Gabrielle Coelho Freitas

Formulation and in vivo evaluation of sodium alendronate spray-dried microparticles intended for lung delivery.

Spray-dried powders for lung delivery of sodium alendronate (SA) were prepared from hydroalcoholic solutions. Formulations display geometric particle size below to 12 μm and spherical shape associated to a hollow structure. The addition of leucine and ammonium bicarbonate leads to porous particles with rough surfaces. The tapped density ranges from 0.016 to 0.062 g/cm(3), decreasing with the increase of the leucine concentration. For all formulations, the calculated aerodynamic diameters are lower than 5 μm. The in vitro aerodynamic evaluation shows that all powders present a high emitted fraction of 100%, a fine particle fraction ranging from 34.4% to 62.0% and an alveolar fraction ranging from to 23.7% to 42.6%. An optimized sample was evaluated regarding sodium alendronate acute pulmonary toxicity and lung bioavailability. The bronchoalveolar lavage study shows that the intratracheal administration of sodium alendronate dry powder and sodium alendronate aqueous solution do not induce significant increases of lung toxicity indicators as compared with the positive control. Moreover, the intratracheal administration of sodium alendronate dry powder results in a 6.23 ± 0.83% bioavailability, a 3.5-fold increase as compared to oral bioavailability. Finally, these results suggest that sodium alendronate pulmonary delivery could be a new and promising administration route.

Renal and cardiorespiratory effects of treatment with lactated Ringer's solution or physiologic saline (0.9% NaCl) solution in cats with experimentally induced urethral obstruction.

OBJECTIVE To compare the renal and cardiorespiratory effects of IV treatment with lactated Ringers solution (LRS) or physiologic saline (0.9% NaCl) solution (PSS) in severely decompensated cats with urethral obstruction (UO). ANIMALS 14 cats (4 cats were used only to establish infusion rates). PROCEDURES An occluded urethral catheter was used to induce UO in each cat. After development of severe metabolic acidosis, hyperkalemia, and postrenal azotemia, the obstruction was relieved (0 hours); LRS or PSS (5 cats/group) was administered IV (gradually decreasing rate) beginning 15 minutes before and continuing for 48 hours after UO relief. Ten minutes before urethral catheter placement (baseline), at start of fluid therapy (SFT), and at intervals during fluid administration, various physical and clinicopathologic evaluations were performed. RESULTS Metabolic acidosis was detected in the PSS-treated group at SFT and 2 hours after relief of UO and in the LRS-treated group only at SFT The PSS-treated group had significantly lower blood pH and bicarbonate concentrations at 8 through 48 hours and lower base excess values at 2 through 48 hours, compared with the LRS-treated group. Hypocalcemia and hypernatremia were detected in the PSS-treated group at 2 and 12 hours, respectively. Absolute serum potassium and chloride concentrations did not differ significantly between groups at any time point. CONCLUSIONS AND CLINICAL RELEVANCE Treatment with LRS or PSS appeared to be safe and effective in cats with experimentally induced UO; however, LRS was more efficient in restoring the acid-base and electrolyte balance in severely decompensated cats with UO.

Allometric scaling for therapeutic protocols in wildlife medicine

In Veterinary Medicine, the empirical extrapolation of protocols indicated for domestic animals is a common practice, which can lead to a failure by ignoring the particularities of each species. The use of scales that allows the use of known doses in domestic animals to calculate the doses for wild species becomes useful. Allometric scales considers the metabolic rate of each species, providing a better comparison between animals of different masses and taxonomic groups. Allometry can be used to define doses and intervals of drugs administration to any animal, knowing only one animal (reference) that already presents the dose and frequency of the desired drug. Allometric scales based on metabolic rate becomes a good option in the use of these calculations, which may provide safety and efficiency in therapeutical procedures of animals whose doses are unknown.

Aplicabilidade da extrapolação alométrica em protocolos terapêuticos para animais selvagens

In Veterinary Medicine, the empirical extrapolation of protocols indicated for domestic animals is a common practice, which can lead to a failure by ignoring the particularities of each species. The use of scales that allows the use of known doses in domestic animals to calculate the doses for wild species becomes useful. Allometric scales considers the metabolic rate of each species, providing a better comparison between animals of different masses and taxonomic groups. Allometry can be used to define doses and intervals of drugs administration to any animal, knowing only one animal (reference) that already presents the dose and frequency of the desired drug. Allometric scales based on metabolic rate becomes a good option in the use of these calculations, which may provide safety and efficiency in therapeutical procedures of animals whose doses are unknown.

Cardiopulmonary effects and eyeball centralization with low-dose atracurium in spontaneously breathing, anesthetized dogs.

The objective was to determine the cardiopulmonary effects and eyeball centralization time obtained with 15 or 30µg kg-1 of atracurium in anesthetized dogs under spontaneous breathing. Eighteen healthy adult mixed-breed dogs were used, which received 0.1mg kg-1 acepromazine and 0.5mg kg-1 morphine IM, followed by 4mg kg-1 propofol IV and maintained on isoflurane anesthesia with spontaneous breathing. Animals received 1mL 0.9% NaCl IV (CG), 15µg kg-1 (G15) or 30µg kg-1 (G30) of atracurium IV. Eyeball centralization time was measured; heart rate (HR), systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures, respiratory rate (RR), tidal volume (Vt) and minute volume (Vm) were determined every 5min, and pH, arterial CO2 pressure (PaCO2 ), arterial O2 pressure (PaO2 ), hemoglobin oxygen saturation (SaO2 ), bicarbonate (HCO3-) and base excess (BE) every 15min until 60min. Both doses of atracurium produced a similar period of eyeball centralization. Vt in groups treated with atracurium was lower than in CG up to 15min. Vm in G15 differed from CG up to 10min and in G30 up to 25min. No differences were observed for cardiovascular parameters, RR, SaO2, PaO2, HCO3- and BE. pH decreased in CG between 30 and 60min and in G15 and G30 at 15min. G30 differed from CG between 15 and 30min. PaCO2 in GC differed from baseline between 30 and 60min and in G15 differed at 15min. Atracurium at the dose of 15µg kg-1 is adequate for short corneal procedures in inhalant-anesthetized dogs under spontaneous breathing.

Tepoxalin on renal function and liver enzymes in cats exposed to hypotension with isoflurane

This study aimed to evaluate the possible renal and hepatic toxicity of tepoxalin administered before or after isoflurane-induced hypotension, as well as for five consecutive days. Twelve healthy mixed-breed cats, adult males, weighing 4.0±0.8kg were allocated into two groups. They received 25mgkg-1 of tepoxalin orally, two hours before the anesthetic procedure (PRE) or after the procedure (POST) and daily for five days. Cats were anesthetized with isoflurane and the concentration was increased until mean arterial pressure reached 40-60mmHg and kept at this level for 60 minutes. During hypotension, the physiological variables were measured at time 0 and every 10 minutes until 60 minutes, and bleeding time was measured at time 0, 30 and 60 minutes. Blood samples were drawn for a hemogram and determination of concentrations of alanine aminotransferase, alkaline phosphatase, urea, creatinine and Na+ at baseline, 24 hours, 48 hours and 7 days post-hypotension. Urine was collected at baseline, 24 hours, 48 hours and 7 days post-hypotension for determination of concentrations of creatinine, gamma-glutamyltransferase, urine specific gravity, protein, albumin and Na+. During the anesthetic procedure there were no important variations in physiological variables and bleeding time. There were differences only in fractional excretion of Na+, which was elevated at 7 days of evaluation in PRE and in the urine protein/creatinine ratio in PRE, which was higher than in POST at 24 and 48 hours post-hypotension. We conclude that tepoxalin does not cause alterations in hepatic enzymes but can cause discrete renal injury, resulting in proteinuria, in cats subjected to 60min of hypotension.

Cloreto de sódio a 0,9%, adicionado ou não de dexametasona, intrapleural, na prevenção de aderências pulmonares após toracotomia intercostal em cães

Pulmonary adhesions in dogs are a common sequel after surgical intervention, undermining any interventions. This study aimed to determine in dogs, the efficacy of sodium chloride solution 0.9% with or without dexamethasone in order to prevent adhesions after intercostal thoracotomy. Fifteen dogs were separated into three groups of five animals, A, B and C and underwent thoracotomy in the fifth left intercostal space. Three other dogs were submitted to a previous study. In the dogs of Group A it was performed only a thoracotomy and thoracorraphy; in group B, it was performed a thoracotomy, thoracorraphy and injection into the pleural cavity of isotonic sodium chloride (10ml) and dexamethasone (1mg kg-1). In the dogs of the group C, it was performed the thoracotomy thoracorraphy and injected isotonic sodium chloride (10ml kg-1) into the pleural cavity. After 15 days of thoracotomy, it was performed transdiaphragmatic thoracocospy to determine the presence and score of adhesions between the lung and chest wall. The results demonstrated the presence of adhesions in the majority of group A and reduced or no adhesions in the other groups. For statistical evaluation, it was pplied the chi-square test with significance level of 5% (P≤0.05). The sodium chloride solution 0.9% with or without dexamethasone in the pleural space prevented or reduced lung adhesions after intercostal thoracotomy.

Efeitos cardiorrespiratórios e analgésicos da cetamina por via epidural, por infusão intravenosa contínua ou pela associação de ambas, em cães submetidos à osteossíntese de fêmur

Ketamine has demonstrated analgesic effects in subanesthetic doses, besides the maintenance of stability of physiological parameters. The study aimed to evaluate the cardiorespiratory effects and the post operative analgesia of ketamine via epidural route, intravenous continuous infusion or association of both, in dogs submitted to femoral osteosynthesis. Twenty-five healthy bitches were randomly assigned to four groups: CEP (2mg kg-1 of ketamine associated with lidocaine 2% via epidural route), CIV (lidocaine 2% via epidural route and 1mg kg-1 of ketamine IV, followed by IV continuous infusion of 100µg kg min-1 of ketamine), CIVEP (epidural anesthesia identical to CEP and ketamine infusion as in CIV) and CON (epidural anesthesia with lidocaine 2%). HR, RR, SAP, MAP, DAP and T°C, sensitive blockade time and post operative analgesia measured with visual analog scale were evaluated. There was an increase in HR in CIV and decrease of this parameter in CEP. Arterial pressures kept within physiological values and differences in RR and T°C were not observed. The anesthetic blockade time was augmented in the groups which received epidural ketamine, differing significantly in relation to the control. The time for rescue analgesia did not differ between the groups. It can be concluded the administration of ketamine via epidural route, intravenous continuous infusion or the association of both promoted cardiorespiratory stability during the operative period; however, it was not able to extend the duration of post operative analgesia in dogs submitted to femoral osteosynthesis.