RESUMEN
Hurricane Harvey was a category four storm that induced catastrophic flooding in the Houston metropolitan area. Following the hurricane there was increased concern regarding chemical exposures due to damage caused by flood waters and emergency excess emissions from industrial facilities. This study utilized personal passive samplers in the form of silicone wristbands in Houston, TX to both assess chemical exposure to endocrine disrupting chemicals (EDCs) immediately after the hurricane and determine participant characteristics associated with higher concentrations of exposure. Participants from the Houston-3H cohort (n = 172) wore a wristband for seven days and completed a questionnaire to determine various flood-related and demographic variables. Bivariate and multivariate analysis indicated that living in an area with a high Area Deprivation Index (ADI) (indicative of low socioeconomic status), identifying as Black/African American or Latino, and living in the Houston neighborhoods of Baytown and East Houston were associated with increased exposure to EDCs. These results provide evidence of racial/ethnic and socioeconomic injustices in exposure to EDCs in the Houston Metropolitan Area. Since the multiple regression models conducted did not fully explain exposure (0.047 < R2 < 0.34), more research is needed on the direct sources of EDCs within this area to create effective exposure mitigation strategies.
Asunto(s)
Tormentas Ciclónicas , Disruptores Endocrinos , Humanos , Inundaciones , Hispánicos o Latinos , Encuestas y CuestionariosRESUMEN
The effects of the (+) and (-) enantiomers of the antidepressant drug tianeptine (5, 10, 20 mg/kg, i.p.) on wet dog shakes (WDS) and faecal pellet production induced by concurrently administered 5-hydroxytryptophan (5-HTP, 100 mg/kg, i.p.) given 30 min after carbidopa (25 mg/kg, i.p.) were investigated in rats. WDS scores peaked approximately 1 hr after giving 5-HTP and gradually declined over the next 2 hr. (-)-Tianeptine dose-dependently and significantly inhibited WDS. Inhibition became less marked with time after administration, but remained significant over the 3 hr period after the 10 and 20 mg/kg doses and during the first 40 min after the 5 mg/kg dose. (+)-Tianeptine caused slight inhibition without dose-dependence and slightly increased net inhibition when added to the (-) isomer (10 mg/kg). The induction of faecal pellet production by 5-HTP was significantly and dose-dependently inhibited by (-)-tianeptine. The (+) isomer neither altered this effect of 5-HTP nor its inhibition by (-)-tianeptine. Results show that inhibition of 5-HTP-induced WDS and faecal pellet formation by tianeptine was almost completely dependent on the (-) isomer.
Asunto(s)
5-Hidroxitriptófano/farmacología , Antidepresivos Tricíclicos/farmacología , Conducta Animal/efectos de los fármacos , Tiazepinas/farmacología , Animales , Antidepresivos Tricíclicos/química , Masculino , Ratas , Ratas Sprague-Dawley , Estereoisomerismo , Tiazepinas/químicaRESUMEN
The widely prescribed appetite suppressants D-fenfluramine and fluoxetine not only decrease feeding and body weight but also increase extracellular brain 5-HT. As central injection of 5-HT also decreases feeding, the drugs are often thought to require an increase of 5-HT at receptors in order to exert their hypophagic effect. However, much evidence now suggests that D-fenfluramine and its metabolite D-norfenfluramine can cause hypophagia by acting directly at unspecified 5-HT receptors and at 5-HT2C receptors, respectively, while fluoxetine may act independently of 5-HT receptors. These hypophagias may involve interference with the hyperphagic action of neuropeptide Y.
Asunto(s)
Depresores del Apetito/farmacología , Encéfalo/metabolismo , Ingestión de Alimentos/efectos de los fármacos , Fenfluramina/farmacología , Fluoxetina/farmacología , Receptores de Serotonina/efectos de los fármacos , Depresores del Apetito/administración & dosificación , Depresores del Apetito/uso terapéutico , Peso Corporal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Agonistas de Dopamina/metabolismo , Agonistas de Dopamina/farmacología , Ingestión de Alimentos/fisiología , Femenino , Fenfluramina/administración & dosificación , Fenfluramina/uso terapéutico , Fluoxetina/administración & dosificación , Fluoxetina/uso terapéutico , Humanos , Masculino , Neuropéptido Y/metabolismo , Receptores de Serotonina/metabolismo , Serotoninérgicos/administración & dosificación , Serotoninérgicos/farmacología , Serotoninérgicos/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéuticoRESUMEN
A tissue-chamber model of inflammation in mice has been modified and used to investigate the kinetics of zymosan-induced inflammatory mediators such as tumour necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta) and prostaglandin E2 (PGE2). In addition, the influx of polymorphonuclear leukocytes (PMN) into the chamber fluid and the granuloma surrounding the chamber was measured by myeloperoxidase (MPO) activity using a new microtitre plate assay. TNF alpha and IL-1 beta reached a peak concentrations at 3 and 6 h respectively after zymosan injection. Intermediate high concentrations of IL-1 beta were observed until the end of the experiment at 72 h, but TNF alpha concentrations decreased from 24 h to biologically insignificant values. In contrast, exudate PGE2 and MPO activity increased up to 24 h after zymosan injection and remained high until 72 h. At 6 h after zymosan challenge, oral pre-treatment with prednisolone (3 to 30 mg/kg) dose-dependently reduced TNF alpha, IL-1 beta and PGE2 concentrations while indomethacin (0.3 to 3 mg/kg) significantly attenuated PGE2, slightly enhanced TNF alpha and had no effect on IL-1 beta concentrations in the exudate. Both drugs had similar potencies against exudate and tissue MPO activities. Prednisolone inhibited IL-1 beta at 72 h post-zymosan. Indomethacin was more potent than prednisolone against PGE2 (ID50 of< 0.3 versus 0.6 mg/kg). The data obtained confirm the usefulness and reliability of this model in evaluating the effects of anti-inflammatory agents on inflammatory mediators induced by zymosan.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios/farmacología , Indometacina/farmacología , Inflamación/tratamiento farmacológico , Prednisolona/farmacología , Animales , Dinoprostona/metabolismo , Exudados y Transudados/citología , Femenino , Granuloma/patología , Inflamación/inducido químicamente , Interleucina-1/metabolismo , Ratones , Ratones Endogámicos , Peroxidasa/antagonistas & inhibidores , Peroxidasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , ZimosanRESUMEN
d-Fenfluramine (2.5 mg/kg i.p.) caused marked hypophagia in food-deprived rats and significantly increased medial hypothalamic extracellular 5-hydroxytryptamine (5-HT) as indicated by in vivo microdialysis. When the drug was given after the 5-HT synthesis inhibitor p-chlorophenylalanine (150 mg/kg per day x 3) the hypophagic response was unimpaired but dialysate 5-HT concentration no longer rose. The d-fenfluramine metabolite d-norfenfluramine (1.5 mg/kg i.p.) caused slightly greater hypophagia than the parent drug and completely blocked feeding in animals pretreated with p-chlorophenylalanine, but dialysate 5-HT was increased in neither circumstance. The results provide evidence against mediation of the hypophagic effects of d-fenfluramine and d-norfenfluramine by increased availability of 5-HT to receptors.
Asunto(s)
Trastornos de Alimentación y de la Ingestión de Alimentos/inducido químicamente , Fenfluramina/farmacología , Hipotálamo/metabolismo , Norfenfluramina/farmacología , Serotonina/metabolismo , Animales , Ingestión de Alimentos , Trastornos de Alimentación y de la Ingestión de Alimentos/metabolismo , Fenclonina/farmacología , Hipotálamo/efectos de los fármacos , Masculino , Microdiálisis , Ratas , Ratas Sprague-Dawley , Receptores de Serotonina/metabolismoRESUMEN
A series of closely related peptide analogues of Lys-Pro-Thr [(interleukin-1 beta-(193-195)] have been investigated in two models of antinociception in mice (acetic acid-induced abdominal constrictions and formalin tests) and compared with morphine, aspirin and indomethacin. Formalin-induced nociceptive responses in the mouse showed early (0-5 min) and late (15-30 min) phases of peak activity. Lys-D-Pro, Lys-D-Pro-Thr, Lys-D-Pro-Arg, Lys-D-Pro-Val, morphine and aspirin, were antinociceptive in both phases after intraperitoneal (i.p.) and oral (p.o.) administrations. Lys-D-Pro-Leu inhibited the early phase response only after i.p. injection. Lys-D-Pro-Val-NH2, Lys-D-Pro-Gln, Lys-D-Pro-Tyr, Lys-D-Pro-Asn, Asp-Lys-D-Pro-Val and indomethacin were active only against the late phase (ED50 values of 64, 32, 44, 94, 67 and 25 mg/kg i.p., respectively). Several of the peptides showed good bio-availability, e.g. Lys-D-Pro-Asn (ED50: 10 mg/kg i.p.; 11.4 mg/kg p.o.) in the abdominal constrictions test, where two modes of action were apparent, non-opioid and opioid; non-opioid (naloxone-insensitive antinociception) mechanisms were illustrated by Lys-D-Pro-Thr and Lys-D-Pro-Asn; opioid (naloxone-sensitive antinociception) mechanisms by Lys-D-Pro-Val and Lys-D-Pro-Leu. These data identify orally active antinociceptive peptides in both antinociceptive tests with varied relative potency profiles to morphine, indomethacin and aspirin in the mouse formalin test.
Asunto(s)
Analgésicos/farmacología , Interleucina-1/farmacología , Fragmentos de Péptidos/farmacología , Abdomen , Administración Oral , Secuencia de Aminoácidos , Animales , Relación Dosis-Respuesta a Droga , Inyecciones Intraperitoneales , Interleucina-1/química , Interleucina-1beta , Masculino , Ratones , Datos de Secuencia Molecular , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Dimensión del Dolor , Fragmentos de Péptidos/químicaRESUMEN
Male and female rats were given d-fenfluramine and its effects on feeding and on hypothalamic concentrations of the drug, its metabolite norfenfluramine and 5-hydroxytryptamine (5-HT) and dopamine determined. ID50 values (i.p.) for the hypophagic effect of the drug on 30-, 42- and 100-day-old rats measured over 2 h during the light phase after 24 h food deprivation did not vary significantly with sex but tended to decrease with age approximately in parallel with daily percentage increases and (after deprivation) of decreases in body weight. However, male but not female 30-day-old rats showed a rebound of feeding during the subsequent 2 h. ID50 values of 42-day-old rats on a palatable diet or measured during the dark phase when freely feeding also did not vary with sex. Male 30-day-old rats killed at 2-10 h after an ID75 (p.o.) dose of d-fenfluramine had substantially lower hypothalamic concentrations of the drug and comparable or slightly lower concentrations of its metabolite norfenfluramine than 30-day-old females. Similarly treated 100-day-old males also had lower concentrations of fenfluramine but significantly higher norfenfluramine levels than females so that drug plus metabolite concentrations were essentially independent of sex. 100-day-old females killed 2 h, 24 h and 7 days after d-fenfluramine (3.8 mg/kg p.o. = ID75) had larger percentage decreases of hypothalamic 5-HT than identically treated males. Percentage decreases of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) tended to become less marked with time after injection in males but not females.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Dopamina/metabolismo , Conducta Alimentaria/efectos de los fármacos , Fenfluramina/farmacología , Hipotálamo/metabolismo , Serotonina/metabolismo , Ácido 3,4-Dihidroxifenilacético/metabolismo , Animales , Dieta , Femenino , Fenfluramina/farmacocinética , Privación de Alimentos , Ácido Hidroxiindolacético/metabolismo , Hipotálamo/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Caracteres SexualesRESUMEN
The involvement of arginine vasopressin (AVP) has been investigated in cold water swim (CWS) stress-induced antinociception (SIA) and CWS-induced hypothermia. The antinociceptive action of AVP (0.5 micrograms, i.c.v.) pre-CWS was antagonized by d(CH2)5Tyr(Me)AVP (0.5 micrograms, i.c.v.) but not by naloxone (5 micrograms, i.c.v.). CWS produced SIA on the hot-plate which was initially naloxone-insensitive. Neither AVP nor its antagonist had any significant effect on CWS SIA. AVP-induced increase in body temperature, during recovery from CWS-induced hypothermia, was significantly (P < 0.001) reduced in the presence of its antagonist. These findings suggest that the antinociceptive and thermoregulatory actions of AVP may be mediated via V1-receptors.
Asunto(s)
Analgésicos , Antagonistas de Receptores de Angiotensina , Arginina Vasopresina/análogos & derivados , Arginina Vasopresina/farmacología , Regulación de la Temperatura Corporal/efectos de los fármacos , Receptores de Vasopresinas , Animales , Inyecciones Intraventriculares , Masculino , Ratones , Ratones Endogámicos , Sensibilidad y EspecificidadRESUMEN
The antinociceptive activities of morphine, and its quaternary analogue methylmorphine, have been compared after intraperitoneal and intracerebroventricular administrations in the mouse paw formalin test. Systemic morphine inhibited both the early and late phases of the formalin-induced licking response and this activity was naloxone sensitive. In contrast, systemic methylmorphine inhibited only the late phase, and this activity was blocked by pre-treatment with methylnaloxone. Central administration of either morphine or methylmorphine inhibited the early phase of the licking response partially and the late phase completely. Systemic naloxone inhibited the central action of both opioids, whilst systemic methylnaloxone did not affect the central action of methylmorphine. The results indicate that the early phase of the response to formalin in the mouse may be inhibited by stimulation of central opioid receptors whilst inhibition of the late phase may involve both peripheral and central opioid receptors.
Asunto(s)
Analgésicos/farmacología , Codeína/farmacología , Morfina/farmacología , Dolor/tratamiento farmacológico , Animales , Codeína/análisis , Relación Dosis-Respuesta a Droga , Formaldehído , Inyecciones Intraventriculares , Masculino , Ratones , Ratones Endogámicos , Morfina/antagonistas & inhibidores , Antagonistas de Narcóticos/farmacología , Oximorfona/farmacología , Dolor/inducido químicamente , Dimensión del DolorRESUMEN
The antinociceptive activity of histamine in male mice has been demonstrated using chemical and thermal noxious stimuli and its involvement in naloxone-sensitive and naloxone-insensitive models of stress-induced antinociception investigated. In the abdominal constriction test, histamine and dimaprit but not histidine, induced antinociception. Compound 48/80 and H1 antagonists (diphenhydramine, mepyramine and promethazine) and large doses of H2 antagonists (cimetidine and zolantidine) produced antinociception in this test. Antinociception induced by histamine was refractory to mepyramine, metiamide and naloxone. Histamine and non-antinociceptive doses of its antagonists had no influence on the naloxone-resistant warm water swim stress-induced antinociception. In the hot-plate test, histamine agonists, except the H3 agonist (R) alpha-methyl histamine (alpha-MeHA), were antinociceptive but all these agents augmented the naloxone-sensitive room temperature swim stress-induced antinociception, after either intraperitoneal or intraventricular injection. The antinociceptive action of dimaprit was not antagonized by zolantidine which, like other histamine antagonists excluding metiamide, also produced antinociception and enhanced room temperature swim stress-induced antinociception. These findings suggest that histamine is involved in pathways mediating antinociception in the mouse and that such pathways are activated in a naloxone-sensitive model of stress-induced antinociception but not in a naloxone-insensitive model.
Asunto(s)
Histamina/fisiología , Naloxona/farmacología , Dolor/fisiopatología , Estrés Fisiológico/fisiopatología , Animales , Tolerancia a Medicamentos , Antagonistas de los Receptores Histamínicos/farmacología , Calor , Masculino , Ratones , Ratones Endogámicos , Esfuerzo Físico , Receptores Histamínicos/efectos de los fármacosRESUMEN
1. L-NG-nitro arginine methyl ester (L-NAME, 1-75 mg kg-1) administered intraperitoneally (i.p.) elicits dose-related antinociception in the mouse assessed by the formalin-induced paw licking procedure. Antinociceptive activity is still present 24 h after injection. L-NAME (75 mg kg-1, i.p.) is also antinociceptive in the acetic acid-induced abdominal constriction and hot plate procedures. 2. L-NAME additionally produces a dose-related inhibition of formalin-induced paw licking following intracerebroventricular (i.c.v., 0.1-100 microgram per mouse) and oral (p.o., 75-150 mg kg-1) administration. 3. L-Arginine (600 mg kg-1, i.p.) but not D-arginine (600 mg kg-1) or naloxone (5 mg kg-1) reverses the antinociceptive effect of L-NAME in the formalin test. 4. High doses of L-NAME (37.5-600 mg kg-1) but not D-NAME (75 mg kg-1) administered i.p. produce dose-related increases in blood pressure of the urethane-anaesthetized mouse whilst i.c.v. injected L-NAME (0.1 and 100 microgram per mouse) in inactive. 5. L-NAME (75 mg kg-1, i.p.) did not inhibit oedema formation in the formalin-injected mouse hindpaw. 6. L-NAME (75 mg kg-1) did not produce any overt behavioural changes in treated mice and failed to influence locomotor activity or the incidence of dipping, crossing, rearing or circling behaviour assessed by a modified 'head-dipping' board procedure. A high dose of L-NAME (600 mg kg-1) reduced dipping behaviour and locomotor activity suggesting a possible sedative effect. D-NAME (600mgkg 1) was inactive. 7. These results suggest that L-NAME produces an opioid-independent and long-lasting antinociception in the mouse most probably by a direct effect within the central nervous system.
Asunto(s)
Analgésicos , Arginina/análogos & derivados , Administración Oral , Animales , Arginina/farmacología , Conducta Animal/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Química Encefálica/efectos de los fármacos , Edema/inducido químicamente , Edema/patología , Formaldehído , Inyecciones Intraventriculares , Masculino , Ratones , Ratones Endogámicos , Actividad Motora/efectos de los fármacos , NG-Nitroarginina Metil Éster , Óxido Nítrico/farmacología , Dolor/inducido químicamente , Dolor/prevención & controlRESUMEN
Three different intensities of swim stress produced stress-induced antinociception (SIA) in mice which was assessed either by the reduction in the number of abdominal constrictions produced by acetic acid or by an increase in reaction time on a hot-plate. The involvement of alpha-adrenoceptors in the three models of SIA was investigated using selective antagonists. SIA produced by the mild stress of a 30 s warm water swim was attenuated by idazoxan (0.5-1 mg kg-1), and by yohimbine at a dose (1 mg kg-1) which reduced antinociception produced by clonidine (12.5-50 micrograms kg-1). Indoramin (1-2 mg kg-1) did not affect this model of SIA, but reversed phenylephrine induced inhibition of the constrictions. A 3 min room temperature swim increased reaction times on the hot-plate and this naloxone-sensitive SIA was reduced significantly by prazosin (1-2 mg kg-1), idazoxan (0.5-1 mg kg-1) and yohimbine (0.5-1 mg kg-1) but enhanced by clonidine (0.5 mg kg-1) and noradrenaline (NA) (10 micrograms i.c.v.). Mice treated with 6-hydroxydopamine (60 + 60 micrograms i.c.v.) were hypersensitive to the hot-plate and did not develop SIA. Levels of noradrenaline in the brain (minus the cerebellum) were decreased after the room temperature swim SIA. The most severe stress of a cold water swim produced SIA on the hot-plate which was initially naloxone-insensitive.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Antagonistas Adrenérgicos alfa/farmacología , Analgesia , Receptores Adrenérgicos alfa/efectos de los fármacos , Estrés Fisiológico , Animales , Encéfalo/metabolismo , Interacciones Farmacológicas , Masculino , Ratones , Norepinefrina/metabolismo , Norepinefrina/farmacología , Dimensión del Dolor , Esfuerzo Físico , NataciónRESUMEN
1. Arginine vasopressin produced antinociception in the hot-plate test after intracerebroventricular injection (0.5 micrograms) and in the acetic acid abdominal constriction test after intraperitoneal injection (0.1 mg kg-1). 2. The antinociception produced by arginine vasopressin was sensitive to deamino(CH2)5Tyr(Me) arginine vasopressin (0.5 micrograms i.c.v.; 0.1 mg kg-1 i.p.) but not to naloxone (5 micrograms i.c.v.; 2 mg kg-1 i.p.) 3. Arginine vasopressin when administered by the intracerebroventricular route, but not by the intraperitoneal route, produced characteristic behaviour which was sensitive to deamino(CH2)5Tyr(Me) arginine vasopressin (0.5 micrograms, i.c.v.). 4. A 3 min swim at 20 degrees C produced antinociception on the hot-plate which was sensitive to naloxone (0.4 mg kg-1, i.p.) but not to deamino(CH2)5Tyr(Me) arginine vasopressin (0.5 micrograms, i.c.v.). 5. The reduction in the number of acetic acid-induced abdominal constrictions produced by a 30 s swim at 30 degrees C was not sensitive to either naloxone (2 mg kg-1, i.p.) or deamino(CH2)5Tyr(Me) arginine vasopressin (0.1 mg kg-1, i.p.). 6. Arginine vasopressin, at high doses, is antinociceptive in the mouse but does not appear to mediate stress-induced antinociception in this species.