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C Molina

Publications and source records attributed to C Molina.

At least 19 recordsLinked to original sources
PubMed2003

Expression of inducible cAMP early repressor is coupled to the cAMP-protein kinase A signaling pathway in osteoblasts.

We previously showed that parathyroid hormone (PTH) induces inducible cAMP early repressor (ICER) in osteoblastic cells and mouse calvariae. PTH signaling in osteoblastic cells is transduced by PTH receptor 1, which is coupled to cAMP-protein kinase A (PKA), protein kinase C (PKC), and calcium signaling pathways. In the present study, we examined the role of these pathways in mediating PTH-induced ICER mRNA and protein expression in osteoblastic MC3T3-E1 cells. Using RT-PCR, we found that PTH(1-34), forskolin (FSK), and 8-bromo-cAMP (8Br-cAMP) induced ICER expression, while phorbol myristate acetate (PMA), ionomycin, and PTH(3-34) did not. Similar results were found for the induction of ICER protein. PKA inhibition by H89 markedly reduced PTH- and FSK-induced ICER expression, while PKC depletion by PMA had little effect. We also tested ICER induction by other osteotropic signaling agonists. Other cAMP-PKA pathway activators, such as PTH-related protein (PTHrP), induced ICER expression, while agents that signal through other pathways did not. PTHrP maximally induced ICER mRNA at 2-4 h, which then returned to baseline by 10 h. Finally, PTH, FSK, and PTHrP induced ICER in cultured mouse calvariae and osteoblastic ROS 17/2.8, UMR-106, and Pyla cells. We conclude that ICER expression in osteoblasts requires activation of the cAMP-PKA signaling pathway.

3T3 Cells↗
PubMed2003

Metabolism of a novel nucleoside analogue, OGT 719, in the isolated perfused rat liver model, in rats, in tumour models and in patients.

1. The metabolic pathway(s) of OGT 719, a novel nucleoside analogue in which galactose is covalently attached to the N1 of 5-fluorouracil (FU), have been investigated with (19)F-NMR spectroscopy in (1) the isolated perfused rat liver (IPRL) model, (2) normal rats, (3) rats bearing the HSN LV10 sarcoma, (4) nude mice xenografted with the human hepatoma HepG2 and (5) urine from patients. 2. The administration of OGT 719 results in the formation of small amounts of FU. IPRL experiments with OGT 719 in combination with asialofetuin, a natural asialoglycoprotein receptor (ASGP-r), suggest competitive binding of OGT 719 to the ASGP-r. 3. The data obtained in non-tumour rats also demonstrated an extremely low metabolization of OGT 719 into FU and alpha-fluoro-beta-alanine, the well-known major metabolite of FU. 4. A comparison of tumour extracts from rats bearing the HSN LV10 sarcoma treated with FU or OGT 719 showed the incorporation of FU into RNA in rats treated with FU but not in rats treated with OGT 719; nevertheless, the incorporation of FU into RNA was observed in the liver from rats treated with OGT 719. 5. In a human hepatoma xenografted to nude mice, both the OGT 719 and FU contents of the tumour were markedly higher than in the corresponding liver, suggesting a tumour-specific trapping of OGT 719 in hepatoma. 6. The metabolism of OGT 719 was also extremely low in patients. 7. In conclusion, the present study shows the value of (19)F-NMR for demonstrating for the first time that OGT 719 is a prodrug of FU although very poorly metabolized.

Animals↗
PubMed2001

Automatic classification of HITS into artifacts or solid or gaseous emboli by a wavelet representation combined with dual-gate TCD.

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) can detect high-intensity transient signals (HITS) in the cerebral circulation. HITS may correspond to artifacts or solid or gaseous emboli. The aim of this study was to develop an offline automated Doppler system allowing the classification of HITS. METHODS: We studied 600 HITS in vivo, including 200 artifacts from normal subjects, 200 solid emboli from patients with symptomatic internal carotid artery stenosis, and 200 gaseous emboli in stroke patients with patent foramen ovale. The study was 2-fold, each part involving 300 HITS (100 of each type). The first 300 HITS (learning set) were used to construct an automated classification algorithm. The remaining 300 HITS (validation set) were used to check the validity of this algorithm. To classify HITS, we combined dual-gate TCD with a wavelet representation and compared it with the current "gold standard," the human experts. RESULTS: A combination of the peak frequency of HITS and the time delay makes it possible to separate artifacts from emboli. On the validation set, we achieved a sensitivity of 97%, a specificity of 98%, a positive predictive value (PPV) of 99%, and a negative predictive value (NPV) of 94%. To distinguish between solid and gaseous emboli, where positive refers now to the solid emboli, we used the peak frequency, the relative power, and the envelope symmetry of HITS. On the validation set, we achieved a sensitivity of 89%, a specificity of 86%, a conditional PPV of 89%, and a conditional NPV of 89%. CONCLUSIONS: An automated wavelet representation combined with dual-gate TCD can reliably reject artifacts from emboli. From a clinical standpoint, however, this approach has only a fair accuracy in differentiating between solid and gaseous emboli.

Adult↗
PubMed2001

Consanguinity and congenital heart disease in Saudi Arabia.

First-cousin marriage may be a significant risk factor for specific types of congenital heart disease in a consanguineous population. Inbreeding studies suggest an autosomal recessive component in the cause of some congenital heart defects. We studied a large sample of patients with structural congenital heart defects (CHD) identified through the Congenital Heart Disease Registry at King Faisal Specialist Hospital in Riyadh, Saudi Arabia. After exclusions of chromosome abnormalities and non-participation, data were collected on 891 consecutive patients who were registered between January and August, 1998. Data on first-cousin consanguinity and type of CHD diagnosis were collected. A z test of proportions was used to determine the association between consanguinity and subtypes of CHD. Data indicate that the proportion of first cousins in the CHD sample is higher than the proportion in the general population, supporting a hypothesis of autosomal recessive gene involvement in congenital heart disease. When subgroups of CHD were analyzed, first-cousin consanguinity was significantly associated with ventricular septal defect (VSD), atrial septal defect (ASD), atrioventricular septal defect (AVSD), pulmonary stenosis (PS), and pulmonary atresia (PA). There was no relationship between consanguinity and tetralogy of Fallot (TOF), tricuspid atresia (TA), aortic stenosis (AS), co-arctation of the aorta (CoA), and patent ductus arteriosus (PDA). Thus, in a population with a high degree of inbreeding, consanguinity may exacerbate underlying genetic risk factors, particularly in the offspring of first cousins. There may be a recessive component in the causation of some cardiac defects.

Adolescent↗
PubMed2001

Cloning of human preprotachykinin-I promoter and the role of cyclic adenosine 5'-monophosphate response elements in its expression by IL-1 and stem cell factor.

Preprotachykinin-I gene (PPT-I) encodes several peptides with organ-specific functions that link the neuroendocrine-immune-hemopoietic axis. We cloned upstream of the initiation site of human PPT-I promoter and identified consensus sequences for two cAMP response elements (CRE). PPT-I is induced by cytokines including those that signal through the cAMP pathway. Therefore, we studied the role of the two CRE in IL-1alpha and stem cell factor (SCF) stimulation of bone marrow stroma because both cytokines induce endogenous PPT-I in these cells and activate the cAMP pathway. Furthermore, bone marrow stroma expresses the transcription factors regulated by the cAMP pathways such as the repressor (ICERIIgamma) and activator (CREMtau). Mutagenesis of the two CRE and/or cotransfection with vectors that express ICERIIgamma or CREMtau indicated that the two CRE have major roles in PPT-I expression. The two CRE are also required for optimal promoter activity by SCF and IL-1alpha. A particular cytokine could concomitantly induce PPT-I and the high affinity G protein-coupled receptor for PPT-I peptides, NK-1R. We showed that SCF, a representative cytokine, induced PPT-I and NK-1R leading to autocrine and/or paracrine cell activation. Because NK-1R activates cAMP through the G protein, the results suggest that the presence of CRE sequences within PPT-I promoter could be important in the regulation of PPT-I expression by cytokines, irrespective of their ability to signal through cAMP. As PPT-I is implicated in hemopoietic regulation, immune responses, breast cancer, and other neural functions, these studies add to the basic biology of these processes and could provide targets for drug development.

5' Untranslated Regions↗
PubMed2001

[Acute phase response after stroke: differences between ischemic stroke and intracerebral hemorrhage].

BACKGROUND: To evaluate differences in the temporal profile of acute phase response (APR) between ischemic stroke (IS) and intracerebral hemorrhage (ICH). PATIENTS AND METHOD: We studied APR parameters (< 24 h and 3-5 day) in 88 consecutive patients (43 ICH and 45 IS). The increase/decrease of the parameters between both dates was analyzed. RESULTS: Leukocyte increase (LI) and fibrinogen increase (FI) is significantly higher in ICH than in IS (p = 0.047 and p = 0.035). CONCLUSIONS: APR temporal profile is different for ICH and IS.

Acute-Phase Reaction↗
PubMed2001

Selecting the target and the message for a stroke public education campaign: a local survey conducted by neurologists.

In order to determine the baseline knowledge of stroke among population (terminology, signs and symptoms, risk factors (RF) and attitude) to select the best target and message, prior to educational campaigns, a structured interview using close-ended questions was conducted by neurologists among 1000 users of several Primary Health Centers around our Hospital, randomly sampled. In our population 10.1% totally ignores the disease; of the remainder, 50% has a good knowledge of signs and symptoms and 37% of RF. To be a woman, (OR: 1.7; 95% CI: 1.2-2.5), the university education (OR: 6.6; 95% CI: 3.0-14.7), the age between 45 and 65 years (OR: 2.5; 95% CI: 1.3-5.0) and to have an afflicted relative (OR: 1.4; 95% CI: 1.001-2.0) are associated with a better stroke knowledge. If symptoms are transient, there is a trend to contact primary physicians (43.5%). Less than a quarter of our population have a good knowledge of the disease. Stroke is considered an emergency unlike TIA. The benefits of public education and the best message for each target population are discussed.

Adult↗
PubMed2001

Matrix metalloproteinase expression after human cardioembolic stroke: temporal profile and relation to neurological impairment.

BACKGROUND AND PURPOSE: Uncontrolled expression of matrix metalloproteinases (MMPs) can result in tissue injury and inflammation. In animal models of cerebral ischemia, the expression of MMP-2 and MMP-9 was significantly increased. However, their role in human stroke in vivo remains unknown. Therefore, we sought to determine the temporal profile of MMP expression in patients with acute ischemic stroke and to investigate its relationship to stroke severity, location of arterial occlusion, and total infarct volume. METHODS: Serial MMP-2 and MMP-9 determinations were made in 39 patients with cardioembolic strokes that involved the middle cerebral artery territory by means of enzyme-linked immunosorbent assay. Blood samples, transcranial Doppler recordings, and National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and at 12, 24, and 48 hours after stroke onset. Infarct volume was measured with CT scanning at 48 hours. RESULTS: No correlation was found between MMP-2 and NIHSS score at any time point, although a close relation appeared between mean MMP-9 and final NIHSS score (r=0.486, P=0.002). MMP-9 value was the only factor associated with the final NIHSS score in the multiple logistic regression model (OR 4.54, 95% CI 1.5 to 13.75). A cut-point of MMP-9 142.18 ng/mL had a positive predictive value of 94.4% to assess a patient's NIHSS (<8 or >/=8) by the end of the study. Final MMP-2 and MMP-9 levels were significantly lower when recanalization occurred (528+/-144.3 versus 681.4+/-239.2 ng/mL, P=0.031 for MMP-2; 110.2+/-100.9 versus 244.8+/-130 ng/mL, P=0.004 for MMP-9). A positive correlation was found between mean MMP-9 and infarct volume (r=0.385, P=0.022). CONCLUSIONS: MMPs are involved in the acute phase of human ischemic stroke. MMP-9 levels are associated with neurological deficit, middle cerebral artery occlusion, and infarct volume.

Acute Disease↗
PubMed2001

[Influence of age and gender on plasma norepinephrine changes produced by orthostatic stress].

The aim of this work was to determine the effect of aging and gender on plasma norepinephrine (NE) response to orthostatic stress. Fifty-six men and sixty women non-smokers, sedentary, non-obese, were studied at supine and standing positions. On the basis of the age of the subjects, they were divided into three groups of either men or women. Group A, young, range 17-34 years, Group B, middle-age, range 40-60 years, and Group C: senescent, range 61-91 years. Senescent subjects had the highest absolute supine values of NE and significant differences between women and men were found in groups B Men: 298 +/- 15 pg/mL; Women: 348 +/- 14 pg/mL), and C (M: 386 +/- 29 pg/mL; W: 473 +/- 19 pg/mL), but not between young (M: 246 +/- 21 pg/mL; W: 261 +/- 18 pg/mL). NE increased markedly in response to the orthostatic stress but the relative (percentage) increases were smaller in the older subjects perhaps related to their elevated baseline levels. The highest percent positive variation was observed in group A (M: 85%; W: 82%). The oldest group (C), had the lowest variation (M: 23%; W: 21%). The relative increases in NE responses were not different in men and women. The orthostatic-induced variation in NE was negatively related to aging in both men and women (M: r = -0.654; p < 0.0001; W: r = -0.557; p < 0.0001). It is concluded that orthostatic stress induced rise of blood NE is attenuated by age but does not appear to be dependent on gender.

Adolescent↗
PubMed2000

Differential expression of matrix metalloproteinases in labial salivary glands of patients with primary Sjögren's syndrome.

OBJECTIVE: To determine the enzymatic activity and cellular localization of matrix metalloproteinases (MMPs) 2, 3, and 9 in labial salivary glands from patients with different degrees of severity of primary Sjogren's syndrome (primary SS). METHODS: Gelatinase activity was determined by zymography and quantified by densitometry. The specificity of MMPs was determined using protease inhibitors and chelators, as well as activators of the latent forms of these enzymes. The cellular localization of MMPs was carried out using monoclonal antibodies that recognize their latent and active forms. RESULTS: Labial glands from control subjects and patients showed gelatinase activity for MMP-2 and MMP-9. Activation studies revealed that both enzymes were predominantly present in their latent forms. The highest levels of MMP-9 activity were detected in patients with severe, active, primary SS (except for patients with severe clinical symptoms for extended periods) and correlated with structural and functional glandular changes. MMP-2 activity was almost the same in patients and controls. MMPs were detected by immunolocalization only in acinar and ductal cells and were homogeneously distributed throughout patients' glands. MMP-2 and MMP-9 expression paralleled their gelatinase activity. MMP-3, detectable only with immunologic methods, was absent in control subjects but abundantly expressed in patients. Importantly, MMP protein levels in acinar and ductal cells were independent of either the presence or the proximity of mononuclear infiltrate cells. CONCLUSION: MMP-3 and MMP-9 expression, as well as MMP-9 catalytic activity, were increased in tissue samples from SS patients in a manner that correlated with the severity of the disease. Most important, increased MMP activity stemmed from exocrine epithelial cells and was not due to infiltrating lymphocytes. Thus, changes in salivary glands as a consequence of proteolysis may lead to severe glandular destruction.

Humans↗
PubMed2000

'Herald hemiparesis' of basilar artery occlusion: early recognition by transcranial Doppler ultrasound.

A transient hemiparesis may be ocassionally present at an early stage of the thrombosis of the basilar artery (herald hemiparesis). We report on one of these cases and the valuable role of transcranial Doppler ultrasound (TCD) to the early detection of the stroke-in-evolution. TCD in the emergency room is a good tool to assess a basilar occlusion, searching for direct (absence of signal at the basilar artery) and indirect (reversal flow of the pre-communicating segment the of posterior cerebral artery through the posterior communicating artery) signs. Early recognition and treatment of this condition could avoid the development of the full syndrome of the basilar artery thrombosis.

Adult↗
PubMed2000

Mitral papillary fibroelastoma as a cause of cardiogenic embolic stroke: report of two cases and review of the literature.

UNLABELLED: Papillary fibroelastoma (PFE) is a rare benign tumour that attaches to the endocardial surface, mostly on cardiac valves. Though usually asymptomatic, it can be the source of several complications. To date, 49 cases have been reported of embolic stroke with a PFE as the probable origin. CASE REPORTS: (i) a 39-year-old male presented with ischemic embolic stroke; the presence of a PFE was assessed by means of transoesophageal echocardiography and confirmed by pathological findings; (ii) a 32-year-old woman presented with sudden onset of left hemiparesis; a cardiogenic embolic stroke was suspected, and a diagnosis of PFE was made based on echocardiographic and pathological findings. In both cases, surgical excision of the tumours was performed with no recurrences at follow-up. Two mechanisms can explain the formation of emboli in PFE: dislodgement of the tumour leaves or fibrin-platelet aggregation on the endocardial surface of these leaves. Transthoracic echocardiography may lead to the suspicion of a PFE, but transoesophageal echocardiography is required for confirmation. Prompt surgical excision is indicated in most cases. Anticoagulation is only recommended in situations of high surgical risk and during the wait for surgery.

Adult↗
PubMed2000

Luteal progesterone relates to histological endometrial maturation in fertile women.

To examine the relationship between endometrial histological maturation and reproductive hormones, we studied 11 fertile women, aged 18-37 yr. All participants had had at least 1 previous pregnancy and cycled regularly, every 25-35 days. Women collected daily, first morning voided urine for measurement of estradiol and progesterone metabolite excretion, estrone conjugates (E1c), and pregnanediol glucuronide (Pdg), respectively, throughout the cycle of study. Hormones were normalized for creatinine. Between 7-9 days after home detection of a LH surge (Sure Step), participants underwent an endometrial biopsy using a small bore (Pipelle) catheter. Tissue was prepared for histological and biochemical analyses. The histological analysis is reported herein. Endometrium was dated by 3 authors (N.S., D.H., and S.P.), all of whom were blinded to the participant's identity or timing of biopsy within her cycle. Final dating was agreed upon based upon the method of Noyes et al. E1c and Pdg were integrated throughout the cycle using the trapezoidal rule, and correlations were sought between deviation from expected histology (based upon urinary hormones and LH surge) and integrated hormone values. E1c varied over a 2-fold range in these normal women, from 1196-2040 ng/cycle. Pdg excretion was much more variable, ranging from 22-119 microg/cycle. No relationship could be found between histological lagging of endometrial maturation and lower excretion of E1c. A moderate correlation was observed (Spearman's r = 0.6; P < 0.05) between degree of histological maturation and integrated Pdg. Of two women with evidence of a disparity between gland and stromal development (glands lagging behind stroma by >2 days), one excreted 24 microg Pdg/cycle, the next to lowest value. We conclude that normal fertile women experience a wide range of hormone concentrations in the face of normal endometrial maturation. Progesterone appears to exert a dose-related effect on endometrial maturation, and the techniques we used, although relatively crude clinical measures, appeared to be sufficient to detect this relationship.

Adolescent↗
PubMed2000

[Consumption of licit and illicit drugs in Chile: results of the 1998 study and comparison with the 1994 and 1996 studies].

The principal results are presented here from the Third National Study of the Consumption of Drugs, which was carried out in Chile by the National Board for Narcotics Control between 1 September 1998 and 15 January 1999. The 1998 study used the same methodological design as the first and second studies, which were done in 1994 and 1996. The 1998 study expanded the sample to 31,665 individuals, who were representative of a population of 6,940,727 people from 12 to 64 years old, both sexes, and five socioeconomic levels and who were residents of urban areas in 62 commune administrative divisions of the 13 regions of the country. Results from the 1998 study are compared with those from 1996 and 1994. The 1998 study shows that 17.5% of Chileans have at some time in their life used one of the three illicit drugs most popular in the country: marijuana (16.8%), coca paste (2.3%), and cocaine hydrochloride (4.0%). The prevalence of use of any of the three drugs, mainly marijuana, during the preceding year was 5.3% and during the preceding month 2.2%. With respect to licit drugs, 28.4% of Chileans have at some time in their lives used antianxiety drugs, 84.4% of them have consumed alcohol, and 71.9% have used tobacco. Most of the people who once used illegal drugs have stopped doing so: 71.6% in the case of marijuana, 64.1% with coca paste, and 66.8% with cocaine hydrochloride. For legal drugs, the percentages were lower: 55.5% for anxiolytics, 16.0% for alcohol, and 34.5% for tobacco. The consumption of licit and illicit drugs was several times greater among men than among women, except for anxiolytics, whose use was three times greater among women. Drug use was more frequent among persons between 19 and 25 years old. Consumption of illegal drugs was more frequent at higher socioeconomic levels, and use of licit drugs was more common in the lower socioeconomic levels. The 50th percentile of the age of initiating drug use was 17 years for alcohol, 15 for tobacco, 30 for antianxiety agents, 17 for marijuana, 20 for coca paste, and 21 for cocaine hydrochloride. Comparing the results of the three studies shows that, after an increase in the use of licit drugs between 1994 and 1996, there was a stabilization in 1998. With illegal drugs there was a modest increase in consumption between 1996 and 1998, following a small reduction between 1994 and 1996.

Adolescent↗
PubMed1999

["Stroke code". Shortening the delay in reperfusion treatment of acute ischemic stroke].

BACKGROUND: "Stroke Code" is a system for the rapid identification, pre-notification and transport of acute ischemic stroke patients. The objective of this study was to evaluate the impact of delay reduction for thrombolytic therapy in these patients. SUBJECTS AND METHODS: We evaluated acute ischemic stroke patients admitted in the emergency unit within the first 6 hours after onset of symptoms and included into reperfusion clinical trials. We compared the delay for initiating reperfusion treatment related to the activation or not of the stroke code. RESULTS: From 454 patients evaluated, 25% were admitted to the hospital in less than 6 hours from stroke onset. 59% of these patients were candidates for reperfusion treatment. "Stroke Code" was activated in 13 (55%). We observed a significant reduction in the delay since the onset of symptoms in relation to "Stroke Code" activation or not (mean X [SD]): emergency room arrival: 49.6 (48) vs 80 (48) min; Stroke Team evaluation: 65.3 (57) vs 133.6 (58) min; CT scan performing: 86.2 (60) vs 171.8 (62) min; Start of treatment; 212.9 (51) vs 287.3 (59) min. CONCLUSIONS: "Stroke Code" activation reduced in 50% pre- and in-hospital delay to start reperfusion treatment in acute ischemic stroke patients.

Acute Disease↗