RESUMEN

PURPOSE: Evaluate the rate of breastfeeding at hospital discharge and then at 3 and 6 months in a population of premature infants. Analyze demographic and neonatal characteristics that may influence breastfeeding. METHOD: Prospective study in children born before 37 weeks of gestation from 1 June 2011 to 31 December 2011 hospitalized in the neonatology department at the Rabat children's hospital. The sociodemographic data and initial breastfeeding decision were collected from mothers. Newborns were reviewed in consultation at 1, 3, and 6 months to determine dietary habits. The association of variables with breastfeeding was analyzed by univariate and multivariate analysis using a logistic regression model. RESULTS: The analysis was based on 170 mother-infant pairs. At discharge, 80% of preterm infants received partial breastfeeding and 12.4% exclusive breastfeeding. At 6 months, 8.8% of mothers breastfed exclusively, 32.4% partially, and 58.8% had stopped breastfeeding. The factors associated with breastfeeding at 6 months were the duration of hospitalization in a neonatology unit and a neonatal intensive care unit, the time to first expressing breast milk, and breastfeeding. There was an inverse link between breastfeeding rates and duration of stay in neonatology in multivariate analysis with an odds ratio (OR) of 1.3 and a 95% confidence interval (1,1; 1,7); P=0.015. CONCLUSION: In our context, the rates of breastfeeding in premature infants remain below the recommended goals. The negative impact of the length of stay in the neonatal unit on breastfeeding is a challenge for health professionals who must adapt and strengthen the strategy of encouragement and support breastfeeding during the stay in neonatology and after discharge to ensure adequate nutrition for premature infants.

Asunto(s)

Lactancia Materna/estadística & datos numéricos , Recien Nacido Prematuro , Adulto , Humanos , Lactante , Recién Nacido , Marruecos , Estudios Prospectivos , Factores Socioeconómicos

RESUMEN

Zygophylle or Zygophyllum gaetulum Emberger and. Maire is a Moroccan medicinal plant which has been used as an anti-inflammatory, antidiabetic, antispasmodic and antidiarrheic. The present study was carried out to study and compare the anti-inflammatory effect of ethanolic extract with aqueous extract of Z. gaetulum. Organic extract of Z. gaetulum was obtained in soxhlet apparatus. Aqueous extract was obtained by infusion. The Wistar albinos rats of either sex weighing 200-300 g aged 2-3 months were used for this experiment. The rats were housed under standard environmental conditions. The anti-inflammatory activity was estimated by measuring the oedema induced by carragenin according to the method of Winter and al. Ethanolic extract of Z. gaetulum reduced the increase of the paw volume with a percentage of inhibition of 46% (p<0.01), this percentage was 47.48% (p<0.01) with aqueous extract. The inhibition decrease in time, it arrived to 39% (p<0.01) at the sixth hour while the activity of aqueous extract decrease a lot. In conclusion, Z. gaetulum is an interesting plant which the aqueous and éthanolic extracts could be used scientifically in the treatment of inflammation.

Asunto(s)

Antiinflamatorios/farmacología , Zygophyllum/química , Animales , Carragenina , Relación Dosis-Respuesta a Droga , Edema/inducido químicamente , Edema/tratamiento farmacológico , Etanol , Femenino , Inflamación/inducido químicamente , Inflamación/prevención & control , Masculino , Marruecos , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Solventes , Agua

RESUMEN

INTRODUCTION: Central nervous system involvement is rare in Wegener granulomatosis. Stroke is the most common event suggestive of the disease. COMMENT: A 35-year-old woman, who was followed for rhinitis and mild asthma, described gradual decline of visual acuity in the right eye over two months, persistent nasal obstruction and fronto-orbital headache since a few weeks. She presented left hemiparesis due to a stroke, associated with exophthalmos and deficits of the optic nerve and abducens of the right eye. The otolaryngological examination found signs of crusty rhinitis and right nasal stenosis. The diagnosis of Wegener's granulomatosis was established on the basis of the clinical findings, radiological aspects and the presence of ANCA. The patient was treated by antiplatelet agents and high-dose corticosteroids associated with immunosuppressive drugs including cyclophosphamide in a monthly bolus. DISCUSSION: This case illustrates two of the three pathogenic mechanisms that may account for central nervous system involvement in Wegener granulomatosis: vasculitis, extension by contiguity of granulomatous tissue from the nasal cavity or sinuses, and in situ formation of a granuloma into the brain parenchyma or meninges.

Asunto(s)

Isquemia Encefálica/etiología , Granulomatosis con Poliangitis/diagnóstico , Enfermedades del Nervio Abducens/etiología , Adulto , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Corteza Cerebral/irrigación sanguínea , Cuerpo Estriado/irrigación sanguínea , Ciclofosfamida/uso terapéutico , Exoftalmia/etiología , Femenino , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/inmunología , Humanos , Inmunosupresores/uso terapéutico , Imagen por Resonancia Magnética , Metilprednisolona/uso terapéutico , Obstrucción Nasal/etiología , Síndromes de Compresión Nerviosa/etiología , Enfermedades del Nervio Óptico/etiología , Paresia/etiología

RESUMEN

Stem bark of Allanblackia monticola has been used in association with others plant in the Cameroonian folk medicine for the treatment of various diseases such amoebic dysentery, diarrhoea, lung infections, and skin diseases. The methylene chloride fraction, its isolated compounds like alpha-mangostin, lupeol and acid betulinic were screened for antioxidant activity using free radical scavenging method. These isolated compounds were further tested for anti-inflammatory properties using carrageenan-induced model. Methylene chloride fraction, showed concentration-dependent radical scavenging activity, by inhibiting 1,1-diphenyl-1-picryl-hydrazyl radical (DPPH) with an IC(50) value of 14.60 microg/ml. alpha-Mangostin and betulinic acid (500 microg/ml), showed weak radical scavenging activity with a maximum inhibition reaching 38.07 microg/ml and 26.38 microg/ml, respectively. Betulinic acid, lupeol and alpha-mangostin (5 mg/kg and 9.37 mg/kg) showed anti-inflammatory activity with a maximum inhibition of 57.89%, 57.14% and 38.70%, respectively. Methylene chloride fraction of Allanblackia monticola and some derivatives, have antioxidant and anti-inflammatory activities.

Asunto(s)

Antiinflamatorios/farmacología , Antioxidantes/farmacología , Clusiaceae/química , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/aislamiento & purificación , Antioxidantes/administración & dosificación , Antioxidantes/aislamiento & purificación , Carragenina , Modelos Animales de Enfermedad , Femenino , Depuradores de Radicales Libres/aislamiento & purificación , Depuradores de Radicales Libres/farmacología , Inflamación/tratamiento farmacológico , Inflamación/fisiopatología , Concentración 50 Inhibidora , Masculino , Triterpenos Pentacíclicos , Corteza de la Planta , Ratas , Ratas Wistar , Triterpenos/administración & dosificación , Triterpenos/aislamiento & purificación , Triterpenos/farmacología , Xantonas/administración & dosificación , Xantonas/aislamiento & purificación , Xantonas/farmacología , Ácido Betulínico

RESUMEN

Saponins from Argania spinosa at a non-haemolytic concentration diminish by 53.2% erythrocyte haemolysis induced by free radicals. 2 mM aspirin and acetaminophen diminish by 75% and 68% , respectively, erythrocyte haemolysis induced by free radicals, while 0.3 microM vitamin E shows no significant antioxidant activity. Interestingly, a combination of 1 mg/l of A. spinosa saponins and vitamin E at 0.3 microM resulted in a 68% level of protection against free radical-induced erythrocyte haemolysis, which may suggest that A. spinosa saponins enhance the antioxidant effect of vitamin E. In contrast, no synergic effect was observed for acetaminophen (2 mM) when in combination with vitamin E (0.3 microM). These results demonstrate the antioxidant properties of saponins from A. spinosa and their ability to potentate the antioxidant effect of vitamin E.

Asunto(s)

Hemólisis/efectos de los fármacos , Saponinas/química , Saponinas/farmacología , Sapotaceae/química , Acetaminofén/farmacología , Animales , Aspirina/farmacología , Células Cultivadas , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Radicales Libres , Hemoglobinas/metabolismo , Humanos , Peróxido de Hidrógeno/química , Oxidación-Reducción

RESUMEN

We investigated the toxicity of the fixed oil of Nigella sativa L seeds in mice and rats through determination of LD50 values and examination of possible biochemical, hematological and histopathological changes. The acute toxicity of Nigella sativa fixed oil was investigated in mice. LD50 values, obtained by single doses, orally and intraperitoneally administered in mice, were 28.8 ml/kg body wt. p.o. [26.2-31.6] and 2.06 ml/kg body wt. i.p. [1.86-2.26], respectively. Chronic toxicity was studied in rats treated daily with an oral dose of 2 ml/kg body wt. for 12 weeks. Changes in key hepatic enzymes levels, including aspartate-aminotransferase, alanine-aminotranferase, and gamma-glutamyltransferase and histopathological modifications (heart, liver, kidneys and pancreas) were not observed in rats treated with Nigella sativa after 12 weeks of treatment. The serum cholesterol, triglyceride and glucose levels and the count of leukocytes and platelets decreased significantly, compared to control values, while hematocrit and hemoglobin levels increased significantly. A slowing of body weight gain was also observed in Nigella sativa treated rats, as compared to control animals. The low toxicity of Nigella sativa fixed oil, evidenced by high LD50 values, key hepatic enzyme stability and organ integrity, suggests a wide margin of safety for therapeutic doses of Nigella sativa fixed oil, but the changes in hemoglobin metabolism and the fall in leukocyte and platelet count must be taken into consideration.

Asunto(s)

Hígado/efectos de los fármacos , Hígado/enzimología , Aceites de Plantas/toxicidad , Enfermedad Aguda , Administración Oral , Alanina Transaminasa/efectos de los fármacos , Animales , Aspartato Aminotransferasas/efectos de los fármacos , Glucemia , Colesterol/sangre , Cromatografía en Capa Delgada , Enfermedad Crónica , Corazón/efectos de los fármacos , Hemoglobinas/efectos de los fármacos , Inyecciones Intraperitoneales , Riñón/efectos de los fármacos , Dosificación Letal Mediana , Recuento de Leucocitos , Ratones , Páncreas/efectos de los fármacos , Aceites de Plantas/administración & dosificación , Recuento de Plaquetas , Ratas , Ratas Wistar , Semillas , Triglicéridos/sangre , gamma-Glutamiltransferasa/efectos de los fármacos

RESUMEN

We investigated the effects of the fixed oil of Nigella sativa seeds in rats by monitoring blood homeostasis and body weight as well as toxicity. Animals were treated daily with an oral dose of 1 ml/kg body weight of the N. sativa seed fixed oil for 12 weeks. Changes in key hepatic enzymes levels were not observed in N. sativa treated rats after 12 weeks of treatment. The serum cholesterol, triglycerides and glucose levels and the count of leukocytes and platelets decreased significantly by 15.5, 22, 16.5, 35 and 32%, compared to control values, respectively; while haematocrit and haemoglobin levels increased significantly by 6.4 and 17.4%, respectively. In parallel, significant slowdown of the body weight evolution was observed in N. sativa treated animals comparatively to the animal control group. On the other hand, no mortality was noted for ten times the therapeutic dose in mice, during 15 days period after the oil administration (10 ml/kg p.o.). These results support the traditional use of N. sativa seeds as a treatment of the dyslipidemia and the hyperglycaemia, and related abnormalities; however, indicate a relative toxicity of this plant. Acute and chronic toxicity, and the mode of the action of the N. sativa fixed oil must be studied.

Asunto(s)

Sangre/efectos de los fármacos , Hígado/efectos de los fármacos , Aceites de Plantas/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Homeostasis/efectos de los fármacos , Hígado/enzimología , Ratones , Ratas , Ratas Endogámicas WKY

RESUMEN

A novel allele of the GXAlu tetranucleotide repeat in intron 27b of the neurofibromatosis 1 (NF1) gene has recently been reported to be present in 4.7% of autistic patients but not in controls. We have found the novel GXAlu allele absent in 204 patients from the South Carolina Autism Project and 200 controls. The autism population studied includes a significant number of patients with hypotonia, stereotyped behaviors, or postural, gait, and motor abnormalities similar to those seen in the patients previously reported to possess the novel GXAlu allele. This suggests that the novel (AAAT)6 GXAlu allele is not associated with autism.

Asunto(s)

Alelos , Trastorno Autístico/genética , Genes de Neurofibromatosis 1/genética , Intrones/genética , Repeticiones de Microsatélite/genética , Trastorno Autístico/patología , Secuencia de Bases , Femenino , Frecuencia de los Genes , Humanos , Masculino

RESUMEN

The 1p31 chromosomal region shows loss of heterozygosity (LOH) in up to 50% of human breast cancer, indicating the presence of a tumor suppressor gene at this location. Many efforts have been made to identify candidate genes responsible for breast cancer on the short arm of chromosome 1. It was shown that prostaglandins have been implicated in the tumorigenesis pathway, perhaps via interactions with their cell surface receptors. The prostaglandin F2 receptor gene (PTGFR) was tentatively mapped to 1p31 adjacent to the region undergoing LOH in human breast cancer. We undertook a mutation study in 34 sporadic human breast tumors using a variant of SSCP, incorporation PCR SSCP (IPS). Several nucleotide variants were detected in different tumors. Here we report the nature of these nucleotide changes and the possible involvement of the PTGFR gene in the etiology of human cancer.

Asunto(s)

Neoplasias de la Mama/genética , Cromosomas Humanos Par 1/genética , Receptores de Prostaglandina/genética , Secuencia de Bases , Mapeo Cromosómico , Cromosomas Artificiales Bacterianos , Cromosomas Artificiales de Levadura , Mapeo Contig , Análisis Mutacional de ADN , ADN de Neoplasias/química , ADN de Neoplasias/genética , Humanos , Mutación , Polimorfismo Conformacional Retorcido-Simple

RESUMEN

Extensive analysis of tumors has demonstrated homozygous and heterozygous deletions in chromosome region 13q14.3 in B-cell chronic lymphocytic leukemia (B-CLL), suggesting the site of a tumor suppressor gene. Since previous searches for this gene have not yielded any viable candidates, we now present the sequence of the BACs which span the minimally deleted approximately 650 kb region between markers D13S319 and D13S25. This sequence has allowed us to create the definitive transcription map for the region which reveals 93 ESTs and 12 Unigene clusters in this region. Using gene prediction programs, a further 19 potential genes are also identified. The genes show an asymmetrical distribution throughout the region with most of them clustering at the extreme ends. This sequencing effort provides for the definitive structure of the B-CLL deletion region and the identification of the vast majority of the potential candidate genes. Of all the genes identified, only three have homologies to known genes: two L1 repeat genes and rabbit epididymal protein 52. This 13q14.3 sequence provides the final substrate from which to characterize the B-CLL tumor suppressor gene.

Asunto(s)

Cromosomas Humanos Par 13/genética , Mapeo Contig/métodos , Eliminación de Gen , Genes Supresores de Tumor , Leucemia Linfocítica Crónica de Células B/genética , Cromosomas Artificiales Bacterianos , Clonación Molecular , Secuencia de Consenso , Etiquetas de Secuencia Expresada , Humanos

RESUMEN

A recent study has suggested that a dodecamer duplication in the HOPA gene in Xq13 may occur in a significant portion of male patients with autism. We have determined the incidence of this duplication in 202 patients from the South Carolina Autism Study. The incidence of the duplication was not significantly different between patients and controls. Three of the female patients inherited the duplication from nonautistic fathers. In addition, there was no systematic skewing of X inactivation in the female patients with the duplication, or in nonautistic mothers and sisters with the duplication. These findings suggest that the dodecamer duplication in the HOPA gene does not play a significant role in the etiology of autism.

Asunto(s)

Trastorno Autístico/genética , Duplicación de Gen , Expresión Génica/genética , Adulto , Trastorno Autístico/epidemiología , Femenino , Ligamiento Genético , Humanos , Incidencia , Masculino , Cromosoma X/genética

RESUMEN

A recent study suggested that a dodecamer duplication in exon 42 of the HOPA gene in Xq13 may be a significant factor in the etiology of X-linked mental retardation. In an effort to investigate this possibility, we determined the incidence of the dodecamer duplication in cohorts of non-fragile X males with mental retardation from three countries, cohorts of fragile X males from two countries, 43 probands from families with X-linked mental retardation and control cohorts from three countries. The duplication was found in 3.6-4.0% of male patients from two non-fragile X groups (Italy and South Carolina), in 1.2% from another non-fragile X group (South Africa), but in no male patients from families with X-linked mental retardation (South Carolina). The dodecamer duplication was also found in several white males with fragile X syndrome from France (5%) and South Africa (22.2%). Additionally, the duplication was found in 1.5% of South Carolinian newborn males, 2.5% South Carolinian male college students, 5% Italian male controls and 4.5% of the white South African controls. None of the black South African non-fragile X individuals with mental retardation, the fragile X or the control samples tested carried the duplication, suggesting that the duplication is rare in the black South African population. The incidence of the duplication was not significantly different between any of the groups in the study. Therefore, results of our studies in four different populations do not corroborate the findings of the previous study, and indicate that the HOPA dodecamer duplication does not convey an increased susceptibility to mental retardation.

Asunto(s)

Síndrome del Cromosoma X Frágil/genética , Duplicación de Gen , Discapacidad Intelectual/genética , Cromosoma X , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Análisis Mutacional de ADN , Femenino , Ligamiento Genético , Humanos , Recién Nacido , Desequilibrio de Ligamiento , Masculino , Polimorfismo Genético

RESUMEN

A novel human gene, TRPC5, was cloned from the region of Xq23 that contains loci for nonsyndromic mental retardation (MRX47 and MRX35) and two genes, DCX and HPAK3, implicated in two X-linked disorders (LISX and MRX30). Within a single YAC, we have determined the order cen-HPAK3(5'-3')-DCX(3'-5')-DXS7012E-TRPC5(3'-5' )-ter. TRPC5 encodes a 974-residue novel human protein (111.5 kDa predicted mass) and displays 99% homology with mouse TRP5, (MGD-approved symbol Trrp5) a novel member of a family of receptor-activated Ca2+ channels. It contains eight transmembrane domains, including a putative pore region. A transcript larger than 9.5 kb is observed only in fetal and adult human brain, with a relatively higher level in the adult human cerebellum. We devised an efficient method, Incorporation PCR SSCP (IPS), for detection of gene alterations. Five single-nucleotide variations in the TRPC5 gene were identified in males with mental retardation. However, these were found to be polymorphic variants. Exclusive expression of the TRPC5 gene in developing and adult brain suggests a possible role during development and provides a candidate gene for instances of mental retardation and other developmental defects.

Asunto(s)

Canales de Calcio/genética , Proteínas de Transporte de Catión , Alineación de Secuencia , Secuencia de Aminoácidos , Animales , Encéfalo , Canales de Calcio/aislamiento & purificación , Clonación Molecular , Análisis Mutacional de ADN , Proteína Doblecortina , Exones , Expresión Génica , Humanos , Discapacidad Intelectual/genética , Ratones , Datos de Secuencia Molecular , Filogenia , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Polimorfismo Conformacional Retorcido-Simple , Canales Catiónicos TRPC , Cromosoma X/genética

RESUMEN

A map has been assembled that extends from the XY homology region in Xq21.3 to proximal Xq24, approximately 20 Mb, formatted with 200 STSs that include 25 dinucleotide repeat polymorphic markers and more than 80 expressed sequences including 30 genes. New genes HTRP5, CAPN6, STPK, 14-3-3PKR, and CALM1 and previously known genes including BTK, DDP, GLA, PLP, COL4A5, COL4A6, PAK3, and DCX are localized; candidate loci for other disorders for which genes have not yet been identified, including DFN-2, POF, megalocornea, and syndromic and nonsyndromic mental retardation, are also mapped in the region. The telomeric end of the contig overlaps a yeast artificial chromosome (YAC) contig from Xq24-q26 and with other previously published contigs provides complete sequence-tagged site (STS)/YAC-based coverage of the long arm of the X chromosome. The order of published landmark loci in genetic and radiation hybrid maps is in general agreement. Combined with high-density STS landmarks, the multiple YAC clone coverage and integrated genetic, radiation hybrid, and transcript map provide resources to further disease gene searches and sequencing.

Asunto(s)

Mapeo Cromosómico/métodos , Cromosomas Artificiales de Levadura , Mapeo Físico de Cromosoma , Lugares Marcados de Secuencia , Cromosoma X , Cartilla de ADN , Bases de Datos Factuales , Etiquetas de Secuencia Expresada , Marcadores Genéticos , Humanos

RESUMEN

Mutations in the human doublecortin (DCX), a brain-specific putative signaling protein, cause X-linked lissencephaly and subcortical band heterotopia. A predicted 740-amino-acid protein from human brain has two distinct regions, an N-terminal 345-amino-acid region 78% similar to the DCX protein and a C-terminal 427-amino-acid region that contains two transmembrane domains and is 98% homologous to a rat Ca2+/calmodulin-dependent protein kinase. We have designated this protein DCAMKL1. It maps to chromosome 13q12.3-q13, within a 540-kb YAC clone containing markers D13S805 and D13S1164. Northern analysis detected three major transcript isoforms of the DCAMKL1 gene expressed differentially and predominantly in human fetal and adult brain and during mouse embryogenesis (11-17 dpc). These results and its homology with the DCX and Ca2+/calmodulin dependent kinase proteins suggest a likely role for DCAMKL1 transmembrane protein in developing and adult brain, possibly in a pathway of cortical development.

Asunto(s)

Química Encefálica/genética , Proteínas Quinasas Dependientes de Calcio-Calmodulina/genética , Cromosomas Humanos Par 13/genética , Proteínas Asociadas a Microtúbulos , Neuropéptidos/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Proteínas de Dominio Doblecortina , Proteína Doblecortina , Quinasas Similares a Doblecortina , Humanos , Péptidos y Proteínas de Señalización Intracelular , Datos de Secuencia Molecular , Proteínas Serina-Treonina Quinasas/genética , Ratas , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico , Factores de Tiempo , Distribución Tisular

RESUMEN

We evaluated the acute and chronic experimental toxicity of a water extract of saponins from Argania spinosa following oral and intraperitoneal (i.p.) administration in mice (Iops Ofa) and rats (Wistar). The DL50 obtained were 79 mg/kg for the i.p. route and 1,300 mg/kg for the oral route. For the chronic toxicity studies, we administred 100 and 200 mg/kg orally once a day during a 3 month period. There was a decrease in blood sugar in the third month of each therapy. Blood creatinine levels increased, thus evoking a renal pathology. A slight increase in transaminases levels was not significatif. Hematologic parameters were unchanged during the treatment and the histopathologic study showed hepatic glycogen decrease and a focal renal tube deterioration.

Asunto(s)

Saponinas/toxicidad , Administración Oral , Animales , Secuencia de Carbohidratos , Esquema de Medicación , Femenino , Inyecciones Intraperitoneales , Riñón/efectos de los fármacos , Riñón/patología , Dosificación Letal Mediana , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones , Datos de Secuencia Molecular , Estructura Molecular , Ratas , Ratas Wistar , Saponinas/administración & dosificación , Árboles

RESUMEN

We studied analgesic and antiinflammatory actions of saponins of Argania spinosa cakes in mice and rats. With oral doses of 50 to 300 mg/kg, we found peripheric analgesic actions equivalent to the acetyl salicylic acid ones. The maximum protection was obtained with 500 mg/kg per os. There is no morphine-like central analgesic effect. Antiinflammatory studies were done in vivo using oedema due to carrageenine or experimental trauma in rats. There was a decrease in the paw swelling at doses of 10 mg/kg per os. At doses of 50 to 100 mg/kg per os, the antiinflammatory effect was similar to the one of indomethacin at doses of 10 to 20 mg/kg per os. In vitro, there was an inhibition of beef synovial fluid degradation by OH. radicals. The inhibition action is evaluated with an IC20 > or = 6 microM. Argania spinosa saponins have also an antiradical action against DPPH (IC25 = 85 mM) and against OH. radicals (IC25 = 0.56 M). Since they do not have any inhibition effect on PGE2 synthesis, their antiinflammatory activity can be explained by their action on leucotriens in the metabolic pathway of arachidonic acid.

Asunto(s)

Analgésicos/farmacología , Antiinflamatorios no Esteroideos/farmacología , Saponinas/farmacología , Animales , Aspirina/farmacología , Edema , Indometacina/farmacología , Ratones , Dolor , Ratas , Árboles

RESUMEN

Subcortical band heterotopia (SBH) and classical lissencephaly (LIS) result from deficient neuronal migration which causes mental retardation and epilepsy. A single LIS/SBH locus on Xq22.3-q24 was mapped by linkage analysis and physical mapping of the breakpoint in an X;2 translocation. A recently identified gene, doublecortin ( DCX ), is expressed in fetal brain and mutated in LIS/SBH patients. We have identified four novel missense mutations in the gene, one familial mutation with LIS in a male and SBH in the carrier females, one de novo mutation in an SBH female, and two mutations in sporadic SBH female patients. The DCX gene is found to be expressed exclusively at a very high level in the adult frontal lobe. We have also cloned the X-linked mouse doublecortin (Dcx) gene. It encodes isoforms of a highly hydrophilic 40 kDa protein, homologous to its human counterpart and containing several potential phosphorylation sites. Both human and mouse DCX proteins are homologous to a CNS protein containing a Ca2+/calmodulin kinase domain, suggesting that the DCX protein may belong to a novel class of intracellular proteins involved in neuronal migration through Ca2+-dependent signaling.

Asunto(s)

Movimiento Celular/genética , Epilepsia/genética , Discapacidad Intelectual/genética , Proteínas Asociadas a Microtúbulos , Neuronas/patología , Neuropéptidos/genética , Cromosoma X , Adulto , Secuencia de Aminoácidos , Animales , Calcio/metabolismo , Proteínas de Dominio Doblecortina , Proteína Doblecortina , Epilepsia/metabolismo , Epilepsia/patología , Femenino , Ligamiento Genético , Humanos , Discapacidad Intelectual/metabolismo , Discapacidad Intelectual/patología , Masculino , Ratones , Datos de Secuencia Molecular , Homología de Secuencia de Aminoácido , Transducción de Señal/genética

RESUMEN

1. Experiments were designed to study the involvement of alpha-adrenoceptors and dopamine receptors in the hypotensive and bradycardic actions of bromocriptine in rats. 2. Intravenous administration of bromocriptine reduced blood pressure and heart rate which was inhibited by ganglionic blocking agents or by pithing. 3. The fall in blood pressure produced by bromocriptine was not modified by atropine, atenolol, prazosin, yohimbine, bilateral vagotomy or carotid ligation, but was blocked by sulpiride, domperidone and haloperidol. 4. The bradycardia produced by bromocriptine in intact rats was assumed to be mediated by the autonomic nervous system since it was partly reduced by bilateral vagotomy or atenolol, and entirely prevented by pithing. Furthermore, sulpiride but not yohimbine antagonized this effect. 5. In pithed rats, bromocriptine decreased both the pressor response (above 10 micrograms kg-1) and the tachycardia (above 50 micrograms kg-1) elicited by electrical stimulation of spinal cord outflow. Both effects were inhibited by sulpiride or yohimbine. 6. In pithed rats, bromocriptine did not affect the hypertension due to exogenous noradrenaline, phenylephrine, B-HT 920, nor the bradycardia evoked by stimulation of the cardiac muscarinic receptors by carbachol. 7. These results suggest that, in rats, bromocriptine produces hypotension via an action on presynaptic and/or ganglionic dopamine receptors, and causes bradycardia by activation of central dopamine receptors.

Asunto(s)

Bromocriptina/farmacología , Hemodinámica/efectos de los fármacos , Receptores Adrenérgicos alfa/efectos de los fármacos , Receptores Dopaminérgicos/efectos de los fármacos , Anestesia , Animales , Presión Sanguínea/efectos de los fármacos , Carbacol/farmacología , Estado de Descerebración , Estimulación Eléctrica , Frecuencia Cardíaca/efectos de los fármacos , Isoproterenol/farmacología , Masculino , Norepinefrina/farmacología , Pentobarbital , Ratas , Ratas Endogámicas

RESUMEN

The effects of local administration of bromocriptine were studied in the isolated autoperfused hindquarters of the rat, and compared to the actions of apomorphine and pergolide. Local injection of bromocriptine (1 microgram kg-1) (into the hindquarters) did not alter perfusion pressure, but reduced the pressor response to electrical stimulation of the lumbar sympathetic chains at all frequencies used (0.5-10 Hz; 5 ms; 35 V). Bromocriptine (1 microgram kg-1) did not alter the increases in perfusion pressure induced by local administration of noradrenaline. The effects of local administration of apomorphine (1 microgram kg-1) and pergolide (1 microgram kg-1) were similar to that of bromocriptine. The inhibitory effect by bromocriptine, apomorphine and pergolide of the stimulation-evoked pressor responses was completely antagonized by intravenous administration of the dopamine receptor antagonist sulpiride (0.3 mg kg-1) but was not by the alpha 2-adrenoceptor antagonist yohimbine (1 mg kg-1). In this dose, yohimbine antagonized the inhibitory effect of the alpha-adrenoceptor agonist clonidine (1 microgram kg-1). The inhibitory effect of clonidine was not altered by sulpiride but was antagonized by yohimbine. The results indicate that bromocriptine like apomorphine and pergolide inhibit neurally-induced pressor responses in the autoperfused hindquarters of the rat by stimulation of presynaptic dopamine receptors. Stimulation of these receptors leading to a fall in noradrenaline release and consequently of vasomotor tone, might at least in part explain the vasodilatator effects of bromocriptine in the rat.

Asunto(s)

Bromocriptina/farmacología , Vasoconstricción/efectos de los fármacos , Animales , Apomorfina/administración & dosificación , Apomorfina/farmacología , Miembro Posterior , Masculino , Perfusión , Pergolida/administración & dosificación , Pergolida/farmacología , Ratas , Ratas Endogámicas , Receptores Dopaminérgicos/efectos de los fármacos , Sulpirida/farmacología