolocalization of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in the cyclic human ovary.

Ghrelin is a novel 28-amino acid peptide identified as the endogenous ligand for the GH secretagogue receptor (GHS-R). Besides its hallmark central neuroendocrine effects in the control of GH secretion and food intake, an unexpected reproductive facet of ghrelin has recently emerged because expression of this molecule and its cognate receptor has been demonstrated in rat testis. However, whether this signaling system is present in human gonads remains to be evaluated. In this study, we have assessed the presence and cellular location of ghrelin and its functional receptor, namely the type 1a GHS-R, in the cyclic human ovary by means of immunohistochemistry using specific polyclonal antibodies. Strong ghrelin immunostaining was demonstrated in ovarian hilus interstitial cells. In contrast, ghrelin signal was not detected in ovarian follicles at any developmental stage, nor was it present in newly formed corpora lutea (CL) at very early development. However, specific ghrelin immunoreactivity was clearly observed in young and mature CL, whereas expression of the peptide disappeared in regressing luteal tissue. Concerning the cognate receptor, ovarian expression of GHS-R1a protein showed a wider pattern of tissue distribution, with detectable specific signal in oocytes as well as somatic follicular cells; luteal cells from young, mature, old, and regressing CL; and interstitial hilus cells. Of particular note, follicular GHS-R1a peptide expression paralleled follicle development with stronger immunostaining in granulosa and theca layers of healthy antral follicles. In conclusion, our results are the first to demonstrate that ghrelin and its functional type 1a receptor are expressed in the cyclic human ovary with distinct patterns of cellular location. The presence of both components (ligand and receptor) of the ghrelin signaling system within the human ovary opens up the possibility of a potential regulatory role of this novel molecule in ovarian function under physiological and pathophysiological conditions.

Antibody Specificity↗
PubMed2003

A reservable antiadhesion barrier gel reduces the perineural adhesions in rats after anastomosis.

AIM: The objective of this experimental study was to assess the effectiveness of ADCON T/N in reducing perinerural adhesions when applied around a previously exposed and then anastomosed peripheral nerve in a rat model. METHODS: Sixteen adult 8-month-old male Wistar rats were used for this study. After the ulnar nerve was exposed bilaterally, the nerves were sectioned and anastomosised. ADCON T/N gel was applied around the nerve suture on 1 limb, while the contralateral limb was left untreated (sham operated control). Treatments were administered according to a randomised schedule revealed to the operator only after the perineural adhesions observed during the 2nd operation had been dissected and complete haemostasis achieved. In other group of 4 Wistar rats, the ulnar nerve was sectioned and the 2 ends connected with a 5 mm silastic tube that was placed bilaterally in each rat but on only one side, chosen randomly, was the nerve treated with ADCON TN and placed within the tube on that side. RESULTS: Three months after the 1st operation, the same nerves were exposed again in all animals under general anesthesia before microsurgical external neurolysis. The neurolysis sites in 16 rats were evaluated by blinded surgical dissection immediately before death. Parameters examined included: quality of wound healing, possible adverse effects, presence of residual implant material and perineural adhesions. Perineural adhesions around the ulnar nerve were visually scored using a 4-point qualitative scale (Mean 2.81 without gel, and 1.18 with ADCON T/N. p=0.017). There was no evidence of persistence of residual implant material in the ADCON T/N treated sites. No significant difference between the average density of myelinated axons was observed in either group. All ADCON T/N treated rats (4 animals) showed axonal growth through the tube connecting the 2 ends. CONCLUSION: ADCON-TN decreased fibrosis around the nerve anastomosis sites and did not impede growth between the severed ends of the axons. If reoperation becomes necessary, a reduction of fibrosis would facilitate access to the old site and decrease the risk of nerve lesions.

Animals↗
PubMed2002

Antitumoral effect of irinotecan (CPT-11) on an experimental model of malignant neuroectodermal tumor.

Irinotecan (CPT-11) is a topoisomerase I inhibitor with antitumor activity on a wide variety of neoplasms in several preclinical studies, but it showed poor efficacy in patients with nervous system tumors. We have carried out an experimental study in order to evaluate the effect of CPT-11 on the growth of a subcutaneously implanted malignant neuroectodermal tumor, after administration by different routes. The results showed that CPT-11 administration by intraperitoneal injections (at dose 10 mg/kg, 5 days per week, for 2 weeks, followed by 7-days rest period--one course--to a total of two courses) had no significant antitumor effect. Nevertheless, continuous infusion by intraperitoneal osmotic minipump over 28 days (at an infusion rate of 4.4 microg/h) showed a significant delay in tumor growth in 4 weeks of the implantation. The best antitumor effects were observed after CPT-11 intratumoral administration (at dose of 5 mg/kg, 5 days per week, for 2 weeks, followed by 7-days rest period, to a total of three courses) reaching tumor regression in the treated animals. These results suggest the utility of CPT-11, by means of intralesional administration, on malignant tumors of the nervous system.

Animals↗
PubMed2002

Antitumor effect of TNP-470 is not associated to decrease of angiogenesis in an experimental malignant neuroectodermic tumor.

The hypothesis that tumor growth depends on neovascularization has been broadly used in oncology research. TNP-470 is a fumagillin synthetic analog that is isolated from Aspergillus fumigatus, and experimental studies suggested that it shows antitumor effect mediated by its strong antiangiogenic effect. Because limited experience exists about the antitumoral effect of TNP-470 in cerebral tumors, we have carried out a study in order to evaluate the effect of TNP-470 on tumor growth and the vascular area in an experimental malignant neuroectodermic tumor growing in the subcutaneous space of immunocompetent Wistar rats. Our results showed a significant tumor growth inhibition in animals treated with TNP-470 when compared to those in the control group (intratumoral injections were administered in 30 mg/kg dose, three times a week on alternate days during four consecutive weeks). Since the quantitative analysis of tumor vascular parameters--number of microvessels and total intratumor vascular area--in the experimental groups did not show significant statistical differences, we conclude that TNP-470 has a significant antitumor effect on our neuroectodermic tumor, but this effect is mediated by other antineoplastic mechanisms that are independent of its previously described angiostatic capacity.

Angiogenesis Inhibitors↗
PubMed2002

Growth-inhibiting effects of intralesional docetaxel and paclitaxel on an experimental model of malignant neuroectodermal tumor.

Taxoids are effective agents against a wide variety of tumors, but their effectiveness on neuroectodermal tumors is not well-known. For this reason we have carried out an experimental study on the effect of intratumoral administration of docetaxel (DC) and paclitaxel (PC) on tumor growth, using a murine model of malignant neuroectodermal tumor. The results showed a delay in tumor growth in animals treated with PC compared with controls (dose of 5 mg/kg, three times per week every other day, forming a cycle; three cycles were completed with a break of a week between each cycle). The total dose administered to each animal was 45 mg/kg. When DC was administered, the results showed distinct tumor growth inhibition and tumor regression in 80% of animals (intratumoral administration at a dose of 5 mg/kg, three times per week every other day forming a cycle; three cycles were completed with a break of a week between each cycle). The total dose administered to each animal was 20 mg/kg. These results suggest the utility of taxoids, mainly DC, by intralesional administration, on malignant tumors of the nervous system.

Animals↗
PubMed2002

Prognostic significance of tumor-enhancement and angiogenesis in oligodendroglioma.

OBJECTIVE: To study the prognostic significance of angiogenesis and enhancement on contrast-enhanced computerized tomography (CT) in oligodendrogliomas. MATERIAL AND METHODS: CD34 immunostaining was employed in samples of 26 low-grade oligodendrogliomas from patients treated by extensive resection and radiotherapy to determine the tumor angiogenesis index (TAI), calculated by measuring the immunostained endothelial surface area, in microm(2), per 1000 tumor cells. Preoperative CT scan was evaluated in each case, and the absence or presence of tumor enhancement after contrast administration was recorded. Survival was analyzed and statistically compared for subgroups of patients with lesions in which the TAI was less than or greater than 15, and for subgroups of patients having tumors showing presence or absence of enhancement on contrast-enhanced CT. RESULTS: Survival of patients with tumors showing a TAI of less than 15 was 100% and 71% at 5 and 10 years, respectively, vs a survival of 50% and 0% for patients showing a TAI of more than 15 (P < 0.05). The 14 patients whose tumors showed enhancement in preoperative contrast-enhanced CT had 5- and 10-year survival rates of 57% and 14%, respectively, vs 100% and 83% for the 12 patients whose tumors presented no enhancement (P < 0.05). Moreover, 79% of the tumors showing contrast enhancement had a TAI greater than 15, while 92% of those exhibiting no enhancement had a TAI of less than 15. CONCLUSION: These findings indicate a relationship between enhancement on preoperative CT scan and endothelial surface area in oligodendrogliomas, and suggest that this enhancement and the TAI may be considered angiogenesis-related factors with similar prognostic significance in terms of survival.

Antigens, CD34↗
PubMed2002

Morphological evidence for uncontrolled proteolytic activity during the ovulatory process in indomethacin-treated rats.

The ovulatory process in cyclic rats was studied after prostanoid synthesis was blocked using indomethacin. Animals were injected at 12:00 h in pro-oestrus with 1.0 mg indomethacin or vehicle (olive oil) and killed at 18:30 h in pro-oestrus, at 02:00, 09:00 and 19:00 h in oestrus and at 09:00 h in metoestrus. Additional rats injected with 0.5 or 4.0 mg indomethacin were killed at 09:00 h in oestrus. No differences in either morphology or serum LH concentrations were found between vehicle or indomethacin-treated rats at 18:30 h in pro-oestrus. However, from 02:00 h in oestrus onward, the process of follicle rupture was altered considerably in indomethacin-treated rats, irrespective of the dose. Early vascular changes, observed in control rats at the apex of the follicle, were absent in indomethacin-treated rats. In some follicles, disruption of the theca layers, invasion of the perifollicular tissue by granulosa cells and follicular fluid, and release of the oocyte to the ovarian interstitium were observed at 02:00 h in oestrus. A small number of follicles ruptured at the ovarian surface. Furthermore, invasion of interstitial tissue, rupture of blood vessel walls, production of emboli of granulosa cells and follicular fluid, and inflammatory reactions were observed in oestrus and metoestrus. The results of the present study demonstrate uncontrolled proteolytic activity, and indicate that abnormal follicle rupture (but not inhibition of follicle rupture) is responsible for ovulation failure in indomethacin-treated rats.

Animals↗
PubMed2001

The fate of corpora lutea in the cyclic golden hamster.

Structural luteolysis shows striking interspecies differences. Morphological changes in the corpus luteum (CL) of the cyclic hamster have been studied alongside the potential involvement of known luteolytic hormones. Ovaries from intact Syrian golden hamsters killed at 1100 h on days 1 and 2 and at 1100 and 1700 h on days 3 and 4 of the estrous cycle were dissected for histological study. The day of ovulation, the day of estrus, was arbitrarily designated day 1 of the estrous cycle. Steroidogenic cells in the CL were scarcely luteinized on day 1 and reached full luteinization on day 2. On the morning of day 3, initial regressive changes (accumulation of lipid droplets, invasion by neutrophils, and accumulation of phagocytic cells) were observed. These regressive changes increased progressively and apoptotic cells as well as phagocytic cells containing phagocytized apoptotic cells were abundant on the evening of day 3. On the morning of day 4, apoptotic cells/bodies and phagocytic cells containing phagocytized material were extremely abundant throughout the CL. However, steroidogenic cells with intact nuclei and well-preserved blood vessels were also found. Surviving cells in the CL showed progressive morphological changes. These cells showed morphological features intermediate between luteal and interstitial cells in the evening of day 4 and were virtually indistinguishable from interstitial cells on day 1 of the following cycle. Additional animals were injected at 1100 h on day 2 with: (a) the dopaminergic agonist CB154 (0.4 mg) to block prolactin secretion, (b) the anti-estrogen LY117018 (1.6 mg) or the anti-androgen Flutamide (3 mg) to block estrogen or androgen receptors, respectively, and (c) progesterone (2 mg) to prevent the fall in serum progesterone concentrations. Ovaries from these animals were collected at 1700 h on day 3 and at 1000 h on day 4. The luteolytic process was not affected by any treatment. These data indicate that, in contrast to its close relatives (e.g., the rat), structural luteolysis in the hamster is independent of the apoptotic inducing luteolytic hormones. In addition, differences in the cellular mechanisms responsible for CL elimination were also present. In the hamster, part of the luteal cells do not undergo apoptosis and seemed to progress through another developmental path giving rise to interstitial-like cells.

Animals↗
PubMed2001

Ginsenoside production in different phenotypes of Panax ginseng transformed roots.

Transformed roots were obtained after the inoculation of sterile root discs of Panax ginseng C.A. Meyer with Agrobacterium rhizogenes A4. The established hairy root lines displayed three morphological phenotypes when cultured on hormone-free liquid Schenk and Hildebrandt medium. Most of the cultures showed the characteristic traits of hairy roots (HR-M), while others were either callus-like (C-M) or thin (T-M) without branching. The growth rate of the transformed root lines was always higher than that of untransformed roots, showing that the genetic changes caused by the A. rhizogenes transformation conditioned a higher biomass formation. When considering the different transformed root phenotypes, we can observe that the highest ginsenoside production was achieved by HR-M root lines, closely followed by C-M ones, whereas the lowest yield was reached by T-M root phenotype. The study of the integration of the TL-DNA and TR-DNA fragments of the pRiA4 in the root genome showed that the aux1 gene was always detected in HR-M and C-M root phenotypes which presented the highest biomass and ginsenoside productions. This fact suggests a significant role of aux genes in the morphology of Panax ginseng transformed roots. The ginsenoside pattern of transformed roots varied according to their morphology, although the ginsenoside contents of the Rg group was always higher than that of the Rb group. From our results, we can infer the potential of some root phenotypes of Panax ginseng hairy root cultures for an improved ginsenoside production.

Ginsenosides↗
PubMed2001

Neuropharmacological profile of ethnomedicinal plants of Guatemala.

We carried out the Irwin's test with some different extracts of the aerial parts of Thidax procumbens L., the leaves of Neurolaena lobata (L.) R. Br., bark and leaves of Byrsonima crassifolia (L.) Kunth. and Gliricidia sepium Jacq. Walp., and root and leaves of Petiveria alliacea L. At dosage of 1.25 g dried plant/kg weight aqueous extracts of bark and leaves of Byrsonima crassifolia (L.) Kunth. and Gliricidia sepium Jacq. Walp. demonstrated the most activity: decrease in motor activity, back tonus, reversible parpebral ptosis, catalepsy and strong hypothermia. These extracts of both plants were assayed for effects on CNS and they caused very significant reductions in spontaneous locomotor activity, exploratory behavior and rectal temperature and they increased the sodium pentobarbital-induced sleeping time.

Animals↗
PubMed2001

Prognostic significance of the endothelial surface in low-grade resected oligodendrogliomas.

The importance of angiogenesis as a prognostic factor in brain tumours has recently been reported. In this study, we analysed the long-term prognostic significance of a morphometric score expressing the endothelial area for every 1000 tumour cells, in tumour tissue from 26 patients with a low-grade oligodendroglioma that has been treated surgically and irradiated, and has a MIB-1 labelling index (MIB-1 LI) of less than 1%. In each tumour, a vascular endothelial surface index (VESI) was determined as the CD-34 immunostained endothelial area in micron 2 per 1000 tumour cells. Patients with a VESI of less than 15 (n = 12) showed a survival at 5 and 10 years of 100 and 71%, respectively, versus a survival of 50 and 0% for patients presenting a VESI greater than 15 (n = 14); p < 0.05). Our present findings suggest the usefulness of VESI as a long-term prognostic pathological factor in low-grade oligodendroglioma.

Adolescent↗
PubMed2001

Luteolytic effect of prolactin is dependent on the degree of differentiation of luteal cells in the rat.

We studied the morphological and quantitative changes in cyclic corpora lutea (CCL) and in CL of pregnancy (CLP) during structural luteolysis. Elimination of CCL takes several cycles, and cell death occurs as successive apoptotic bursts, from 2100 h in proestrus to 1300 h in estrus. Each apoptotic burst determined a 60% decrease in the CL volume and an 80% decrease in the number of steroidogenic cells (SC). All these changes were inhibited by blocking the preovulatory prolactin (PRL) surge with bromocryptine (CB154). Neither apoptotic cells nor changes in the number of SC were found in regressing CLP from Day 21 of pregnancy to Day 2 postpartum, although there was a 50% decrease in the CLP volume and a 30% decrease in the mean cross-sectional area of SC. Treatment with CB154 on the day of parturition did not modify these regressive changes. On Day 5 postpartum, the volume of the CLP and the number of SC were equivalent in lactating rats (showing high PRL concentrations induced by pup suckling) and nonlactating noncycling rats (in which cyclicity and, therefore PRL surges, were blocked by treatment with LHRH antagonist). However, on Day 10 postpartum, the CLP volume and the number of SC were significantly decreased in lactating rats, and apoptotic cells were frequent. In postpartum cycling rats, the CLP did not show apoptotic cells on the day of the second postpartum estrus (on Day 5 postpartum), whereas on the day of the third postpartum estrus (on Day 9 postpartum), apoptotic cells were abundant. These results indicate that PRL does not induce apoptosis in the CLP before Day 5 postpartum and strongly suggest that the proapoptotic effect of PRL is dependent on the degree of differentiation of luteal cells.

Animals↗
PubMed2001

Interactions and nuclear import of the N and P proteins of sonchus yellow net virus, a plant nucleorhabdovirus.

We have characterized the interaction and nuclear localization of the nucleocapsid (N) protein and phosphoprotein (P) of sonchus yellow net nucleorhabdovirus. Expression studies with plant and yeast cells revealed that both N and P are capable of independent nuclear import. Site-specific mutagenesis and deletion analyses demonstrated that N contains a carboxy-terminal bipartite nuclear localization signal (NLS) located between amino acids 465 and 481 and that P contains a karyophillic region between amino acids 40 and 124. The N NLS was fully capable of functioning outside of the context of the N protein and was able to direct the nuclear import of a synthetic protein fusion consisting of green fluorescent protein fused to glutathione S-transferase (GST). Expression and mapping studies suggested that the karyophillic domain in P is located within the N-binding domain. Coexpression of N and P drastically affected their localization patterns relative to those of individually expressed proteins and resulted in a shift of both proteins to a subnuclear region. Yeast two-hybrid and GST pulldown experiments verified the N-P and P-P interactions, and deletion analyses have identified the N and P interacting domains. N NLS mutants were not transported to the nucleus by import-competent P, presumably because N binding masks the P NLS. Taken together, our results support a model for independent entry of N and P into the nucleus followed by associations that mediate subnuclear localization.

Cell Nucleus↗
PubMed2001

Focal arterial injuries of the proximal extremities: helical CT arteriography as the initial method of diagnosis.

PURPOSE: To present our experience with helical computed tomographic (CT) arteriography as the initial diagnostic examination in patients suspected to have focal arterial injuries of the proximal extremities. MATERIALS AND METHODS: During 19 months, 142 arterial segments in the proximal portions of the extremities of 139 patients with trauma were evaluated with helical CT arteriography. CT arteriograms were interpreted on site by the radiologist in charge of emergency procedures and retrospectively with consensus interpretation between two radiologists. CT study quality and the presence of arterial injuries were noted. CT arteriographic findings were compared with those of surgery, conventional arteriography, and/or clinical follow-up. RESULTS: Five (3.6%) patients had nondiagnostic studies and underwent conventional arteriography. In the remaining 137 arterial segments in 134 patients, helical CT arteriography demonstrated arterial injuries in 61 segments and normal arteries in 76 segments. These segments were treated initially with surgery (55 segments) or endovascular intervention (four segments) or were observed (78 segments); 77 of the 78 observed segments remained stable at 3-18 months (mean follow-up, 5.2 months). There were no differences between the on-site and consensus interpretations (kappa = 1.0). The sensitivity of CT arteriography was 95.1%, and the specificity was 98.7%. CONCLUSION: Helical CT arteriography can be performed as the initial diagnostic method in most patients suspected to have focal arterial injuries of the proximal portions of the extremities.

Adolescent↗
PubMed2001

Penetrating stab wounds to the abdomen: use of serial US and contrast-enhanced CT in stable patients.

PURPOSE: To evaluate the usefulness of computed tomography (CT) and ultrasonography (US) for the initial assessment of penetrating abdominal stab wounds in patients who presented to the emergency department without indication for immediate laparotomy. MATERIALS AND METHODS: During 36 months, 32 patients with a penetrating stab wound to the abdomen were examined with serial US (at admission and 12 hours later) and helical CT, with contrast material administered orally, intravenously, and rectally. Presence of hemoperitoneum and integrity of solid and hollow viscera were evaluated with both methods. Sonograms were interpreted by the radiologist who performed the examination, and CT images were independently evaluated by two radiologists. Findings of both techniques were compared with clinical outcome and/or surgical findings. RESULTS: One (3.1%) of 32 patients required surgery: Surgical findings were massive hemoperitoneum and an extensive hepatic laceration. Both US and CT depicted these abnormalities. Thirty-one (96.9%) patients were treated conservatively, without surgery, and remained asymptomatic during 28 days of clinical follow-up after discharge from the hospital. US and/or CT showed intraperitoneal abnormalities in 21 of these patients. In 11 patients, both methods showed no evidence of visceral injury or hemoperitoneum, and none of these patients required surgery. CONCLUSION: Serial US and CT help guide treatment for stable patients with penetrating stab injuries to the abdomen.

Abdominal Injuries↗
PubMed2001

Cyclic changes in the responsiveness of regressing corpora lutea to the luteolytic effects of prolactin in rats.

In cyclic rats, apoptosis of luteal cells during structural luteolysis occurs cyclically at the transition from pro-oestrus to oestrus in response to the preovulatory prolactin surge. This finding indicates that cyclic changes in apoptosis during luteolysis are dependent on prolactin surge cyclicity. In this study, the effects of prolactin on structural luteolysis were studied under different experimental conditions in relation to the phase of the oestrous cycle. In rats treated with prolactin at metoestrus and dioestrus, apoptosis did not occur in regressing corpora lutea, whereas in rats treated with prolactin on the morning of pro-oestrus, a 12.3-fold and 3.4-fold increase were observed in the number of apoptotic cells in regressing corpora lutea of the current and previous oestrous cycles, respectively. However, when the preovulatory prolactin surge and hence the subsequent apoptotic burst were blocked, prolactin treatment at the dioestrus phase induced a 13-fold increase in the number of apoptotic cells and significant changes in the volume of the corpus luteum (38% decrease) and the number of steroidogenic cells per corpus luteum (70% decrease). The results of this study indicate that the responsiveness of the regressing corpus luteum to the pro-apoptotic effects of prolactin are dependent on the phase of the oestrous cycle and on the presence or absence of an apoptotic burst in response to the preovulatory prolactin surge on the evening of pro-oestrus. Steroidogenic cells surviving to the apoptotic burst during the transition from pro-oestrus to oestrus became refractory to the lytic effect of prolactin. Furthermore, these cells also responded to the luteotrophic effects of prolactin, reaching full morphological luteinization, as indicated by the rescue of regressing cyclic corpora lutea during pregnancy.

Animals↗