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Biomedical subjects

Martín Santos

Publications and source records attributed to Martín Santos.

10 recordsLinked to original sources

Cell therapy using bone marrow stromal cells in chronic paraplegic rats: systemic or local administration?

Recent studies showed the therapeutic effect of bone marrow stromal cells (BMSC) after spinal cord injury (SCI). In the present study, we compared the effect of systemic and local administration of BMSC in adult Wistar rats suffering chronic paraplegia as consequence of severe SCI. Adult Wistar rats were subjected to a weight-drop impact causing complete paraplegia, and 3 months later, all the animals remained without signs of functional recovery. At this moment, 3 x 10(6) BMSC were injected intravenously (n: 20) or into traumatic spinal cord cavity (n: 20). Outcome was evaluated until sacrifice of the animals, 6 months later, using the Basso-Beattie-Bresnehan (BBB) score, the cold spray test, and measuring the thigh perimeter. After sacrifice, samples of spinal cord tissue were studied histologically. The results showed that intravenous administration of BMSC achieves some degree of functional recovery when compared to controls. Nevertheless, administration of BMSC into postraumatic spinal cord cavity promotes a clear and progressive functional recovery, significantly superior to the recovery obtained by means of the intravenous administration. This effect is associated to long-term presence of BMSC in the injured spinal cord tissue, with images suggesting neuronal differentiation and spinal cord reconstruction.

Animals↗

Fe-based nanoparticulate metallic alloys as contrast agents for magnetic resonance imaging.

Pharmaceutical grade magnetic colloidal dispersions have been prepared from iron alloys synthesized by laser pyrolysis. The colloids were obtained by simultaneous dispersion and coating of the particles with dextran in a strong alkaline solution. Both powders and dispersions have been analyzed in terms of microstructural characteristics, chemical composition and magnetic properties. The powders consist of uniform spherical nanoparticles (12 nm of diameter) showing a metallic core encapsulated into an iron-oxide shell. On the other hand, the colloidal dispersions consist of magnetic particles-aggregates with hydrodynamic sizes of approximately 75 nm. Magnetic resonance images of rats were taken after the intravenously administration of the Fe colloidal dispersions, and compared with those obtained using a commercial iron oxide magnetic resonance imaging contrast agent. The results showed a contrast improvement of 60% in the liver with respect to the commercial sample, which suggests that this product could be a suitable contrast agent for NMR imaging of liver and spleen.

Alloys↗

Cardiopulmonary effects of desflurane in horses.

OBJECTIVE: To determine the cardiopulmonary effects of desflurane (DES) in horses. ANIMALS: Six healthy adult horses, three males and three females, aged 9 +/- 4 (mean +/- SD) years and weighing 370 +/- 36 kg. MATERIALS AND METHODS: Anaesthesia was induced with an O2 (10 L minute(-1)) and DES mixture (vaporizer setting 18%). After oro-tracheal intubation, horses were positioned in right lateral recumbency. Anaesthesia was maintained with DES in O2 (20 mL kg(-1) minute(-1)) delivered through a large animal circle breathing system. The minimum alveolar concentration of DES (MAC(DES)) that prevented purposeful movement in response to 60 seconds of electrical stimulation of the oral mucous membranes was determined for each horse. The delivered concentration of DES was then increased to achieve end-tidal concentrations corresponding to 1.5 x MAC(DES), 1.75 x MAC(DES), and 2.0 x MAC(DES). Heart rate (HR), mean arterial blood pressure (MAP), respiratory rate (fr), tidal volume (VT), minute volume (VM) and core temperature were determined, and blood samples for arterial blood gas analysis taken at each DES concentration. All data were analysed by two-way anova for repeated measures and Fisher's test for multiple comparisons. A probability level of p < 0.05 was applied. RESULTS: Desflurane concentrations of 2.0 x MAC(DES) increased HR whereas lower concentrations did not. Mean arterial pressure was not affected by 1.0 x MAC(DES) 1.5 x MAC(DES) or 1.75 x MAC(DES), whereas it decreased at 2.0 x MAC(DES). All concentrations of DES examined significantly depressed fr, VT and VM. CONCLUSIONS AND CLINICAL RELEVANCE: Desflurane concentrations between 1.0 and 1.75 x MAC(DES) reduces fr and VM but does not affect HR or MAP in horses.

Analysis of Variance↗

Large concentrations of nitrous oxide decrease the isoflurane minimum alveolar concentration sparing effect of morphine in the rat.

Many adjuvant drugs have demonstrated anesthetic-sparing properties when combined with volatile anesthetics. Nitrous oxide is combined with volatile anesthetics to reduce the concentrations of volatile anesthetics required to produce anesthesia. Analgesic doses of opioids clearly reduce the requirement for inhaled anesthetics in both human patients and experimental animals. We performed this study to determine whether the combination of nitrous oxide and morphine decreased isoflurane minimum alveolar anesthetic concentration (MAC) even further in the rat. Fifty-eight female rats were used. The rats were divided into 8 groups: isoflurane in 4 possible nitrous oxide concentrations (0%, 30%, 50%, or 70%) with saline or morphine (1 mg/kg). Then the MAC of isoflurane (MAC(ISO))was determined from alveolar gas samples at the time of tail clamp. The MAC of isoflurane was significantly different at each nitrous oxide concentration, and increasing nitrous oxide concentrations reduced anesthetic requirements for isoflurane. The administration of morphine reduced the MAC(ISO) when used with 0% or 30% nitrous oxide. This MAC(ISO) by morphine reduction was less with 50% nitrous oxide and nonexistent at 70% nitrous oxide. However, with morphine present the MAC(ISO) was independent of the nitrous oxide concentration in the 30%-70% range.

Analgesics, Opioid↗

Evaluation of safety and pharmacokinetics of vancomycin after intravenous regional limb perfusion in horses.

OBJECTIVE: To evaluate clinical variables, regional concentrations, and pharmacokinetics of vancomycin in the synovial fluid of distal forelimb joints of horses after IV regional limb perfusion. ANIMALS: 6 horses. PROCEDURE: Vancomycin was administered via IV regional limb perfusion to the distal portion of the forelimbs of anesthetized horses. Drug (300 mg of vancomycin hydrochloride in 60 mL of saline [0.9% NaCl] solution) was infused into 1 forelimb, whereas the contralateral limb served as a control and was perfused with 60 mL of saline solution. Solutions were injected into the lateral digital vein after digital exsanguination. Synovial fluid from the metacarpophalangeal (MTCP) and distal interphalangeal (DIP) joints and systemic blood were collected prior to perfusion and 15, 30, 45, 65, and 90 minutes after initiation of the infusion. Synovial fluid from the MTCP joint and blood were also obtained at 4, 8, 12, and 24 hours after infusion. Plasma urea and creatinine concentrations, degree of lameness, and certain clinical variables involving the MTCP joint and infusion site were assessed for 7 days. Results were compared between the vancomycin treatment and control groups. RESULTS: No complications or significant differences in renal function, lameness, or clinical variables were observed between groups. Vancomycin concentrations exceeded 4 microg/mL in MTCP joints for approximately 20 hours. Higher concentrations were reached in DIP joints than in MTCP joints. CONCLUSIONS AND CLINICAL RELEVANCE: IV regional limb perfusion with 300 mg of vancomycin as a 0.5% solution was safe and may be useful in horses as treatment for distal limb infections.

Analysis of Variance↗

Inhaled nitric oxide affects endogenous surfactant in experimental lung transplantation.

BACKGROUND: Inhalation of nitric oxide (NO) has been proposed as a therapy to improve lung transplantation outcome. We investigated the effect that inhaled NO has on the surfactant system in the context of ischemia-reperfusion injury. METHODS: Single left-lung transplantation was performed in weight-matched pairs of Landrace pigs. A double-lung block from the donor animal was flushed with University of Wisconsin solution at 4 degrees C followed by immersion in cold University of Wisconsin solution for 22 hr. The left donor lung was transplanted into the recipient. Recipients were divided into two groups: (1) treated with inhaled NO (40 ppm) (n=6) immediately after initiating lung reperfusion and (2) without treatment (n=6). Lung function was measured during 2 hr of reperfusion. Surfactant components in small and large aggregates, isolated from cell-free bronchoalveolar lavages, and surfactant function were measured. RESULTS: NO inhalation significantly decreased arterial oxygenation. With respect to the surfactant system, NO inhalation worsened the surfactant adsorption rate to an air-liquid interface and affected levels of hydrophobic surfactant proteins (SPs), SP-B and SP-C, and phospholipids, which decreased in large surfactant aggregates but not in small surfactant aggregates. SP-A was reduced in large surfactant aggregates of transplanted lungs from both untreated and NO-treated groups. CONCLUSION: A decreased level of SP-A, SP-B, and SP-C in large surfactant aggregates of transplanted lungs treated with NO is a marker of lung injury. We conclude that treatment with inhaled NO after lung transplantation is deleterious for the surfactant system and causes a parallel worsening of arterial oxygenation.

Adenosine↗

Meloxicam, a specific COX-2 inhibitor, does not enhance the isoflurane minimum alveolar concentration reduction produced by morphine in the rat.

UNLABELLED: A synergistic effect of nonselective cyclooxygenase (COX) inhibitors on morphine-induced decrease of isoflurane minimum alveolar concentration (MAC(ISO)) has been observed in the rat. We studied the influence of specific COX-2 inhibitors on this decrease of MAC. Sixty-four female rats were anesthetized with isoflurane in oxygen. The animals were grouped into saline solution, aspirin (30 mg/kg), morphine (1 mg/kg), morphine (1 mg/kg) + aspirin (30 mg/kg), meloxicam (1 and 3 mg/kg), and morphine (1 mg/kg) + meloxicam (1 and 3 mg/kg). Then the MAC(ISO) was determined from alveolar gas samples at the time of tail clamp. The groups treated with saline solution, aspirin, and 1 and 3 mg/kg meloxicam did not express any statistically relevant changes among them. The administration of morphine + meloxicam 1 or 3 mg/kg significantly reduced the MAC(ISO) just as in the group where only morphine was administered (morphine 1.35% +/- 0.07%, morphine + 1 mg/kg meloxicam 1.36% +/- 0.04%, and morphine + 3 mg/kg meloxicam 1.37% +/- 0.08%). The greatest reduction of MAC(ISO) was after administration of morphine + aspirin (1.19% +/- 0.05%). The administration of meloxicam does not potentiate the morphine-induced decrease of MAC(ISO) in the rat. IMPLICATIONS: A synergistic effect between morphine and aspirin on isoflurane minimum alveolar concentration has been observed in the rat--an effect that does not occur between morphine and meloxicam.

Analgesics, Opioid↗

Antioxidant effect of gamma-tocopherol supplied by propofol preparations (Diprivan) during ischemia-reperfusion in experimental lung transplantation.

Free radicals are involved in ischemia-reperfusion injury and inflammatory processes. The commercial formulation of the anesthetic propofol contains gamma-tocopherol and delta-tocopherol, which may exert antioxidant effects during transplantation. Animals were randomly assigned to a control group or experimental groups for lung transplantation after 3 and 24 h of ischemia. Individual tocopherols, malondialdehyde, biochemical indices, and hemodynamic, blood gas, and ventilatory parameters were determined during reperfusion. Results showed that administration of commercially available propofol provoked a time- and dose-dependent increment in serum gamma-tocopherol and delta-tocopherol in control animals and in the group receiving lungs subjected to 3 h of ischemia, but not in the group with 24 h of ischemia. Malondialdehyde levels increased during reperfusion and did not differ significantly between the two experimental groups, which did not differ with respect to lung function either. gamma-Tocopherol, supplied by the anesthetic, may act as an antioxidant that is consumed during reperfusion. This potential effect could be relevant to the choice of anesthetic agents in situations where free radical damage to tissues is expected.

Analysis of Variance↗

Evaluation of the local analgesic effect of ketamine in the palmar digital nerve block at the base of the proximal sesamoid (abaxial sesamoid block) in horses.

OBJECTIVE: To evaluate the local analgesic effect of ketamine in a palmar digital nerve block at the base of the proximal sesamoid (abaxial sesamoid block) in horses. ANIMALS: 36 mature healthy Andalusian horses. PROCEDURE: Horses were randomly assigned to 4 groups of 9 horses each and received an abaxial sesamoid block in a randomly chosen forelimb with 1 of the following: saline (0.9% NaCl) solution, 1% ketamine solution, 2% ketamine solution, or 3% ketamine solution. To determine analgesia, the radiant heat lamp-hoof withdrawal model was used as a noxious thermal stimulus. Before each nerve block, baseline hoof withdrawal reflex latency (HWRL, time between lamp illumination and withdrawal of the hoof) was determined; after the nerve block, local analgesic effects were determined by measuring HWRL at 2 and 5 minutes after injection and then every 5 minutes for a total period of 1 hour. RESULTS: Significant differences in HWRL were found between baseline values and values at 2 to 15 minutes following a nerve block with ketamine. Significant differences were found between HWRL values at every time point from 2 to 10 minutes following a nerve block with saline solution, compared with 1 or 2% ketamine solution. Similarly, significant differences were found between HWRL values at every time point from 2 to 15 minutes following a nerve block with saline solution, compared with 3% ketamine solution. CONCLUSIONS AND CLINICAL RELEVANCE: Abaxial sesamoid block with ketamine ensures adequate analgesia in horses with an onset of action of 2 minutes and a maximal duration of action of 15 minutes.

Anesthesia, Local↗

Medullary plasma pharmacokinetics of vancomycin after intravenous and intraosseous perfusion of the proximal phalanx in horses.

OBJECTIVE: To study the pharmacokinetics of vancomycin in plasma obtained from the medullary sinusoids of the proximal phalanx (P1) after intravenous (IV) and intraosseous (IO) regional limb perfusion (RLP). STUDY DESIGN: Experimental study. ANIMALS: Twelve horses. METHODS: IV and IO RLP were performed in 2 groups (n = 6) of horses. Vancomycin hydrochloride (300 mg in 60 mL 0.9% NaCl) was randomly infused in 1 front limb, with the contralateral limb as control (60 mL 0.9% NaCl). A hole was drilled in the lateral cortex of P1, and blood samples from the medullary sinusoids of P1 were collected before infusion, and 15, 30, 45, 65, and 90 minutes after beginning infusion. Samples were centrifuged and plasma vancomycin concentrations determined. Vancomycin concentrations were compared over time and between routes using a 2-way repeated measures ANOVA. Pharmacokinetic variables were compared with a Kolmogorov-Smirnov test. Significance was set at P<.05. RESULTS: No vancomycin-induced clinical side effects such as lameness or swelling were observed. Both techniques, IV and IO, produced high vancomycin concentrations in the sinusoidal plasma of the P1, which remained above the minimum inhibitory concentration value for methicillin-resistant Staphylococcus aureus (MRSA) during the 90 minutes study. Concentrations and pharmacokinetic variables were not significantly different comparing both routes. CONCLUSIONS: IV and IO routes produced similar antimicrobial perfusion of the medullary cavity of P1. CLINICAL RELEVANCE: Either IV or IO routes for perfusion are likely to be equally selected when planning RLP with vancomycin.

Analysis of Variance↗