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Biomedical subjects

R Alvarez

Publications and source records attributed to R Alvarez.

At least 163 records · Page 9Linked to original sources

The action of SDZ 205,557 at 5-hydroxytryptamine (5-HT3 and 5-HT4) receptors.

1. The interaction of the novel antagonist, SDZ 205,557 (2-methoxy-4-amino-5-chloro benzoic acid 2-(diethylamino) ethyl ester), at 5-HT3 and 5-HT4 receptors has been assessed in vitro and in vivo. 2. In guinea-pig hippocampus and in the presence of 0.4 microM 5-carboxamidotryptamine, 5-HT4-mediated stimulation of adenylyl cyclase was competitively antagonized by SDZ 205,557, with a pA2 value of 7.5, and a Schild slope of 0.81. In rat carbachol-contracted oesophagus, 5-HT4-receptor mediated relaxations were surmountably antagonized by SDZ 205,557 with a similar pA2 value (7.3). This value was agonist-independent with the exception of (R)-zacopride, against which a significantly lower value (6.4) was observed. 3. In functional studies of 5-HT3 receptors, SDZ 205,557 exhibited an affinity of 6.2 in guinea-pig ileum compared with 6.9 at binding sites labelled by [3H]-quipazine in NG108-15 cells. In the anaesthetized, vagotomized micropig, SDZ 205,557 produced only a transient blockade of 5-HT4-mediated tachycardia. This contrasted with tropisetron, which was active for over 60 min after administration. The half-lives for the inhibitory responses of SDZ 205,557 and tropisetron were 23 and 116 min, respectively. 4. In conclusion, SDZ 205,557 has similar affinity for 5-HT3 and 5-HT4 receptors. The apparent selectivity observed in guinea-pig is due to the atypical nature of the 5-HT3 receptor in this species. The short duration of action of this novel antagonist may complicate its use in vivo. SDZ 205,557 should, therefore, be used with appropriate caution in studies defining the 5-HT4 receptor.

4-Aminobenzoic Acid↗

[Effect of cholelithiasis and cholecystectomy on duodenogastric biliary reflux].

The aim of this work was to study the influence of cholelithiasis and cholecystectomy on duodenogastric biliary reflux. Total bile acid concentration (TBAC) in fasting gastric juice was measured in 23 consecutive patients with cholelithiasis and functioning gallbladder before and at least 3 months after cholecystectomy (group 1) and in 14 healthy volunteers (group II). In group two, TBAC was 8.5 +/- 2.8 uMol/l (mean +/- sem), the preoperative value in group I was 32.8 +/- 8.9 uMol/l and the postoperative value 69.9 +/- 14 uMol/l (p < 0.002 compared with group II and < 0.035 compared with preoperative values). These results suggest that cholelithiasis, even with a functioning gallbladder is associated with a significant increase in bile reflux to the stomach, with raises further after cholecystectomy.

Adult↗

[Post sinusoidal obstruction of the hepatic venous flow associated with antiphospholipid syndrome in 3 cases].

Three cases of post-sinusoidal hepatic blood flow obstruction as the main feature of antiphospholipid syndrome are reported. Clinically, these patients developed jaundice, malaise, ascites and hepatomegaly. Ultrasonography-Doppler and hepatic venography showed small hepatic vein disease in two and partial occlusion in the suprahepatic segment of inferior vena cava in the remaining patient. In all, anticardiolipin antibodies were positive and activated partial thromboplastin time was prolonged. This experience emphasizes that in patients with post sinusoidal portal hypertension, a systematic search for antiphospholipid syndrome must be carried out.

Adult↗

Comparison of engraftment and acute GVHD in patients undergoing cryopreserved or fresh allogeneic BMT.

Coordination of marrow donation for allogeneic BMT is a common logistical problem. The use of cryopreserved donor marrow would facilitate scheduling and avoid potential problems due to donor employment, injury, infection or death. We analysed results of 10 matched related BMTs performed with cryopreserved donor marrow and compared them with 33 matched related BMTs using fresh bone marrow over a 4 year period. No difference in time to engraftment of granulocytes and platelets or transfusion requirements were demonstrated for the two groups. However, there was less GVHD in patients who received cryopreserved donor marrow (chi 2, p = 0.03; Fisher's exact test (two-sided) p = 0.067) despite comparable risk factors. The reason for this difference is unclear. Our results indicate that the use of cryopreserved bone marrow for allogeneic BMT patients is at least equivalent to the use of fresh bone marrow. A prospective randomized trial is needed to determine if a true difference exists in the incidence or severity of acute GVHD and to determine if recurrence rate is different between the two groups.

Acute Disease↗

Effector-target interactions: saturability, affinity and binding isotherms. A study of such interactions in the human NK cell-K562 tumour cell system.

Effector-target interactions at the cell-to-cell level have been studied. This has revealed that saturability, i.e., the existence of a finite number of specific receptor sites, applies to both the effector and target cell populations and plays a key role in the formation of conjugates. As a result, two maximum conjugate frequencies, alpha max and beta max, are recognised for the effector and target cell populations, respectively. The dissociation constant of the conjugates formed, KD, characterizes effector-target affinity. This constant, together with the maximum conjugate frequencies, are the three parameters which make it possible to describe the binding process quantitatively. The existence of binding isotherms for effector-target interactions has been demonstrated. These isotherms contain all the relevant information necessary to interpret quantitatively the formation of conjugates. Quantitative procedures to determine the three binding parameters are described together with the modifications necessary to use Scatchard plots in the analysis of conjugate frequencies in these kinds of cell-to-cell interactions. A quantitative study of these interactions in the NK-K562 tumour cell system has been performed. For this purpose, nine different cell source donors were used to test the model proposed. Relationships with related phenomena--CMC and the adhesion process--are also discussed.

Adult↗

Pharmacological profile of a native dermatan sulfate.

We performed different "in vivo" investigations to study the pharmacological properties of a native DS: anti-thrombosis by the stasis model, bleeding potential by tail transection bleeding time and template bleeding time, and profibrinolysis by a growing thrombus model and by an established thrombus model. The results suggest that DS is a safe antithrombotic drug by i.v. administration without bleeding potential, even at very high doses (up to 16 mg/Kg). DS has shown a protective index of at least 4 in contrast to heparin that has shown a protective index of 1. The profibrinolytic models so far studied did not evidence a clear profibrinolytic contribution to the antithrombotic properties of DS, but showed a prolonged antithrombotic action that cannot be explained only by the heparin cofactor II potentiation.

Animals↗

A separation method for the assay of adenylylcyclase, intracellular cyclic AMP, and cyclic-AMP phosphodiesterase using tritium-labeled substrates.

A method for the separation of cyclic AMP from adenosine and polyvalent adenine nucleotides is described. The method consists of the sequential elution of adenosine and cyclic AMP from a single column of acidic aluminum oxide (alumina) with dilute hydrochloric acid and ammonium acetate. Adenosine, adenine, xanthine, and hypoxanthine are rapidly eluted with the application of 0.005 N hydrochloric acid while cyclic AMP remains adsorbed to the alumina. A subsequent application of 0.1 M ammonium acetate elutes more than 90% of the cyclic AMP. Under these conditions, polyvalent nucleotides (AMP, ADP, and ATP) remain adsorbed to the alumina. The method permits the measurement of adenylylcyclase activity using [3H]ATP as the labeled substrate. The same technique can be used to measure the accumulation of cyclic AMP in intact cells after labeling the ATP pool with [3H]adenine. With slight modification, the technique can be used to measure the activity of cyclic-AMP phosphodiesterase using [3H]cyclic AMP as the substrate. The proposed technique provides rapid, highly reproducible assays using inexpensive, disposable columns.

3',5'-Cyclic-AMP Phosphodiesterases↗

Skeletal malformations in hatchery reared Rana perezi tadpoles.

Skeletal malformations at metamorphosis in Rana perezi tadpoles reared in culture have been studied. Tadpoles were fed ten artificially compounded and fresh diets and kept at two different temperatures. Animals were maintained in fiberglass tanks. Bone damages are related to the nourishment with compound diets. Tadpoles fed such diets showed variable percentages of scoliosis, kyphosis, luxations, and subluxations in the hind limbs, aplasia in phalanges, and wide failures of ossification. The data suggest the origin of the lesions is a deficiency in some compounded diets that could alter collagen metabolism during skeletal adjustments at metamorphosis.

Abnormalities, Multiple↗

Comparative effects of dopaminergic agonists on cardiovascular, renal, and renin-angiotensin systems in hypertensive patients.

The role of dopaminergic receptors on renal function has been extensively studied. Recently dopaminergic receptor has been classified in two subtypes D1 and D2, which seem to have different modulatory function. However, the role of dopaminergic receptors on cardiovascular function and more specifically the potential role of dopaminergic agonists as antihypertensive agents has not yet been clarified. Nine outpatients with mild and moderate hypertension were studied in the Cardiology Service of Vargas Hospital with a D1 agonist, piribedil, at 50-100 mg/day, orally, for 8 weeks, and with a D2 agonist, bromocriptine, at 2.5 - 5 mg/day, orally, for an another 8 weeks by using a placebo comparative crossover design. Piribedil reduced blood pressure with a modest increase in heart rate, plasma renin activity, and of plasma aldosterone, and an important increment of renal function. Bromocriptine reduced blood pressure with a decrease in heart rate and plasma aldosterone without altering renal function. There was no orthostatic hypotension with either agent. The authors conclude that activation of dopaminergic D1 receptor induces a vasodilatory and antihypertensive effect with a reflex increase in sympathetic tone, whereas activation of dopaminergic D2 receptor induces a decrease in sympathetic tone, probably due to a decrease in norepinephrine release at adrenergic endings. The potential effect of these compounds as antihypertensive agents is of great interest because blood pressure reduction can be induced by a new mechanism, i.e. activation of dopaminergic receptors which results in a decrease of the renin angiotensin system or a vasodilatory action.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

Functional stages in the interrenal cells of Rana perezi (Anura: Ranidae).

The electron density of the lipid droplets and mitochondrial matrix of the interrenal cells of Rana perezi differs during the year. This makes it possible to characterize the different stages of interrenal cell activity. A droplet/mitochondria index, based on their relative size, may provide an indicator of cellular activity.

Adrenal Glands↗

Tubular antigen-binding proteins repress transcription of type IV collagen in the autoimmune target epithelium of experimental interstitial nephritis.

We have been studying immune interactions with somatic cells using a tubular antigen-binding protein (ThF) secreted by helper T lymphocytes harvested from mice that have an autoimmune form of interstitial nephritis called anti-tubular basement membrane disease. This ThF, although characterized originally because of its ability to induce effector T cells, additionally recognizes the nephritogenic 3M-1 antigen expressed by its target renal tubular epithelium. We believe these proteins, in general, may modulate directly some homeostatic functions in organ-derived cells, and now report that our ThF represses specifically the cellular transcription and secretion of basement membrane type IV collagen in tubular epithelium. These in vitro findings of reduced levels of mRNA encoding type IV collagen correlate well with in situ hybridization studies performed on kidneys expressing early autoimmune lesions, and predict a progressive drop in the expression of type IV collagen in the interstitium. Such a novel and unexpected repression of transcription of type IV collagen might easily impart or facilitate permanent change in the infrastructure of kidney architecture during autoimmune injury and, perhaps, contributes to the process of tubular atrophy attendant to prolonged renal inflammation.

Animals↗

Prevalence of anticardiolipin antibodies in subacute cutaneous lupus erythematosus.

We examined the prevalence of the antibodies to cardiolipin measured by solid-phase enzyme immunoassay during a prospective study of patients with subacute cutaneous lupus erythematosus (SCLE). Seven of 44 (16%) consecutive patients with SCLE had positive anticardiolipin antibodies; of these only three satisfied the American Rheumatism Association's revised criteria for the classification of systemic lupus erythematosus. Clinical findings probably associated with the positive anticardiolipin antibodies were found in four cases, including clotting abnormalities, thrombocytopenia, hemolytic anemia, livedo reticularis, chilblain lupus erythematosus lesions, migraine, leg venous thrombosis and pulmonary embolism after surgery, and spontaneous abortion. Our data suggest that it is reasonable to screen SCLE patients for these antibodies to confirm the presence of the antiphospholipid syndrome.

Adult↗

[Kidney retransplantation: prognostic factors in a series of 84 cases].

Results are presented of a series of 84 patients receiving renal retransplants over the last 12 years. One year survival rate of patients and transplants was 87.6% and 79.1% respectively, compared with 92.5% and 81.2% for the 783 first grafts performed during the same period. Positive prognostic features were the absence of sensitization, survival of the first transplant for more than 6 months, and the inclusion of cyclosporin in the immunodepressive treatment.

Actuarial Analysis↗

[Adrenal myelolipoma: our experience and a review].

Four additional cases of adrenal myelolipoma that had been treated at our hospital are reported. All patients were male, aged 31-59 years. The largest diameter of the tumor ranged from 7-10 cm. Only one of the cases was symptomatic (arterial hypertension). In the remaining 3 patients with unremarkable clinical findings, the tumor and been detected incidentally during patient evaluation with CT and ultrasound (US) for other pathologies. Treatment was by surgery for the symptomatic case. For the remaining 3 patients, we adopted a conservative approach that included regular CT or US control evaluation. Treatment of this tumor type continues to be a controversy. Our therapeutic approach is described and the literature reviewed.

Adrenal Gland Neoplasms↗