RESUMO
Animal models have an important role in cutaneous research. The guinea pig has proven to be a useful model in a wide spectrum of these cutaneous studies; however, its usefulness is often compromised by the need for depilation. A euthymic hairless guinea pig (HGP) model avoids the problems associated with depilation. Morphologically, as in human skin, these animals have a multi-cell-layer epidermis. Proliferation kinetic studies, as well as documentation of the degree of immunologic cross-reactivity between available antibodies to human cutaneous antigens, could extend the usefulness of this animal model. We performed a battery of anti-human antibodies on formalin fixed tissue, to a variety of antigens present within the skin and on inflammatory cells. These included CD3, UCHL-1, OPD4, L-26, KP-1, Factor XIIIa, S-100 protein, cytokeratin (AE1, AE3 and CK1), CAM 5.2, vimentin, CD 34, Factor VIII, fibronectin, SM actin, collagen IV, laminin, Bcl-2, p53, Ki-67, and PCNA. Cross-reacting antibodies included: CD3, S-100 protein, cytokeratin (AE1, AE3 and CK1), vimentin, Factor VIII, SM actin, collagen IV, p53, Ki-67, and PCNA. Although this battery of antibodies is limited, the markedly increased staining of Ki-67 and PCNA within keratinocytes in the epidermis as compared to normal human skin reflects a high proliferative rate. In addition, positive staining for p53, Ki-67, and PCNA may be useful in studying effects on cell cycle kinetics and apoptosis.
Assuntos
Anticorpos/análise , Antígeno Ki-67/análise , Antígeno Nuclear de Célula em Proliferação/análise , Dermatopatias/patologia , Pele/química , Pele/patologia , Proteína Supressora de Tumor p53/análise , Actinas/análise , Actinas/imunologia , Actinas/metabolismo , Animais , Anticorpos/imunologia , Especificidade de Anticorpos , Apoptose/fisiologia , Complexo CD3/análise , Complexo CD3/imunologia , Complexo CD3/metabolismo , Divisão Celular/fisiologia , Colágeno/análise , Colágeno/imunologia , Colágeno/metabolismo , Reações Cruzadas , Modelos Animais de Doenças , Fibronectinas/análise , Fibronectinas/imunologia , Fibronectinas/metabolismo , Cobaias , Humanos , Imuno-Histoquímica/métodos , Queratinócitos/química , Queratinócitos/patologia , Queratinas/análise , Queratinas/imunologia , Queratinas/metabolismo , Antígeno Ki-67/imunologia , Antígeno Ki-67/metabolismo , Masculino , Antígeno Nuclear de Célula em Proliferação/imunologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas S100/análise , Proteínas S100/imunologia , Proteínas S100/metabolismo , Pele/imunologia , Dermatopatias/metabolismo , Dermatopatias/fisiopatologia , Proteína Supressora de Tumor p53/imunologia , Proteína Supressora de Tumor p53/metabolismo , Vimentina/análise , Vimentina/imunologia , Vimentina/metabolismo , Fator de von Willebrand/análise , Fator de von Willebrand/imunologia , Fator de von Willebrand/metabolismoRESUMO
Although no animal is a perfect skin model for the study of toxicological and therapeutic agents, structurally the pig may be superior to even non-human primates. Because our work involves effects of toxicological and therapeutic agents on the skin, we wanted to identify stains which may prove useful as well as determine cross-reactivity of some newer antihuman antibodies. We performed a battery of formalin-fixed skin from weanling pigs and minipigs. The battery of antibodies included LCA, CD3, OPD-4, CD34, UCHL-1, L-26, KP-1, MAC-387, Factor XIIIa, Leu-7, S-100 protein, HMB-45, GFAP, synaptophysin, neurofilament protein, ubiquitin, vimentin, type IV collagen, laminin, fibronectin, Factor VIII related antigen, Desmin-M, smooth muscle actin, cytokeratin 7, cytokeratin 20, AEI/AE3, CAM 5.2, EMA, GCDFP, Ki-67, and PCNA. Immunohistochemical stains for CD3, Leu-7, S-100 protein, type IV collagen, laminin, Factor VIII related antigen, GFAP, synaptophysin, neurofilament protein, ubiquitin, smooth muscle actin, vimentin, Desmin-M, cytokeratin 7, cytokeratin 20, AE1/AE3, CAM 5.2, Ki-67 and PCNA showed consistent cross-reactivity. In formalin-fixed tissue, only antibodies to lymphoreticular cells showed poor cross-reactivity. A high percentage of the remaining antibodies did show good cross-reactivity but with some interesting similarities and differences in specificity.
Assuntos
Anticorpos/imunologia , Queratinas/imunologia , Antígeno Ki-67/imunologia , Antígeno Nuclear de Célula em Proliferação/imunologia , Pele/citologia , Pele/imunologia , Animais , Especificidade de Anticorpos , Biomarcadores , Divisão Celular/imunologia , Reações Cruzadas , Formaldeído , Humanos , Imuno-Histoquímica , Queratinócitos/citologia , Queratinócitos/imunologia , Especificidade da Espécie , Suínos , Fixação de TecidosRESUMO
The influence of early graft surface thromboreactivity on long-term arterial polyester (Dacron) graft patency was investigated with separate ex vivo and in vivo animal models. First, parallel, flow-regulated external aortocaval fistulae were created in five pigs with use of paired 8 mm X 35 cm crimped, warp-knitted, low-profile filamentous velour Dacron tubes: one tube preclotted with autologous blood, the other autoclaved after being soaked in human albumin. Autologous radiolabeled platelets, red cells, and radiolabeled human fibrinogen were injected at initiation of graft flow, with timed graft samples submitted for isotope gamma well-counting. Flow surface accumulation of radiolabeled blood elements was greater on the preclotted graft limb at-all time intervals studied, greatest after 5 minutes of flow initiation with RBC accumulation on the preclotted limb 5.19 +/- 0.84 (x +/- S.E.), platelet accumulation 5.57 +/- 1.00, and fibrinogen accumulation 1.82 +/- 0.14 times greater than that on the albumin-treated limb. Second, bilateral iliofemoral artery bypass grafts were placed in 12 mongrel dogs using 6 mm X 10 cm externally supported, noncrimped, warp-knitted, low-profile filamentous Dacron tubes. Before implant in each dog, one graft limb was clotted with autologous blood and the other was autoclaved after being soaked in 25% human albumin. Fresh autologous radiolabeled platelets were injected after wound closure in seven of these dogs. Postimplant graft imaging at 24 and 72 hours showed radiolabeled platelet accumulation to be 1.43 +/- 0.21 and 2.05 +/- 0.18 times greater on the preclotted graft limb. Six of 12 preclotted graft limbs and 7 of 12 albumin-treated graft limbs were patent when animals were killed 5 to 6 months after implant (not significant). Heat-denatured albumin-coated Dacron surfaces have a reduced early thromboreactivity but do not appear to greatly potentiate long-term arterial graft patency.
Assuntos
Prótese Vascular , Polietilenotereftalatos , Trombose/prevenção & controle , Grau de Desobstrução Vascular , Albuminas/metabolismo , Animais , Sangue/metabolismo , Modelos Animais de Doenças , Cães , Estudos de Avaliação como Assunto , Temperatura Alta , Microscopia Eletrônica , Agregação Plaquetária , Desnaturação Proteica , Cintilografia , Propriedades de Superfície , Suínos , Trombose/diagnóstico por imagem , Fatores de TempoRESUMO
BACKGROUND AND PURPOSE: Soman, an organophosphorus, anticholinergic, chemical warfare nerve agent, is studied at few research facilities, and there have been few pathologic studies of soman-exposed primates. We describe the brain, heart, and skeletal muscle lesions, review lesions described in literature, and discuss possible pharmacologic mechanisms for soman-induced neuron necrosis. METHODS: In this retrospective, histopathologic study, records were obtained for 36 rhesus macaques (Macaca mulatta) that were euthanized 10 days after soman exposure, from a larger group of 103 monkeys that were exposed to soman and used for pharmacologic and lethality studies. RESULTS: Brain lesions were seen in 9 of 15 animals that convulsed and in only 1 of 21 that did not convulse. The brain lesions in our primates were limited to the hippocampus, amygdala, and thalamus (of one animal), and consisted of neuron necrosis and dropout, spongiosis, gliosis, astrocytosis, and vascularization. Heart lesions consisted of myocardial degeneration and necrosis. Three animals had brain and heart lesions, 7 had brain lesions only, and 3 had heart lesions only. Skeletal muscle lesions, although minimal to mild, were in most of the animals, whether they had convulsed, but most had muscular tremors. These lesions were in the biceps brachii (11 of 22 monkeys), anterior tibialis (8/22), biceps femoris (7/22), flexor carpi radialis (5/22), gastrocnemius (3/22), and diaphragm (1/22). The limited literature on soman lesions in primate brain and heart, and the limited information on skeletal muscle lesions, is reviewed. CONCLUSIONS: Brain lesions were not as wide-spread as reported in other studies of primates and rodents, and were significantly associated with convulsions. Unlike other studies using rodents, we observed poor correlation between heart and brain lesions; thus, a single hypothesis to explain the pathogenesis for the brain and heart lesions may be difficult to establish.
Assuntos
Encéfalo/efeitos dos fármacos , Inibidores da Colinesterase/toxicidade , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Compostos Organofosforados/toxicidade , Soman/toxicidade , Animais , Anticonvulsivantes/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrócitos/patologia , Encéfalo/patologia , Substâncias para a Guerra Química/toxicidade , Relação Dose-Resposta a Droga , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/induzido quimicamente , Gliose/patologia , Coração/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Macaca mulatta , Masculino , Miocárdio/patologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Tremor/induzido quimicamente , Tremor/tratamento farmacológicoRESUMO
We have examined the effects of direct current (DC) conducted through silver-nylon dressings on the healing time and morphologic maturation of split-thickness grafts placed on tangentially excised deep partial-thickness burn wounds. Male guinea pigs (n = 120) were used as the experimental hosts. The DC-treated animals required 2 days for complete revascularization of their grafts; control animals required 7 days (p less than 0.01). The DC-treated animals had increased epithelial proliferation at the graft-wound interface as compared with controls (p less than 0.01). Grafts from DC-treated animals were firmly adherent within 4 days, whereas graft adherence in controls was weak before 7 days after grafting. At 3 months after grafting, control animal grafts had mild contraction with moderate hair loss and thick subepidermal fibrosis; the grafts in DC-treated animals expanded with the growth of the animals and had abundant hair growth and significantly reduced dermal fibrosis (p less than 0.01).
Assuntos
Queimaduras/fisiopatologia , Terapia por Estimulação Elétrica , Transplante de Pele , Cicatrização/fisiologia , Animais , Queimaduras/patologia , Queimaduras/cirurgia , Divisão Celular , Cobaias , Masculino , Pele/patologia , Transplante de Pele/patologia , Transplante AutólogoRESUMO
Fifty-two, 8-week-old, male White Pekin ducklings (Anas platyrhynchos domesticus) were allotted into control (n = 7) and isoproterenol-injected groups (n = 45). One control duck and 5 to 7 isoproterenol-injected (200 mg/kg of body weight) ducklings were euthanatized at postinjection hours (PIH) 1, 12, and 24 and at postinjection days (PID) 2, 4, 7, and 14. The left ventricular myocardium was examined, using electron microscopy. The earliest ultrastructural alteration in damaged myocytes was myofibrillar lysis at PIH 12. At PIH 24, affected myocytes had necrosis with mineralization of mitochondria. By PID 2, macrophages had invaded into areas of myocardial necrosis, mineralization was prominent in myocyte mitochondria, and dedifferentiated myocytes with reduced numbers of myofibrils, increased numbers of polysomes, large nuclei, and prominent nucleoli were first observed. The primary myocardial finding at PID 4, 7, and 14 was 2 populations of sublethally damaged myocytes. One population of injured myocytes had numerous polysomes in the sarcoplasm and large nuclei with prominent nucleoli, indicating attempts at repair of myofibrillar damage. The 2nd population of myocytes with myofibrillar lysis did not have morphologic evidence of myofibrillar repair. Therefore, the sequential ultrastructural alterations of damage and repair induced by isoproterenol in the duckling myocardium provided model for comparative studies of cardiotoxicity.
Assuntos
Cardiomiopatias/patologia , Miocárdio/ultraestrutura , Animais , Cardiomiopatias/induzido quimicamente , Patos , Isoproterenol , Masculino , Microscopia Eletrônica , Miocárdio/patologia , NecroseRESUMO
A 1.5-year-old male Belgian Malinosis Military Working Dog presented with a 1-month history of intermittent hematuria. Diagnostic ultrasound and contrast radiography demonstrated large blood clots in the urinary bladder and a filling defect in the right renal pelvis. At surgery, clotted blood was present in the right ureter and bladder. Following right nephrectomy, the dog returned to training. One month later, elevations in urea nitrogen and creatinine were noted. Hematuria recurred at 3 months and the dog was found dead in its kennel. Necropsy showed a blood-filled left renal pelvis and ureter.
Assuntos
Cães , Hematúria/veterinária , Nefropatias/veterinária , Militares , Animais , Bélgica , Hematúria/patologia , Rim/patologia , Nefropatias/patologia , MasculinoRESUMO
Dacron fabrics with a wide range of porosities were autoclaved for 3 minutes after being soaked in serum, 5% albumin, or 25% albumin. Porosity of compound Dacron grafts made with 25% albumin was less than 1 ml/min/cm2 regardless of the fabric base, whereas porosity of grafts made with serum or 5% albumin was proportional to the porosity of the base fabric. Porosity of the compound grafts remained stable for more than 48 hours and to pressure greater than 450 mm Hg, if the grafts were kept moist. Tubes of Marlex mesh coated with heat-denatured albumin, implanted as infrarenal aortic replacements in dogs, showed complete albumin absorption by 3 weeks. However, perigraft tissue reaction and graft incorporation were minimal and extensive false aneurysm formation resulted. Knitted filamentous Dacron 6 mm tubes coated with heat-denatured albumin were implanted as iliofemoral bypass grafts in 12 dogs, with blood-preclotted knitted filamentous Dacron grafts implanted as contralateral control grafts. Comparison of the albumin-coated grafts with the blood-preclotted control grafts showed no differences in healing or patency at 4 to 6 months. Heat-denatured 25% albumin forms a strong and hemostatic coating regardless of fabric base. Albumin-Dacron compound grafts are easily and rapidly made in the operating room, handle well, and are suitable for large and medium-sized arterial replacements without changes in healing or patency. Because of slow tissue incorporation, however, albumin-coated knitted Dacron grafts should be avoided in patients who require long-term anticoagulation therapy.
Assuntos
Albuminas , Prótese Vascular , Polietilenotereftalatos , Polipropilenos , Animais , Sangue , Prótese Vascular/efeitos adversos , Cães , Feminino , Oclusão de Enxerto Vascular , Hemorragia/etiologia , Temperatura Alta , Masculino , Plasma , Polietilenos , Complicações Pós-Operatórias/etiologia , Desnaturação ProteicaRESUMO
The time required for wound healing, contraction, and hypertrophic scarring often limit the use of deep partial-thickness burn wounds as donor sites for split-thickness grafts. We have examined the effects of weak direct current and silver nylon dressings on the healing of partial-thickness scald burns, split-thickness grafts taken from these wounds when healed, and the resulting donor sites in a guinea pig model. Dorsal scald wounds treated with weak direct current reepithealized by 12 days postinjury. Split-thickness grafts taken from healed scald wounds showed more rapid revascularization with direct current treatment than did control grafts. Grafts and donor sites treated with direct current showed more rapid reepithelialization, decreased contraction, improved hair survival, and decreased dermal fibrosis when compared to controls not treated with direct current. Only donor wounds treated with weak direct current were reusable as donor sites.
Assuntos
Bandagens , Queimaduras/fisiopatologia , Terapia por Estimulação Elétrica/métodos , Transplante Autólogo , Cicatrização , Animais , Queimaduras/terapia , Epitélio/crescimento & desenvolvimento , Cobaias , Masculino , Nylons , Prata , Pele/irrigação sanguínea , Pele/citologia , Transplante de PeleRESUMO
Pulmonary injury resulting from inhalation of chemical and particulate products of incomplete combustion is one of the principal determinants of mortality following burn injury. In this study, the histopathology of inhalation injury was examined in sheep. Mild, moderate, or severe smoke injury was produced in anesthetized sheep by insufflation with various doses of ambient temperature smoke, generated by burning polyethylene, wood pulp, and nonwoven cellulose pads. A total of 64 sheep were exposed and evaluated at times ranging from 15 minutes to 4 weeks after exposure. Morphologic changes in the lungs were studied using light microscopy and both transmission and scanning electron microscopy. The primary, dose-responsive injury observed was acute cell membrane damage in the trachea and bronchi leading to edema, progressive necrotic tracheobronchitis with pseudomembrane formation, and airway obstruction. These inflammatory and occlusive effects were followed by congestion, alveolar space edema, atelectasis, and bronchopneumonia. Morphologic changes occurring in the alveolar epithelium following high smoke dosage included intracellular edema in type-I cells, changes in the membrane-bound vacuoles of type-II cells, and septal thickening caused by interstitial edema. No capillary endothelial changes were observed.
Assuntos
Queimaduras por Inalação/patologia , Animais , Cílios/ultraestrutura , Epitélio/ultraestrutura , Pulmão/patologia , Pulmão/ultraestrutura , Masculino , Microscopia Eletrônica de Varredura , Necrose , Ovinos , Traqueia/patologia , Traqueia/ultraestruturaRESUMO
Sulfur mustard (SM), a chemical warfare agent first used early in the 20th century, has re-emerged in the past decade as a major threat around the world. At present, there are no effective therapeutic measures for SM exposure. Because the skin as well as other interface epithelial surfaces are the first tissues effected as this agent is absorbed, reactions within the skin are an area of active research into the mechanism of action of this alkylating agent. The euthymic hairless guinea pig has been used as the animal model for the study of SM induced injuries because of morphologic similarity of its skin to human skin, with a multiple layer epidermis, and because this animal has a normal immune system. We reviewed 102 biopsy specimens from 51 animals exposed to three different dose times of saturated SM vapor. Histopathologic evidence exists for increased programmed cell death as well as cellular necrosis, subepidermal blister formation, and delayed re-epithelialization secondary to problems with adhesion. Information obtained from this study adds to the body of information important in the investigation of the mechanisms of action of SM.
Assuntos
Substâncias para a Guerra Química/toxicidade , Gás de Mostarda/toxicidade , Dermatopatias/patologia , Pele/patologia , Animais , Modelos Animais de Doenças , Cobaias , Pele/efeitos dos fármacos , Dermatopatias/induzido quimicamenteRESUMO
In the course of developing a model of inhalation injury, the relationship between the severity of pulmonary injury and specific techniques and doses of smoke exposure was examined in pairs of rabbits simultaneously exposed to smoke. In group I (5 pairs), one animal in each pair was exposed to smoke with a breath hold (BH) at the end of each exposure; the second animal received an exposure producing the same level of carboxyhemoglobin without BH. In group II (6 pairs), both animals were exposed to 25 units of smoke simultaneously, with BH. In group III (3 pairs), one animal received a 20-unit exposure and the other a 25-unit exposure, both with BH. In group IV, 9 animals received 25-unit exposures with BH and were observed for 4 days. Groups V and VI served as controls. Smoke exposure with BH regularly produced severe injury in terms of decreased PaO2 and histopathologic changes, while exposure without BH did not, despite high levels of carboxyhemoglobin after smoke inhalation. The mean differences in percent residual PaO2 (PaO2 at 48 hours x 100/pre-injury PaO2) and in extravascular lung water (EVLW) at 48 hours within pairs of animals receiving 25 units with BH were 12.3% +/- 5.33%, and 0.271 +/- 0.157 mL/g, respectively. Histologic findings such as necrotic tracheobronchitis with pseudomembrane were consistently present. No differences were observed between animals receiving exposure of 20 and 25 units. During the 4 days of observation, three animals in group IV died. PaO2 was lowest on the second day and rose thereafter in all surviving animals except in one that had massive pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Lesão por Inalação de Fumaça/fisiopatologia , Animais , Carboxihemoglobina/metabolismo , Modelos Animais de Doenças , Água Extravascular Pulmonar , Masculino , Prognóstico , Coelhos , Lesão por Inalação de Fumaça/sangue , Lesão por Inalação de Fumaça/patologiaRESUMO
Administration of a long-acting prostaglandin E, 16,16-dimethyl-PGE (dPGE), to rats improves their survival of bacterial peritonitis. We examined the mechanism of this protective effect with reference to its interaction with the release of cachectin (TNF). Sixty rats received saline, 20 micrograms/kg dPGE, or 80 micrograms/kg dPGE 12 hr prior to endotoxin and continuing for 48 hr. Survival rates for the saline, 20 micrograms/kg dPGE, and 80 micrograms/kg dPGE groups were 0, 40, and 85%, respectively. Forty rats received saline or 80 micrograms/kg dPGE, with the initial dose being 3 hr following endotoxin challenge and continuing for 48 hr. Survival rates for both groups were 0%. Sixty rats received saline or 80 micrograms/kg dPGE at 12 and 1 hr prior to endotoxin. Two hours after challenge, they were sacrificed and plasma TNF levels were assayed. The plasma TNF level in saline-treated rats was 22.72 +/- 0.83 ng/ml and in the dPGE-treated group, 16.03 +/- 1.13 ng/ml (P less than 0.001).
Assuntos
Prostaglandinas E Sintéticas/uso terapêutico , Choque Séptico/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Animais , Infecções por Escherichia coli , Masculino , Peritonite/tratamento farmacológico , Peritonite/etiologia , Ratos , Ratos Endogâmicos LewRESUMO
Smoke inhalation is a significant comorbid factor in thermal trauma. The effect of inhaled nitric oxide (NO) on smoke inhalation injury was evaluated in an ovine model. Following smoke exposure, group 1 animals (n = 9) spontaneously breathed room air, and group 2 animals (n = 8) breathed 20 parts per million of NO in air for 48 hours. Cardiopulmonary variables and blood gases were serially measured; bronchoalveolar lavage (BAL) was performed and wet-to-dry lung weight ratios (W/D) determined at 48 hours. Pulmonary vasoconstriction following smoke inhalation was significantly attenuated by inhaled NO (p < 0.05), which exerted no apparent effect on the systemic circulation. In group 2, the serial decline in pulmonary oxygenation was less than in group 1, consistent with a smaller physiologic shunt (p < 0.05). There were no significant differences in W/D, lung compliance, BAL fluid analysis results, or histologic evaluation findings between the two groups. These results suggest that inhaled NO exerted beneficial effects on pulmonary arterial hypertension and oxygenation following smoke inhalation without apparent amelioration of airway inflammation.
Assuntos
Óxido Nítrico/uso terapêutico , Lesão por Inalação de Fumaça/tratamento farmacológico , Administração por Inalação , Animais , Gasometria , Brônquios/patologia , Líquido da Lavagem Broncoalveolar/química , Hipertensão Pulmonar/fisiopatologia , Pulmão/patologia , Masculino , Óxido Nítrico/administração & dosagem , Tamanho do Órgão , Ovinos , Lesão por Inalação de Fumaça/patologia , Lesão por Inalação de Fumaça/fisiopatologia , Traqueia/patologia , Vasoconstrição/efeitos dos fármacosRESUMO
Alpha- and beta-hydroxy acids are compounds that have been used extensively in cosmetic and dermatological formulations. Clinical and qualitative effects of alpha- and beta-hydroxy acids have been well characterized, but little is known about their mechanism of action or acute and chronic biochemical effects. In the present study, we examined the acute proliferative effects of glycolic and salicylic acids on cell proliferation in the epidermis of SKH-1 female mice, using BrdU incorporation as a marker of epidermal proliferation. In preliminary experiments, we observed an increase in the rate of proliferation after 3 days of treatment with 10% glycolic acid-containing cream and this was sustained throughout a 6.5-week (treatment 5 days/week) time course compared with untreated control animals. After each treatment with cream containing glycolic acid there was a wave of proliferation that was maximal 12 to 16 h (significant at p < 0.05) after treatment, followed by a subsequent increase in epidermal thickness at 18 to 20 h (significant at p < 0.05). The effects of the concentration and pH level of glycolic acid- and salicylic acid-containing creams on the rate of proliferation and increases in skin thickness in SKH-1 epidermis were also investigated. We observed a dose-dependent increase in epidermal proliferation of animals treated with either glycolic or salicylic acid. A similar time-dependent response was observed in the epidermal thickness in animals treated with salicylic acid, but not with glycolic acid. Differences in pH (3.5 or 4.0) had no significant effect on either epidermal proliferation or skin thickness. The data that we present here should be useful in characterizing not only the beneficial but also the adverse effects that occur following acute or chronic usage of alpha-hydroxy acids.
Assuntos
Epiderme/efeitos dos fármacos , Glicolatos/farmacologia , Ceratolíticos/farmacologia , Ácido Salicílico/farmacologia , Animais , Divisão Celular/efeitos dos fármacos , Cosméticos/química , Relação Dose-Resposta a Droga , Células Epidérmicas , Epiderme/fisiologia , Feminino , CamundongosRESUMO
Bronchopulmonary injury secondary to smoke inhalation is a significant comorbid factor following major thermal trauma. The present study evaluates the effects of pentoxifylline (PTX) on pulmonary function in an ovine model of inhalation injury. Following smoke exposure to produce a moderate inhalation injury, 16 animals were divided into two groups. Group 1 animals (n = 8) were untreated; Group 2 animals (n = 8) were treated continuously with pentoxifylline following smoke exposure. The animals were observed in the unintubated, awake state for 48 hr. Cardiopulmonary variables and blood gases were measured serially. Ventilation perfusion distribution (VA/Q), analyzed using the multiple inert gas elimination technique, and bronchoalveolar lavage (BAL) were performed at 48 hr. The wet to dry lung weight ratio was measured following necropsy. In Group 2, the progressive hypoxemia observed following smoke inhalation was attenuated with less VA/Q mismatching than in Group 1 (P < 0.05). Pulmonary hypertension secondary to increased vascular resistance was also attenuated in Group 2 (P < 0.05). In BAL fluid, polymorphonuclear leukocytes, total protein content, and conjugated dienes were less in Group 2 than in Group 1 (P < 0.05). Plasma-conjugated diene levels were also lower in Group 2 at 48 hr. Extravascular lung water and decrease in lung compliance were greater in Group 1. There was less morphologic evidence of airway injury in Group 2 compared to Group 1. The improvement of pulmonary function following treatment with PTX suggests that this agent may be useful in the management of smoke inhalation injury.