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Biomedical subjects

R Zapata-Sirvent

Publications and source records attributed to R Zapata-Sirvent.

At least 19 recordsLinked to original sources
PubMed1996

Effects of E-selectin and P-selectin blockade on neutrophil sequestration in tissues and neutrophil oxidative burst in burned rats.

OBJECTIVE: Neutrophil deposition in tissues (leukosequestration) after shock may produce local tissue injury from proteases and high-energy oxygen species released from sequestered neutrophils. The initial step in the binding of neutrophils to capillary endothelium is the interaction of adhesion molecule (selectin) receptors between neutrophils and endothelial cells. We quantified leukosequestration in the tissues of burned rats using two methods of analysis: a) measurement of lung myeloperoxidase; and b) measurement of radiolabeled neutrophils and erythrocytes deposited in multiple tissues. We then determined the ability of a selectin receptor blocking agent to affect neutrophil deposition in tissues after burn injury. DESIGN: Prospective, controlled, laboratory study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats (200 to 300 g). INTERVENTIONS: After tracheostomy and venous cannulation, rats received 17% total body surface area full-thickness contact burns and were resuscitated with saline (20 mL i.p.). Experimental animals received 2 mg/kg body weight i.v. administration of a P- and E-selectin blocking monoclonal antibody, CY-1747, immediately after burn. Lung tissue neutrophils were estimated by measuring myeloperoxidase in lung tissue. Neutrophil retention in lung, liver, spleen, gut, skin, muscle, kidney, and brain tissues was determined by removing (preburn) and differentially radiolabeling neutrophils (111In) and erythrocytes (51Cr), reinfusing cells 4.5 hrs after burn, and measuring tissue radioactivity 30 mins later. Edema was estimated by measuring extravasated 125 I-labeled albumin in the various tissues. Peripheral blood neutrophils were analyzed for intracellular hydrogen peroxide content, utilizing a fluorescent dye that reacts with hydrogen peroxide, coupled with analysis of cell fluorescence by flow cytometry. MEASUREMENTS AND MAIN RESULTS: Myeloperoxidase concentration was increased in lungs 5 hrs after burn (p < .05), indicating neutrophil deposition. Radioisotope studies demonstrated significant (p < .05) leukosequestration into the lung, gut, kidney, skin, and brain tissues at 5 hrs after burn. Flow cytometry showed increased intracellular hydrogen peroxide content in peripheral blood neutrophils 5 hrs after burn. Tissue edema, manifested by radiolabeled albumin retention, was not seen in any tissues. Postburn neutrophil deposition in lungs and liver was blocked (p < .05) by administration of CY-1747 after burn, but maximal neutrophil hydrogen peroxide content was unaffected. CONCLUSION: Burn injury in rats results in accumulation of neutrophils in multiple tissues. Neutrophil deposition in the lungs and liver is blocked by administration of the E/P-selectin blocking antibody, CY-1747. Since sequestration of metabolically active neutrophils may induce tissue injury, therapies that block postburn leukosequestration may improve clinical outcomes by limiting remote tissue injury.

Animals↗
PubMed1995

Soft tissue infection prophylaxis with gentamicin encapsulated in multivesicular liposomes: results from a prospective, randomized trial.

OBJECTIVES: Systemically administered antibiotic agents are not evenly distributed in the body, which frequently results in subtherapeutic regional drug concentrations, particularly in areas of poor vascularization, including wound sites. We have developed a lipid-based drug delivery system to provide prolonged levels of gentamicin in local tissues after local administration. Multivesicular liposomes are microspheres composed of lipid bilayer membranes surrounding multiple aqueous compartments that can contain drug. The preparation may be effective for the prevention and treatment of a variety of infections, including infections associated with indwelling vascular catheters. DESIGN: Prospective, randomized trial. SETTING: Animal laboratory. SUBJECTS: Mice, 6 to 12 wks of age, weighing 20 to 30 g. INTERVENTIONS: We administered 0.5 mg of gentamicin encapsulated in multivesicular liposomes to dorsal subcutaneous tissue in mice. Animals were inoculated with 10(5) to 10(7) colony-forming units (cfu) of Staphylococcus aureus 2, 4, 6, and 8 days later. The cfu/g of tissue values were determined 2 days after inoculation. MEASUREMENTS AND MAIN RESULTS: With a 10(7) cfu challenge, animals that received 2- and 4-day pretreatment with multivesicular liposome/gentamicin had a 4 log10 reduction in cfu/g of tissue compared with controls. When 10(5) cfu of Staphylococcus aureus were inoculated after 2- and 4-day pretreatment with multivesicular liposome/gentamicin, a 6 log10 reduction in bacteria colony-forming units was observed. CONCLUSION: Local injection of multivesicular liposome/gentamicin provides sustained drug concentrations in regional tissues that protect against a massive bacterial challenge for at least four subsequent days.

Animals↗
PubMed1994

Treatment of burned mice with hyperbaric oxygen reduces mesenteric bacteria but not pulmonary neutrophil deposition.

OBJECTIVE: Hyperbaric oxygen (HBO) is used but unproven for many conditions, including burns. We hypothesized that HBO therapy might increase oxygen delivery to intestine during burn shock and decrease mucosal injury. SETTING: University research laboratory. DESIGN AND STUDY PARTICIPANTS: We studied the effects of HBO therapy (100% oxygen at 2.4 atm absolute) on mesenteric bacterial colonies (MBCs) in mice following 32% total body surface area burns. MBCs were counted 24 or 48 hours postburn by culturing mesenteric tissue. Intestinal histologic features were examined, acid-base balance was measured, and pulmonary neutrophil deposition was estimated by lung myeloperoxidase content. INTERVENTIONS: HBO delivered in a compression chamber. MAIN OUTCOME MEASURE: Numbers of mice with MBCs. RESULTS: With twice-daily HBO treatments, each treatment lasting 1.5 or 2 hours, fewer burned mice had MBCs. Three HBO treatments within 24 hours produced seizures, death, and increased numbers of mice with MBCs. Numbers of mice with MBCs were not influenced when compressed air (2.4 atm absolute) or 100% oxygen (1 atm absolute) was used. Villus histologic findings showed less damage in burned mice that received HBO therapy than in controls. Metabolic acidosis was not affected by HBO therapy, nor were lung myeloperoxidase levels. CONCLUSION: HBO therapy was associated with reduced numbers of mice with MBCs after burn injury and reduced histologic evidence of mucosal damage, but lung myeloperoxidase levels and metabolic acidosis were not affected. HBO therapy may increase oxygen delivery to ischemic intestine and improve cellular metabolism; alternatively, increased tissue oxygen may augment killing of translocated bacteria by phagocytic cells. HBO deserves further investigation for burn treatment, but because of the narrow therapeutic window and continued neutrophil sequestration in the lungs, we should proceed cautiously.

Acid-Base Equilibrium↗
PubMed1990

Postburn immune suppression: an inflammatory response to the burn wound?

In an effort to elucidate the causes of immune suppression which follows severe burn injury, we studied the immunologic effects of subcutaneous implantation of burned skin, as well as implantation of other materials, in mice. Ten days following the implantation, splenic lymphocyte proliferation and lymphocyte surface expression of activation antigens (IL-2R and Ia) were analyzed following a 3-day culture period. In addition, peritoneal neutrophils were analyzed for oxidative burst activity using flow cytometry and a dye which reacts with intracellular hydrogen peroxide. Implantation of a 2 x 2 cm section of burned/unburned skin as well as implantation of a similar-sized piece of cotton gauze or collagen sheet resulted in subsequent suppression of both lymphocyte activation proliferation and neutrophil oxidative burst activity. An intense local inflammatory response to the burn wound may play a role leading to the profound systemic immune suppression which follows severe burn injury.

Animals↗
PubMed1986

Prevention of posttraumatic alterations in lymphocyte subpopulations in mice by immunomodulating drugs.

Infection is a major cause of morbidity and mortality in traumatized victims, as well as an unfortunate complication following surgical procedures. The incidence of such infections is probably related to immune suppression occurring after severe trauma and surgery. Cell-mediated immunity is an arm of immunity that is probably important in defense against bacterial as well as fungal and viral infections. The status of cell-mediated immunity appears to be reflected by the helper/inducer to suppressor/cytotoxic lymphocyte (Ly1+/Ly2+ in the mouse model) ratio. A depressed ratio has been shown to correlate with other measures of suppressed immunity. Using monoclonal antibodies and immunofluorescent analysis, splenic lymphocyte subpopulations were enumerated at different intervals after injury in mice receiving various injuries (laparotomy, 40% liver resection, burn injury covering 20% of total body surface area, and crush injury-amputation of hind limb). An immediate fall in the Ly1+/Ly2+ ratio was observed following the most severe injuries, namely, liver resection, burn, and crush injury-amputation, but not following laparotomy. Changes in the ratio were reflected by both decreases in helper populations (Ly1+) and increases in suppressor populations (Ly2+). Prostaglandins and histamines have been implicated as possible mediators in producing down-regulation of the immune system. Posttraumatic lymphocyte alterations were prevented in crush injury-amputation group mice when drugs (ibuprofen and cimetidine) to block such mediators were administered prior to trauma; changes were also prevented by administering cyclophosphamide, a drug which in low dose might inhibit proliferation of suppressor lymphocyte populations.

Animals↗
PubMed1985

Comparison of Biobrane and Scarlet Red dressings for treatment of donor site wounds.

Two methods of autograft donor site management were tested in 31 patients with burn injuries. Two donor sites of equivalent size were respectively covered with Biobrane and Scarlet Red, two commercial dressing materials available for donor wound coverage. Pain, the amount and type of exudate developing underneath the dressing, adherence, and cellulitis were evaluated on a daily basis, and healing time was determined. Biobrane proved superior to Scarlet Red with respect to control of pain, accumulation of exudate, and healing time; the materials were equal with regard to adherence to the wound, the character of exudate, and the appearance of cellulitis.

Adolescent↗
PubMed1985

Prevention of suppressed cell-mediated immunity in burned mice with histamine-2 receptor antagonist drugs.

Thermal injury has been shown to suppress many aspects of both specific and nonspecific immune responses. We investigated the effect of two histamine H-2 antagonist drugs on cell-mediated immunity in burned mice, utilizing a method of quantitating the degree of contact sensitivity elicited to the antigen. 2,4-dinitrofluorobenzene (DNFB). Following sensitization by painting the abdomen with DNFB, animals were challenged 5 days later by painting the ears; subsequent ear swelling is a sensitive and reproducible measure of cell-mediated immunity. We have previously demonstrated that burned mice are maximally immunosuppressed 10 to 14 days following burn injury. In the present study we found that daily intraperitoneal administration of appropriate doses of the H-2 antagonists cimetidine (2 and 10 mg/kg/day) and ranitidine (2 and 10 mg/kg/day) resulted in maintenance of normal cell-mediated immunity in burned animals. Neither a lower dose of ranitidine (0.2 mg/kg/day) nor higher doses of cimetidine (20 and 50 mg/kg/day) restored immunity, and diphenhydramine, an H-1 antagonist, had no effect. There was no augmentation of contact sensitivity in unburned mice treated with cimetidine. The immunorestorative effect is probably secondary to antagonism of histamine H-2 receptors on suppressor T lymphocytes, and may reflect increased suppressor cell activity in burned mice; however, other mechanisms may be involved.

Animals↗
PubMed1985

The effect of histamine receptor antagonists on specific and nonspecific suppression of experimental contact sensitivity.

We studied the effects of H1 and H2 histamine receptor antagonists on down regulation of contact sensitivity (CS) to dinitrofluorobenzene (DNFB). Two H2 receptor antagonists, cimetidine and ranitidine, reversed the nonspecific immunosuppression of CS induced by burns. On the other hand, these two drugs did not affect the antigen-specific suppressor T cell-mediated tolerance to DNFB induced by dinitrobenzene sulfonic acid. Two H1 antagonists did not affect the down regulation of CS induced by either tolerance or burning. The differential sensitivities to histamine 2-receptor antagonists indicate that the mechanisms for nonspecific burn-induced immunosuppression are different from those for hapten-specific tolerance to DNFB.

Animals↗
PubMed1985

Restoration of immunity in burned mice by cimetidine.

We have previously described a mouse model of postburn suppression of cell-mediated immunity (CMI). Ear swelling (ES) in response to contact antigen challenge is depressed maximally 14 days following a 25% steam burn and recovers to control levels 3 weeks postburn. Splenic lymphocyte proliferation in response to Concanavalin A (Con A) is also depressed 14 days postburn. Splenic T-lymphocyte subset analysis with monoclonal antibodies for helper cells (Lyt 1.2) and suppressor cells (Lyt 2.2) reveals that T-helper cells reach a minimal level and T suppressor cells reach a maximum level 14 days postburn. The helper: suppressor ratio (HSR) reaches its nadir at day 14. Treatment of burned mice with low-dose cimetidine (2 or 10 mg/kg/day), but not high-dose (50 mg/kg/day), for 14 days restores CMI. Low-dose cimetidine also normalizes the HSR but does not effect postburn depression of mitogen responsiveness. Low-dose cimetidine probably restores CMI by inhibiting suppressor cells, whereas high doses provide more global inhibition. Recovery of mitogen responsiveness may require continued cimetidine presence in culture.

Animals↗
PubMed1985

Hydrocarbon contact injuries.

Cutaneous injury caused by exposure to gasoline and other hydrocarbons is a clinical entity with potentially life-threatening effects. We report four cases of such injury. One patient developed full-thickness skin loss following gasoline immersion, and another developed severe systemic complications following contact with a carburetor cleaning solvent. Initial therapy should consist of removal of solvent-containing clothing and extensive lavage or soaking with water, followed by wound care that is generally similar to that used in the treatment of partial-thickness burns. In most cases this includes debridement, topical antimicrobial agents, and dressing changes. Severe pulmonary, cardiovascular, neurologic, renal, and hepatic complications may accompany hydrocarbon absorption, particularly in cases involving gasolines containing lead additives. Therefore immediate surgical debridement should be considered if there is suspicion of continued absorption of toxic compounds from the wound.

Absorption↗
PubMed1985

Topical cerium nitrate prevents postburn immunosuppression.

Suppression of cell-mediated immunity (CMI) follows a major thermal injury and is associated with an increased incidence of serious infections. Adult female CF-1 mice received a 20% full-thickness steam burn and were then treated with various topical antimicrobial creams in an attempt to alter the course of postburn immunosuppression. Topical agents included cerium nitrate (CE), silver sulfadiazine (SSD), mafenide (SML), silver nitrate (AG), and a mixture of CE and SSD (CE-SSD). CMI was determined in vivo by measuring ear swelling in response to 2,4-dinitrofluorobenzene (DNFB) challenge in previously sensitized mice. The usual nadir in CMI (ear swelling) when mice were sensitized at day 14 postburn did not occur in burned mice treated with CE or CE-SSD, AG was only modestly effective, and SML or SSD failed to restore CMI. These studies suggest that topical CE may have potential as an immunomodulator in the treatment of burns.

Animals↗
PubMed1984

Altered helper and suppressor lymphocyte populations in surgical patients. A measure of postoperative immunosuppression.

Although a wealth of evidence has suggested that cell-mediated immunity is suppressed after simple surgical trauma, there have been contradictory results using stimulation assays of lymphocyte function. We quantitated T-lymphocyte subsets in 11 patients undergoing routine cholecystectomy by immunofluorescence microscopy using specific monoclonal antibodies. T-helper to T-suppressor cell ratios were calculated on the preoperative day and the first postoperative day in all patients, and on the third or fourth postoperative day in five patients. Helper to suppressor ratios decreased in all patients on the first postoperative day (p greater than 0.01), but returned to within normal limits on subsequent days. Changes were due more to decreases in helper cells than to increases in suppressor cells, although changes in both populations were statistically significant. The measurement of T-cell subsets by antibody-specific labeling and immunofluorescence microscopy may prove to be a more sensitive, quantifiable, and reproducible assay of immune function in surgical or traumatized patients than use of stimulation assays. Measurements of specific helper and suppressor lymphocyte populations may prove useful in predicting morbidity and mortality, and may also help in studying the effect of immunomodulating agents on the immune response.

Adolescent↗
PubMed1984

Characterization of the immunosuppressive effect of burned tissue in an animal model.

The immunosuppressive effect of burned tissue was studied using a mouse burn model. To evaluate the immunologic status an in vivo measure of cell-mediated immunity (CMI) involving contact sensitization of mice by painting the skin with dinitrofluorobenzene was used; mice were challenged 5 days later by painting the ear with the same antigen. Ear swelling in response to antigenic challenge was used as a quantitative measure of CMI; diminution in ear swelling in treatment mice compared to sensitized, unburned control mice indicated the degree of immunosuppression. A full-thickness steam burn covering 20% body surface ares (BSA) was profoundly immunosuppressive as reflected by ear swelling of 45 to 60% of that found in normal mice; partial thickness burns and burns of 10% BSA extent were not significantly immunosuppressive. Transfer into unburned mice of burned skin equivalent in size to a 20% BSA burn eschar resulted in marked immunosuppression, but transfer of smaller amounts of burned skin, or of larger amounts of unburned skin and normal and burned liver tissue, did not produce immunosuppression. Mice receiving a very high-temperature (300 degrees C), dry burn were only slightly more suppressed than mice receiving a standard steam burn. Normal immunity was preserved in burned mice which received daily application of cerium nitrate to the wound for 7 days, but application of other topical agents commonly used in burn treatment did not preserve immunity. Postburn immunosuppression thus appears related quantitatively to toxic factors in burned skin, and these toxic factors can be abrogated in burned mice by the topical application of cerium nitrate.

Animals↗
PubMed1984

Clinical experience with Biobrane biosynthetic dressing in the treatment of partial thickness burns.

Biobrane, a synthetic, bicomposite wound dressing, has been used to treat 17 patients with partial thickness burn wounds covering 0.5-12.5 per cent of the total body surface area (mean 4.4 per cent). In 16 patients we found complete healing of the wound after removal of the dressing, 6-15 days after the injury. In one patient, the wounds were determined on the third day post-injury to be deeper than initially suspected, and she was taken to the operating room for surgical debridement and grafting. Biobrane is an effective wound covering for clean, superficial partial thickness burns of limited extent; the simultaneous use of topical antimicrobial agents for such wounds is not necessary.

Adult↗
PubMed1984

Vitamin E improves cell-mediated immunity in the burned mouse: a preliminary study.

Profound immunosuppression occurs after major burn injuries. The ability of vitamin E to prevent post-burn immunosuppression was tested in mice using ear swelling in response to a challenge with 2,4-dinitrofluorobenzene (DNFB) as an in vivo measure of cell-mediated immunity (CMI). Vitamin E was administered to burned mice every other day for 14 days by either the topical or intraperitoneal route. Dimethyl sulphoxide (DMSO) was compared to white petroleum jelly (VAS) as a vehicle for topically administered vitamin E. Mean CMI +/- the standard error of the mean (SEM) was depressed to 55 +/- 4 per cent of normal control in untreated burned mice. Treatment with either parenteral vitamin E in corn oil or topical vitamin E in DMSO improved CMI dramatically compared to burned controls (P less than 0.005) while vitamin E in VAS had a less beneficial effect on CMI (P less than 0.05). We conclude that vitamin E is an effective immunomodulator in burned mice.

Administration, Topical↗