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2.
Claves odontol ; 20(71): 47-54, nov. 2013. tab
Article in Spanish | LILACS | ID: lil-719602

ABSTRACT

El interés por los biotipos periodontales se ha acrecentado en el último tiempo, por lo cual en los años recientes el estudio de las dimensiones de los diferentes tejidos periodontales se ha desarrollado desde un punto de vista epidemiológico, estético y terapéutico en varias áreas de la odontología, especialmente en periodoncia. Esta revisión bibliográfica tiene por objetivo mostrar las últimas evidencias relacionadas con esta temática.


Subject(s)
Humans , Esthetics, Dental , Gingiva/anatomy & histology , Dental Papilla/anatomy & histology , Somatotypes , Crowns , Dental Implants , Mouth Rehabilitation , Reference Values , Surgery, Oral
3.
Claves odontol ; 20(71): 47-54, nov. 2013. tab
Article in Spanish | BINACIS | ID: bin-130053

ABSTRACT

El interés por los biotipos periodontales se ha acrecentado en el último tiempo, por lo cual en los años recientes el estudio de las dimensiones de los diferentes tejidos periodontales se ha desarrollado desde un punto de vista epidemiológico, estético y terapéutico en varias áreas de la odontología, especialmente en periodoncia. Esta revisión bibliográfica tiene por objetivo mostrar las últimas evidencias relacionadas con esta temática.(AU)


Subject(s)
Humans , Somatotypes , Gingiva/anatomy & histology , Dental Papilla/anatomy & histology , Esthetics, Dental , Dental Implants , Crowns , Mouth Rehabilitation , Reference Values , Surgery, Oral
4.
Rev Gastroenterol Peru ; 21(2): 153-6, 2001.
Article in Spanish | MEDLINE | ID: mdl-12172569

ABSTRACT

This is to report on a 44-year old female patient diagnosed with gastric cancer who was surgically treated with a total D-2 radical gastrectomy, block splenectomy and a lateral esophagus-jejunal anastomosis. A month after surgery and various post-surgery complications, a total stenosis of the esophagus-jejunal anastomosis was detected which was endoscopically solved with a needle-knife type obtaining an adequate recanalization of the lumen, which is the subject of this report.


Subject(s)
Anastomosis, Surgical/adverse effects , Endoscopy, Digestive System , Esophagus/surgery , Jejunum/surgery , Postoperative Complications , Adult , Constriction, Pathologic/surgery , Female , Gastrectomy , Humans , Postoperative Complications/surgery , Reoperation , Stomach Neoplasms/surgery , Time Factors
5.
Rev Gastroenterol Peru ; 21(3): 185-97, 2001.
Article in Spanish | MEDLINE | ID: mdl-11818978

ABSTRACT

UNLABELLED: The incidence of adenocarcinoma around the esophagogastric junction is increasing. The significance of intestinal metaplasia found in biopsy taken from normal appearing squamocolumnar junction is not clear. The aim of this study was to define the frequency of intestinal metaplasia at normal-appearing esophagogastric junction and clinical, endoscopic and histological associations. METHODS: 239 patients referred for gastroscopy participated in the study. Of 192 patients, two groups were compared. Group I included 40 patients with metaplasia intestinal at the esophagogastric junction and group II included 152 patients with no metaplasia intestinal at the same location. Biopsy specimens were taken from above and below the squamocolumnar junction, and gastric antrum The biopsy specimens were stained with haematoxylin-eosin. RESULTS: Intestinal metaplasia at the squamocolumnar junction was found in 40 patients (21%). Metaplasia was associated with increasing age (p=0.002) and antral intestinal metaplasia (p<0.001)(OR 14.6). There was no association with gastro-oesophageal reflux disease. CONCLUSION: Intestinal metaplasia at the esophagogastric junction occurs frequently in Peruvian patients. It is associated with increasing age and antral intestinal metaplasia but not gastro-esophageal reflux disease.


Subject(s)
Esophagogastric Junction/pathology , Female , Humans , Male , Metaplasia , Middle Aged
6.
Eur Radiol ; 10(3): 531-3, 2000.
Article in English | MEDLINE | ID: mdl-10757011

ABSTRACT

It is currently very rare to find mammary involvement in cases of tuberculosis, in either primary or secondary form. Diagnosis is classically clinical and microbiological, and the basic techniques used in imaging diagnosis are mammography and ultrasound. Computed tomography may define the involvement of the thoracic wall in those cases which present as mammary masses adhering to deep levels, and is also able to evaluate accompanying pulmonary disease, if it is present. Traditionally, treatment has consisted of quadrantectomy and specific antibiotic therapy. We present a case of tuberculous mammary abscess secondary to pulmonary disease, which was treated by percutaneous drainage controlled by CT and specific antibiotic therapy. We revise the diagnosis, differential diagnosis and treatment of mammary tuberculosis.


Subject(s)
Abscess/therapy , Antitubercular Agents/therapeutic use , Breast Diseases/therapy , Suction/methods , Tuberculosis/therapy , Abscess/diagnosis , Breast Diseases/diagnosis , Diagnosis, Differential , Female , Humans , Mammography , Middle Aged , Tomography, X-Ray Computed , Tuberculosis/diagnosis , Ultrasonography, Mammary
7.
Invest Ophthalmol Vis Sci ; 41(1): 294-304, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10634634

ABSTRACT

PURPOSE: The abnormal retinal electrophysiology observed in patients with Duchenne muscular dystrophy (DMD) has been attributed to an altered expression of C-terminal products of the dystrophin gene. It has been shown that Dp260 is expressed by photoreceptor cells, whereas Dp71 is present in glial cells. The present study was intended to identify all known members of the dystrophin superfamily and their associated proteins expressed in Müller glial cells (MGC). METHODS: The expression of the proteins and of their messengers was studied in MGC cultures from 2-week-old rats, by polymerase chain reaction amplification, Western blot analysis, and immunocytochemistry. An immunocytochemical localization of the proteins was also performed on enzymatically dissociated Müller cells from adult rat retinas. RESULTS: MGCs expressed a spliced isoform of Dp71 called Dp71f, as well as utrophin, beta-dystroglycan, delta and gamma-sarcoglycans, and alpha1-syntrophin. In morphologically preserved differentiated Müller cells, Dp71f was localized in clusters, utrophin was diffusely distributed in the cytoplasm, and dystrophin-associated proteins (DAPs) were membrane-bound. Most of these proteins were preferentially expressed in the vitread portion of the cells. Dp71f and utrophin expression was restricted to MGCs, whereas all DAPs were also present in other retinal cell types. CONCLUSIONS: The exclusive localization of Dp71f and utrophin in MGCs suggests that these proteins, together with DAPs, play a specific role in these cells. Further knowledge of possible interactions of these proteins within a functional complex may provide new insights into the molecular basis of the electroretinogram phenotype in DMD.


Subject(s)
Cytoskeletal Proteins/genetics , Dystrophin/analogs & derivatives , Eye Proteins/genetics , Membrane Proteins/genetics , Neuroglia/metabolism , RNA, Messenger/metabolism , Animals , Blotting, Western , Cells, Cultured , Cytoplasm/metabolism , Cytoskeletal Proteins/biosynthesis , DNA Primers/chemistry , Dystrophin/biosynthesis , Dystrophin/genetics , Electrophoresis, Polyacrylamide Gel , Eye Proteins/biosynthesis , Fluorescent Antibody Technique, Indirect , Gene Expression , Membrane Proteins/biosynthesis , Polymerase Chain Reaction , Rats , Rats, Wistar , Utrophin
8.
Rev Esp Cardiol ; 50 Suppl 4: 53-6, 1997.
Article in Spanish | MEDLINE | ID: mdl-9411588

ABSTRACT

The left ventricular hypertrophy is a deleterious consequence of the arterial hypertension, recognized as independent risk factor. The left ventricular hypertrophy has a myocytic component, of hemodynamic origin, where all the antihypertensive treatments known would be active, in greater or smaller degree, and it's been demonstrated the benefit of the intervention in the sense of the fact that exist improvement indications of the morbi-mortality (cardio-protection). The left ventricular hypertrophy has at the same time a fibrotic component, of neuro-hormonal origin that can be reversed (cardio-reparation) fundamentally by influence of the ACEIs, that would improve furthermore all the components of the called "hypertensive syndrome".


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Hypertension/complications , Hypertrophy, Left Ventricular/etiology , Humans , Hypertension/drug therapy , Hypertension/physiopathology , Hypertrophy, Left Ventricular/physiopathology , Hypertrophy, Left Ventricular/prevention & control , Syndrome
9.
Rev Invest Clin ; 48(6): 457-9, 1996.
Article in Spanish | MEDLINE | ID: mdl-9132890

ABSTRACT

OBJECTIVE: To report a case of a patient who developed a Graves' ophthalmopathy class III two weeks after receiving radiotherapy in the neck. CASE HISTORY: He was a male of 51 years of age with a stage IIIB Hodgkin's disease who received chimio- and radio-therapy two weeks previous to the ophthalmopathy. The computed axial tomography showed retroorbital changes. The thyroid function tests, including the stimulation with thyrotropin releasing hormone and the microsomal and thyroglobulin antibodies were normal. The patient was treated with oral prednisone, followed by retroocular radiotherapy on the right eye. The exophthalmos improved and the diplopia disappeared.


Subject(s)
Graves Disease/etiology , Radiation Injuries , Graves Disease/therapy , Hodgkin Disease/radiotherapy , Humans , Male , Middle Aged , Neck
10.
Stem Cells ; 13(2): 112-22, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7787778

ABSTRACT

Post-remission high-dose chemotherapy has been an important advance in the treatment of adult acute leukemia (AAL). Without the use of colony-stimulating factors (CSFs) in this program, the mortality rate varies from 5 to 17%, and infectious complications arise in more than 50%. These findings limit the widespread use of such forms of therapy. The use of high-dose ara-C (HIDAC) alone or in combination with other drugs is the most common regimen studied, however neither other drug combinations nor the addition of supporting CSFs have been extensively explored. For this reason we studied the effect of high-dose cyclosphosphamide-etoposide (CECY) plus recombinant human granulocyte-macrophage (rHuGM)-CSF with the intention of decreasing morbimortality and prolonging disease-free survival (DFS). Since 1992 we have included 51 complete remission patients with AAL in the CECY plus rHuGM-CSF protocol. The maximal myelosuppression occurred in a mean of 6.4 days, and the mean days required for absolute neutrophil count recovery was 13 days and for platelets 21 days (p < 0.0001). No toxic deaths occurred and only two serious infectious complications were seen. After two years of follow-up, 50% of de novo acute myelogenous leukemia patients had relapsed at 13 months, and 50% of de novo adult acute lymphocytic leukemia patients had relapsed at 15 months. In a recent update, we have not seen a significant difference when compared to historic groups. The CECY protocol does not appear to be superior in prolonging DFS compared to HIDAC as a post-remission strategy for newly diagnosed AAL. The main difference was the absence of toxic deaths and minimal serious infectious complications in the CECY protocol. Therefore, we suggest that the use of rHuGM-CSF in post-remission programs should be included in future studies.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Recombinant Proteins/therapeutic use , Acute Disease , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/administration & dosage , Cytarabine/adverse effects , Cytarabine/therapeutic use , Etoposide/administration & dosage , Female , Granulocyte-Macrophage Colony-Stimulating Factor/adverse effects , Humans , Leukemia-Lymphoma, Adult T-Cell/drug therapy , Male , Middle Aged , Recombinant Proteins/adverse effects
11.
Cytogenet Cell Genet ; 69(1-2): 18-26, 1995.
Article in English | MEDLINE | ID: mdl-7835080

ABSTRACT

Cytogenetic analyses were performed on several populations of the Central American tree frog Agalychnis callidryas, using conventional methods and banding techniques. The karyotype of this species is distinguished by an inversion polymorphism in chromosome 9, which is either submetacentric or telocentric. The populations examined are in Hardy-Weinberg equilibrium with respect to the two alternative morphs of chromosome 9. This is the first report of the occurrence of an intrapopulational chromosomal inversion polymorphism in the order Anura. In male meiosis, the two chromosomes 9 form a bivalent exhibiting a ring-like pairing configuration with terminal chiasmata in both arms, regardless of whether the paired homologs are heteromorphic or homomorphic. Furthermore, individual specimens of A. callidryas exhibit one or two unexpected 18S + 28S ribosomal RNA gene clusters, in addition to the standard nucleolus organizers. The chromosomal localization of these extra nucleolus organizers is identical in all metaphases from the same specimen and shows a specific intraindividual pattern. The karyotype evolution in the phyllomedusine hylids, the structure of the various classes of heterochromatin, and the occurrence and possible origin of the rare inversion polymorphisms and multiple nucleolus organizers in A. callidryas and a few other amphibian species are discussed.


Subject(s)
Anura/genetics , Chromosome Inversion , Chromosome Mapping , Nucleolus Organizer Region/genetics , Polymorphism, Genetic , Animals , Chromosome Banding , Costa Rica , Female , Geography , Karyotyping , Male
12.
Neuropharmacology ; 33(3-4): 423-31, 1994.
Article in English | MEDLINE | ID: mdl-7984280

ABSTRACT

The effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), an alkylating agent producing irreversible blockade of various membrane bound receptors in brain, were investigated on four different types of serotonin receptors, 5-HT1A, 5-HT1B, 5-HT2A and 5-HT3, in various brain regions in the rat. In addition, the fate of central benzodiazepine- and "R"-zacopride-specific binding sites was also examined in rats treated with EEDQ. Membrane binding assays and/or quantitative autoradiography with appropriate radioligands indicated that EEDQ inactivated 5-HT1A, 5-HT1B and 5-HT2A sites, but was poorly active on 5-HT3, benzodiazepine and "R" sites. Among the receptors affected by EEDQ, hippocampal 5-HT1A sites were the most sensitive to the alkylating agent (ID50 approximately 1 mg/kg i.p.), followed by the cortical 5-HT2A (ID50 approximately 3 mg/kg i.p.) and the striatal 5-HT1B (ID50 approximately 6 mg/kg i.p.) sites. Pretreatment by selective ligands partially protected hippocampal 5-HT1A sites from irreversible inactivation by EEDQ (10 mg/kg i.p.) with the following order of efficacy: WAY 100635 > spiperone > BMY 7378 > ipsapirone. Similarly, pretreatment by spiperone (5 mg/kg i.p.) also reduced the ability of EEDQ to inactivated cortical 5-HT2A receptors. Analyses of the time-course recovery of respective binding sites after EEDQ administration showed that the turnover rate of 5-HT1A sites did not significantly differ in the dorsal raphe nucleus and in various forebrain areas (hippocampus, septum, cerebral cortex; half-life: approximately 4 days), but was lower than that of cortical 5-HT2A sites (half-life: 2.9 days).


Subject(s)
Brain Chemistry/drug effects , Bridged Bicyclo Compounds, Heterocyclic , Quinolines/pharmacology , Receptors, Serotonin/drug effects , Serotonin Antagonists/pharmacology , Animals , Autoradiography , Benzamides/pharmacology , Bridged Bicyclo Compounds/pharmacology , Flunitrazepam/pharmacology , GTP-Binding Proteins/metabolism , In Vitro Techniques , Ion Channel Gating/drug effects , Ligands , Male , Membranes/drug effects , Membranes/metabolism , Nerve Tissue Proteins/metabolism , Radioligand Assay , Rats , Rats, Sprague-Dawley , Serotonin/metabolism , Stereoisomerism
13.
Eur J Pharmacol ; 198(1): 59-67, 1991 May 30.
Article in English | MEDLINE | ID: mdl-1680714

ABSTRACT

The tritiated derivative of the potent antihypertensive agent, 5-methyl-urapidil, was used as a radioligand in binding studies with rat brain membranes and tissue sections. Serotonin and prazosin inhibited [3H]5-methyl-urapidil binding to membranes from the rat hippocampus, cerebral cortex and brainstem biphasically, leading to the definition of serotonin high-affinity and prazosin high-affinity [3H]5-methyl-urapidil binding sites. Comparison of these serotonin-sensitive [3H]5-methyl-urapidil binding sites with the 5-HT1A sites labelled by [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) revealed striking similarities regarding pharmacological properties, respective densities and regional distribution. On the other hand, the prazosin-sensitive [3H]5-methyl-urapidil binding sites should correspond to the alpha 1A-subtype of adrenoceptors which has recently been defined. Detailed autoradiographic investigations allowed the detection of 5-HT1A sites labelled by both [3H]5-methyl-urapidil and [3H]8-OH-DPAT in the posterior raphe nuclei (pallidus and obscurus) which are possibly involved in the hypotensive action of 5-methyl-urapidil. These data demonstrate that [3H]5-methyl-urapidil is a useful radioligand for the visualization and quantification of both 5-HT1A serotonin receptors and alpha 1A-adrenoceptors in the central nervous system.


Subject(s)
Adrenergic alpha-Antagonists/pharmacology , Brain/drug effects , Piperazines/pharmacology , Receptors, Adrenergic, alpha/drug effects , Receptors, Serotonin/drug effects , 8-Hydroxy-2-(di-n-propylamino)tetralin , Animals , Autoradiography , Binding, Competitive/drug effects , Brain/metabolism , In Vitro Techniques , Kinetics , Male , Membranes/drug effects , Membranes/metabolism , Prazosin/pharmacology , Rats , Rats, Inbred Strains , Receptors, Adrenergic, alpha/metabolism , Receptors, Serotonin/metabolism , Serotonin/pharmacology , Tetrahydronaphthalenes/metabolism
15.
J Pharmacol Exp Ther ; 255(3): 1335-47, 1990 Dec.
Article in English | MEDLINE | ID: mdl-1702155

ABSTRACT

Inasmuch as sustained treatment with the 5-hydroxytryptamine1A (5-HT1A) agonist, ipsapirone, is necessary for inducing anxiolytic and antidepressant effects in the clinic, investigations were performed for assessing the possible changes in serotoninergic and dopaminergic neurotransmission in the brain of rats 24 hr after a 2-week treatment with this drug. Receptor binding assays with membranes and quantiative autoradiography indicated that the twice-daily administration of ipsapirone (5 mg/kg i.p.) for 14 days did not alter the characteristics of 5-HT1A sites in the hippocampus, septum and dorsal raphe nucleus. In contrast, significant decreases in the Bmax values for 5-HT2 sites (-24%) and 5-HT3 sites (-19%) were found in the frontal and posterior cortex, respectively. As expected from unchanged postsynaptic 5-HT1A receptors, inhibition of forskolin-stimulated adenylate cyclase by 5-HT1A agonists (8-hydroxy-2-(di-n-propylamino)tetralin, ipsapirone) exhibited the same characteristics in hippocampal homogenates from both control and ipsapirone-treated animals. An acute administration of 8-hydroxy-2-(di-n-propylamino)tetralin (0.5 mg/kg i.p.) or ipsapirone (1 or 5 mg/kg i.p.) 24 hr after the last injection for the chronic treatment produced a similar decrease in the rate of 5-HT turnover in various brain areas in rats treated for 2 weeks with saline or ipsapirone. At the highest dose (5 mg/kg i.p.), acute ipsapirone also increased the rate of dopamine turnover in the striatum and cerebral cortex approximately to the same extent in both treatment groups. In vitro recording of the firing of serotoninergic neurons in brain stem slices revealed a desensitization of the somatodendritic 5-HT1A receptors, which might be responsible for the increased 5-HT turnover in the brain stem and striatum of rats chronically treated with ipsapirone as compared with controls. These data demonstrated that chronically administered ipsapirone produces adaptive changes in central serotoninergic neurotransmission which might account for the anxiolytic and antidepressant properties of this drug after sustained treatment.


Subject(s)
Biogenic Amines/physiology , Brain/physiology , Dopamine/physiology , Pyrimidines/pharmacology , Serotonin/physiology , Synaptic Transmission/physiology , 3,4-Dihydroxyphenylacetic Acid/metabolism , 5-Hydroxytryptophan/biosynthesis , 8-Hydroxy-2-(di-n-propylamino)tetralin , Adenylyl Cyclases/metabolism , Animals , Autoradiography , Behavior, Animal/drug effects , Binding Sites , Biogenic Amines/metabolism , Body Weight/drug effects , Brain/metabolism , Brain/ultrastructure , Brain Stem/anatomy & histology , Brain Stem/ultrastructure , Dihydroxyphenylalanine/metabolism , Dopamine/metabolism , Drug Administration Schedule , Electrophysiology , Hippocampus/ultrastructure , Homovanillic Acid/metabolism , Hydroxyindoleacetic Acid/metabolism , Male , Membranes/ultrastructure , Neurons/physiology , Pyrimidines/administration & dosage , Pyrimidines/therapeutic use , Raphe Nuclei/drug effects , Raphe Nuclei/physiology , Rats , Rats, Inbred Strains , Receptors, Serotonin/classification , Receptors, Serotonin/physiology , Serotonin/metabolism , Serotonin Antagonists/pharmacology , Synaptic Transmission/drug effects , Tetrahydronaphthalenes/pharmacology , Time Factors
16.
J Neurochem ; 55(5): 1526-36, 1990 Nov.
Article in English | MEDLINE | ID: mdl-2213008

ABSTRACT

Specific binding sites with pharmacological properties typical of serotonin 5-HT3 receptors were identified in membranes of the murine hybridoma cell line NG 108-15, using [3H]zacopride as a ligand. Optimal solubilization of these sites (yield, 50%) could be achieved using the detergent 3-[3-(cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS) at 24 mM plus 0.5 M NaCl in 25 mM Tris-HCl, pH 7.4. Specific [3H]zacopride binding to soluble sites in the 100,000-g CHAPS extract was saturable and showed characteristics (Bmax = 425 +/- 81 fmol/mg of protein; KD = 0.19 +/- 0.02 nM) closely related to those of membrane-bound sites (Bmax = 932 +/- 183 fmol/mg of protein; KD = 0.60 +/- 0.03 nM). Determination of association (k+1 = 0.17 nM min-1) and dissociation (k-1 = 0.02 min-1) rate constants for the soluble sites gave a KD value of 0.12 nM, a result consistent with that calculated from saturation studies. As assessed from the displacement potencies (IC50) of 10 different drugs, the pharmacological profile of [3H]zacopride specific binding sites was essentially the same (r = 0.99) in the CHAPS-soluble extract and in cell membranes, although some increase in the affinity for 5-HT3 antagonists (zacopride, ICS 205-930, and MDL 72222) and decrease in the affinity for 5-HT3 agonists (2-methyl-5-hydroxytryptamine and phenylbiguanide) were noted for the soluble sites. Sucrose density gradient sedimentation of the CHAPS-soluble extract gave a Svedberg coefficient of 12S for the material with [3H]zacopride specific binding capacity. Chromatographic analyses using Sephacryl S-400 and wheat germ agglutinin-agarose columns indicated marked enrichment (by 2.5- and 10-fold, respectively) in [3H]zacopride specific binding activity in the corresponding eluates compared with the starting soluble extract, a finding suggesting that both steps are of potential interest for the partial purification of solubilized 5-HT3 receptors. Two soluble materials with apparent molecular masses of approximately 600 and approximately 36 kDa were found to bind [3H]zacopride specifically in the Sephacryl S-400 eluate. Interestingly, molecular mass determination by radiation inactivation of [3H]zacopride binding sites in frozen NG 108-15 cells gave a value of approximately 35 kDa.


Subject(s)
Bridged Bicyclo Compounds, Heterocyclic , Receptors, Serotonin/chemistry , Animals , Benzamides/metabolism , Binding Sites , Bridged Bicyclo Compounds/metabolism , Cell Membrane/metabolism , Chemical Phenomena , Chemistry, Physical , Cholic Acids/pharmacology , Detergents , Glioma/metabolism , Glioma/pathology , Molecular Weight , Neuroblastoma/metabolism , Neuroblastoma/pathology , Serotonin Antagonists/metabolism , Solubility , Tumor Cells, Cultured
17.
Biochem Pharmacol ; 40(7): 1541-50, 1990 Oct 01.
Article in English | MEDLINE | ID: mdl-2222509

ABSTRACT

On account of the postulated existence of 5-HT3 receptor subtypes, the respective physico-chemical and pharmacological properties of specific binding sites for the potent 5-HT3 antagonist [3H]zacopride were compared using membranes from the rat posterior cortex or neuroblastoma-glioma NG 108-15 clonal cells. In both membrane preparations, [3H]zacopride bound to a single class of specific sites with a Kd close to 0.5 nM. However, the Bmax value in NG 108-15 cell membranes (970 +/- 194 fmol/mg protein) was approximately 50 times larger than that in cortical membranes (19 +/- 2 fmol/mg protein). The specific binding of [3H]zacopride was equally affected by temperature, pH and molarity of the assay medium, and equally insensitive to thiol- and disulfide-reagents (N-ethylmaleimide, p-chloromercuribenzene sulfonic acid, dithiothreitol) and GTP in cortical as well as NG 108-15 cell membranes. Determination of the molecular size of [3H]zacopride specific binding sites by radiation inactivation yielded values close to 35 kDa for both membrane preparations. Finally, a highly significant positive correlation (r = 0.979) was found between the respective pKi values of 34 different drugs for their inhibition of [3H]zacopride specific binding to cortical or NG 108-15 cell membranes. Among them, the most potent was S(-)zacopride (pKi = 9.55), followed by BRL 43964, ICS 205-930, quipazine, R(+)zacopride, GR 38032F and MDL 72222. Atypical antidepressants (mianserin, amoxapine) and neuroleptics (clotiapine, loxapine and clozapine) were active in rather low concentrations (pKi less than 6.5), suggesting that recognition of 5-HT3 sites might be relevant to part of the in vivo effects of these drugs. Such identical physico-chemical and pharmacological properties of [3H]zacopride specific binding in cortical and NG 108-15 cell membranes strongly suggest that the same 5-HT3 receptor (subtype?) exists in these two preparations.


Subject(s)
Bridged Bicyclo Compounds, Heterocyclic , Cerebral Cortex/drug effects , Receptors, Serotonin/drug effects , Serotonin/pharmacology , Animals , Benzamides/pharmacology , Binding Sites/drug effects , Binding Sites/radiation effects , Bridged Bicyclo Compounds/pharmacology , Cations , Cell Membrane/drug effects , Clone Cells/drug effects , Hydrogen-Ion Concentration , Male , Rats , Rats, Inbred Strains , Receptors, Serotonin/chemistry , Serotonin Antagonists/pharmacology , Temperature
18.
Neuropsychopharmacology ; 3(5-6): 349-60, 1990.
Article in English | MEDLINE | ID: mdl-2078271

ABSTRACT

The 5-HT1 receptor family comprises five different pharmacologic subtypes, designated 5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, and 5-HT1E, whose common property is to bind 5-HT with nanomolar affinity. Recent investigations with molecular biology approaches led to the cloning and sequencing of 5-HT1A receptors in the rat and in the human, and of the 5-HT1C receptor in the rat. Although the 5-HT1A and 5-HT1C protein binding subunits exhibit the same structure with seven hydrophobic transmembrane domains, an extracellular N terminal and an intracellular C tail, their respective amino-acid sequences are markedly different. Indeed, a higher degree of sequence homology is found between the 5-HT1C and 5-HT2 receptors than between the former and 5-HT1A receptors, suggesting that the 5-HT1C subtype in fact belongs to the 5-HT2 class of central 5-HT receptors. All other 5-HT1 receptor subtypes are negatively coupled to adenylyl cyclase, whereas the 5-HT1C subtype, like 5-HT2 receptors, is positively coupled to phospholipase C. The respective regional distributions and regulatory properties, as well as pending questions regarding the ultrastructural localization, synthesis, mutual interactions, and axonal flow of 5-HT1 receptor subtypes, are also discussed.


Subject(s)
Central Nervous System/metabolism , Receptors, Serotonin/metabolism , Animals , Humans
19.
Am J Obstet Gynecol ; 163(1 Pt 1): 151-7, 1990 Jul.
Article in English | MEDLINE | ID: mdl-2375339

ABSTRACT

This is a prospective study of differential morbidity among subgroups of intrauterine growth retardation. Cases of intrauterine growth retardation (N = 3450) (greater than or equal to 37 weeks, less than 10th percentile birth weight for gestational age) were classified by their ponderal index (weight/length3) in four subgroups using the 10th, 25th, and 90th percentiles of the Lubchenco's ponderal index-gestational age distribution. There were 432 cases (12.5%) with low ponderal index or disproportionate intrauterine growth retardation, 936 (27.1%) with intermediate ponderal index, 2030 (58.8%) with adequate ponderal index or proportionate intrauterine growth retardation, and 52 (1.5%) with high ponderal index. The low ponderal index group or disproportionate intrauterine growth retardation group had a statistically significant higher risk (between 1.6 and 12.5 times) for low 1- and 5-minute Apgar scores, aspiration syndrome, hypoglycemia, and perinatal asphyxia than the adequate ponderal index group. The low ponderal index group also had an increased risk (relative risk = 2.0 [95% confidence interval, 1.0 to 3.8]) for hospital stay of more than 1 week. These differences persist after a stratified analysis by birth weight and in a multiple logistic regression analysis. Similarly, higher neonatal morbidity is observed among infants with normal birth weights but with low ponderal index. These data provide further evidence of the heterogeneity of the intrauterine growth retardation syndrome and of the independent effect of body disproportion on neonatal morbidity, even among infants with normal birth weights. Because there are significant clinical implications attributed to the low ponderal index group, this subgroup should be identified as early as possible.


Subject(s)
Fetal Growth Retardation/epidemiology , Birth Weight , Body Height , Cohort Studies , Delivery, Obstetric/methods , Fetal Growth Retardation/pathology , Follow-Up Studies , Humans , Infant, Low Birth Weight , Infant, Newborn , Morbidity , Prospective Studies
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