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INTRODUCTION[|]On-demand treatment protocols in the maintenance treatment of gastroesophageal reflux disease (GERD) are cost-efficient and easy-to-use treatments.This study aimed to compare the efficacies of H2 receptor antagonists (H2RA) and proton pump inhibitors (PPI) in on-demand treatment of GERD.[¤]METHODS[|]Patients with persistent GERD symptoms were enrolledbetween January-November 2015 and were randomly separated into two equal groups. The patients in the first group were commenced on ranitidine 300 mg as H2RA and the patients in the second group were commenced on pantoprazole 40 mg. A 4-point Likert-type scale generated by the researchers was applied to evaluate the frequencies of reflux symptoms and their impacts on activities of life and business life.[¤]RESULTS[|]Fifty-two patients were included, of whom 26 (50.0%) were in the PPI group and 26 (50.0%) were in the H2RA group. There were no significant differences between the study groups both before and after treatment in terms of the severity of reflux symptoms. There were significant decreases in the H2RA group in terms of the domains of retrosternal burning sensation, regurgitation, nausea and vomiting, and burping (p=0.036, p=0.027, p=0.020, and p=0.038, respectively).[¤]DISCUSSION AND CONCLUSION[|]PPIs and H2RAs were both effective in maintaining symptom control and improving the limitations in work or activities in on-demand treatment.Nonetheless, the higher amount of the medication use in the H2RA group compared with the PPI group led us to conclude that using PPIs during on-demand treatment might be more appropriate than using H2RA in this setting.[¤]

Background Nonsteroidal anti-inflammatory drugs induces gastric mucosal lesions because of its acidic properties. Ranitidine, an H2 receptor antagonist, has proved beneficial in patients with gastric ulcers. Objective The present study was performed to assess the effect of administering ranitidine in Nonsteroidal anti-inflammatory drugs (diclofenac, nimesulide) induced gastropathy, and their effect on the histopathology of stomach, kidney and liver. Methods Diclofenac, nimesulide, and ranitidine were administered in doses of 2, 4, and 6 mg/kg, p.o. once daily for 14 days, and their effect on gastric volume, acidity, mean ulcer number, and gastric pH. In addition, histopathological examination was also performed on sections of stomach, kidney and liver. Results Following the administration of diclofenac or nimesulide, all the gastric parameters were significantly altered as well as the histopathology of stomach, liver and kidney. In the control group, the renal sections showed normal glomeruli with no thickening of glomerular basement membrane, while in diclofenac alone, nimesulide alone, and ranitidine with nimesulide groups, the thickening of glomerular basement membrane was observed. These alterations were observed to be reversed in the ranitidine with diclofenac group. In the sections from the liver, the control group showed anastomosing plates and cords of cuboidal hepatocytes with round well stained nuclei and abundant cytoplasm. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, mild dilatation of sinusoids is seen coupled with prominence of central vein. In the diclofenac alone and nimesulide alone groups, the proximal and distal convoluted tubules show mild focal tubular necrosis. In the gastric sections, the control group showed several folds forming villi, and the epithelial lining surface of the mucosa. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, the duodenum showed scattered inflammatory cells composed predominantly of lymphocytes. In diclofenac alone and nimesulide alone group, the sections from the gastric areas showed partial necrosis and mild chronic inflammation respectively. Conclusion The study, therefore, has provided therapeutic rationale towards simultaneous administration of H2 receptor blocker ranitidine with diclofenac to be more beneficial as compared to ranitidine with nimesulide, to minimise the gastric intolerance of diclofenac in long term treatment of inflammatory conditions. RESUMO Contexto Anti-inflamatórios não esteroidais induzem lesões da mucosa gástrica devido às suas propriedades ácidas. Ranitidina, um antagonista dos receptores H2, revelou-se benéfico em pacientes com úlceras gástricas. Objetivo - O presente estudo foi realizado para avaliar o efeito da administração de ranitidina em gastropatia induzida por anti-inflamatórios não esteroidais (diclofenaco, nimesulida) e seu efeito sobre a histopatologia do estômago, dos rins e fígado. Métodos Diclofenaco, nimesulida e ranitidina foram administradas em doses de 2, 4 e 6 mg/kg, p.o. uma vez diariamente por 14 dias e seu efeito sobre o volume gástrico, acidez, significam o número de úlcera e o pH gástrico. Além disso, o exame histopatológico também foi realizado em seções do estômago, dos rins e fígado. Resultados Após a administração de diclofenaco ou nimesulida, todos os parâmetros gástricos foram significativamente alterados assim como a histopatologia do estômago, fígado e rim. No grupo controle, as seções renais mostraram glomérulos normais sem espessamento da membrana basal glomerular, enquanto em diclofenaco isolado, nimesulida isolado e grupos com ranitidina e nimesulida, foi observado espessamento da membrana basal glomerular. Estas alterações observou-se serem revertidas no grupo ranitidina com diclofenaco. As seções do fígado, o grupo controle mostrou placas e cordões de hepatócitos cuboidais anastomosados com núcleos bem demarcados e citoplasma abundante. Nos grupos ranitidina com diclofenaco e ranitidina com nimesulida, leve dilatação dos sinusoides é vista acoplados com proeminência de veia central. Nos grupos diclofenaco e nimesulida sozinhos, túbulos proximais e distais contorcidos mostram necrose tubular focal leve. Nas secções gástricas, o grupo controle mostrou várias dobras formando vilosidades e a superfície do revestimento epitelial da mucosa. Nos grupos ranitidina com diclofenaco e ranitidina com nimesulida, o duodeno mostrou dispersas células inflamatórias predominantemente compostas por linfócitos. Nos grupos diclofenaco e nimesulida sozinhos, as secções de áreas gástricas mostraram necrose parcial e inflamação crônica moderada respectivamente. Conclusão - O estudo, portanto, forneceu o fundamento terapêutico para administração simultânea de bloqueador de receptor H2 (ranitidina) com diclofenaco, sendo mais benéfica em comparação com ranitidina com nimesulida para minimizar a intolerância gástrica de diclofenaco no tratamento a longo prazo de condições inflamatórias.

Objective: To investigate whether exposure to inhibitors of gastric acidity, such as H2 blockers or proton pump inhibitors, can independently increase the risk of infections in very low birth weight (VLBW) preterm infants in the neonatal intensive care unit. Study design: This is a secondary analysis of prospectively collected data from a multicenter, randomized controlled trial of bovine lactoferrin (BLF) supplementation (with or without the probiotic Lactobacillus rhamnosus GG) vs placebo in prevention of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants. Inhibitors of gastric acidity were used at the recommended dosages/schedules based on the clinical judgment of attending physicians. The distribution of days of inhibitors of gastric acidity exposure between infants with and without LOS/NEC was assessed. The mutually adjusted effects of birth weight, gestational age, duration of inhibitors of gastric acidity treatment, and exposure to BLF were controlled through multivariable logistic regression. Interaction between inhibitors of gastric acidity and BLF was tested; the effects of any day of inhibitors of gastric acidity exposure were then computed for BLF-treated vs -untreated infants. Results: Two hundred thirty-five of 743 infants underwent treatment with inhibitors of gastric acidity, and 86 LOS episodes occurred. After multivariate analysis, exposure to inhibitors of gastric acidity remained significantly and independently associated with LOS (OR, 1.03; 95% CI, 1.008-1.067; P = .01); each day of inhibitors of gastric acidity exposure conferred an additional 3.7% odds of developing LOS. Risk was significant for Gram-negative (P < .001) and fungal (P = .001) pathogens, but not for Gram-positive pathogens (P = .97). On the test for interaction, 1 additional day of exposure to inhibitors of gastric acidity conferred an additional 7.7% risk for LOS (P = .003) in BLF-untreated infants, compared with 1.2% (P = .58) in BLF-treated infants. Conclusion: Exposure to inhibitors of gastric acidity is significantly associated with the occurrence of LOS in preterm VLBW infants. Concomitant administration of BLF counteracts this selective disadvantage. Trial registration: isrctn.org: ISRCTN53107700.

Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of complex cause. Gastro-oesophageal reflux (GER) and microaspiration have been proposed as risk factors for the development and progression of IPF, but robust definitive data are few. A recent international guideline conditionally recommended the use of antacid therapy (proton pump inhibitors or histamine-2-receptor antagonists) for patients with IPF, in the absence of oesophageal reflux or symptoms. In this Position Paper, we summarise the literature addressing the association between GER and IPF, and also identify future research priorities that could clarify this issue. We shed light on the process through which the guideline recommendation was achieved and aim to contextualise the recommendation for providers caring for patients with IPF.

INTRODUCTION The prescription and costs of antiulcer medications for in-hospital use have increased during recent years with reported inadequate use and underused. AIM To determine the patterns of prescription-indication and also perform an economic analysis of the overcost caused by the non-justified use of antiulcer medications in a third level hospital in Colombia. MATERIALS AND METHODS Cross-sectional study of prescription-indication of antiulcer medications for patients hospitalized in "Hospital Universitario San Jorge" of Pereira during July of 2012. Adequate or inadequate prescription of the first antiulcer medication prescribed was determined as well as for others prescribed during the hospital stay, supported by clinical practice guidelines from the Zaragoza I sector workgroup, clinical guidelines from the Australian Health Department, and finally the American College of Gastroenterology Criteria for stress ulcer prophylaxis. Daily defined dose per bed/day was used, as well as the cost for 100 beds/day and the cost of each bed/drug. A multivariate analysis was carried out using SPSS 21.0. RESULTS 778 patients were analyzed, 435 men (55.9 %) and 343 women, mean age 56.6 +/- 20.1 years. The number of patients without justification for the prescription of the first antiulcer medication was 377 (48.5 %), and during the whole in-hospital time it was 336 (43.2 %). Ranitidine was the most used medication, in 438 patients (56.3 %). The cost/month for poorly justified antiulcer medications was € 3,335.6. The annual estimated cost for inadequate prescriptions of antiulcer medications was € 16,770.0 per 100 beds. CONCLUSION A lower inadequate prescription rate of antiulcer medications was identified compared with other studies; however it was still high and is troubling because of the major costs that these inadequate prescriptions generates for the institution.

Introduction: The prescription and costs of antiulcer medications for in-hospital use have increased during recent years with reported inadequate use and underused. Aim: To determine the patterns of prescription-indication and also perform an economic analysis of the overcost caused by the non-justified use of antiulcer medications in a third level hospital in Colombia. Materials and methods: Cross-sectional study of prescription-indication of antiulcer medications for patients hospitalized in "Hospital Universitario San Jorge" of Pereira during July of 2012. Adequate or inadequate prescription of the first antiulcer medication prescribed was determined as well as for others prescribed during the hospital stay, supported by clinical practice guidelines from the Zaragoza I sector workgroup, clinical guidelines from the Australian Health Department, and finally the American College of Gastroenterology Criteria for stress ulcer prophylaxis. Daily defined dose per bed/day was used, as well as the cost for 100 beds/day and the cost of each bed/drug. A multivariate analysis was carried out using SPSS 21.0. Results: 778 patients were analyzed, 435 men (55.9%) and 343 women, mean age 56.6 ± 20.1 years. The number of patients without justification for the prescription of the first antiulcer medication was 377 (48.5%), and during the whole in-hospital time it was 336 (43.2%). Ranitidine was the most used medication, in 438 patients (56.3%). The cost/month for poorly justified antiulcer medications was € 3,335.6. The annual estimated cost for inadequate prescriptions of antiulcer medications was € 16,770.0 per 100 beds. Conclusion: A lower inadequate prescription rate of antiulcer medications was identified compared with other studies; however it was still high and is troubling because of the major costs that these inadequate prescriptions generates for the institution. Introducción: la prescripción y coste de antiulcerosos a nivel hospitalario se incrementaron en años recientes, reportándose usos inadecuados. Objetivo: determinar los patrones de prescripción-indicación y el análisis económico del sobrecoste por uso injustificado de antiulcerosos en un hospital de tercer nivel de atención en Colombia. Materiales y métodos: estudio de corte transversal, de prescripción-indicación de antiulcerosos en pacientes internados en el Hospital Universitario San Jorge de Pereira en julio 2012. Se determinaron: indicación adecuada o inadecuada del primer antiulceroso prescrito y del prescrito durante la hospitalización, apoyados en guías de práctica clínica del Grupo de Trabajo Sector Zaragoza I, del Departamento Gubernamental Australiano de la Salud y los criterios del Colegio Americano de Gastroenterología para profilaxis de úlceras de estrés. Se definió la dosis diaria definida por cama/día, se obtuvo el coste por 100 camas/día y costes de cada medicamento. Se hizo análisis multivariado mediante SPSS 21.0. Resultados: se analizaron 778 pacientes, 435 hombres (55,9%) y 343 mujeres, edad promedio 56,6 ± 20,1 años. No tenían justificación para la prescripción del primer antiulceroso 377 pacientes (48,5%), ni durante toda la hospitalización 336 pacientes (43,2%). Ranitidina fue el más usado en 438 pacientes (56,3%). El coste/mes por antiulcerosos no indicados fue 3.335,62 €. El coste anual estimado por inadecuada prescripción de antiulcerosos fue 16.770,0 € por 100 camas. Conclusión: se presentó una menor prescripción inadecuada de antiulcerosos en comparación con otros estudios, sin embargo sigue siendo alta y preocupante por los importantes costes en que incurre la institución para financiar medicamentos que no requieren los pacientes.

Histamine H2 receptor antagonism by T-593 was investigated in Hepa cells expressing canine histamine H2 receptors. T-593 inhibited generation of cAMP in Hepa cells stimulated by 10–5 mol/l histamine with an IC50 value of 2.3 × 10–6 mol/l, (S)-(–)-T-593, one of the enantiomers comprising racemic T-593, inhibited cAMP generation with an IC50 value of 6.1 × 10–7 mol/l. On the other hand, the other enantiomer (R)-(+)-T-593 exhibited only a negligible effect. Incubation of the cell with (S)-(–)-T-593 for 60 min depressed the maximal response of the concentration-response curve of histamine with a nonparallel rightward shift. The slope of a Schild plot was 1.27. In contrast, (S)-(–)-T-593 caused a parallel rightward shift of the curve, with a Schild plot slope that did not significantly differ from unity, by treating the cells for 15 min. The H2 receptor-blocking action of (S)-(–)-T-593 remained almost unaffected after washing out the drug, whereas the effect of ranitidine was reversible after washing. These results suggest that T-593 possesses a time-dependent unsurmountable antagonistic action against histamine H2 receptor. T-593 may interact with the histamine H2 receptor molecule in a slowly associable and dissociable manner.

The effects of co-administration of antacid (Maaloxreg; 15ml) and sucralfate (1g) on the pharmacokinetic actions of roxatidine acetate (75mg), a typical histamine H2 antagonist, were evaluated in six healthy volunteers following a meal. After the coadministration of roxatidine and sucralfate or antacid, no significant difference was demonstrated in the pharmacokinetics of roxatidine. However, when sucralfate administered together with roxatidine before the meal, the pharmacokinetic actions of roxatidine were significantly decreased compared to roxatidine alone. There was no effect in the absorption of roxatidine, when Maaloxreg; and sucralfate were taken by oral administration.

OBJECTIVE. Gastric acidity (GA) inhibitors, including histamine-2 receptor antagonists (H2 blockers) and proton pump inhibitors (PPIs), are the mainstay of gastroesophageal reflux disease (GERD) treatment. A prolonged GA inhibitor–induced hypochlorhydria has been suggested as a risk factor for severe gastrointestinal infections. In addition, a number of papers and a meta-analysis have shown an increased risk of pneumonia in H2-blocker–treated intensive care patients. More recently, an increased risk of community-acquired pneumonia associated with GA inhibitor treatment has been reported in a large cohort of adult patients. These findings are particularly relevant to pediatricians today because so many children receive some sort of GA-blocking agent to treat GERD. To test the hypothesis that GA suppression could be associated with an increased risk of acute gastroenteritis and pneumonia in children treated with GA inhibitors, we conducted a multicenter, prospective study. METHODS. The study was performed by expert pediatric gastroenterologists from 4 pediatric gastroenterology centers. Children (aged 4–36 months) consecutively referred for common GERD-related symptoms (for example, regurgitation and vomiting, feeding problems, effortless vomiting, choking), from December 2003 to March 2004, were considered eligible for the study. Exclusion criteria were a history of GA inhibitors therapy in the previous 4 months, Helicobacter pylori infection, diabetes, chronic lung or heart diseases, cystic fibrosis, immunodeficiency, food allergy, congenital motility gastrointestinal disorders, neuromuscular diseases, or malnutrition. Control subjects were recruited from healthy children visiting the centers for routine examinations. The diagnosis of GERD was confirmed in all patients by standard criteria. GA inhibitors (10 mg/kg ranitidine per day in 50 children or 1 mg/kg omeprazole per day in 50 children) were prescribed by the physicians for 2 months. All enrolled children were evaluated during a 4-month follow-up. The end point was the number of patients presenting with acute gastroenteritis or community-acquired pneumonia during a 4-month follow-up study period. RESULTS. We obtained data in 186 subjects: 95 healthy controls and 91 GA-inhibitor users (47 on ranitidine and 44 on omeprazole). The 2 groups were comparable for age, gender, weight, length, and incidence of acute gastroenteritis and pneumonia in the 4 months before enrollment. Rate of subjects presenting with acute gastroenteritis and community-acquired pneumonia was significantly increased in patients treated with GA inhibitors compared with healthy controls during the 4-month follow-up period. In the GA inhibitor-treated group, the rate of subjects presenting with acute gastroenteritis and community-acquired pneumonia was increased when comparing the 4 months before and after enrollment. No differences were observed between H2 blocker and PPI users in acute gastroenteritis and pneumonia incidence in the previous 4 months and during the follow-up period. On the contrary, in healthy controls, the incidence of acute gastroenteritis and pneumonia remained stable. CONCLUSIONS. This is the first prospective study performed in pediatric patients showing that the use of GA inhibitors was associated with an increased risk of acute gastroenteritis and community-acquired pneumonia in GERD-affected children. It could be interesting to underline that we observed an increased incidence of intestinal and respiratory infection in otherwise healthy children taking GA inhibitors for GERD treatment. On the contrary, the majority of the previous data showed that the patients most at risk for pneumonia were those with significant comorbid illnesses such as diabetes or immunodeficiency, and this points to the importance of GA suppression as a major risk factor for infections. In addition, this effect seems to be sustained even after the end of therapy. The results of our study are attributable to many factors, including direct inhibitory effect of GA inhibitors on leukocyte functions and qualitative and quantitative gastrointestinal microflora modification. Additional studies are necessary to investigate the mechanisms of the increased risk of infections in children treated with GA inhibitors, and prophylactic measures could be considered in preventing them.

An unclassified amicrobial pustular dermatosis particularly affecting the main cutaneous folds, external auditory canals and scalp and coexisting with systemic lupus erythematosus has been recently described.We studied 3 young females bearing such cutaneous manifestations in association with subacute cutaneous lupus erythematosus, celiac disease and various serum autoantibodies, respectively, in order to further characterize this possibly new entity.Various routine and immunological laboratory tests, histopathologic and direct immunofluorescence examinations and in vitro studies of neutrophil function were performed in each patient.We reported our findings and compared our cases with the few others appearing in the literature. We documented an impaired neutrophil chemotaxis in 2 subjects, but neutrophil dysfunction does not seem to be one of the verifying criteria.All of these cases may represent a distinctive form in the clinicopathological spectrum of neutrophilic dermatoses (ND) because of the typical distribution and the close link with different autoimmune disorders. Cimetidine in combination with ascorbic acid can be indicated as an effective and safe alternative to the classic medications of ND, although the action of both drugs remains unexplained.

Omeprazole is a very potent and long-acting inhibitor of gastric acid secretion. These characteristics make the drug very suitable for the management of gastric acid hyper-secretion and symptom relief

Twenty-five flavone-6-carboxylic acids were synthesized and tested as to their ability to inhibit histamine-induced gastric acid secretion in the rat. 3-Isopropoxy-4'-methoxyflavone-6-carboxylic acid (41) showed consistent oral activity while being devoid of any other noteworthy pharmacological effects. In vitro, this compound was found to be inactive as a histamine H2 antagonist, and its mode of action remains unknown.

Thirty-seven compounds were evaluated for their ability to inhibit histamine stimulated adenylate cyclase and to inhibit 3H-tiotidine binding. The compounds examined included a number of known H2-antagonists and a number of potential H2-antagonists of diverse chemical structure. The correlation between the Ki values from the binding assay and from the inhibition of adenylate cyclase was calculated to be r = 0.99, p less than 0.001. Thus 3H-tiotidine binding in guinea-pig cerebral cortex can be used to give a valid assessment of histamine H2-receptor activity.

The combination of the histamine H2 antagonist cimetidine (CMT) and the anticancer agent cisplatin (CDDP) was studied in normal and tumorbearing mice. CMT doses of 100 mg/kg produced no alteration in the survival of DBA/2J mice bearing P388 leukemia treated with CDDP doses of 3 mg/kg or 6 mg/kg. In these groups, the median survival was 13 days and 16 days, respectively, compared to 10 days in untreated controls. However, when adult CD-1 mice were given higher but nonlethal CDDP doses of 10, 15, or 18 mg/kg, the addition of CMT significantly increased CDDP lethality (P less than 0.05 by Wilcoxon analysis). For the 3 groups, CMT-enhanced lethality occurred in 10% of mice given 10 mg/kg CDDP, 80% of mice given 15 mg/kg, and 100% of mice given 18 mg/kg CDDP. Thus, CMT can acutely alter CDDP toxicity without affecting antitumor efficacy in mice.

With the aim of developing new atiulcer agents, a series of 4-quinazolinone derivatives was synthesized and tested for histamine H2-antagonist activity and gastric antisecretory activity. Thus, 2-alkylamino- (8a-d, 10a-s), 2-alkylthio- (15), and 2-alkyl-4-quinazolinones (18a-k) were prepared by the condensation of alkylamines with 2-chloro- or 2-methlthio-4-quinazolinones, the condensation of alkyl bromides with 2-mercapto-4-quinazolinones, and the condensation of alkylcarboxylic acids with anthranilamides, respectively.Several of the 4-quinazolinone derivatives thus synthesized showed potent H2-antagonist activity, and one of them, 2-[3-[3-(1-piperidinylmehyl)phenoxy]propylamino]-4(3H)-quinazo-linone (8d) showed the most potent antisecretory activity. The structure-activity relationships are discussed.

La cimetidine forme des complexes 1:1 et 1:2 avec l'ion Cu(II) en solutions aqueuses. Constantes de stabilite. Role important de Cu dans les activites pharmacologiques de la cimetidine

With the aim of developing new atiulcer agents, a series of 4-quinazolinone derivatives was synthesized and tested for histamine H2-antagonist activity and gastric antisecretory activity. Thus, 2-alkylamino- (8a-d, 10a-s), 2-alkylthio- (15), and 2-alkyl-4-quinazolinones (18a-k) were prepared by the condensation of alkylamines with 2-chloro- or 2-methlthio-4-quinazolinones, the condensation of alkyl bromides with 2-mercapto-4-quinazolinones, and the condensation of alkylcarboxylic acids with anthranilamides, respectively.Several of the 4-quinazolinone derivatives thus synthesized showed potent H2-antagonist activity, and one of them, 2-[3-[3-(1-piperidinylmehyl)phenoxy]propylamino]-4(3H)-quinazo-linone (8d) showed the most potent antisecretory activity. The structure-activity relationships are discussed.

Twenty-five flavone-6-carboxylic acids were synthesized and tested as to their ability to inhibit histamine-induced gastric acid secretion in the rat. 3-Isopropoxy-4'-methoxyflavone-6-carboxylic acid (41) showed consistent oral activity while being devoid of any other noteworthy pharmacological effects. In vitro, this compound was found to be inactive as a histamine H2 antagonist, and its mode of action remains unknown.

Treatment of rats with high doses (200-1000 mg/kg) of a histamine H2-antagonist, SKF 93479 (2-(2-(5-(dimethylaminomethyl)furan-2-ylmethylthio)-furan-2-ylmethyl-amino)-5-(6-methylpyrid-3-ylmethyl)pyrimidin-4-one trihydrochloride), is associated with histological changes in the thyroid glands. These changes were observed as early as 3 days after the start of treatment, and include follicular cell hypertrophy and colloid depletion, which are indicative of increased thyroid activity. Similar thyroid histological changes have previously been observed in rats following treatment with classical antithyroid compounds such as methimazole (Owen et al. 1973). Several investigations were carried out in order to determine the mechanism of the effect of SKF 93479 on thyroid activity. In particular, the possibility of a direct or indirect effect of the compound (the latter via alterations in the pituitary feedback mechanism) was examined by studying plasma thyroxine (T4) and thyroid stimulating hormone (TSH) concentrations, thyroidal iodide-125 uptake and T4 clearance in rats treated with SKF 93479.