Levels of circulating plasma immune complexes after thiacetarsamide treatment in dogs naturally infected with Dirofilaria immitis.
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Biomedical subjects
Publications and source records attributed to M C Muñoz.
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The effect of low molecular weight heparin (LMWH) with or without antithrombin III (AT III) has been studied in a rabbit model of disseminated intravascular coagulation (DIC) induced by continuous infusion of 100 microg/kg/hr of Escherichia coli endotoxin for 6 hr. LMWH (5 and 10 IU/kg/hr/6 hr), alone or in combination with AT III (20 U/kg/hr/6 hr), or saline were administered simultaneously with endotoxin. Hemostatic markers at 0, 2, and 6 hr as well as kidney fibrin deposits and the mortality rate at 24 hr were determined. Rabbits receiving only endotoxin showed an impairment in hemostasis, as well as high kidney fibrin deposits and a high mortality rate. LMWH alone did not exert any effect. The simultaneous infusion of LMWH and AT III exerted a beneficial effect on the hemostatic markers and reduced the kidney fibrin deposits as well as the mortality rate in a LMWH dose-dependent manner. Fibrinogen and protein C consumption were significantly higher and renal fibrin deposits more intense in the rabbits that had died in the first 24 hr. There was also a significant positive correlation between kidney fibrin deposits and platelets, fibrinogen, and protein C consumption, taking the whole rabbit population. It is concluded that the simultaneous infusion of LMWH and AT III is useful in this DIC model and would make it possible to reduce significantly the AT III doses used when AT III is given alone.
We evaluated the effect of r-hirudin and/or tissue-plasminogen activator (t-PA) in a model of DIC in rabbits induced by i.v. infusion of 100 micrograms/kg/h/6 h endotoxin. Rabbits were treated with saline (endotoxin control group), r-hirudin at 0.3 mg/kg/h/6 h, t-PA at 0.3 mg/kg for 90 min and r-hirudin plus t-PA at the doses described above. The best results were achieved when r-hirudin and t-PA were infused together. This treatment reduced the consumption of platelets and protein C and attenuated the increase of PAI-1 more efficiently than r-hirudin or t-PA alone. r-Hirudin plus t-PA also resulted in the lowest formation of fibrin deposits in the kidneys. Finally, mortality at 24 h dropped from 70% in the endotoxin control group to 40%, 10% and 0% in the t-PA, r-hirudin and r-hirudin plus t-PA groups respectively. None of the t-PA-infused rabbits which had died by 24 h showed macroscopic signs of haemorrhage. r-Hirudin alone was better than t-PA alone, as was shown by fibrin deposits and mortality. We conclude that r-hirudin and t-PA given simultaneously were more efficient than either given alone in this model of DIC. Effective thrombin inhibition, which could influence other pathophysiological mechanisms apart from coagulation, together with the improvement in fibrinolysis, would explain these results.
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BACKGROUND: Since the first surgical coronary revascularization done in Chile in 1971, 5000 such procedures have been performed. AIM: To assess the long term results of coronary revascularization surgery in our institution and to identify prognostic factors. PATIENTS AND METHODS: Five groups of 100 patients each, composed by the first consecutive patients subjected exclusively to coronary bypass surgery in the years 1975, 1980, 1985, 1990 and 1995 were retrospectively studied. RESULTS: Mean age of patients increased from a median of 52 years old in 1975 to 62 years old in 1995. No changes in the frequency of diabetes, hypertension, high serum cholesterol or previous myocardial infarction were observed. There was an increase in the proportion of patients with a recent (< 30 days) infarction that were operated along time. Seventy percent of patients had triple vessel disease or LMT and this proportion did not change. The number of grafts per patients increased form 1.9 to 3.4 and the use of arterial conduits from 0.18 to 0.81. Perioperative mortality remained constant and was 1.6%. Follow up information was obtained for 93% of 492 survivors. Actuarial survival at 5, 10, 15 and 20 years was 93 +/- 1, 82 +/- 2, 62 +/- 3 and 41 +/- 4% respectively. Ninety eight +/- 0.7, 89 +/- 2, 73 +/- 4 and 65 +/- 5% of patients remained free of a new myocardial infarction in the same lapses, respectively. Ninety seven +/- 1, 94 +/- 2, 76 +/- 4 and 47 +/- 7% of patients remained free of a new operation. Stepwise logistical regression analysis identified as bad prognostic factors, in decreasing order: cardiac failure, diabetes, smoking, hypercholesterolemia and age at the moment of operation. CONCLUSIONS: Coronary artery bypass surgery provides good and long lasting clinical improvement. The prognosis of patients is influenced by the presence of cardiac failure, some well known coronary risk factors and age at the moment of operation.
BACKGROUND AND OBJECTIVE: The control of well-known atherosclerotic risk factors represents the optimal strategy in the prevention of acute coronary syndromes. It was the aim of this work to analyze the effects of a long-term cardiac rehabilitation program on the changes of fibrinolysis parameters and plasma lipid profile in coronary patients. DESIGN AND METHODS: The study was carried out in 30 (M/F:22/8, mean age 47 years) survivors of a first acute myocardial infarction (AMI) and in 30 healthy controls who underwent a cardiac rehabilitation program (9 months duration). Samples were taken before, at 3 and 9 months after the beginning of the program to measure: tissue-type plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI-1) activity and antigen. A lipid profile including cholesterol (both HDL and LDL) and lipoprotein(a) was also assessed. The Wilcoxon and Mann-Whitney tests were used for statistical comparisons. RESULTS: There was a marked decrease of functional PAI-1 after 3 and 9 months as compared with baseline in AMI patients (p < 0.01). Results showed a significant increase of HDL-cholesterol (p < 0.01) and decrease of lipoprotein(a) levels after the exercise program (p < 0.01). INTERPRETATION AND CONCLUSIONS: The cardiac rehabilitation program improved fibrinolysis, by reducing the functional levels of PAI-1, and ameliorated the lipid profile by decreasing lipoprotein(a) and increasing HDL-cholesterol in patients with AMI. A long-term cardiac rehabilitation has positive effects on some risk factors for coronary disease.
The effect of melatonin (MEL) on the nephropathy and the oxidative stress induced by a single and high dose of Adriamycin (AD) has been studied in Wistar male rats. MEL (50 microg/kg/day) was injected intraperitoneally 3 and 7 days, respectively, before and after AD injection (20 mg/kg i.p.). Trunk blood was drawn and triglycerides, total cholesterol, phospholipids, high-density lipoprotein cholesterol, urea, creatinine, total protein, lipoperoxides, and reduced glutathione (GSH) levels and catalase activity (CAT) were determined in serum. In kidney homogenates, lipoperoxides, GSH, and CAT were measured as well as total protein in urine. AD administration resulted in hyperlipidemia and high-grade proteinuria and a marked increase in serum lipoperoxides, urea, and creatinine. In the kidney, the increase in lipoperoxides was accompanied by a significant decrease of GSH and CAT. The efficiency of MEL was specially remarkable in restoring GSH, CAT, and proteinuria to the levels of controls. These results confirm the involvement of free radicals in the pathogenesis of nephrotoxicity induced by AD. Likewise, they show the high antioxidative power of MEL and its marked effect on the prevention and suppression of this nephropathy.
The effect of melatonin administration on the oxidative stress induced by a high dose of Adriamycin (AD, doxorubicin hydrochloride) in plasma, hypothalamus and brain cortex of rats, as well as lipoperoxide changes, and catalase activity (CAT) levels have been studied. After administration of a single high AD dosis (25 mg/kg, i.p.), melatonin was injected daily three days before and after oxidative stress induction. The AD injection produced a significant lipoperoxide increase in plasma, hypothalamus and brain cortex, which was prevented by melatonin. CAT activity mean values decreased in hypothalamus by AD, effect which was reverted and increased by simultaneous melatonin administration. CAT activity was not changed after AD, melatonin or AD + melatonin administration in plasma and brain cortex. These results, especially those concerning lipoperoxide content changes, showed a powerful antioxidative effect of melatonin at both neural and extraneural levels in rats. CAT changes in the presence of melatonin suggest that there is a relationship between a scavenger role of the pineal hormone and a high oxidative activity in the brain hypothalamy area. When these results are taken together, they also show that melatonin, besides, producing the extraneural effect, can act as a powerful antioxidative agent in organs such as the brain, very rich in lipid susceptible to oxidation in the neuronal as well as the extraneuronal tissues.
A 16-year-old, male, Hanoverian horse had a three-month history of weight loss, hirsutism and polyuria/polydypsia. Examinations revealed neutrophilia, lymphopenia, hyper glycaemia and abnormalities in hepatic function. A tentative diagnosis of hyperadrenocorticism was made. The results of thyroid-releasing hormone and combined dexamethasone suppression and ACTH stimulation tests suggested the presence of a pituitary adenoma. The horse was treated with pergolide and beneficial clinical and biochemical responses were observed within one to six months.
We are reporting three patients who experienced delayed cutaneous reactions after treatment with paracetamol (acetaminophen). These reactions were confirmed in controlled challenge tests. Patch tests with paracetamol were positive in all patients. A biopsy performed of the case 1 patch test confirmed that the lesion was compatible with delayed hypersensitivity reaction-type allergic contact dermatitis.
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The aim of this study was to compare the relative effect of (1) a single dose of a rapid release theophylline, (2) treatment for 1 week with a sustained release theophylline, and (3) placebo after a washout period of at least 2 weeks on bronchial hyperresponsiveness to methacholine and on exercise-induced bronchoconstriction in 14 mildly asthmatic children. A dose of rapid release theophylline increased geometric mean (GM) PC20 (mg/mL) for methacholine from 0.25 to 0.85 (P < .001) at a mean (+/- SD) serum theophylline concentration of 9.5 +/- 2.5 mg/L (52.3 +/- 14.24 mumol/L). After 1 week on a slow release theophylline, GM PC20 increased to 0.41 (P < .01) at a mean serum theophylline concentration of 13.63 +/- 4.7 mg/L (74.9 +/- 25.8 mumol/L), (P < .01) compared with rapid release theophylline. The difference in PC20 between both theophylline treatments was statistically significant (P < .05). No significant changes in PC20 were noted after placebo compared with baseline values. During baseline and after placebo mean maximum FEV1 fall (MMFF) after exercise was 40 +/- 19.9% and 31.7 +/- 15.5%, respectively (n.s.). After a dose of rapid release theophylline, MMFF on exercise test was 8.7 +/- 8.2% (mean serum theophylline concentration 10 +/- 3.2 mg/L (55.4 +/- 17.82 mumol/L)), P < .001 compared with baseline and placebo. After 1 week of treatment with slow release theophylline, MMFF was 26.2% +/- 18.3 (mean serum theophylline concentration 12.2 +/- 3.9 mg/L (67.43 +/- 21.5 mumol/L)) (P = .01 and P = .30 compared with baseline and placebo, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of changes in brain serotonin content after injections of p-chlorophenylalanine (p-CPA), L-5-hydroxytryptophan (L-5HTP) and 5-6-dihydroxytryptamine (5-6DHT) on the mean arterial pressure (MAP), plasma renin activity (PRA) and peripheral levels of atrial natriuretic peptide (ANP) have been studied in normal and hypertensive (2K:1C model) male Wistar rats. The p-CPA (250 mg/kg) and L-5HTP (200 mg/kg) were injected i.p., while 5-6 DHT (15 micrograms/animal in 10 mu/animal vehicle) was injected into lateral brain ventricles. The effects were studied 24 h after the p-CPA injection, 2 h after L-5HTP and 10 or 20 days after 5-6DHT administration. The fall in brain serotonin produced by p-CPA and 5-6DHT did not modify the MAP values in the normal and hypertensive rat model, whereas the increase induced after L-5HTP injection only caused a slight decrease in arterial pressure in normotensive animals. The ARP experimented remarkable rises in the normal and hypertensive rats, these values increasing after L-5HTP and falling after p-CPA and 5-6 DHT injections. Similar changes are detected in the normal group after administration of these substances related to serotoninergic brain activity. The ANP levels rose after renal artery constriction, and they are not affected by the above mentioned substances. Only p-CPA and 5-6DHT reduced a low decrease in the ANP levels 10 days after their administration.(ABSTRACT TRUNCATED AT 250 WORDS)
The role of brain serotonin (5HT) on the hypothalamus-pituitary-adrenal system (HPAs) under basal condition and after injections of p-chlorophenylalanine (pCPA) and L-5-hydroxytryptophan (L-5HTP) has been studied in 6, 12 and 28 month old male Wistar rats. Four experimental groups were made for each age: control, saline, injected with pCPA (250 mg/kg i.p.) and L-5HTP (200 mg/kg i.p.), the effects being valued 2 hours after L-5HTP administration and 24 hours after pCPA injection. In all groups the plasmatic ACTH, the corticosterone levels as well as the simultaneous changes of the 5TH content tryptophan hydroxylase activity in whole brain were estimated two hours after the L-5HTP injection and 24 hours after that of pCPA. Significant changes are not found in the plasmatic ACTH and corticosterone values with respect to age under basal condition. Nevertheless, the response of HPAs differs with the age after pCPA or L-5HTP injection. The ACTH and corticosterone levels augment by L-5HTP and decrease by pCPA in all age groups, but this corresponding increase or decrease was less marked in the older rats. The 5HT content as tryptophan hydroxylase activity in brain decreased in old animals. pCPA and L-5HTP determine, respectively, high falls and rise of 5TH values, these changes being more intense for pCPA in old rats and for L-5HTP in young and mature animals. The tryptophan hydroxylase activity is decreased by pCPA as L-5HTP injections.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of ACTH (100 micrograms/animal/day, i.p.), dexamethasone (75 micrograms/animal/day, s.c.), both for three consecutive days, and adrenalectomy, with or without dexamethasone, maintained according to the group, one, two or three days, on the plasmatic testosterone and corticosterone levels, has been studied in adult male Wistar rats. ACTH and adrenalectomy produced a high decrease in testosterone levels (p less than 0.001 for the three days studied). Dexamethasone produced lower testosterone levels in the first day followed by partial recuperation between the second and the third days of its administration. Dexamethasone produced the effects mentioned for intact animals. The changes in corticosterone levels were according to an adequate response of the hypothalamus-pituitary-adrenal system under these experimental circumstances. ACTH exerts an inhibitory effect on testosterone secretion in the rat, so that such an effect from the data obtained after adrenalectomy and simultaneous dexamethasone injections, does not seems to be mediated either by the presence of adrenals or high corticosterone levels.
The effect of two doses of oxytocin (2 or 4 UI/kg i.p.) has been studied in the male Wistar rats, either preceded or not by a naloxone administration (10 mg/kg i.p.), on the response of the hypothalamus-pituitary-adrenal system, the latter being valued by changes produced in the plasmatic corticosterone levels. Oxytocin produced significant increases of the plasmatic corticosterone levels, this effect being stronger and longer lasting after the superior dose. Naloxone alone produced the same effect, but not as intense and stable as that of oxytocin. Pretreatment with naloxone modified the response of the hypothalamus-pituitary-adrenal system to oxytocin, producing partial blockade. The results suggest that the oxytocin action on the hypothalamus-pituitary-adrenal axis might be mediated by the endogenous opiates.
The response of hypothalamus-pituitary-adrenal system to insulin administration was studied in the male Wistar rats submitted to a strong and prolonged blockade of serotonin brain synthesis by repetitive injections of p-chlorophenylalanine (PCPA) a 5-hydroxytryptophan inhibitor. After 24, 48, 72 or 96 hours of either one or two doses of PCPA (250 mg/kg, i.p.) were administered with insulin (0.25 UI/kg s.c.), the plasmatic glucose and corticosterone levels being estimated at 0, 30 and 60 minutes. When PCPA was injected twice, the lapse between them was 48 hours. Insulin produced decrease of plasmatic corticosterone values and inhibition of the response to insulin, specially between 48 and 72 hours, for a single management of PCPA, and stronger and more prolonged for the double dose. The fall of serotonin content in brain maintained great correlation with effects referred above. The results support that stimulatory action of insulin on the pituitary-adrenal system is mediated by central serotoninergic neurons and reaffirms the hypothesis that serotonin (5HT) positively modulates the activity of hypothalamus-pituitary-adrenal system.
The effect of naloxone on the L-leucinaminopeptidase (LAP) activity has been determined in the hypothalamus of normal female rats or after different periods of time from ovariectomy (15th or 30th day). Castration at 15th and 30th days produced a not very important fall of LAP activity. The naloxone injections (2.5 or 5 mg/kg vía i.p.) determined a significant decrease in LAP activity in the intact and ovariectomized rats, greater for 5 mg/kg. A significant LAP activity decrease was found only after a 30 day postcastration period when naloxone treated intact animals were compared with the castrated rats. These data are discussed in relation to the physiological significance of brain peptidases and the pharmacological effect of naloxone on the function of the hypothalamic-pituitary-gonadal axis.