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Biomedical subjects

R Garrido

Publications and source records attributed to R Garrido.

28 records · Page 2Linked to original sources

The effect of an orally active leukotriene (LT) antagonist YM-16638 on antigen-induced early and late airway responses in allergic sheep.

In this study we examined the effects of an orally active leukotriene (LT) antagonist YM-16638 [[5-[[3-(4-acetyl-3-hydroxy-2-propyl-phenoxy)propyl]thio]-1,3,4- thiadiazol-2-yl]thio] acetic acid on antigen-induced early and late responses in allergic sheep. For all studies YM-16638 was administered via intragastric tube 1 h before airway challenge with Ascaris suum antigen. Six allergic sheep were challenged on four occasions (2 control and 2 drug trials) each greater than or equal to 14 days apart and the tests were conducted in the following order: control-1; YM-16638 30 mg/kg; control-2; YM-16638 10 mg/kg. Specific lung resistance (SRL) was used as an index of the airway response to antigen and was measured before and serially after antigen challenge. In both control trials antigen challenge resulted in significant early and late airway responses (i.e. increases in SRL); however, there was a significant difference between the peak late increases of SRL in control-1 (206%) and control-2 (115%) suggesting a carry-over effect of the 30 mg/kg dose of YM-16638. At both doses, YM-16638 reduced the early response and blocked the late response when compared to either control trial. These results suggest that sulfidopeptide LTs contribute to both antigen-induced early and late airway responses in allergic sheep.

Airway Resistance↗

A possible role for PAF in allergen-induced late responses: modification by a selective antagonist.

We determined whether platelet-activating factor (PAF) plays a role in allergen-induced airway responses by studying the effects of a selective PAF antagonist WEB-2086 on antigen-induced early and late airway responses in allergic sheep. In seven sheep, inhaled Ascaris suum produced significant early (282%) and late (176%) increases in specific lung resistance (sRL). WEB-2086 (1 mg/kg iv) given 20 min before antigen challenge did not affect the early response, but the peak late increase in sRL was only 37% over base line (P less than 0.05 vs. control). To study the mechanism by which PAF contributes to antigen-induced responses, we evaluated the effects of pharmacological probes on PAF-induced bronchoconstriction. Inhaled PAF (dose range 75-700 micrograms) caused reproducible (r = 0.781, P less than 0.05) increases in sRL in eight sheep. The PAF-induced bronchoconstriction was blocked by WEB-2086 (1 mg/kg iv) and by the leukotriene antagonist FPL-55712 (30 mg by aerosol); however, neither the cyclooxygenase blocker indomethacin (2 mg/kg iv) nor the histamine H1-antagonist chlorpheniramine (2 mg/kg iv) blocked the PAF response. WEB-2086, however, did not block bronchoconstriction induced by aerosol leukotriene D4, indicating that PAF acts indirectly through leukotrienes. Finally, we determined whether PAF could induce late airway responses. Inhaled PAF produced an immediate increase in sRL in all seven sheep tested, but late airway responses were observed in only three of the seven sheep.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗

The effect of an orally active leukotriene (LT) D4 antagonist WY-48, 252 on LTD4 and antigen-induced bronchoconstrictions in allergic sheep.

In this study we examined the effects of a new orally active leukotriene (LT) D4 receptor antagonist, WY-48,252 (1,1,1-trifluoro-N-[3-(2-quinolinylmethoxy)phenyl]methanesulfonamide), on LTD4-induced bronchoconstriction and antigen-induced early and late responses in allergic sheep. For all studies WY-48,252 10 mg/kg, was administered via intragastric tube 1 h prior to airway challenge. In seven sheep, airway challenge with LTD4 [delivered dose mean +/- SE, 53 +/- 2 micrograms] resulted in an immediate increase in SRL to 600 +/- 18% over baseline. When these same sheep were treated with WY-48,252, airway challenge with LTD4 (delivered dose, 61 +/- 5 micrograms) resulted in only a 220 +/- 50% increase in SRL (p less than 0.05 vs placebo). The drug had no effect on baseline SRL. WY-48,252 was also effective in reducing early responses and blocking late responses to inhaled antigen in allergic sheep (n = 7). In the control trial, airway challenge with Ascaris suum antigen resulted in immediate and late (i.e. 6-8 h) increases in SRL of 499% and 138% over baseline (both responses, p less than 0.05). When these same sheep were pretreated with WY-48,252 the immediate antigen-induced increase in SRL was 171% and the late response was 49% over baseline (both responses p less than 0.05 vs control). These results indicate that WY-48,252 is a LTD4 antagonist in allergic sheep. The ability of this compound to modify antigen-induced early responses and to block antigen-induced late responses suggests that the generation of LTD4 during airway anaphylaxis contributes to both responses.

Aerosols↗

Nedocromil sodium in allergen-induced bronchial responses and airway hyperresponsiveness in allergic sheep.

We examined the effects of nedocromil sodium, a new drug developed for the treatment of reversible obstructive airway disease, on allergen-induced early and late bronchial responses and the development of airway hyperresponsiveness 24 h after challenge in nine allergic sheep. On occasions greater than 2 wk apart the sheep were treated with 1) placebo aerosol (buffered saline) before and 3 h after antigen challenge, 2) an aerosol of nedocromil sodium (1 mg/kg in 3 ml buffered saline) before antigen challenge and placebo 3 h after challenge, and 3) placebo aerosol before and nedocromil sodium aerosol 3 h after challenge. Early and late bronchial responses were determined by measuring specific lung resistance (sRL) before and periodically after challenge. Airway responsiveness was assessed by determining from dose-response curves the carbachol concentration (in % wt/vol) that increased sRL to 5 cmH2O/s. In the placebo trial, antigen challenge resulted in early and late increases in sRL over a base line of 353 +/- 32 and 131 +/- 17% (SE), respectively. Both early and late increases in sRL were blocked (P less than 0.05) when the sheep were pretreated with nedocromil sodium. When nedocromil was given after the early response, the late response was reduced significantly. Eight of nine sheep developed airway hyperresponsiveness 24 h after antigen challenge. In these eight sheep, carbachol concentration before antigen challenge was 2.6 +/- 0.3%, 24 h later carbachol concentration was significantly lower (1.8 +/- 0.3%). Both nedocromil sodium treatments blocked (P less than 0.05) this antigen-induced airway hyperresponsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

Intestinal angiodysplasia: retrospective study of 18 cases.

Eighteen patients operated on for intestinal angiodysplasia are reported. Visceral angiography was the diagnostic procedure of choice, providing evidence in most cases of lesions in the right colon. Right hemicolectomy was the surgical treatment normally provided. Mortality in our series was nil. This report looks at the main clinical features of these lesions, paying particular attention to their etiopathogenesis.

Aged↗

A leukotriene and thromboxane inhibitor (Sch 37224) blocks antigen-induced immediate and late responses and airway hyperresponsiveness in allergic sheep.

Peptide leukotrienes and thromboxane A2 are putative mediators of allergen-induced late responses and allergen-induced airway hyperresponsiveness (AHR), respectively. Sch 37224 blocks antigen-induced leukotriene D4 and thromboxane B2 release in guinea pig lung fragments. It also inhibits leukotriene-mediated allergic guinea pig bronchospasm. Sch 37224 was, therefore, tested in allergic sheep (n = 6) with documented immediate and late airway responses and AHR to inhaled Ascaris suum antigen. For these studies, base-line airway dose-response curves to histamine and carbachol were determined on the same day. The sheep were challenged 1 to 2 days later with Ascaris suum antigen, once after placebo treatment and once after 10 mg/kg of Sch 37224, administered orally 18 and 2 hr before challenge (total dose, 20 mg/kg). Airway dose-response curves were subsequently performed 24 hr after antigen challenge. In the placebo trial, antigen challenge caused significant peak immediate and peak late increases over base line in specific lung resistance (SRL) of 286 +/- 51 and 196 +/- 29%, respectively. SRL returned to baseline values 24 hr later, but the sheep had AHR to both histamine and carbachol as indicated by 2.6- and 3.1-fold increases in the slopes of the dose-response curves (P less than .05). Sch 37224 treatment reduced the peak immediate and peak late increases in SRL to 128 +/- 32 and 43 +/- 17%, respectively (both P less than .05 vs. placebo). Furthermore, 24 hr later, the antigen-induced AHR to both histamine and carbachol was blocked (P less than .05 vs. placebo).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ru-Tuss in the symptomatic treatment of allergic rhinitis.

In the treatment of allergic rhinitis with a placebo only one symptom, nasal itching, was reduced significantly. Where Ru-Tuss tablets were used, all symptoms improved and statistically significant reduction of symptoms were obtained for lacrimation, nasal itching, sneezing, itching of the mouth, itching of the pharynx, rhinorrhea and the condition of the nasal mucosa. Ridit analysis was used to evaluate differences between the Ru-Tuss Tablet and the placebo treated groups.

Atropine↗

[Retroperitoneal hematoma secondary to traumatic rupture of the psoas muscle].

Rupturing of the psoas muscle by closed injury as a result of the formation of a retroperitoneal hematoma is a very uncommon pathological entity, which may rise problems of differential diagnosis with kidney lesions. Supplementary explorations do not always clear up diagnostic doubts, and it is surgery, if indicated, that confirms the picture. We present a case of retroperitoneal hematoma of traumatic origin in a one-kidney ipsilateral patient, in whom the abdominal CAT revealed affection of the renal capsule associated with rupture of teh psoas. In the surgery carried out due to formation of an abscess in the hematoma we verified that the kidney was undamaged.

Adult↗