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Biomedical subjects

D Davila

Publications and source records attributed to D Davila.

At least 19 recordsLinked to original sources

Disk diffusion sensitivity testing and antibacterial activity of azithromycin.

Azithromycin (CAS 83905-01-5) disks with the selected loading (10, 15, 20 micrograms) were used for determination of the most suitable azithromycin disk concentration. Estimation was carried out by means of the regression line related to the zone size inhibition. Testing was performed on a variety of freshly isolated gram-positive, gram-negative and anaerobic bacteria derived from various specimens collected from patients. Using the disk diffusion method with 10 micrograms of azithromycin per disk in total 431 gram-positive, 875 gram-negative bacterial strains and 59 anaerobic bacteria were analysed. It was concluded that azithromycin disk containing 10 micrograms is sufficient for determination of bacterial sensitivity.

Anti-Bacterial Agents

Pharmacokinetics of azithromycin after single oral dosing of experimental animals.

Azithromycin, a macrolide antibiotic with an enhanced antimicrobial spectrum, was found to have a longer half-life than erythromycin, with marked tissue penetration. The pharmacokinetics of azithromycin after oral administration were compared with those of erythromycin in rats (200 mg kg-1) and rabbits (80 mg kg-1). Concentrations of azithromycin in liver, lung, kidney, ileum, and brain were higher than serum concentrations. The slow decline in tissue concentrations was evident from the biphasic elimination profile. Thus, advantageous pharmacokinetic properties and the broader antimicrobial spectrum of azithromycin relative to erythromycin appear to further support its therapeutic potential.

Administration, Oral

[Supraselective or proximal gastric vagotomy. Report of 1,250 surgical cases. 777 special cases with objective follow-up for over 10 years].

From August, 1970 to February, 1989, we performed 1,105 elective and 145 emergency PGVs (proximal gastric vagotomy). The emergent cases included 118 perforations and 27 bleeding lesions. Since September, 1973, we have been able to measure the pH of the mucosa using a GR282C transesophageal electrode. Two cases of exitus (0.2%) were noted. With an intraoperative test (pH) or the systematic section of the gastroepiploic nerve (n.ge) (randomized with 269 cases followed up over 57 months) the rate of recurrence does not exceed 2%. Without these "tools", it is as high as 10%. Since this rate is still a cause of confusion in this 20th year of PGV, we analyse 684 "stabilized" (excluding the first 10 patients of each surgeon). PGVs followed up (88% of 777 PGVs) over 10 to 17 years. The study was clinical and radiological in 100% of cases, based on acid secretion in 2/3, and fiberscopic in 47%. Between 5 and 17 years, 318 patients had a fiberscopic study and 325 an analysis of the basal and stimulated acid secretion (76% were already evaluated preoperatively). Two types of recurrence were defined: those due to failure of the surgeon or technique (gastroepiploic nerve in 1/5 of cases) involving acidity--this being the "persistent" ulcer (3/4 of cases during the first years); and disorders in gastric evacuation (?) with a very low acidity level, also causing more delayed gastric ulcers. The non-cumulative probability of R in successive years stays around 0.2 to 0.1% after the 3rd or 4th year following the PGV, and the total rate after 10 years or more is about 10%. If performed by experienced surgeons and with the intraoperative test (or systematic section of the n.ge), PGV should have only a low rate of failure, these cases being more amenable to treatment than an anastomotic mouth ulcer following resection, for instance.

Adult

Right ventricular function in Chagas disease.

To study right ventricular function, we performed cardiac catheterization, and right and left cineventriculograms in 60 chagasic patients and 15 non-chagasic, non-heart disease patients. Chagasic patients with normal electrocardiograms and left cineventriculograms also had normal right ventricular function. Nine of 14 chagasic patients with normal Ecg's and early left ventricular damage had right ventricular dilatation and/or segmental inferior-apical asynergy. Fourteen of 19 chagasic patients with abnormal Ecg's and advanced left ventricular damage, but without signs of congestive heart failure, and all chagasic patients with congestive heart failure, had marked right ventricular dilatation, severe right contractility depression and abnormal right apical or para-apical motion. These findings indicate that Chagas disease is a diffuse cardiomyopathy in which the left ventricle seems to be affected earlier and to a greater extent than the right ventricle. Since segmental abnormalities were predominantly observed in apical and para-apical areas of the ventricles, performance of right and left cineventriculograms is recommended before implantation of cardiac pacemakers.

Adult

Inhibitory effect of two steroids on the accumulation of [3H]metaraminol by rat tissues in vivo.

The present experiments were designed to investigate the effect of methylprednisolone and dexamethasone on tritiated metaraminol uptake in the whole animal. Rats received i.p. injections of methylprednisolone (5, 10 and 20 mg kg-1) or dexamethasone (1, 2 and 4 mg kg-1) on each of 3 consecutive days. Under light ether anaesthesia 5 min before death the rats received radioactive metaraminol (3 microgram kg-1) via the femoral vein. Samples of various organs were removed and prepared for scintillation counting. The highest radioactivity was observed in the lungs and heart, followed by the kidney medulla, aorta, kidney cortex and submaxillary gland. Both steroids significantly inhibited uptake of metaraminol in the tissues examined. Dexamethasone seems to be more potent that methylprednisolone. It is concluded that these steroids may modify the uptake mechanism responsible for inactivation of the sympathomimetic neurotransmitter.

Animals

Thiazide diuretics inhibit contractions of isolated smooth muscles.

The interaction between thiazide diuretics and contractile responses produced by 5-hydroxytryptamine, acetylcholine, noradrenaline and angiotensin II, has been examined on isolated rat uterus and guinea pig aorta. Hydrochlorothiazide, polythiazide and cyclopenthiazide inhibited the contraction of isolated tissue induced by the spasmogens. These data demonstrated that the tested diuretics possess antagonistic activity on contractions induced by various spasmogens.

Animals

Renal prostaglandins and sodium balance in the rabbit: lack of effect of aspirin-like drugs.

Urinary prostaglandin E2 (PGE2) and PGF2 excretion was previously found to be inversely related to sodium intake in the rabbit. Renal prostaglandin (PG) synthesis might therefore be involved in the renal handling of sodium. This possibility was tested by studying sodium excretion during inhibition of renal PG synthesis with four different nonsteroidal anti-inflammatory drugs in unanaesthetized, female rabbits. The rabbits n = 5-6) were kept in metabolic cages and chronically maintained on different sodium containing diets. On a medium salt diet (0.4% NaCl), neither treatment with indomethacin (1.5 mg/kg x 2 or 3 mg/kg x 2) nor diclofenac (1.5 mg/kg x 2) for three days changed the urinary excretion of sodium and water although the mean excretion of immunoreactive PGE2 (iPGE2) and iPGF2 were reduced by between 43-78%. On a very low salt diet (0.05% NaCl), two days treatment with aspirin (30 mg/kg x 2), diclofenac (3 mg/kg x 2), indomethacin (3.5 mg/kg x 2) or naproxen (10 mg/kg x 2) did not alter sodium excretion in any significant direction. The mean urinary PGE2 and PGF2 excretion was reduced by 35-63% and 63-85%, respectively. These results do not support a major role of PGs in the chronic regulation of sodium balance in the rabbit. The possible influence of mineralocorticoids on renal PG synthesis was studied by administration of aldosterone (100 microgram/kg x 2) for two days to rabbits on a high salt diet (2% NaCl) and cancrenoate (10 mg/kg x 2), an aldosterone antagonist, to rabbits on the very low salt diet. However, neither drug significantly changed the urinary excretion of PGF2 alpha, indicating that renal PG synthesis is not influenced by mineralocorticoids in the rabbit.

Aldosterone

The influence of dietary sodium on urinary prostaglandin excretion.

The influence of dietary sodium chloride on the urinary excretion of prostaglandins (PGs) was studied in unanesthetized female rabbits housed in metabolic cages. Urinary PG levels were determined by radioimmunoassay, bioassay and gas chromatography-mass spectrometry. In the first experiment rabbits were fed at high (2.5%) and later a low (0.25%) sodium chloride diet ad libitum. A 2--5 fold increase in excretion of immunoreactive PGF2alpha (iPGF2alpha) and iPGE2 was noticed when animals were given the low salt diet. Since it could not be excluded that dietary factors other than sodium chloride contributed to the changes a second, more controlled experiment was undertaken. Rabbits were fed 30 g/kg per day of diets offering only in the content of sodium chloride, 2% and 0.37% respectively. On the high salt diet the rabbits excreted 0.1 +/- 0.04 microgram/day of PGE2 and 2.0 +/- 0.5 microgram/day of iPGF2alpha. After equilibration on the low salt diet the PGE2 excretion rate increased to 1.5 +/- 0.3 microgram/day (p less than 0.001) and that of iPGF2alpha to 3.4 +/- 0.4 microgram/day (p less than 0.01). These results thus point to an inverse relationship between renal sodium excretion and the activity of the renal prostaglandin system.

Animals

Effect of angiotensin II and its analogs on uptake and release of 14C-5-hydroxytryptamine by rat brain.

Uptake of 14C-labelled 5-hydroxytryptamine (14C-5-HT) has been investigated by perfusion of the rat brain ventricular system. When angiotensin II was present during perfusion, a dose-dependent inhibition of 14C-5-HT uptake in rat brain was observed. A similar effect was obtained with angiotensin II analogs (8-alanine angiotensin II or 1-dimethylglycine, 8-isoleucine angiotensin II). The inhibitory effect of angiotensin II can be almost completely blocked with 1-dimethylglycine, 8-isoleucine angiotensin II. In washout experiments, the radioactivity remaining in the brain was greater in the presence of angiotensin II.

Angiotensin II

Uptake and release of 3-H-metaraminol by rat lung. Basic aspects, ionic and energy requirements.

The accumulation of 3H-metaraminol in incubated lung tissue of the rat was examined in vitro. Lung tissue concentrated tritium after incubation with 3H-metaraminol. This uptake proceeds against a concentration gradient and shows saturation kinetics (Km 12.5 X 10(-7) M and Vmax 2.105 nM/g/15 min.) with great affinity for 3H-metaraminol. The accumulation of 3H-metaraminol is dependent of temperature and energy supply, and requires the presence of sodium ions. The loss of accumulated radioactivity showed the possibility that a small fraction of metaraminol is apparently firmly boune (e.g. neuronal sites), while a greater portion is taken up by extraneuronal structures (e.g. capillary endothelial cells). The first localization could represent uptake-1 and the second uptake-2. The results obtained also confirm the important role of the lungs as an organ which participates in the fate of endogenous substances and drugs.

Animals

Uptake and release of 3H-metaraminol by rat lung. The influence of various drugs.

Uptake and release of 3H-metaraminol was measured in vitro incubating rat lung tissue in the presence of ouabain (1.5-45 mug/ml), cocaine (1-30 mug/ml), tyramine (0.1-3 mug/ml, reserpine (0.05-1.5 mug/ml), imipramine (0.1-3 mug/ml) and desipramine (0.3-10 mug/ml. All drugs significantly inhibited uptake and release of 3H-metaraminol from lung tissue. This blockade most probably occurs at membrane levels of both neuronal uptake-1 sites and extraneuronal uptake-2 sites. These results further emphasize the importance of the lung in the fate of drugs and endogenous substances.

Animals