CARDIORESPIRATORY EFFECTS of ISOFLURANE ANESTHESIA IN CRESTED CARACARAS (CARACARA PLANCUS)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Métodos para estudo das respostas metabólicas de cães e gatos a diferentes alimentos

Durante o processo de assimilação e uso dos alimentos, diferentes respostas metabólicas podem ser desenvolvidas pelo organismo dos animais. Estas respostas são fruto da integração de mecanismos complexos, que envolvem os sistemas neuro-endócrino e o funcionamento dos órgãos, sendo influenciadas pela dieta, espécie animal, idade, condição fisiológica e composição corporal. Este trabalho enfoca a importância fisiológica e os métodos de estudo das respostas pós-prandiais aos carboidratos, bem como as alterações fisiológicas conseqüentes ao balanço eletrolítico da dieta. A quantidade, estrutura química e processamento industrial do amido determinam boa parte da resposta pós-prandial de glicose e insulina de cães. em gatos, outros mecanismos parecem ser mais importantes, como a ingestão de aminoácidos. A fibra alimentar também altera a resposta pós-prandial ao alimento, devendo ser consideradas sua quantidade, solubilidade e fermentabilidade no desenvolvimento das dietas. Os métodos de estudo destas respostas incluem avaliação das respostas glicêmica e insulínca pós-prandiais, teste endovenoso de tolerância à glicose e à arginina. O clâmp euglicêmico apresenta-se também como ferramenta de estudo, no entanto revela informações mais relacionadas ao animal do que à dieta. A compreensão do conjunto de alterações metabólicas aos carboidratos é importante no estudo do controle da saciedade, composição corporal e inúmeras doenças degenerativas e endócrinas. A concentração e relação entre os macro-elementos da dieta (Na, Cl, K, P, Ca, Mg e S) e dos aminoácidos sulfurados (metionina, cistina e taurina) interferem em inúmeras funções orgânicas, como a cardiovascular, neuromuscular, metabolismo ósseo, renal e pulmonar, refletindo-se no equilíbrio hidro-eletrolítico e ácido-básico orgânicos. de importância prática para cães e gatos encontram-se a relação destes nutrientes com cardiopatias, nefropatias, osteodistrofias e urolitíases. A relação entre os macro-elementos é estabelecida em mmol/kg de matéria seca da dieta, calculando-se seu balanço cátion-ânion (excesso de bases ou ânions dietéticos não determinados). Suas repostas orgânicas são medidas, dentre outros métodos, pela hemogasimetria, balanço hídrico, mensuração do volume dos espaços extracelular e vascular, supersaturação e pH urinários.

Lactate sequestration by osteoderms of the broad-nose caiman, Caiman latirostris, following capture and forced submergence

Lactate accumulation in osteoderms; of the broad-nose caiman, Caiman latirostris, was determined following capture and surgery and after a period of forced submergence and related to concurrent values in blood. Control samples of bone and blood were taken after recovery from surgery and before submergence. In addition, samples of osteoderm were incubated in a lactate solution to determine equilibrium concentration, and additional samples were analyzed for elemental and CO2 concentrations. The composition of the osteoderms closely resembles that of typical vertebrate bone, with a high concentration of calcium and phosphate. Plasma and osteoderm lactate concentrations were both elevated following surgery and decreased significantly after 1 day of recovery. Submergence produced a typical lactate pattern in the plasma, with only a modest increase during the dive and then a sharp increase during recovery to a peak of 31.2 +/- 1.9 mumol ml(-1) after 1 h. When caimans were anesthetized 2 h after submergence, osteoderm lactate in the same animals was significantly increased to 14.8 mumol g(-1) wet mass. The ratio of the osteoderm: plasma lactate concentration after submergence was similar to the ratio observed in the incubated samples, suggesting that osteoderm lactate concentrations in vivo were equilibrated with circulating plasma levels. We conclude that caiman osteoderms sequester lactate during lactic acidosis and that the time course is fast enough to have benefit to these animals following normal anaerobic burst activity.

Níveis de cloreto de sódio para aves de corte da linhagem Colonial criadas em semiconfinamento

Objetivou-se determinar níveis de inclusão de cloreto de sódio (NaCl) em rações para aves machos e fêmeas da linhagem Colonial nas fases inicial (1 a 28 dias), de crescimento (28 a 56 dias) e final (56 a 84 dias) criadas em semiconfinamento. em cada ensaio, 480 aves com idade correspondente à fase de criação foram alojadas em 24 unidades experimentais contendo áreas de abrigo e de pastejo. O delineamento experimental utilizado foi o inteiramente casualizado, em esquema fatorial 4 × 2 (níveis de NaCl e sexos), totalizando oito tratamentos e três repetições de 20 aves. Os níveis de NaCl avaliados foram: 0,20; 0,40; 0,60 e 0,80% na fase inicial; 0,10; 0,30; 0,50 e 0,70% na fase de crescimento e 0,10; 0,25; 0,40 e 0,55% na fase final. Foram avaliados o ganho de peso, o consumo de ração, a ingestão de água, a conversão alimentar, o potencial hidrogeniônico, a pressão parcial de gás carbônico no sangue, a concentração de hematócritos e os teores de sódio e cloro no sangue. Para a fase inicial, o nível recomendado é de 0,53% de NaCl na ração para aves de ambos os sexos. Para a fase de crescimento, os níveis de 0,40 e 0,43% de NaCl, respectivamente, para machos e fêmeas e, para a fase final, de 0,25% para aves de ambos os sexos, atendem às exigências nutricionais.

Preparation of polymeric micelles for use as carriers of tuberculostatic drugs

Purpose: This paper focuses on the characterization of polymeric micelle-forming tuberculostatic prodrugs and the antimycobacterial activity of these prodrugs.Method: By the condensation of hydroxymethylpyrazinamide, isoniazid and rifampin with free carboxyl groups on the copolymer poly(ethyleneglycol)-poly(aspartic acid), micelle-forming carrier-drug conjugates were obtained. These micelles were characterized by dynamic light scattering, to measure the micelle diameter; by acid-base titration, to determine the percentage of carboxylic groups occupied by the tuberculostatic; by Sudan III solubility tests, to estimate the critical micelle concentration (CMC); and visual control and spectrophotometric measurement, to determine the stability of micelles. These micelles were tested in vitro against several Mycobacterium strains.Results: As expected, the size and distribution of the micelle-forming tuberculostatic prodrugs found to be small (78.2nm, 84.2nm and 98.9 nm) while the level of the drug conjugated was high (65.02-85.7%). Furthermore, the micelles were stable in vitro, exhibiting a low level of CMC and stronger antimycobacterial activity than the original drugs.Conclusion: the results demonstrate that polymeric micelles can be used as efficient carriers for drugs, which alone, exhibit undesired pharmacokinetics, poor solubility, and low stability. The synthesized micelle-forming tuberculostatic prodrugs opens a perspective of alternative prodrugs that prolong action and decrease the toxicity of the tuberculostatic drugs of choice.

Development of a Validated Stability-Indicating LC Assay and Stress Degradation Studies of Linezolid in Tablets

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A theoretical study on cytosine tautomers in aqueous media by using continuum models

B3LYP/6-31 + + G** and MP2/6-31 + + G** calculations have been carried out to study six tautomers of the nucleic acid base cytosine in aqueous media. Solvent effects have been analyzed using the self-consistent reaction field theory with two continuum methods. Relative stabilities and optimized geometries have been calculated for the tautomers and compared with experimental data. The present results show the importance of electrostatic solvent effects in determining observable properties of the cytosine tautomers. The amino-oxo form (C1) is the most abundant tautomer in aqueous media while the other amino-oxo form (C4) is the most energetically favored when solvent effects are included. These results can be justified by the larger values of the dipole moments for both C1 and C4 tautomers. Theoretical and experimental results of the harmonic vibrational frequencies and rotational constants show good agreement. (C) 2000 Elsevier B.V. B.V. All rights reserved.

Continuous peritoneal dialysis compared with daily hemodialysis in patients with acute kidney injury

Background: In some parts of the world, peritoneal dialysis is widely used for renal replacement therapy (RRT) in acute kidney injury (AKI), despite concerns about its inadequacy. It has been replaced in recent years by hemodialysis and, most recently, by continuous venovenous therapies. We performed a prospective study to determine the effect of continuous peritoneal dialysis (CPD), as compared with daily hemodialysis (dHD), on survival among patients with AKI.Methods: A total of 120 patients with acute tubular necrosis (ATN) were assigned to receive CPD or dHD in a tertiary-care university hospital. The primary endpoint was hospital survival rate; renal function recovery and metabolic, acid-base, and fluid controls were secondary endpoints.Results: of the 120 patients, 60 were treated with CPD (G1) and 60 with dHD (G2). The two groups were similar at the start of RRT with respect to age (64.2 +/- 19.8 years vs 62.5 +/- 21.2 years), sex (men: 72% vs 66%), sepsis (42% vs 47%), shock (61% vs 63%), severity of AKI [Acute Tubular Necrosis Individual Severity Score (ATNISS): 0.68 +/- 0.2 vs 0.66 +/- 0.22; Acute Physiology and Chronic Health Evaluation (APACHE) II: 26.9 +/- 8.9 vs 24.1 +/- 8.2], pre-dialysis blood urea nitrogen [BUN (116.4 +/- 33.6 mg/dL vs 112.6 +/- 36.8 mg/dL)], and creatinine (5.85 +/- 1.9 mg/dL vs 5.95 +/- 1.4 mg/dL). In G1, weekly delivered Kt/V was 3.59 +/- 0.61, and in G2, it was 4.76 +/- 0.65 (p < 0.01). The two groups were similar in metabolic and acid-base control (after 4 sessions, BUN < 55 mg/dL: 46 +/- 18.7 mg/dL vs 52 +/- 18.2 mg/dL; pH: 7.41 vs 7.38; bicarbonate: 22.8 +/- 8.9 mEq/L vs 22.2 +/- 7.1 mEq/L). Duration of therapy was longer in G2 (5.5 days vs 7.5 days; p = 0.02). Despite the delivery of different dialysis methods and doses, the survival rate did not differ between the groups (58% in G1 vs 52% in G2), and recovery of renal function was similar (28% vs 26%).Conclusion: High doses of CPD provided appropriate metabolic and pH control, with a rate of survival and recovery of renal function similar to that seen with dHD. Therefore, CPD can be considered an alternative to other forms of RRT in AKI.

Parâmetros hemogasométricos e equilíbrio ácido-básico de cabritos nascidos de partos normais

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cardiopulmonary and analgesic effects of caudal epidurally administered ropivacaine in cattle

Objective To assess cardiopulmonary and analgesic effects after administration of ropivacaine into the caudal epidural space of cattle.Study design Prospective, single-dose trial.Animals Eight healthy mixed breed cows aged 8 +/- 5 years and weighing 507 +/- 112 kg.Methods Caudal epidural anesthesia was produced in cows with 0.75% ropivacaine (0.11 mg kg(-1)). Onset time, duration and cranial spread of analgesia were recorded. Heart rate (HR), respiratory rate (f(R)), rectal temperature (RT), and mean arterial blood pressure (MAP) were measured prior to epidural administration (T-0) and at 15, 30, 60, 120, 180 and 240 minutes after epidural administration (T-15, T-30, T-60, T-120, T-180 and T-240). Arterial blood acid-base balance (pH, standard bicarbonate and base excess), gas tension (PaO2, PaCO2, SaO(2)) and electrolytes (Na+, K+, iCa(2+), Cl-) were recorded at T-0, T-30, T-60, T-120, T-180 and T-240. Ataxia was evaluated at T-0, T-30, T-60, T-120, T-180 and T-240 and at 1 hour intervals thereafter until analgesia was no longer present in each animal.Results Epidurally administered ropivacaine induced variable analgesia extending bilaterally from the coccyx to S3. Time to onset of analgesia and mean duration in the perineal area were 15 +/- 4 and 359 +/- 90 minutes, respectively. Respiratory rate and RT increased from T-120 to T-240 when compared to the value at T-0. Ionized calcium and chloride concentrations increased at T-180 and T-240 when compared to T-0. The other variables were not significantly different from baseline values (p > 0.05). Four animals were mildly ataxic.Conclusion and clinical relevance Ropivacaine (0.75%, 0.11 mg kg(-1)) can be administered by caudal epidural injection to produce prolonged bilateral perineal analgesia with minimal ataxia and cardiopulmonary changes in standing cattle.

Antagonism of myotoxic and paralyzing activities of bothropstoxin-I by surarnin

Polyanionic substances are known to inhibit the myotoxic effects of some crotalide snake venoms. Bothropstoxin-I (BthTX-I), a basic Lys49 phospholipase (PLA(2)) homologue from Bothrops jararacussu venom, besides inducing muscle damage, also promotes the blockade of both directly and indirectly evoked contractions in mouse neuromuscular preparation. In this work, we evaluated the ability of suramin, a polysulfonated naphtylurea derivative, to antagonize the myotoxic and the paralyzing activities of BthTX-I on mice neuromuscular junction in vitro. Myotoxicity was assessed by light and electronic microscopic analysis of extensor digitorum longus (EDL) muscles; paralyzing activity was evaluated through the recording of both directly and indirectly evoked contractions of phrenic-diaphragm (PD) preparations. BthTX-I (1 muM) alone, or pre-incubated with suramin (10 muM) at 37degreesC for 15 min was added to the preparations for 120 min. BthTX-I induced histological alterations typical of myonecrosis in 14.6 +/- 1.0% of EDL muscle fibers. In addition, BthTX-I blocked 50% of both directly and indirectly evoked contractions in PD preparations in 72.1 +/- 9.1 and 21.1 +/- 2.0 min, respectively. Pre-incubation with suramin abolished both the muscle-damaging and muscle-paralyzing activities of BthTX-I. Since suramin is a polyanionic substance, we suggested that its effects result from the formation of inactive acid-base complexes with BthTX-I. (C) 2003 Elsevier Ltd. All rights reserved.

Ventilatory compensation of the alkaline tide during digestion in the snake Boa constrictor

The increased metabolic rate during digestion is associated with changes in arterial acid-base parameters that are caused by gastric acid secretion (the 'alkaline tide'). Net transfer of HCl to the stomach lumen causes an increase in plasma HCO3- levels, but arterial pH does not change because of a ventilatory compensation that counters the metabolic alkalosis. It seems, therefore, that ventilation is controlled to preserve pH and not P-CO2, during the postprandial period. To investigate this possibility, we determined arterial acid-base parameters and the metabolic response to digestion in the snake Boa constrictor, where gastric acid secretion was inhibited pharmacologically by oral administration of omeprazole. The increase in oxygen consumption of omeprazole-treated snakes after ingestion of 30% of their own body mass was quantitatively similar to the response in untreated snakes, although the peak of the metabolic response occurred later (36 h versus 24 h). Untreated control animals exhibited a large increase in arterial plasma HCO3- concentration of approximately 12 mmol 1(-1), but arterial pH only increased by 0.12 pH units because of a simultaneous increase in arterial P-CO2 by about 10 mmHg. Omeprazole virtually abolished the changes in arterial pH and plasma HCO3- concentration during digestion and there was no increase in arterial P-CO2. The increased arterial P-CO2 during digestion is not caused, therefore, by the increased metabolism during digestion or a lower ventilatory responsiveness to ventilatory stimuli during a presumably relaxed state in digestion. Furthermore, the constant arterial P-CO2, in the absence of an alkaline tide, of omeprazole-treated snakes strongly suggests that pH rather than P-CO2 normally affects chemoreceptor activity and ventilatory drive.

Effects of temperature on lung and blood gases in the South American rattlesnake Crotalus durissus terrificus

The effects of temperature on lung and blood gases were measured in the South American rattlesnake (Crotalus durissus terrificus). Arterial blood and lung gas samples were obtained from chronically cannulated animals at 15, 25, and 35 degrees C. As expected for reptiles, arterial pH fell with increased temperature (0.018 U degrees C-1 between 15 and 25 degrees C and 0.011 U degrees C-1 between 25 and 35 degrees C) while lung gas PCO2 rose from 5.8 mmHg at 15 degrees C to 13.2 mmHg at 35 degrees C. Concurrently, lung gas PO2 declined from 132 mmHg at 15 degrees C to 120 mmHg at 35 degrees C, and arterial PO2 increased from 33 to 76 mmHg in that temperature range. Arterial haemoglobin O-2 saturation rose from 0.53 at 15 degrees C to 0.83 at 25 degrees C but became slightly reduced (0.77) with a further elevation of temperature to 35 degrees C. Arterial haemoglobin concentration increased from 1.96 to 2.53 mM between 15 and 35 degrees C, consistent with higher demands on oxygen delivery to tissues at elevated temperatures. Moreover, the substantial increase of haemoglobin O-2 saturation between 15 and 25 degrees C conforms to the idea that reduction of the central vascular right-to-left shunt (pulmonary bypass of systemic venous return) is associated with high metabolic demands. (C) 1998 Elsevier B.V. All rights reserved.

Structural insights into the catalytic mechanism of sphingomyelinases D and evolutionary relationship to glycerophosphodiester phosphodiesterases

Spider venom sphingomyelinases D catalyze the hydrolysis of sphingomyelin via an Mg2+ ion-dependent acid-base catalytic mechanism which involves two histidines. In the crystal structure of the sulfate free enzyme determined at 1.85 angstrom resolution, the metal ion is tetrahedrally coordinated instead of the trigonal-bipyramidal coordination observed in the sulfate bound form. The observed hyperpolarized state of His47 requires a revision of the previously suggested catalytic mechanism. Molecular modeling indicates that the fundamental structural features important for catalysis are fully conserved in both classes of SMases D and that the Class II SMases D contain an additional intra-chain disulphide bridge (Cys53-Cys201). Structural analysis suggests that the highly homologous enzyme from Loxosceles bonetti is unable to hydrolyze sphingomyelin due to the 95G1y -> Asn and 134Pro -> Glu mutations that modify the local charge and hydrophobicity of the interfacial face. Structural and sequence comparisons confirm the evolutionary relationship between sphingomyelinases D and the glicerophosphodiester phosphoesterases which utilize a similar catalytic mechanism. (c) 2006 Elsevier B.V. All rights reserved.

Structural basis for metal ion coordination and the catalytic mechanism of sphingomyelinases D

Sphingomyelinases D (SMases D) from Loxosceles spider venom are the principal toxins responsible for the manifestation of dermonecrosis, intravascular hemolysis, and acute renal failure, which can result in death. These enzymes catalyze the hydrolysis of sphingomyelin, resulting in the formation of ceramide 1-phosphate and choline or the hydrolysis of lysophosphatidyl choline, generating the lipid mediator lysophosphatidic acid. This report represents the first crystal structure of a member of the sphingomyelinase D family from Loxosceles laeta (SMase I), which has been determined at 1.75-angstrom resolution using the quick cryo-soaking technique and phases obtained from a single iodine derivative and data collected from a conventional rotating anode x-ray source. SMase I folds as an (alpha/beta)(8) barrel, the interfacial and catalytic sites encompass hydrophobic loops and a negatively charged surface. Substrate binding and/or the transition state are stabilized by a Mg2+ ion, which is coordinated by Glu(32), Asp(34), Asp(91), and solvent molecules. In the proposed acid base catalytic mechanism, His(12) and His(47) play key roles and are supported by a network of hydrogen bonds between Asp(34), Asp(52), Trp(230), Asp(233), and Asn(252).