Effects of intracerebroventricular injections of losartan or PD123319 on arterial pressure and heart rate of sodium replete and sodium deplete rats

Angiotensin II (Ang II) non-peptide antagonists were injected i.c.v. (6.25-200 nmol, n = 5-8 rats/group): In sodium replete rats, losartan (AT1 receptor antagonist) induced an increase in mean arterial pressure (MAP) and in heart rate (HR) by 3rd ventricular (3rdV) injection, and a weaker pressor response and bradycardia by 4th ventricular (4thV) injection. PD123319 (AT2 receptor antagonist) induced an increase in MAP and in HR by 3rdV injection, and an increase in MAP and no alteration in HR by 4thV injection. In sodium deplete (furosemide plus removal of ambient sodium for 24 h) rats, losartan induced an increase in MAP and no alteration in HR by 3rdV injection, and no alteration in MAP and bradycardia by 4thV injection. PD123319 induced an increase in MAP and in HR by 3rdV injection, and an increase in MAP and bradycardia by 4thV injection. Thus, there was no fall in MAP by central injections of Ang II antagonists. Intravenous injection of losartan, but not of PD123319, induced a fall in MAP in both sodium replete and sodium deplete animals. Therefore, losartan and PD123319 can have similar effects on MAP and HR when injected intracerebroventricularly, although some differences are also present. The bradycardia is consistent with an withdrawal of Ang II inhibitory action on baroreflex.

Lipossomas: Estrategia biotecnologica para liberacao controlada e direcionamento intracelular de farmacos com efeito antimicobacteriano

This text highlights the state of research related with the application of liposomes in the control of drug delivery and drug target to intracellular bacterial diseases, such as the tuberculosis. Liposome have several pharmaceutical applications and this article is primarily focused on the potential of this agregate on drug encapsalation especially antimycobacterial compounds. Case studies in which liposomes have successfully been used to improve pharmacological drug effect are presented. Mechanisms involved in intracellular drug delivery, possibilities of application, research and development efforts to address these objectives are discussed.

The deep mycoses in HIV infection

The deep mycoses are uncommon infections, usually acquired from the inhalation or ingestion of fungal spores, sometimes from the soil in areas of endemicity, such as in the Americas and south-east Asia, or from decaying vegetable matter. They are also seen in immunocompromised persons and, increasingly, in HIV-infected persons. Respiratory involvement is frequent, with granuloma formation, and mucocutaneous involvement may be seen. Oral lesions of the deep mycoses are typically chronic but non-specific, though nodular or ulcerative appearances are common. Person-to-person transmission is rare. In HIV disease, the most common orofacial involvement of deep mycoses has been in histoplasmosis, cryptococcosis, aspergillosis and zygomycosis. Diagnosis is usually confirmed by lesional biopsy although culture may also be valuable. Treatment is with amphotericin or an azole.

Endocrine changes in cerebrospinal fluid, pituitary effluent, and peripheral plasma of anesthetized ponies

Objective - To investigate the effects of inhalation and total IV anesthesia on pituitary-adrenal activity in ponies. Animals - 9 healthy ponies: 5 geldings and 4 mares. Procedure - Catheters were placed in the cavernous sinus below the pituitary gland and in the subarachnoid space via the lumbosacral space. After 72 hours, administration of acepromazine was followed by induction of anesthesia with thiopentone and maintenance with halothane (halothane protocol), or for the IV protocol, anesthesia induction with detomidine and ketamine was followed by maintenance with IV infusion of a detomidine-ketamine-guaifenesin combination. Arterial blood pressure and gas tensions were measured throughout anesthesia. Peptide and catecholamine concentrations were measured in pituitary effluent, peripheral plasma, and CSF. Peripheral plasma cortisol, glucose, and lactate concentrations also were measured. Results - Intravenous anesthesia caused less cardiorespiratory depression than did halothane. ACTH, metenkephalin, arginine vasopressin, and norepinephrine pituitary effluent and peripheral plasma concentrations were higher during halothane anesthesia, with little change during intravenous anesthesia. Pituitary effluent plasma β-endorphin and peripheral plasma cortisol concentrations increased during halothane anesthesia only. Dynorphin concentrations did not change in either group. Hyperglycemia developed during intravenous anesthesia only Minimal changes occurred in CSF hormonal concentrations during anesthesia. Conclusion - The pituitary gland has a major role in maintaining circulating peptides during anesthesia. Compared with halothane, IV anesthesia appeared to suppress pituitary secretion.

Peridural com ropivacaina a 1%: Experiencia com volume proporcional a estatura

Background and Objectives - Ropivacaine - a local amino amide anesthetic agent - is a plain S enantiomer which makes it a potent and low toxicity drug. The aim of our study was to evaluate 1% ropivacaine for epidural block in lower doses than those described in the literature. Methods - Thirty-eight patients, physical status ASA I and II, aged 15 to 70 years, weighing 50 to 100 kg were selected. Premedication consisted of 15 mg oral midazolam given 60 min before anesthesia induction. In the OR, after standard monitoring a catheter was inserted intravenously to administer 10 ml.kg-1 Ringers lactate solution. Epidural puncture was performed with the patient in the sitting position and 1% ropivacaine was administered in a volume corresponding to 10% of patient's height in centimeters. With the patient in the supine position, motor blockade intensity, temperature sensitivity and sensory block extension at 1, 3, 5, 7, 10, 15, 20, 30 minutes after drug injection were evaluated. Blood pressure, heart rate and adverse side effects during the course of anesthesia and in the post-anesthetic period were also observed. In the recovery room patients were followed-up until motor blockade intensity temperature sensitivity and sensory block had returned to level L2. Results - Mean values were 41.4 years of age, 68.8 kg of body weight and 165 cm height. Upper thermal blockade level was T4 and upper sensory block level was T6. Most patients showed motor block level 1 (Bromage scale) after 30 minutes of observation. Motor block mean duration was 254 minutes and temperature sensitivity 426 minutes. Only three patients had complications: two cases of hypotension and one of bradycardia. Conclusions - In the volumes used in this study, ropivacaine produced adequate analgesia and a less intense lower limb motor block which, however, was sufficient to allow for surgical procedures with low incidence of side-effects.

Characterization of the antinociceptive and sedative effect of amitraz in horses

Amitraz, an acaricide used to control ectoparasites in animals has a complex pharmacological activity, including α2-adrenergic agonist action. The purpose of this research was to investigate the possible antinociceptive and/or sedative effect of amitraz in horses. The sedative effect of the intravenous (i.v.) injection of dimethylformamide (DMF, 5 mL, control) or amitraz (0.05, 0.10, 0.15 mg/kg), was investigated on the head ptosis test. The participation of α2-adrenergic receptors in the sedative effect provoked by amitraz was studied by dosing yohimbine (0.12 mg/kg, i.v.). To measure the antinociception, xylazine hydrochloride (1 mg/kg, i.v., positive control) and the same doses of amitraz and DMF were used. A focused radiant light/heat directed onto the fetlock and withers of a horse were used as a noxious stimulus to measure the hoof withdrawal reflex latency (HWRL) and the skin twitch reflex latency (STRL). The three doses of amitraz used (0.05, 0.10 and 0.15 mg/kg) provoked a dose-dependent relaxation of the cervical muscles. The experiments with amitraz and xylazine on the HWRL showed that after i.v. administration of all doses of amitraz there was a significant increase of HWRL up to 150 min after the injections. Additionally, there was a significant difference between control (DMF) and positive control (xylazine) values up to 30 min after drug injection. On the other hand, the experiments on the STRL show that after administration of amitraz at the dose of 0.15 mg/kg, a significant increase in STRL was observed when compared with the control group. This effect lasted up to 120 min after injection. However, no significant antinociceptive effect was observed with the 0.05 and 0.10 mg/kg doses of amitraz or at the 1.0 mg/kg dose of xylazine.

Comparacao da recuperacao de anestesia venosa com propofol e anestesia inalatoria com sevoflurano para laparoscopia ginecologica

Backgrounds and Objectives: Both continuous venous anesthesia with propofol and inhalational anesthesia with sevoflurane propitiate fast arousal with few side effects. The aim of this study was to compare the arousal and post anesthestic recovery times in patients submitted to these two agents. Methods: Forty three patient aged 18 to 50 years, physical status I or II, submitted to gynecological laparoscopy were distributed in two groups: G1 - propofol in continuous infusion of 115 μg.kg -1.min -1 and G2 sevoflurane. All the patients were pre-medicated with 7.5 mg midazolam, sufentanil 0.5 μg.kg -1, propofol 2 mg.kg -1, atracurium 0.5 mg.kg -1, N 2O in 50% of oxygen in a no-rebreathing system. The depth of the anesthesia and arousal time were assessed by the Bispectral index (BIS). The time between end of anesthesia and eye opening, time for command response and time for orientation were also evaluated. Results: The times recorded in minutes were: G1 - eye opening 8.2 ± 2.9, command response 8.6 ± 3.1, orientation 9.8 ± 3.4, recovery 31.6 ± 3.8; G2 - eye opening 4.5 ± 3, command response 4.9 ± 3.4, orientation 6.2 ± 3.4, recovery 66 ± 8. Except the recovery time, all the values were larger in G1. Conclusions: Both intravenous propofol or inhalational sevoflurane were considered excellent anesthetic techniques as to recovery time and recovery room discharge. Sevoflurane provided an earlier arousal with a longer recovery room stay as compared to propofol.

Effect of allopurinol in the course of adriamycin induced nephropathy

The role of superoxide in adriamycin-induced nephropathy (single dose; i.v. 3 mg/kg) has been studied by blocking superoxide synthesis through the administration of allopurinol (500 mg/L in drinking water). In Experiment I (EI), allopurinol administration was started 3 days prior to nephropathy induction and continued until day 14. In Experiment II (EII) allopurinol administration was started 2 weeks after nephropathy induction and was maintained until the end of the experiment (26 weeks). Affected glomeruli frequency and tubulointerstitial lesion index (TILI) were determined at Weeks 2 and 4 (EI) and Week 26 (EII). In EI, and 24 h mean proteinuria in the nephrotic control group (NCG-I) differed from that of the treated nephrotic group (TNG-I) at Week 1 (TNG = 33.3 ± 6.39 mg/24 h; NCG = 59.8 ± 6.3 mg/24 h; p < 0.05) and 2 (NCG-I = 80.0 ± 17.5 mg/24h; TNG-I = 49.1 ± 8.4 mg/24 h; p < 0.05). No glomerular alterations were observed and TILI medians were not different in both nephrotic groups at week 2 (NCG-I = 1+: TNG = 1+) and 4 (NCG = 4+; TNG = 4+). In EII, NCG-II and TNG-II presented different 24 h proteinuria values only at Week 6, (136.91 ± 22.23 mg/24 h ad 72.66 ± 10.72 mg/24 h, respectively; p < 0.05). Between nephrotic groups, there was no statistical difference in the median of affected glomeruli (CNG-II = 56%; TNG-II = 48% and TILI (NCG-II = 8+; TNG-II = 9+). Thus, allopurinol was associated with a transient reduction in proteinuria and it did not alter the progression of the nephropathy.

Effects of glucose infusion on the endocrine, metabolic and cardiorespiratory responses to halothane anaesthesia of ponies

Glucose was infused intravenously into six ponies during halothane anaesthesia, to evaluate its effect on their endocrine response to anaesthesia. The ponies were premedicated with acepromazine, and anaesthesia was induced with thiopentone and maintained with halothane in oxygen for two hours. Glucose was infused to maintain the plasma glucose concentration above 20 mmol/litre. Anaesthesia was associated with hypothermia, a decrease in haematocrit, hypotension, hyperoxaemia, respiratory acidosis and an increase in the plasma concentrations of lactate and arginine vasopressin. The concentration of β-endorphin in plasma increased transiently after 20 minutes but there were no changes in concentrations of adrenocorticotrophic hormone, dynorphin, cortisol or catecholamines. These data suggest that the glucose infusion attenuated the normal adrenal response of ponies to halothane anaesthesia.

Role of ticlopidine on adriamycin-induced nephropathy

The effect of ticlopidine on rats with adriamycin nephropathy was observed during 26 weeks. In the ticlopidine-treated nephrotic animals (TNG), proteinuria was less than in the untreated nephrotic animals (NG), but this difference was significant only at week 6 (TNG = 47.27 ± 16.52 versus NG = 100.08 ± 13.83 mg/24h, p < 0.01) and week 26 (TNG = 157.00 ± 28.73 versus NG = 217.00 ± 21.73 mg/24h, p< 0.01) after ADR injection. NG presented severe tubulointerstitial abnormalities with a tubulointerstitial lesion index of 3+. No difference in glomerular lesions was observed among the groups (NG median = 6%, TNG median = 4% and TCG median = 2%). The tubulointerstitial lesion index of TNG was less intense (median = 2+) but not different from those of the control groups (CG median = 1+; TCG median = 0+) nor NG (median = 3+). We concluded that the treatment with ticlopidine produced some partially beneficial effects but did not prevent the development of adriamycin-induced nephropathy.

Investigation into the use of the Laryngeal Mask Airway in pentobarbital anesthetized dogs

Objective - To investigate the use of the laryngeal mask airway (LMA) in dogs. Study Design - Prospective experimental study. Animals - Eight healthy adult mixed breed dogs weighing from 15 to 20 kg. Methods - The dogs were anesthetized with intravenous pentobarbital. An LMA was introduced after the induction of anesthesia and 1 L/min O2 plus 1 L/min air was delivered using a circle anesthetic system. Respiratory rate, tidal volume, arterial O2 saturation (pulse oximetry), end tidal CO2, inspired fraction of O2, pulse rate, and mean arterial blood pressure were measured after the insertion of the LMA and 30, 60, 90, and 120 minutes afterwards. Results - There were no changes in respiratory rate, tidal volume, arterial O2 saturation, and pulse rate during anesthesia. End tidal CO2 decreased significantly by the end of anesthesia and ventilation appeared satisfactory. Conclusions - An LMA appeared to be an alternative option to maintain the patency of the airway in dogs. Clinical Relevance - This device may allow safe maintenance of an airway in dogs when intubation is difficult or when it interferes with the procedure (eg, cervical myelography). ©Copyright 1999 by The American College of Veterinary Surgeons.

Increased natural killer activity does not prevent progression of experimental kala-azar

Kala-azar is the visceral form of leishmaniasis and it is caused by intracellular parasites from the complex Leishmania donovani. Golden hamster (Mesocricetus auratus) infected with Leishmania donovani develop a disease very similar to human Kala-azar. There is conspicuous hipergammaglobulinaemia and their T cells do not respond to stimulation with parasite antigens. We used this experimental model to evaluate the natural killer (NK) activity during the initial phase of the disease. Outbred hamsters infected by intravenous route with 5.106 amastigotes of L. donovani 1S showed a concurrent increase in the spleen weight and in the spleen cell number. Using the single cell assay we detected a significant increase in the percentage of NK effector cells on the 4th day of infection. Imprints from spleen and liver showed at days 14 and 28 a significant increase in the parasite burden. These results show that the increased NK activity in the beginning of the infection was not able to restrain the progression of the disease in this experimental model.

Eficácia e segurança do uso inalatório da adrenalina-L na laringite pós-intubação utilizada em associação com a dexametasona

Objective: to assess the efficacy and safety of the use of nebulized L-epinephrine associated with dexamethasone in post-intubation laryngitis. Method: we carried out a prospective, randomized, double-blind, placebo controlled study with two cohorts of patients with postintubation laryngitis graded 3 to 6 by Downes and Raphaely score and during two years. Our population was divided into two groups: A and B; both groups received intravenous dexamethasone and nebulized saline with (group B) and without (group A) L-epinephrine. The efficacy was assessed by Downes and Raphaely's score. The side effects of epinephrine were evaluated according to occurrence of arrhythmia, to increased blood pressure, and to average heart rate of group B in comparison to group A. Results: twenty-two patients were included in group A (average score = 4.8) and 19 in group B (average score = 5.2). During treatment, 3 patients in group A presented a score of 8 and were reintubated. This group also showed higher clinical scores than group B during the first two hours of the protocol; these results were not statistically significant. No side effects were observed due to epinephrine. The gasometric parameters were adequate in both groups, but better in the control group. Conclusions: we did not observe increased efficacy for the treatment of post-intubation laryngitis when nebulized L-epinephrine was used simultaneously with intravenous dexamethasone. Some indicators, however, did present a favorable trend when combined therapy was used and should be submitted to further evaluation.

Hepatic bleeding induced by streptokinase and heparin in a patient with acute myocardial infarction

Although rare, major bleeding is the most important side effect of thrombolytic therapy in acute myocardial infarction (AMI) (Levine et al., 1995). Spontaneous hepatic bleeding in normal liver after thrombolytic administration has rarely been reported in literature. To our knowledge, there are only three cases of hepatic bleeding related to thrombolytic therapy in AMI. In these, the used drugs were anisolylated plasminogen streptokinase activator complex (APSAC) (Garcia-Jiménez et al., 1997; Fox et al., 1991) and rt-PA (Garcia-Jiménez et al., 1997). We report a case of hepatic bleeding after streptokinase followed by units over 60 minutes). The next day, the patient developed third-degree atrioventricular block and a temporary pacemaker was inserted. Twenty-seven hours after streptokinase infusion, the patient complained of refractory chest pain that was interpreted as post-myocardial infarction angina; clotting screen was normal and intravenous heparin was started (80 U/kg followed by 18 U/kg/hour). After four hours of heparin administration, the patient presented abdominal pain and distension, and his blood pressure and hematocrit level dropped. Abdominal ultrasonography revealed free fluid in the peritoneal cavity (about 3,000 mL). A laparotomy disclosed blood in the abdominal cavity with bleeding from the right lateral hepatic segment, which was removed. The remaining abdominal viscera were normal and there was no other evidence of hemorrhage. The partial liver resection presented subcapsular hemorrhage with small parenchymal hemorrhage. Histopathological examination also revealed focal areas of ischemic centrilobular necrosis. The patient died of multiple organ system failure 21 days after admission. Copyright © 2002 By PJD Publications Limited.

Effects of contrast material on computed tomographic measurements of lung volumes in patients with acute lung injury

Background. Intravenous injection of contrast material is routinely performed in order to differentiate nonaerated lung parenchyma from pleural effusion in critically ill patients undergoing thoracic computed tomography (CT). The aim of the present study was to evaluate the effects of contrast material on CT measurement of lung volumes in 14 patients with acute lung injury. Method. A spiral thoracic CT scan, consisting of contiguous axial sections of 10 mm thickness, was performed from the apex to the diaphragm at end-expiration both before and 30 s (group 1; n=7) or 15 min (group 2; n=7) after injection of 80 ml contrast material. Volumes of gas and tissue, and volumic distribution of CT attenuations were measured before and after injection using specially designed software (Lungview®; Institut National des Télécommunications, Evry, France). The maximal artifactual increase in lung tissue resulting from a hypothetical leakage within the lung of the 80 ml contrast material was calculated. Results. Injection of contrast material significantly increased the apparent volume of lung tissue by 83 ± 57 ml in group 1 and 102 ± 80 ml in group 2, whereas the corresponding maximal artifactual increases in lung tissue were 42 ± 52 ml and 31 ± 18 ml. Conclusion. Because systematic injection of contrast material increases the amount of extravascular lung water in patients with acute lung injury, it seems prudent to avoid this procedure in critically ill patients undergoing a thoracic CT scan and to reserve its use for specific indications.