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M Pacheco

Publications and source records attributed to M Pacheco.

At least 55 records · Page 3Linked to original sources
PubMed1993

Manganese induces spreading and process outgrowth in rat pheochromocytoma (PC12) cells.

Mn2+ has been shown to promote cell-substrate adhesion and cell spreading in many cell culture systems. In this study, we present data demonstrating that Mn2+ not only promotes spreading, but also induces process outgrowth in rat pheochromocytoma (PC12) cells. In the presence of 1.0 mM MnCl2, cell spreading was apparent by 6 hr, and nearly 50% of the exposed cells extended neurite-like processes. These morphological effects of Mn2+ were both time- and dose-dependent. In the presence of cycloheximide, a protein synthesis inhibitor, both Mn(2+)-induced spreading and neurite outgrowth were prevented, indicating that de novo protein synthesis is required for the effects of Mn2+ to take place. Of the other divalent cations tested, Mg2+, Cd2+, Cu2+, Ni2+, and Zn2+ were ineffective, and only Co2+ partially mimicked the effects of Mn2+. Although Mn(2+)-induced cell adhesion and spreading have been extensively studied, this is the first report that this divalent cation can cause neurite outgrowth. The neurite outgrowth-promoting effects of Mn2+ were distinct from those of nerve growth factor in that the response to Mn2+ was considerably more rapid, but apparently lacked the ability to sustain continuous outgrowth and networking of neurites. Mn2+ also induced the levels of GAP-43 and peripherin, two proteins associated with neuronal differentiation of PC-12 cells. In cells grown in serum-free defined medium, Mn2+ was capable of promoting neurite outgrowth when the cells were plated on surfaces pretreated with normal growth medium, vitronectin, or fibronectin, while it failed to cause these morphological changes in cells plated on untreated or poly-D-lysine-coated substrata. Similarly, Mn2+ also promoted neurite outgrowth from rat sympathetic neurons attached to laminin-treated substrate, but had no effect on neurons maintained on substrate with polylysine only. The pentapeptide Gly-Arg-Gly-Asp-Ser nearly completely prevented the morphological effects of Mn2+ on PC12 cells. These findings are consistent with a hypothesis that Mn(2+)-mediated alteration of an RGD-dependent extracellular matrix-integrin interaction is responsible for the neuritogenic effects.

Amino Acid Sequence↗
PubMed1993

Determinants of the geographic variation of invasive cervical cancer in Costa Rica.

The incidence of cervical cancer in Costa Rica is about twice as high in the coastal regions as in the interior. To study these regional variations, we used data from a 1986-1987 case-control study of 192 Costa Rican women with invasive cervical cancer and 372 controls. Risk factors identified included the following: The study participant's (1) number of sexual partners, (2) age at first sexual intercourse, (3) number of live births, (4) presence of type 16/18 human papillomavirus (HPV) DNA, (5) venereal disease (VD) history, (6) Pap smear history, and (7) socioeconomic status. The adjusted relative risks (RR) and 95% confidence intervals (CI) for each of these risk factors were as follows: (1) > or = 4 vs. 1 sexual partner: RR = 2.0, 95% CI = 1.1-3.5; (2) age of initiation < or = 15 vs. > or = 18 years: RR = 1.5, 95% CI = 0.9-2.5; (3) > or = 6 vs. < or = 1 live birth: RR = 1.7, 95% CI = 0.7-3.9; (4) HPV 16/18 DNA in cervix: RR = 2.8, 95% CI = 1.9-4.2; (5) VD history: RR = 2.2, 95% CI = 1.2-4.0; (6) no Pap smear: RR = 2.4, 95% CI = 1.5-3.8; and (7) low socioeconomic status: RR = 2.0, 95% CI = 1.2-3.2. The population-attributable risks related to HPV detection, four or more sexual partners, six or more live births, no prior Pap smear, and low socioeconomic status were 39%, 38%, 29%, 23%, and 22%, respectively. Several of the sexual and reproductive risk factors were relatively more prevalent in the high-risk region, but Pap screening and detection of HPV were equally prevalent in the high-risk and low-risk regions. Though differences in screening quality (laboratory and follow-up) may have been involved, we conclude that the observed regional differences reflect behavioral more than screening differences. This suggests that screening programs should be more aggressive in the high-risk area, given the more frequent occurrence of the disease there. Failure to detect a higher prevalence of HPV in the high-risk region could reflect weaknesses in the in situ hybridization test employed. Alternatively, cofactors may have to be present in order for HPV to exert its role in cervical carcinogenesis.

Adult↗
PubMed1992

Opioid and cannabinoid receptor inhibition of adenylyl cyclase in brain.

Both opioids and cannabinoids bind to G-protein-coupled receptors to inhibit adenylyl cyclase in neurons. These reactions were assayed in brain membranes, where maximal inhibitory activity occurred in the following regions: mu-opioid inhibition in rat thalamus, delta-opioid inhibition in rat striatum, kappa-opioid inhibition in guinea pig cerebellum, and cannabinoid inhibition in cerebellum. The inhibition of adenylyl cyclase by both cannabinoid and opioid agonists was typical of G-protein-linked receptors: they required GTP, they were not supported by non-hydrolyzable GTP analogs, and they were abolished (in primary neuronal cell culture) by pertussis toxin treatment. The immediate targets of this system were determined by assaying protein phosphorylation in the presence of receptor agonists and App(NH)p, a substrate for adenylyl cyclase. In striatal membranes, opioid agonists inhibited the phosphorylation of at least two bands of MW 85 and 63 kDa, which may be synapsins I and II, respectively. Other experiments determined the long-term effects of this second messenger system. In primary neuronal cultures, opioid-inhibited adenylyl cyclase attenuated forskolin-stimulated pro-enkephalin mRNA levels, thus providing a feedback regulation of opioid synthesis. Finally, in cerebellar granule cells, both cannabinoid and opioid receptors may exist on the same cells. In these cells, agonists which bind to different receptor types may produce similar biological responses.

Adenylyl Cyclase Inhibitors↗
PubMed1991

Adverse reactions to vancomycin prophylaxis in cardiac surgery.

Several adverse effects of vancomycin have been reported. The aim of this study was to assess the incidence of adverse responses to antibiotic prophylaxis with vancomycin in cardiac surgical patients. Prospectively, 116 consecutive patients (106 adults and 10 children) undergoing cardiac surgical procedures in this institution from January to June 1990 were studied. After the anesthetic induction, vancomycin, 1 g in adults and 10 mg/kg in children, was intravenously administered over 30 minutes. The infusion rate was slowed if any adverse effect was observed. As a control group, 10 similar patients were evaluated during the same period of 30 minutes after anesthetic induction but prior to vancomycin administration and surgical stimulation. Thirty-one patients (26.72%) developed an adverse effect, mainly hypotension (29 patients, 25%), which was considered severe in 15 patients (12.93%). Seven patients (6.03%) developed a maculopapular erythema that was associated with hypotension (Red-Man's syndrome) in 5 patients and with bronchospasm in 1 patient. The incidence of adverse reactions in children (20%) was similar to the overall incidence. Only 1 patient in the control group (10%) developed hypotension during the period studied. The incidence of adverse reactions was not related to age, body weight, vancomycin dose administered per kilogram body weight, type of surgical procedure, or associated disease. Mean duration of the infusion was similar in patients with and without adverse responses (34.60 +/- 12.41 minutes and 37.38 +/- 14.55 minutes, respectively). It is concluded that perioperative prophylaxis with vancomycin in cardiac surgery produces a high and unpredictable risk of significant hypotension.

Adult↗
PubMed1991

Aminoalkylindoles: actions on specific G-protein-linked receptors.

Aminoalkylindoles (AAIs) are antinociceptive agents which act through two distinct mechanisms: inhibition of cyclooxygenase and a novel mechanism retained by AAI analogs which do not inhibit cyclooxygenase. This latter mechanism is reflected by inhibition of neuronally mediated contractions in several smooth muscle bioassays. The present studies explored the potential receptor interactions of AAIs in smooth muscle preparations and in rat brain membranes. Experiments in an electrically stimulated mouse vas deferens preparation (MVD) demonstrated that several AAI agonists inhibited neuronally mediated muscle contractions over a wide potency range (0.1-1000 nM) and in a stereospecific manner. Also, a putative AAI antagonist analog selectively attenuated AAI-induced inhibition in the MVD: 10 microM of the antagonist analog produced 16- to 40-fold rightward shifts in the concentration-effect curves for AAI agonists but failed to attenuate the inhibitory actions of several receptor agonists and other pharmacological agents. AAI agonists also inhibited adenylyl cyclase in membranes from rat striatum and cerebellum. AAI agonists inhibited adenylyl cyclase through G-proteins, because AAI-inhibited adenylyl cyclase required GTP, and was not supported by nonhydrolyzable guanine nucleotides. Inhibition of adenylyl cyclase by several AAI agonists was stereospecific and was not blocked by antagonists of several traditional neurotransmitter receptors. The potencies of AAI agonists to inhibit cerebellar adenylyl cyclase were highly correlated (r = 0.97) with their potencies to inhibit contractions of MVD. These results suggest that AAIs bind to specific receptors which are coupled through G-proteins to inhibit adenylyl cyclase.

Adenylyl Cyclase Inhibitors↗
PubMed1990

Amrinone in perioperative low cardiac output syndrome.

Amrinone has been shown to have a beneficial effect on left ventricular function in low output syndrome (LOS), but its use after open-heart surgery has not been extensively revised. We studied 10 patients with LOS post-cardiopulmonary bypass (CPB), who failed to respond to conventional treatment (vasoactive drugs plus intraaortic balloon pump) and were treated with amrinone, 0.75 mg.kg-1 followed by a continuous infusion of 5 to 10 micrograms.kg-1-min-1. One patient failed to respond to the treatment and subsequently died, but in the other nine patients blood pressure and cardiac index increased, left filling pressure decreased and they were successfully weaned from the CBP and survived. These results suggest that amrinone, either alone or combined with other inotropic drugs and mechanical support, is a valuable drug in the management of LOS after CPB.

Aged↗
PubMed1980

Primary afferent depolarization. Distribution of the gamma-aminobutyric acid system in frog spinal cord.

In the frog spinal cord primary afferent depolarization (PAD) constitutes a powerful inhibitory control mechanism. It has been suggested that gamma-aminobutyric acid (GABA) is the transmitter substance involved in the genesis of PAD. In these studies we show that maximal glutamic acid decarboxylase activity is localized roughly 400-600 micrometers from the dorsal surface, and that correlates well with the intraspinal distribution of field potentials associated with PAD. Measurements of GABA in serial spinal cord sections cut in a dorsal--ventral direction shows that high levels of GABA are seen at 400--600 micrometers, with a peak at 800 micrometers from the dorsal surface. Stimulation at frequencies shown to produce PAD augments the release of endogenous GABA from a superfused frog hemicord preparation.

Animals↗
PubMed1979

The filum terminale of the frog spinal cord, a non transformed preparation: I. Morphology and uptake of gamma-aminobutyric acid.

The filum terminale of the frog spinal cord is a rather pure glial cell preparation, largely devoid of neuronal elements. gamma-Aminobutyric acid (GABA) is taken up by the frog filum terminale (FT) via a Na+-dependent, ouabain-inhibited, saturable high affinity transport system with a Km of 2.7 x 10(5) M. The rate of the FT GABA uptake is significantly greater than the velocities observed in the spinal cord. In fact, the Vmax increases caudally beyond the level of the last root, and is maximal in the FT per se. beta-Alanine is a competitive inhibitor of the FT high affinity transport system for GABA (Ki 11.1 x 10(-5) M). In addition to GABA, the FT also takes up beta-alanine, glycine, glutamate and aspartate at rates significantly higher than those shown by the spinal cord of the frog. Light and electron microscope level radioautography clearly shows that GABA uptake occurs primarily in the glial cells and also in ependymal cells present in the FT. In that the FT contains few ependymal cells and a large number of glia, it is fair to state that most of the GABA accumulated by the FT reflects the glial transport of this amino acid. Unlike the adult frog, the spinal cord of the tadpole does not show any regional differences in the rate of GABA transport during early development. However, during later developmental stages, the rates of GABA transport increase in the caudal portion of the tadpole cord as compared to the more rostral areas. Close to metamorphosis, the terminal portion of the tadpole cord, which is destined to become the filum terminals of the frog, accumulates GABA at rates not greatly different from those observed in the FT of the adult frog. Therefore, the tadpole spinal cord is a useful preparation in which to study the dynamic properties of normal non-transformed glia as influenced by a changing neuronal population, whereas the frog FT is a unique preparation for the study of some properties of normal glia largely in the absence of neurons.

Amino Acids↗
PubMedDate not supplied

Induction of liver EROD and erythrocytic nuclear abnormalities by cyclophosphamide and PAHs in Anguilla anguilla L.

The induction of liver ethoxyresorufin O-deethylase (EROD) activity and erythrocytic nuclear abnormalities (NA) after treatment with two different polycyclic aromatic hydrocarbons (PAHs) and cyclophosphamide (CP) was investigated in the eel Anguilla anguilla L. EROD activity significantly increases either 3 days after one single i.p. injection or 6 days after two i.p. injections (on days 0 and 3) of 4 mg/kg beta-naphthoflavone (BNF). EROD activity was determined after different lengths of exposure to 4 mg/kg BNF (i.p. injection). The results indicated significant increases from 8-h to 12-day exposure, with a maximum increase at 4 days and a decline between 4 and 12 days. The induction of liver EROD activity and erythrocytic NA was studied, 3 days after one 14.7-mumol/kg treatment (i.p. injection) with BNF, benzo[a]pyrene (BaP), and CP, in three three different groups of eels. The EROD activity significantly increases after BNF and BaP treatment, whereas the erythrocytic NA frequency was kept constant; however, CP induces a significant increase in the erythrocytic NA frequency, but it does not induce a significant increase in liver EROD activity. The sensitivity of A. anguilla liver EROD assay was assessed 3 days after one i.p. injection of BNF (0.0, 0.03, 0.06, 0.125, 0.25, 0.5, 1.0, 2.0, and 4.0 mg/kg). This species exhibits a dose response to BNF at the concentration range 0-4 mg/kg. The NOEL is between 0.125 and 0.25 mg/kg. The eels 3-day exposure to water containing BNF (0.0, 0.1, 0.3, 0.9, and 2.7 microM) induced a significant increase in liver EROD activity, specifically in concentrations of 0.9 and 2.7 microM. The NOEC for the eels external exposure to BNF is between 0.3 and 0.9 microM.

Anguilla↗
PubMedDate not supplied

Serum protein markers in the Piaroa Indians of Amazonia (Venezuela).

A sample of 121 Piaroa Indians from the Federal Amazonia Territory (Venezuela) was studied for the following serum protein polymorphisms: haptoglobin (HP), group-specific component subtypes (GC), orosomucoid (ORM), third component of complement (C3), transferrin C subtypes (TF) and alpha 1-antitrypsin subtypes (PI). The gene frequencies in the whole sample were: HP1 = 0.821; GC1S = 0.698; GC1F = 0.058; GC2 = 0.244; ORMS = 0.434; C3S = 0.699; C3F = 0.289; C3var = 0.012; TFC1 = 0.955; PIM1 = 0.467; PIM2 = 0.004; PIM3 = 0.529. The studied Piaroa sample came from three different communities: Gavilan, Paria and Alto Carinagua. The distribution of GC, C3 and HP polymorphisms was heterogeneous within the three groups. All the examined serum protein markers were polymorphic, in contrast to some enzymatic markers (ADA, DIA, 6PGD, AK) previously studied, which were shown to be monomorphic in the Piaroa. The results were compared with data from other populations living in the same territory.

Analysis of Variance↗
PubMedDate not supplied

[Estimation of the number of potential organ donors in the city of São Paulo].

BACKGROUND: There is a concept that the small number of transplants is due to the shortage of donors or the refusal of the next of kin to make to donation. In order to evaluate the potential number of donors in São Paulo the autopsies performed at the Forensic Medical Institute (IML) were studied during 1990 and 1991. MATERIAL AND METHOD: The autopsies carried out during 1990 and 1991 were studied. During the same period we also analysed the reports of possible donors received by the organ searching team of the Escola Paulista de Medicina (EPM). RESULTS: During 1990 and 1991, 11601 and 11607 autopsies were respectively carried out (32 autopsies/day). The analysis of 500 autopsies during 10/90 and of 1039 during 05/91 showed that 27% had a traumatic brain injury (TBI) as the sole cause of death and 70% were cared for in a hospital. From 01/90 to 12/91 the organ searching team of the EPM received reports of 296 possible donors. Of the 296 reports, 219 families were contacted and 59% authorized the donation. CONCLUSION: Considering the number of deaths exclusively caused by TBI that passed through any hospital and the rate of donations obtained by our team, there is a number of potential donors in São Paulo sufficient to saturate the working capacity of all teams, if the seeking system is efficient.

Adolescent↗