Intravenous versus nebulized ceftazidime in ventilated piglets with and without experimental bronchopneumonia: Comparative effects of helium and nitrogen

Background: Lung deposition of intravenous cephalosporins is low. The lung deposition of equivalent doses of ceftazidime administered either intravenously or by ultrasonic nebulization using either nitrogen-oxygen or helium-oxygen as the carrying gas of the aerosol was compared in ventilated piglets with and without experimental bronchopneumonia. Methods: Five piglets with noninfected lungs and 5 piglets with Pseudomonas aeruginosa experimental bronchopneumonia received 33 mg/kg ceftazidime intravenously. Ten piglets with noninfected lungs and 10 others with experimental P. aeruginosa bronchopneumonia received 50 mg/kg ceftazidime by ultrasonic nebulization. In each group, the ventilator was operated in half of the animals with a 65%/35% helium-oxygen or nitrogen-oxygen mixture. Animals were killed, and multiple lung specimens were sampled for measuring ceftazidime lung tissue concentrations by high-performance liquid chromatography. Results: As compared with intravenous administration, nebulization of ceftazidime significantly increased lung tissue concentrations (17 ± 13 vs. 383 ± 84 μg/g in noninfected piglets and 10 ± 3 vs. 129 ± 108 μg/g in piglets with experimental bronchopneumonia; P < 0.001). The use of a 65%/35% helium-oxygen mixture induced a 33% additional increase in lung tissue concentrations in noninfected piglets (576 ± 141 μg/g; P < 0.001) and no significant change in infected piglets (111 ± 104 μg/g). Conclusion: Nebulization of ceftazidime induced a 5- to 30-fold increase in lung tissue concentrations as compared with intravenous administration. Using a helium-oxygen mixture as the carrying gas of the aerosol induced a substantial additional increase in lung deposition in noninfected piglets but not in piglets with experimental bronchopneumonia. © 2005 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.

Genotoxic and antigenotoxic effects of organic extracts of mushroom Agaricus blazei Murrill on V79 cells

Agaricus blazei Murrill, popularly known as the sun mushroom, is a native mushroom in SP, Brazil, that has been widely used in the treatment of cancer and many other pathologies in different parts of the world. A water-soluble protein-polysaccharide complex (1 → 6)β-D-glucan has been isolated from its fruiting body that showed immune-modulation activity. From organic extracts, linoleic acid has been isolated and determined to be the main substance with antimutagenic activity. Using both the micronucleus (MN) and comet (single cell microgel electrophoresis) assays, this study determined the genotoxic and antigenotoxic potential of A. blazei (AB) obtained from commercial sources or the following strains: a) strains AB 97/29 (young and sporulated phases); b) a mixture taken from AB 96/07, AB 96/09 and AB 97/ 11 strains; and c) commercial mushrooms from Londrina, PR and Piedade, SP, designated as AB PR and AB SP, respectively. The extracts from these mushrooms were isolated in chloroform:methanol (3:1) and used in vitro at three different concentrations. V79 cells (Chinese hamster lung cells) were exposed to the extracts under pre-, simultaneous and post-treatment conditions, combined with methyl methanesulfonate (MMS). Under the circumstances of this study, these organic extracts did not show any genotoxic or mutagenic effects, but did protect cells against the induction of micronuclei by MMS. Copyright by the Brazilian Society of Genetics.

Comparison of the effects of barbiturate, benzodiazepine and ketamine on visual evoked potentials in rabbits

The aim of this study was to compare the effects of barbiturate, benzodiazepine and ketamine on flash-evoked potentials (F-VEP) in adult rabbits. A total of 36 animals were studied, 16 after pentobarbital endovenous (EV) inffusion, 10 after midazolam EV administration, and 10 after ketamine EV inffusion. Pentobarbital induced triphasic F-VEP, first negative (N1), secondpositive (P1), third negative (N2) waves, all with large amplitudes and P1 with well-defined morphology. Mean P1 latency was 33ms. Midazolam induced similar but less defind triphasic waves, with mean latency of 27ms. Ketamine induced poliphasic and poorly defined F-VEP, with mean first positive (P1) latency of 27ms. Statistical analysis showed more elongated latency for the pentobarbital group than the midazolam and ketamine groups. The results of this study suggest that the pharmacological effects of pentobarbital and midazolam on GABA neurotransmission in rabbit visual cortex may be different; another neurotransmission system, possibly cholinergic, may be involved. The ketamine effect seen in rabbit visual cortex seems to be different from pentobarbital and midazolam.

Farming technology, biochemistry characterization, and protective effects of culinary-medicinal mushrooms Agaricus brasiliensis S. Wasser et al. and Lentinus edodes (Berk.) Singer: Five years of research in Brazil

The biotechnology, biochemical characterization, and protective effects of the himematsutake and shiitake mushrooms were studied for the Thematic Project, from 1998 to 2003. A new species, Agaricus Brasiliens is Wasser et al. (= A. blazei Murrill ss. Heinem.), was proposed for the cultivated lineages in Brazil. Interactions among lineages, substrates, casing layers, and fructification inductions (temperature alternations) significantly increased the productivity of A. brasiliensis in Brazil (from 40 g to 200 g of fresh mushroom kg -1 moist compost). However, pests and diseases (mainly Sciaridae flies and false truffle), drastically reduced the productivity of A. brasiliensis (below 50 g kg -1). Biochemically for each mushroom species, the polar extracts, no polars, and medium polarity presented the same organic substances; however, their concentrations differed as a result of the lineages, maturation of the fruit bodies, and cultivation conditions. In this aspect, concentration of linoleic acid in A. brasiliensis (added to animal food) was related directly to the chemical protection against carcinogenic drugs in mice. Aqueous extracts of Lentinus edodes (= Lentinula edodes (Berk.) Pegler) and A. brasiliensis may be preventive chemical protectors against mutagenic and carcinogenic drugs, depending on the lineage and extraction method (tea or juice). However, immunomodulator effects and tumor reduction were only observed with concentrated fractions (hexanic, methanolic, and ATF extracts). Aqueous extracts of A. brasiliensis and L. edodes have antibiotic-like substances and substances able to act as elicitors of resistance responses in some plants (local and systemic) and show a potential to be used in the alternative control of plant pathogens. © 2005 by Begell House, Inc.

Action of anti-bothropic factor isolated from Didelphis marsupialis on renal effects of Bothrops erythromelas venom

Acute renal failure is the most common complication in the lethal cases caused by snakebites in Brazil. Among the Brazilian venom snakes, Bothrops erythromelas is responsible for the majority of accidents in Northeastern Brazil. Didelphis marsupialis serum could inhibit myonecrotic, hemorrhagic, edematogenic hyperalgesic and lethal effects of envenomation determined by ophidian bites. In the present study, we evaluated the action of the anti-bothropic factor isolated from D. marsupialis on the renal effects promoted by B. erythromelas venom without systemic interference. Isolated kidneys from Wistar rats were perfused with Krebs-Henseleit solution containing 6% bovine serum albumin. We analyzed renal perfusion pressure (PP), renal vascular resistance (RVR), glomerular filtration rate (GFR), urinary flow (UF), and the percentages of sodium and potassium tubular transport (%TNa +, %TK +). The B. erythromelas venom (10 μg mL -1) decreased the PP (ct=108.71±5.09 mmHg; BE=65.21±5.6 mmHg*) and RVR (ct=5.76±0.65 mmHg mL -1 g -1 min -1; BE=3.10±0.45 mmHg mL -1 g -1 min -1*) . On the other hand, the GFR decreased at 60 min (ct 60=0.76±0. 07 mL g -1 min -1; BE 60=0.42±0.12 mL g -1 min -1*) and increased at 120 min (ct 120=0.72±0.01 mL g -1 min -1; BE 120=1.24±0.26 mL g -1 min -1*). The UF increased significantly when compared with the control group (ct=0.14±0.01 mL g -1 min -1; BE=0.47±0.08 mL g -1 min -1*). The venom reduced the %TNa + (ct 90=79.18±0.88%; BE 90=58.35±4.86%*) and %TK + (ct 90=67.20±4.04%; BE 90=57. 32±5.26%*) The anti-bothropic factor from D. marsupialis (10 μg mL -1) incubated with B. erythromelas venom (10 μg mL -1) blocked the effects on PP, RVR, %TNa +, and %TK +, but was not able to reverse the effects in UF and GFR promoted by venom alone. However, the highest concentration of D. marsupialis serum (30 μg mL -1) reversed all the renal effects induced by the venom. In conclusion, B. erythromelas venom altered all the renal functional parameters evaluated and the anti-bothropic factor from D. marsupialis was able to inhibit the effects induced by the venom in isolated kidney. © 2005 Elsevier Ltd. All rights reserved.

Comparison of hemodynamic, clinicopathologic, and gastrointestinal motility effects and recovery characteristics of anesthesia with isoflurane and halothane in horses undergoing arthroscopic surgery

Objective - To compare hemodynamic, clinicopathologic, and gastrointestinal motility effects and recovery characteristics of halothane and isoflurane in horses undergoing arthroscopic surgery. Animals - 8 healthy adult horses. Procedure - Anesthesia was maintained with isoflurane or halothane (crossover study). At 6 intervals during anesthesia and surgery, cardiopulmonary variables and related derived values were recorded. Recovery from anesthesia was assessed; gastrointestinal tract motility was subjectively monitored for 72 hours after anesthesia. Horses were administered chromium, and fecal chromium concentration was used to assess intestinal transit time. Venous blood samples were collected for clinicopathologic analyses before and 2, 24, and 48 hours after anesthesia. Results - Compared with halothane-anesthetized horses, cardiac index, oxygen delivery, and heart rate were higher and systemic vascular resistance was lower in isoflurane-anesthetized horses. Mean arterial blood pressure and the dobutamine dose required to maintain blood pressure were similar for both treatments. Duration and quality of recovery from anesthesia did not differ between treatments, although the recovery periods were somewhat shorter with isoflurane. After isoflurane anesthesia, gastrointestinal motility normalized earlier and intestinal transit time of chromium was shorter than that detected after halothane anesthesia. Compared with isoflurane, halothane was associated with increases in serum aspartate transaminase and glutamate dehydrogenase activities, but there were no other important differences in clinicopathologic variables between treatments. Conclusions and clinical relevance - Compared with halothane, isoflurane appears to be associated with better hemodynamic stability during anesthesia, less hepatic and muscle damage, and more rapid return of normal intestinal motility after anesthesia in horses undergoing arthroscopic procedures.

Effects of olive oil and its minor constituents on serum lipids, oxidative stress, and energy metabolism in cardiac muscle

Recent lines of evidence suggest that the beneficial effects of olive oil are not only related to its high content of oleic acid, but also to the antioxidant potential of its polyphenols. The aim of this work was determine the effects of olive oil and its components, oleic acid and the polyphenol dihydroxyphenylethanol (DPE), on serum lipids, oxidative stress, and energy metabolism on cardiac tissue. Twenty four male Wistar rats, 200 g, were divided into the following 4 groups (n = 6): control (C), OO group that received extra-virgin olive oil (7.5 mL/kg), OA group was treated with oleic acid (3.45 mL/kg), and the DPE group that received the polyphenol DPE (7.5 mg/kg). These components were administered by gavage over 30 days, twice a week. All animals were provided with food and water ad libitum The results show that olive oil was more effective than its isolated components in improving lipid profile, elevating high-density lipoprotein, and diminishing low-density lipoprotein cholesterol concentrations. Olive oil induced decreased antioxidant Mn-superoxide dismutase activity and diminished protein carbonyl concentration, indicating that olive oil may exert direct antioxidant effect on myocardium. DPE, considered as potential antioxidant, induced elevated aerobic metabolism, triacylglycerols, and lipid hydroperoxides concentrations in cardiac muscle, indicating that long-term intake of this polyphenol may induce its undesirable pro-oxidant activity on myocardium. © 2006 NRC Canada.

Effects of acetylsalicylic acid and acetic acid solutions in VX2 carcinoma cells. In vitro analysis

Purpose: To analyze, in vitro, the effects of acetylsalicylic acid (aspirin) and acetic acid solutions on VX2 carcinoma cells in suspension and to examine the correlation between these effects and neoplastic cell death. Methods: The VX2 tumor cells (107 cells/ml) were incubated in solutions containing differing concentrations (2.5% and 5%) of either acetylsalicylic acid or acetic acid, or in saline solution (controls). Every five minutes, cell viability was tested (using the trypan blue test) and analyzed under light microscopy. Results: Tumor cell viability (in %) decreased progressively and, by 30 minutes, neoplastic cell death had occurred in all solutions. Conclusion: Based on this experimental model and the methodology employed, we conclude that these solutions cause neoplastic cell death in vitro.

Cardiopulmonary effects of buprenorphine in horses

Objective - To investigate the effects of buprenorphine on cardiopulmonary variables and on abdominal auscultation scores in horses. Animals - 6 healthy adult horses. Procedures - Horses were restrained in stocks and allocated to 2 treatments in a randomized crossover design, with 1-week intervals between each treatment. Saline (0.9% NaCl) solution was administered IV as a control, whereas buprenorphine (10 μg/kg, IV) was administered to the experimental group. Cardiopulmonary data were collected for 120 minutes after buprenorphine or saline solution administration. Abdominal auscultation scores were monitored for 2 and 12 hours after drug administration in the control and experimental groups, respectively. Results - Following control treatment, horses remained calm while restrained in the stocks and no significant changes in cardiopulmonary variables were observed throughout the study. Buprenorphine administration caused excitatory phenomena (restlessness and head shaking). Heart rate, cardiac index, and arterial blood pressure were significantly increased after buprenorphine administration until the end of the observational period (120 minutes). Minimal changes were found in arterial blood gas tensions. Abdominal auscultation scores decreased significantly from baseline for 4 hours after buprenorphine administration. Conclusions and Clinical Relevance - Buprenorphine induced excitement and hemodynamic stimulation with minimal changes in arterial blood gas tensions. These effects may impact the clinical use of buprenorphine in horses. Further studies are indicated to investigate the effects of buprenorphine on gastrointestinal motility and fecal output.

In vitro cytotoxic and non-genotoxic effects of gutta-percha solvents on mouse lymphoma cells by single cell gel (comet) assay

Chloroform and eucalyptol are widely used in clinical dentistry as gutta-percha solvents. However, these compounds may represent a hazard to human health, especially by causing injury to genetic apparatus and/or inducing cellular death. In this study, the genotoxic and cytotoxic potentials associated with exposure to chloroform and eucalyptol were assessed on mouse lymphoma cells in vitro by the single cell gel (comet) assay and trypan blue exclusion test, respectively. Both gutta-percha solvents proved to be cytotoxic at the same levels in concentrations of 2.5, 5 and 10 μL/mL (p<0.05). On the other hand, neither of the solvents induced DNA breakage. Taken together, these results suggest that although both tested compounds (chloroform and eucalyptol) are strong cytotoxicants, it seems that they are not likely to increase the level of DNA damage on mammalian cells.

Evaluation of antidiarrhoeal effects of Psidium guajava L. (Myrtaceae) aqueous leaf extract in mice

A crude aqueous extract of the leaves of the guava tree, Psidium guajava L. (Myrtaceae), were studied for antidiarrhoeal effects, to place one of its traditional medical uses. The extract induced a decrease in the propulsive movements of the intestinal contents in mice. These findings suggested that an aqueous extract of guava leaves may be used as an effective treatment for non-specific diarrhoea in folk medicine.

Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs

Objective - To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. Animals - 36 adult dogs. Procedures - Values for CBC, urinalysis, serum biochemical urinalyses, and occult blood in feces were investigated before and 7, 30, 60, and 90 days after daily oral administration (n = 6 dogs/group) of lactose (1 mg/kg, control treatment), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), carprofen (4 mg/kg), and ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg daily thereafter) or flunixin (1 mg/kg for 3 days, with 4-day intervals). Gastroscopy was performed before and after the end of treatment. Results - For serum γ-glutamyltransferase activity, values were significantly increased at day 30 in dogs treated with lactose, etodolac, and meloxicam within groups. Bleeding time was significantly increased in dogs treated with carprofen at 30 and 90 days, compared with baseline. At 7 days, bleeding time was significantly longer in dogs treated with meloxicam, ketoprofen, and flunixin, compared with control dogs. Clotting time increased significantly in all groups except those treated with etodolac. At day 90, clotting time was significantly shorter in flunixin-treated dogs, compared with lactose-treated dogs. Gastric lesions were detected in all dogs treated with etodolac, ketoprofen, and flunixin, and 1 of 6 treated with carprofen. Conclusions and Clinical Relevance - Carprofen induced the lowest frequency of gastrointestinal adverse effects, followed by meloxicam. Monitoring for adverse effects should be considered when nonsteroidal anti-inflammatory drugs are used to treat dogs with chronic pain.

Molecular hybridization: A useful tool in the design of new drug prototypes

Molecular hybridization is a new concept in drug design and development based on the combination of pharmacophoric moieties of different bioactive substances to produce a new hyrid compound with improved affinity and efficacy, when compared to the parent drugs. Additionally, this strategy can results in compounds presenting modified selectivity profile, different and/or dual modes of action and reduced undesired side effects. So, in this described several example of different strategies for drug design, discovery and pharmacomodulation focused on new innovative hybrid compounds presenting analgesic, anti-inflammatory, platelet anti-aggregating, anti-infections, anticancer, cardio- and neuroactive properties.

Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 mimics Epstein-Barr virus EBNA1 immune evasion through central repeat domain effects on protein processing

Kaposi's sarcoma-associated herpesvirus (KSHV/human herpesvirus 8 [HHV8]) and Epstein-Barr virus (EBV/HHV4) are distantly related gammaherpesviruses causing tumors in humans. KSHV latency-associated nuclear antigen 1 (LANA1) is functionally similar to the EBV nuclear antigen-1 (EBNA1) protein expressed during viral latency, although they have no amino acid similarities. EBNA1 escapes cytotoxic lymphocyte (CTL) antigen processing by inhibiting its own proteosomal degradation and retarding its own synthesis to reduce defective ribosomal product processing. We show here that the LANA1 QED-rich central repeat (CR) region, particularly the CR2CR3 subdomain, also retards LANA1 synthesis and markedly enhances LANA1 stability in vitro and in vivo. LANA1 isoforms have half-lives greater than 24 h, and fusion of the LANA1 CR2CR3 domain to a destabilized heterologous protein markedly decreases protein turnover. Unlike EBNA1, the LANA1 CR2CR3 subdomain retards translation regardless of whether it is fused to the 5′ or 3′ end of a heterologous gene construct. Manipulation of sequence order, orientation, and composition of the CR2 and CR3 subdomains suggests that specific peptide sequences rather than RNA structures are responsible for synthesis retardation. Although mechanistic differences exist between LANA1 and EBNA1, the primary structures of both proteins have evolved to minimize provoking CTL immune responses. Simple strategies to eliminate these viral inhibitory regions may markedly improve vaccine effectiveness by maximizing CTL responses. Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Effects of basic fibroblast growth factor on density and morphology of fibroblasts grown on root surfaces with or without conditioning with tetracycline or EDTA.

A study was conducted to evaluate in vitro the effect of root surface conditioning with basic fibroblast growth factor (b-FGF) on morphology and proliferation of fibroblasts. Three experimental groups were used: non-treated, and treated with 50 microg or 125 microg b-FGF/ml. The dentin samples in each group were divided into subgroups according to the chemical treatment received before application of b-FGF: none, or conditioned with tetracycline-HCl or EDTA. After contact with b-FGF for 5 min, the samples were incubated for 24 h with 1 ml of culture medium containing 1 x 10(5) cells/ml plus 1 ml of culture medium alone. The samples were then subjected to routine preparation for SEM, and random fields were photographed. Three calibrated and blind examiners performed the assessment of morphology and density according to two index systems. Classification and regression trees indicated that the root surfaces treated with 125 microg b-FGF and previously conditioned with tetracycline-HCl or EDTA presented a morphology more suggestive of cellular adhesion and viability (P = 0.004). The density of fibroblasts on samples previously conditioned with EDTA, regardless of treatment with b-FGF, was significantly higher than in the other groups (P < 0.001). The present findings suggest that topical application of b-FGF has a positive influence on both the density and morphology of fibroblasts.