Free radical production by azomethine H: Effects on pancreatic and hepatic tissues

The antimalarial properties of azomethine H represent the basis for its use as a chemotherapeutic agent. This work was carried out in order to verify the biological side effects of azomethine H and to clarify the contribution of reactive oxygen species (ROS) in this process. It was shown that azomethine H increased serum activities of amylase, alanine transaminase (ALT) and the TEARS concentrations, in rats. No changes were observed in glutathione peroxidase and catalase activities. The drug-induced tissue damage might be due to superoxide radicals (O-2(.-)), since Cu-Zn superoxide dismutase activities were increased by azomethine I-I treatment. This study allows tentative conclusions to be drawn regarding which reactive oxygen metabolites play a role in azomethine H activity. We concluded that (O-2(.-)) maybe produced as a mediator of azomethine H action.

Haematological and biochemical alterations in leprosy patients already treated with dapsone and MDT

Dapsone (DDS) is useful in the treatment of a number of inflammatory conditions which are characterized by neutrophil infiltration. It is the drug of choice for the treatment of leprosy and prophylaxis of malaria. Haematological side effects of methaemoglobinaemia and haemolysis have been long recognized. However, the frequency and severity of these side effects in patients already treated with DDS as a single drug or as part of a multidrug therapy (MDT) have not been well documented. We report herein an investigation of the effect of dapsone long-term treatment on the haematological and biochemical alterations in leprosy patients undergoing dapsone as a single drug (DDS group) or as part of a multidrug therapy in combination with rifampin and clofazimine (MDT group). Methaemoglobinaemia and haemolytic anaemia were the principal side effects observed. Reticulocytes were found to be elevated (> 1.5%) in 90% of the patients. Heinz bodies were also detected (6.6% of the patients). The osmotic fragility test showed a reduction in cell resistance and in the evaluation of white cells a severe eosinophilia was found. Hepatic, pancreatic and renal evaluation by the determination of biochemical parameters showed rare and occasional changes of no apparent clinical significance. We conclude that haematological side effects of dapsone are significant even at doses currently used to treat leprosy (100 mg/day) and that rifampin and clofazimine do not increase the incidence of these effects during long-term treatment.

Treatment of fibrinolytic alveolitis with rifamycin B diethylamide associated with gelfoam: a histological study.

The most common complication in the healing of extraction wounds is fibrinolytic alveolitis, which may also be termed dry socket. Reduction in the incidence of this condition after the application of topical antibiotics and the use of systemic antibiotics has been reported. A histological study of disturbed alveolar socket healing in rats was carried out to analyze the influence of application of rifamycin B diethylamide (Rifocin M) associated or not with Gelfoam. Sixty-four male rats (Rattus norvegicus albinus, Wistar), weighing 120-150 g, were divided into 4 groups of 16 animals each. In the second group of rats which received implants of Gelfoam, there was an intense resorption of bone walls in the initial stage. The rats that received implants of Gelfoam saturated with Rifocin M (fourth group) showed better results than the second group. The third group (only irrigation with rifamycin) showed better bone formation in the alveolar socket compared to the first, second and fourth groups. Thus, these results showed that rifamycin irrigation is useful in the control of alveolar infections.

Use of fibrin glue derived from snake venom in testicular biopsy of rams

Sequelae due to testicular biopsy such as hemorrhage, adhesion and fibrosis may be limiting factors to the use of this surgical procedure. Fibrin glue (FG) derived from snake venom was used to minimize these sequelae, as well as to evaluate its healing property in tunica vaginalis and scrotal skin of rams. Applicability of fibrin glue derived from snake venom was tested in different tissues of other animals such as in sciatic nerve and colon of rats and skin of rabbits. In the present study, 30 healthy adult rams were used. They were divided into 3 groups of 10 animals each as follows: G1: fibrin glue group (application of fibrin glue on puncture sites and skin incisions after bilateral testicular biopsy with a Tru-Cut needle); G2: swab/nylon group (hemostasis by compression with a swab on puncture sites and skin suturing with nylon after biopsy) and G3: control group (the animals were not subjected either to biopsy or to surgery). On the 20th day after biopsy, the presence of adhesion strands between the sites of skin incision and testicle was evaluated by palpation Adhesion strands were found in three testicles (15%) in G1 and in two testicles (10%) in G2. One hundred days after biopsy, orchiectomy was carried out and the material collected was assessed for subcutaneous (SC) and/or tunica vaginalis adhesions. G3 did not present any abnormality. Groups G1 and G2 presented four testicles each (20%) with adhesion between the tunics at biopsy site. On the other hand, subcutaneous adhesions were found once (5%) in G1 and three times (15%) in G2. Fibrin glue showed to be of easy application, required short postoperative monitoring, presented fast and good-quality healing property and tended to reduce formation of subcutaneous adhesion.

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.

Use of lytic bacteriophage for control of experimental Escherichia coli septicemia and meningitis in chickens and calves

A lytic bacteriophage, which was previously isolated from sewage and which attaches to the K1 capsular antigen, has been used to prevent septicemia and a meningitis-like infection in chickens caused by a K1+ bacteremic strain of Escherichia coli. Protection was obtained even when administration of the phage was delayed until signs of disease appeared. The phage was able to multiply in the blood. In newly borne colostrum-deprived calves given the E. coli orally, intramuscular inoculation of phage delayed appearance of the bacterium in the blood and lengthened life span. With some provisos there is considerable potential for this approach to bacterial-disease therapy.

REDUCAO DA CONCENTRACAO ALVEOLAR MINIMA DO ISOFLURANO E DO SEVOFLURANO PELO SUFENTANIL

Background and Objectives - Inhalational anesthetics have a mild analgesic effect. The reduction of alveolar concentration (MAC) of potent volatile anesthesics by increasing plasma concentrations of opioids is desired in inhalational anesthesia. The purpose of this study was to determine the role of sufentanil in reducing sevoflurane and isoflurane MAC. Methods - Thirty eight adult patients of both genders, physical status ASA I or II, submitted to major abdominal procedures were randomly allocated into two groups. Group I (n = 24) received inahalational anesthesia with sevoflurane and Group II (n = 14) received inhalational anesthesia with isoflurane, both diluted in a mixture of N2O (1 liter) and O2 (0.5 liter). A semi-closed system with CO2 absorber and partial reinhalation was used. Ventilation was mechanically controlled. Sufentanil infusion was administered aiming at obtaining 0.5 ng.ml-1 of plasma concentration. Sufentanil plasma concentration was previously calculated by a computer software. End-tidal concentrations were obtained through a gas analyzer and measured at 15 minutes (M1), 30 minutes (M2), 60 minutes (M3), 90 minutes (M4) and 120 minutes (M5). Systolic and diastolic blood pressure (SBP and DBP) and heart rate (RR) were measured during the same periods with the addition of M0 (pre-anesthetic period). Hourly consumption of the inhalational anesthetic agent (IAC), extubation time (ET = time between admission to the recovery room and extubation) and stay in the post anesthesia recovery room (PA-RR) were also measured. Results - Type and duration of surgeries were similar for both groups. There were no statistically significant differences in MAC, SBP, DBP, RR, IAC, TE and PA-RR between groups. Systolic blood pressure in group I (sevoflurane) showed differences among periods F = 3.82 p < O.05; (M2 = M3)(M4 = M5) and M1 had a intermediate value. MAC in group I showed differences among periods F = 9.0 p < 0.05; M1 < M3. MAC in group II also showed differences among periods F = 13.03 p < O.05; M1 < (M2,M3,M4,M5). Conclusions - Both groups had similar behavior when associated to sufentanil in major abdominal surgeries. Group II showed a higher cardiac and circulatory stability.

Efficacy, safety and tolerability of terbinafine for Tinea capitis in children: Brazilian multicentric study with daily oral tablets for 1, 2 and 4 weeks

Background: Tinea capitis is a common skin disease seen predominantly in children. The standard therapies for this disease are griseofulvin and ketoconazole. Nevertheless, these drugs have drawbacks in that they are only fungistatic and require treatment for at least 6 weeks. Previous studies with oral terbinafine for the treatment of Tinea capitis have shown that this agent is effective when given for 4 weeks, comparable to an 8-week regimen with griseofulvin. To date there is no data on the use of oral terbinafine in Brazilian children. Objectives: To assess the efficacy, safety and tolerability of oral terbinafine in short-term treatments (1-, 2- and 4-week treatment) of Tinea capitis in children. Patients and methods: One hundred and thirty-two children aged 1-14 years were enrolled in this study, but only 107 were considered for the final efficacy analysis. Diagnosis included clinical assessment and examination by Wood's light. Confirmation was obtained by direct microscopy and culture for fungus. Terbinafine dosage (125 or 250 mg/day) was adjusted according to patient weight. Efficacy was evaluated both by clinical and mycological assessment. Safety and tolerability variables included data on adverse reaction and clinical laboratory evaluations. Results: Mycological evaluation in the follow-up visit at week 12 showed negative direct microscopy and culture results in 48.6, 60.5 and 69.7% patients in groups 1-, 2- and 4-week, respectively (n.s.). At week 12, 84.8% patients in group 4-week achieved clinical cure with a significant difference compared to groups 1- and 2-week, 54.3 and 60.5%, respectively (P < 0.01). Adverse reactions were present in 4.8, 6.8 and 10.9% of patients in groups 1-, 2- and 4-week, respectively. Terbinafine was not associated with clinically relevant increases in liver function tests. Conclusions: Terbinafine is an effective, well tolerated and safe antifungal agent for the treatment of Tinea capitis m children. The shorter duration of treatment resulted in lower cure rates. However, it is important to note that depending on the severity of the disease, a 1-week-only treatment can also be effective in this indication.

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.

Associacao de opioides lipofilicos a bupivacaina na anestesia peridural. Ha vantagem no aumento da dose do opioide?

Background and Objectives: - The effects of associating lipophilic opioids to local anesthetics in epidural anesthesia are not well defined. There are still questions and controversies about opioid doses to be used and their major effects in the epidural block. This study aimed at evaluating the epidural block effects in humans of the association of different fentanyl and sufentanil doses to bupivacaine with 1:200.000 epinephrine. Methods: - A double-blind randomized study was performed in 94 patients of both genders, physical status ASA I, aged between 18 and 60 years, submitted to lower abdomen, perineal or lower limb surgery. Patients without preanesthetic medication were epidurally injected with 100 mg (20 ml) 0.5% bupivacaine, 0.1 mg (0.1 ml) 1%o epinephrine plus a combination of the following drugs: BUPI Group (15 patients): 2 ml of 0.9% saline solution (SS); FENT50 Group (19 patients): 50 μg (1 ml) fentanyl + 1 ml SS; FENT100 Group (20 patients): 100 μg (2 ml) fentanyl; SUF30 Group (20 patients): 30 μg (0.6 ml) sufentanil + SS (1.4 ml); SUF100 Group (20 patients): 50 μg (1 ml) sufentanil + SS (1 ml). The following parameters were studied: onset of sensory block, analgesic block (onset time) in T12, T10 and T8, analgesic block duration in T10 and T12, motor block degree, consciousness degree, need for supplemental perioperative sedation and analgesia, hypotension, bradycardia and peri and post operative side-effects, analgesia duration, proportion of patients needing supplemental analgesia and evaluation of postoperative pain (pain analog visual scale). Results: Groups were demographically uniform. The addition of fentanyl or sufentanil did not alter major characteristics of perioperative epidural block and has not significantly increased postoperative analgesia duration as compared to the use of bupivacaine only. However, the addition of lipophilic opioids has increased the quality of perioperative anesthetic block, translated into a lesser need for supplemental analgesia (p < 0.02). The increased dose of fentanyl and especially of sufentanil has increased the incidence of perioperative drowsiness (p < 0.001) without significant increase in other side effects. Conclusions: In the conditions and doses used, the addition of lipophilic opioids to bupivacaine and the increased dose of lipophilic opioids have improved anesthetic block quality without changes in the epidural block characteristics or a significant increase in side effects, with the exception of drowsiness mainly caused by sufentanil. However, they were not able to provide a significant increase in postoperative analgesia duration.

Efeitos do tratamento oral com sulfato de vanadila em ratos diabeticos jovens

This work intends to evaluate the effects of oral vanadyl treatment (VOSO 4, 1 mg/mL) in young streptozotocin-diabetic rats during 19 and 29 days. In several times of treatment the rats were monitored to determine body weight, food and water intakes, glycemia, and the urinary excretion of glucose and urea. The animals were killed in the 19(th) and 29(th) days, and the glycemia level was determined again, as well as the weight of pancreas, muscles (Soleus and Extensor digitorum longus - EDL) and adipose tissues (epididymal and retroperitoneal). The results showed that the treatment of young diabetic rats with VOSO 4 promotes the reduction of hyperglycemia (p < 0.01), food (p < 0.01) and water intakes (p < 0.05) and body weight (p < 0.05). Neither the tissues and pancreas weights nor the urinary urea level of the treatment group varied in comparison to the control group. In conclusion, the vanadyl treatment in the studied period is able to reduce the main metabolic alterations often found in diabetes. These data are very useful and important for the future experiments to verify the effects of vanadyl sulfate on muscle protein metabolism in diabetic rats.

Efeitos de diferentes doses de tenoxicam sobre a medula espinhal e as meninges. Estudo experimental em caes

Background and Objectives. The analgesic actions of nonsteroidal anti-inflammatory drugs (NSAID) result from the inhibition of the peripheral synthesis of prostaglandins. In spite of the emphasis on the peripheral action, several studies have shown the potential central action of such drugs. In rats, NSAID doses insufficient to block pain when systemically administered were effective when intrathecally injected. This effect could be mediated by interaction with descending serotoninergic ways together with neurotransmission modulation of glycine or N-methyl-D-aspartate receptors. Our goal was to study the effect of different tenoxican doses in the histology of dogs spinal cord and meninges. Methods. Thirty two dogs (7 to 17 kg) were randomly distributed in four groups: G1 - Control with distilled water (DW); G2 - 2 mg tenoxican diluted in DW; G3 - 4 mg tenoxican diluted in DW; G4 - 10 mg tenoxican diluted in DW in a constant volume of 1 ml. Anesthesia was induced with etomidate and fentanyl and dural puncture was performed with a 25G spinal needle in interspace L6-7. Animals were observed for 72 hours and subsequently euthanized by electrocution. Lumbar and sacral spinal cord segments were removed for further histologic examination. Results. All animals were clinically normal during the observation period and there has been no histologic alteration of the nervous system and meninges. Conclusions. In our experimental model intrathecal tenoxican doses up to 10 mg have not triggered nervous tissue or meningeal injuries in dogs.

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.