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Melatonin reduces oxidative damage to skin and normalizes blood coagulation in a rat model of thermal injury.

This study was designed to determine the effect of melatonin treatment on the glutathione (GSH) and lipid peroxidation (LPO) levels in the skin as well as prothrombin time (PT) and fibrin degradation products (FDPs) in the blood of rats with thermal injury. Under ether anaesthesia, the shaved dorsum of the rats was exposed to 90 degrees C bath for 10 s to induce burn injury. Rats were decapitated either 3 or 24 hours after burn injury. Melatonin (10 mg/kg) was administered i.p. immediately after burn injury to same animals. In the 24 hour burn group, melatonin injections were repeated for two more occasions 8 and 16 h after burn injury. In the control group the same protocol was applied except that the dorsum was exposed to a 25 degrees C water bath for 10 s. Severe skin scald injury (30% of total body surface area) caused a significant decrease in PT at post burn 3 and 24 hours. FDPs was not increased at post burn 3 hour but was significantly increased at post burn 24 hour. GSH levels were significantly depressed at post burn 3 hour but were not changed at post burn 24 hour. LPO levels were significantly increased both at post burn 3 and 24 hours. Skin protein levels were significantly reduced at post burn 24 hour as evidenced by electrophoresis. Treatment of rats with melatonin normalized PT levels both at post burn 3 and 24 hours. FDP decreased at post burn 24 hour due to melatonin treatment. GSH levels significantly increased as a result of melatonin treatment both at post burn 3 and 24 hours melatonin treatment. LPO levels were not changed by melatonin at post burn 3 hour; however, the melatonin significantly decreased LPO values at post burn 24 hours. In conclusion, exogenously administered melatonin reduced skin oxidant damage and normalized the activated blood coagulation induced by thermal trauma.

Animals↗

Immunosuppression after injury in aged mice is associated with a TH1-TH2 shift, which can be restored by estrogen treatment.

Aged mice are less likely to survive following traumatic injury and are more immunosuppressed than young mice who sustain comparable injuries. Immunosuppression in severely injured patients is associated with a TH1-TH2 shift. Young mice had robust delayed-type hypersensitivity (DTH) responses after receiving scald or sham injury, whereas the response was diminished in aged sham-injured mice (P < 0.05), and completely absent in aged burn-injured mice (P < 0.01). Production of interferon-gamma (IFN-gamma) did not differ between splenocytes from sham-injured young and aged mice. Splenocytes from burn-injured young and aged mice yielded similar (63-68%) decreases in IFN-gamma, relative to sham-injured mice (P < 0.05). In the absence of injury, cells from aged mice produced 2-fold more interleukin-4 (IL-4) than cells from young (P < 0.01). Interestingly, after burn, less IL-4 was produced by cell from young and aged mice, when compared to age-matched sham-injured animals (P < 0.05). Further studies revealed that estrogen replacement in aged mice restored the post-injury DTH responses (P < 0.05). Interestingly, this restoration paralleled a recovery in IFN-gamma production by splenocytes, but not IL-4 production. Additional studies will be required to determine if age-specific therapies are needed for the treatment of all trauma patients.

Aging↗

Burn-induced oxidative injury of the gut is ameliorated by the leukotriene receptor blocker montelukast.

There is increasing evidence that oxidative stress has an important role in the development of multiorgan failure after major burn injury. In the present study, we investigated whether the leukotriene receptor blocker montelukast is protective against burn-induced injury of the gut. Under brief ether anaesthesia, shaved dorsum of the rats was exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10 s. Montelukast (10 mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn injury. Rats were decapitated 24 h after burn injury and the skin samples, as well as tissue samples from stomach, ileum and colon, were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Tissues were also examined microscopically. Tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) were assayed in serum samples. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum TNF-alpha and LDH were elevated in the burn group as compared to control group. On the other hand, montelukast treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by thermal trauma. Findings of the present study suggest that montelukast possesses an anti-inflammatory effect on burn-induced gastrointestinal damage and protects against oxidative injury by a neutrophil-dependent mechanism.

Acetates↗

Identification of Salmonella spp. isolates from chicken abattoirs by multiplex-PCR.

The present study was carried out to report the occurrence Salmonella spp., Salmonella Enteritidis, and Salmonella Typhimurium in chicken abattoirs. Samples of feces; feathers; scald, evisceration, and chiller water; and rinse water of non-eviscerated, eviscerated, and chilled carcass were collected from six chicken abattoirs. Salmonella isolates were identified by a multiplex-PCR using three sets of primers targeting the invA, pefA, and sefA gene sequences from Salmonella spp., S. Typhimurium and S. Enteritidis, respectively. Salmonella spp. was detected in 10% (29/288) of the samples, whereas serovars Enteritidis and Typhimurium were identified in 62% (7/288), respectively. The results indicate the need to improve hygiene and sanitary standards in poultry slaughter lines, besides the education of food handlers and information to consumers.

Abattoirs↗

Microwave oven injuries in patients with complex partial seizures.

Microwave ovens are often recommended as a safe cooking alternative for persons with epilepsy. We report four patients who suffered serious burns to their hands while handling microwave-heated liquids during a complex partial seizure (CPS). Injuries were due to the contact of the skin with a very hot container. The fact that all patients held on to the hot containers despite being burned and that they did not remember experiencing any pain at the time of the accident indicates that neither high temperatures nor pain will prevent patients who are having a CPS from suffering this type of injury. Unfortunately, there is no foolproof way to prevent the individual from opening the oven and removing its contents during a CPS. The only solution for this problem is "prevention"-individuals with poorly controlled CPS should be cautioned about these risks. The use of microwave settings that permit the heating but not boiling of liquids and the use of gloves while heating food and liquids to scalding temperatures may minimize the risk of this type of injury.

Accidents, Home↗

Epidemiological, clinical and serological studies on trichinellosis in Henan Province, China.

The epidemiological, clinical and serological studies on human trichinellosis in Henan Province were carried out from January 1992 to December 1996. The results showed that 467 patients attending our department came from 12 administrative areas and cities of the Province and they acquired the infection mainly by eating undercooked dumplings, tasting the raw pork filling for dumplings, ingesting scalded pork or mutton. There was the high incidence season of trichinellosis during the winter. Most of the patients were workers, officers and merchants aged 20-49 years, and the incidence was higher in males than in females. The main clinical manifestations of trichinellosis were fever, general myalgia, muscle tiredness and eosinophilia. Most of the patients had not any gastrointestinal symptoms and rash. Eyelid edema was only seen in the early courses of the disease. Eosinophil count increased with time, reached to the peak 3 weeks and decreased markedly 6 weeks after the onset of the disease. Eosinophil levels elevated obviously 1 week after therapy, began to drop rapidly 2 weeks after therapy, and decreased to a near normal levels 4 weeks after therapy. Anti-Trichinella antibodies were detected by IFAT using the frozen sections of the purified T. spiralis larvae as antigen. The specific antibodies were observed in only 70.2% of patients one week after onset of disease, and increased to 91, 94.3, and 100%; 2, 3, and 4 weeks, respectively after the onset. The antibody positive rate was evidently increased to 100% 1 week after therapy with abendazole, then decreased to 25% 4 months after therapy.

Adolescent↗

Prophylactic antibiotics for the prevention of early infection in multiple myeloma.

PURPOSE: Patients with multiple myeloma are at increased risk for bacterial infection. During the first 2 months of initial chemotherapy the rate of infection is twice that experienced during the remainder of the disease course. As many as one-third of these early infections are fatal, and many more prevent adequate administration of chemotherapy. This study was designed to determine whether the morbidity and mortality of early infection can be prevented by prophylactic administration of trimethoprim-sulfamethoxazole (TMP-SMX). PATIENTS AND METHODS: Eligible patients about to begin chemotherapy for multiple myeloma were randomly assigned to prophylaxis for 2 months or to no prophylaxis (control). Antibiotic prophylaxis consisted of TMP-SMX 160/800 mg orally every 12 hours administered for the first 2 months of initial chemotherapy. All patients were observed for infection for 3 months after the start of chemotherapy. RESULTS: Of 57 patients entered into the study, 54 were evaluable, representing 13.1 patient-years of observation. The 28 TMP-SMX patients and 26 control patients were comparable in terms of chemotherapy regimen, age, gender, stage, and bone marrow function. Bacterial infection during the 3-month study period occurred in 11 control patients but in only 2 patients assigned TMP-SMX (P = 0.004). Eight severe infections occurred in controls compared with 1 in a TMP-SMX patient (P = 0.010) leading to 4 and 1 infection deaths, respectively (P = not significant). Severe infections included 5 pneumonias (3 with sepsis), 2 urinary tract infections with complicating pneumonia or sepsis, 1 diverticulitis with perforation, and 1 staphylococcal scalded skin syndrome. None of the 4 nonbacterial infections was severe. The rate of bacterial infection was 2.43 per patient-year for controls and 0.29 per patient-year for the TMP-SMX group (P = 0.001). Toxicity (skin rash 6 patients, nausea 1 patient) was not life-threatening but required discontinuation of TMP-SMX in 25% of patients. CONCLUSION: Administering TMP-SMX for the first 2 months of initial chemotherapy is effective, inexpensive prophylaxis for early bacterial infection in multiple myeloma.

Aged↗

The elderly burn patient.

During a 16-year period, 547 patients who were older than 64 years of age with a mean total body surface area (TBSA) (third-degree burns) of 25% were treated. Etiologies were flame/flash in 81% of patients, scald in 11%, solids in 7%, and electrical/chemical in 1%. Seventeen percent of patients had significant causal factors. An inhalation injury was present in 13% of patients, and the mortality in these patients was 100%. Burn excision was performed 239 times in 165 patients. The majority of excisions were for full-thickness burns. Excision did not improve overall survival in patients with third-degree burns of 0% to 10%, but the length of stay (LOS) in excised and nonexcised survivors was improved (9 versus 21 days, respectively). The LOS and survival were not significantly different in patients with burns between 11% and 20%. Postburn complications occurred in 28% of patients. Overall mortality was 50% (mean age: 77 years; TBSA: 40%). There were no survivors with over 47% TBSA burns. The leading cause of death was pulmonary sepsis. Most surviving patients returned to a satisfactory lifestyle after discharge.

Aged↗

A review of thermal injuries in young children.

A group of 472 children under 3 yr of age were treated for thermal injuries in a 5-yr period; 65% were boys. Injuries were due mainly to scalding (82%) and involved predominantly the upper part of the body. Full thickness skin loss resulted in 30% of cases, and skin grafting was needed in 29%. Forty-two episodes of infection arose, and 50 patients (11%) developed other complications--hyperpyrexia, respiratory problems, fluid imbalance and convulsions were the commonest. The mortality rate was 1% (4 cases) and the mean duration of stay in hospital was 17 days. The plan of management is outlined with emphasis on the essential differences in treatment of young children, and the results are reported.

Age Factors↗

The surgical management of hyperinsulinism in infancy due to nesidioblastosis.

Severe neonatal hypoglycemia due to nesidioblastosis demands prompt diagnosis and treatment to prevent mental retardation. Early central venous catheter placement is essential for a constant glucose infusion. At surgery, near-total (95%) pancreatectomy is done, starting at the tail and preserving the spleen. Bipolar electrocoagulation is very useful for the tiny vessels. The uncinate process is removed leaving a small amount of pancreas adjacent to the preserved common bile duct. Three patients, diagnosed shortly after birth, had surgery at 34 days, 2 years, and 17 days of life. Two patients developed staphylococcal infections, one of whom exhibited the "scalded baby" syndrome and required reoperation for evisceration. Insulin was required for one to seven days in two and for three months in one. Diazoxide was needed for 18 months in the initial patient, who did not have uncinate resection. All patients are healthy and off medication with a postoperative follow-up period of 11, 12, and 65 months.

Adenoma, Islet Cell↗

Interleukin-11 improves survival and reduces bacterial translocation and bone marrow suppression in burned mice.

PURPOSE: Major burns are associated with a high mortality, an increased rate of bacterial translocation, and bone marrow suppression. This study evaluates the effect of interleukin-11 (IL-11), a bone marrow-derived growth factor on survival, intestinal cytoarchitecture, bacterial translocation, and bone marrow suppression in a highly lethal murine burn model with a lethal dose greater than 50. METHODS: C3H/HeJ 8 to 10-week-old mice underwent a standardized 32% total body surface area (TBSA) scald burn using a burn template. Mice were divided equally between groups receiving IL-11 (125 micrograms/kg, twice daily, subcutaneously [SC]) and 0.1% same-volume Bovine Serum Albumin (BSA) (0.2 mL, twice daily, sc). Animals were evaluated for mesenteric lymph node bacterial counts, intestinal mucosal villus height, number of mucosal crypt cell mitoses per 100 crypts, and peripheral platelet and total lymphocyte counts. Survival was calculated to 7 days postburn. RESULTS: At 24 hours postburn, IL-11-treated mice had significantly less enteric bacteria cultured from mesenteric lymph nodes (P < .001), increased intestinal crypt cell mitoses (P = .002) and intestinal villus height (P = .002), increased peripheral platelet (P = .002) and lymphocyte counts (P = .004), and an improved survival compared with BSA controls (P = .003). CONCLUSION: These data show that IL-11 improves survival, intestinal cytoarchitecture, reduces bacterial translocation, and reduces bone marrow suppression after a 32% TBSA burn in mice. These data imply that IL-11 cytokine therapy may be a useful adjunct in extensive burn injury.

Animals↗

Burns to the genitalia and the perineum.

PURPOSE: We conducted a study to determine the treatment of perineal and genital burns, the results of therapy and the complications of such burns. MATERIALS AND METHODS: A review of the records of 4,216 patients treated between 1981 and 1995 at the Burn Center of the Academic Surgical Center Stuivenberg, revealed 87 male and 30 female patients, 6 months to 86 years old who had associated burns to the perineum or genitalia. Mean burn size was 21% of the total body surface area. Causes of burn injury were scald in 55% of the cases, flame in 24%, chemical in 16% and others in 4%. RESULTS: There were 16 deaths in this group (13.6%) but none was related to the perineal or genital burns. Of the 101 survivors 41% required Foley catheters but the catheters were indwelling during resuscitation only (range 1 to 99 days). Perineal and genital burns were treated by topical antimicrobials. Only 10 patients (9.9%) required split-thickness skin grafts. As late complication 2 patients had scar formation of the penile shaft, which was treated with multiple Z-plasties, and of the prepuce, which was treated by circumcision, respectively. In 1 patient, who presented with erectile dysfunction diagnostic evaluation was negative. CONCLUSIONS: Conservative management of perineal and genital burns is recommended.

Adolescent↗

Melatonin prevents oxidative kidney damage in a rat model of thermal injury.

Animal models of thermal trauma implicate oxygen radicals as causative agents in local wound response and distant organ injury following burn. This study was designed to determine the effect of melatonin treatment on levels of glutathione (GSH), malondialdehyde (MDA), protein oxidation (PO) and myeloperoxidase (MPO) activity in the kidney tissues of rats with thermal injury. Under ether anaesthesia, shaved dorsum of the rats was exposed to 90 degrees C bath for 10 s to induce burn injury. Rats were decapitated either 3 h or 24 h after burn injury. Melatonin was administered i.p. immediately after burn injury. In the 24-h burn group melatonin injections were repeated for two more occasions. In the sham group the same protocol was applied except that the dorsum was dipped in a 25 degrees C water bath for 10 s. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, and significant increases in MDA and PO levels, and MPO activity at post-burn 3 and 24 hours. Treatment of rats with melatonin (10 mg/kg) significantly elevated the reduced GSH levels while it decreased MDA and PO levels as well as MPO activity.

Animals↗

Protective effect of aqueous garlic extract against oxidative organ damage in a rat model of thermal injury.

Oxygen free radicals have been implicated in mediating various pathological processes including burn-induced organ damage. This study was designed to determine the possible protective effect of aqueous garlic extract against oxidative organ damage distant from the original burn wound. Under ether anaesthesia, rats were subjected to severe skin scald injury covering 30% of total body surface area. Rats were decapitated either 2 h or 24 h after burn injury. Aqueous garlic extract (1 ml/kg) was administered i.p. immediately after burn injury. In the 24-h burn group injection was repeated once more (at 12 hour) following the burn injury. Liver, intestine and lung tissues were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and protein oxidation (PO). Burn injury caused a significant decrease in GSH level, and significant increases in MDA and PO levels, and MPO activity at post-burn 2 and 24 hours. Since garlic extract reversed these oxidant responses it seems likely that garlic extract protects tissues against oxidative damage.

Animals↗

Interleukin-6 production after thermal injury: evidence for nonmacrophage sources in the lung and liver.

BACKGROUND: Thermal injury induces circulating levels of interleukin-6 (IL-6). The liver and lung have been proposed as major sources of IL-6 after injury; however, multiple cell types within these organs are capable of IL-6 production. In these experiments we further characterize cellular sources of IL-6 after thermal injury by examining tissue macrophage response in the liver and lung and IL-6 production of cultured pulmonary microvascular endothelial cells (PMECs). METHODS: Serum, liver and lung tissue, and tissue macrophage IL-6 response was determined in Wistar rats subjected to a 35 to 40% total body surface area scald injury. Cultured PMEC IL-6 production was determined after treatment with serum from the burned animals. IL-6 bioactivity was assayed by 7TD1 proliferation, and IL-6 messenger RNA levels were determined by reverse transcriptase-polymerase chain reaction. Alveolar macrophages were obtained by bronchoalveolar lavage. Kupffer cells and PMECs were obtained by enzyme digestion of liver and lungs. RESULTS: Burn increases circulating IL-6 activity through postburn day 3 (388 +/- 50 units/0.1 ml versus 80 +/- 12 units/0.1 ml in controls). Burn increases lung and liver IL-6 messenger RNA without concurrent increase in the alveolar macrophages or Kupffer cells and persists in the lung after bronchoalveolar lavage. PMECs cultured in the presence of postburn day 3 serum (10% vol) release more IL-6 activity (1118 +/- 333 units/culture versus sham rat serum with 288 +/- 146 units/culture) than control cultures and have more readily detectable levels of IL-6 messenger RNA. CONCLUSIONS: Non-tissue macrophage sources including microvascular endothelium may be a contributing source of IL-6 in the lung after thermal injury.

Animals↗

Regulation of the acute phase response genes alpha 1-acid glycoprotein and alpha 1-antitrypsin correlates with sensitivity to thermal injury.

BACKGROUND: The response to thermal injury is a complex physiologic process requiring communication between sites of injury and distal target organs. The liver, one of these target organs, synthesizes a family of secretory proteins, the acute phase reactants (APRs), that carries out specific protective functions. This study investigates the response of positively regulated (alpha 1-acid glycoprotein and alpha 1-antitrypsin) and negatively regulated (albumin) APR genes to severe thermal injury in three rat strains with differing abilities to survive thermal stress. METHODS: Age and weight matched male Buffalo, Sprague-Dawley, and Fischer 344, 12- to 16-week-old rats (275 to 325 gm) received a 40% total body surface area scald burn. Total RNA was isolated from livers at 0, 2, 5, 12, 24, and 48 hours. Northern blot hybridization was performed with 32P-labeled rat alpha 1-glycoprotein, rat albumin, and mouse alpha 1-antitrypsin cDNAs. Relative amounts of alpha 1-glycoprotein, alpha 1-antitrypsin, and albumin mRNAs were determined by means of densitometric analyses. RESULTS: All three strains elicit both a positive and negative acute phase (AP) response. Significant differences were observed in the degree and kinetics between strains. Those more sensitive to thermal injury exhibited a more intense positive AP response and possibly a delayed recovery. The AP response between these strains correlates with the variation in ability to survive severe trauma. CONCLUSIONS: The differences in the kinetics and intensity of induction of APR genes between Buffalo, Sprague-Dawley, and Fischer rat strains suggest that the least intense AP response and its timely recovery correlated with the ability to survive a severe thermal injury and that, conversely, the more intense and prolonged response correlated with sensitivity to severe thermal injury. We propose that this may be a basis for variation in survival to thermal injury.

Animals↗

Interleukin-12 treatment restores normal resistance to bacterial challenge after burn injury.

BACKGROUND: Preliminary studies in this laboratory have shown that treatment with interleukin-12 (IL-12), a cytokine that induces expression of the T-helper-1 lymphocyte phenotype, in an animal model of burn injury increased survival after a septic challenge. The purpose of this study was to define the efficacy of IL-12 therapy and to explore its mechanism of action. METHODS: Adult male A/J mice were subjected to 25% full-thickness scald or sham burn. Starting on day 3 after burn, groups of mice received five daily injections of IL-12, interferon-gamma (IFN-gamma), or saline solution. Some animals received anti-IFN-gamma monoclonal antibody. At day 10 most animals underwent cecal ligation and puncture (CLP) and were observed for survival. Some animals were killed at day 10, and CD4-enriched splenocytes were stimulated with anti-CD3 antibody or concanavalin A and were studied for cytokine production and mRNA expression. RESULTS: IL-12 treatment, 25 ng daily for 5 days, increased survival of the burn group after CLP to that of the sham burn control group. Anti-IFN-gamma antibody, 500 micrograms, administered 1 day before IL-12 treatment, reduced the efficacy of IL-12. IFN-gamma treatment, 7000 units, moderately increased survival. IL-12 had no effect on survival of the sham burn group. At the time of CLP IL-12 therapy had induced a marked decrease in CD4+ lymphocyte IL-4 and a moderate increase in IFN-gamma production and mRNA expression without affecting IL-2. CONCLUSIONS: IL-12 is the most effective therapy so far tested in this burn plus CLP model. It acts at least in part through IFN-gamma. However, IFN-gamma therapy was not as effective as IL-12.

Animals↗

Anti-interleukin-10 antibody restores burn-induced defects in T-cell function.

BACKGROUND: Studies have shown that susceptibility to sepsis after severe injury correlated with reduced production of T-helper 1 (Th1) cytokines (interleukin-2 [IL-2] and interferon-gamma [IFN-gamma]) and a persistence of T-helper 2 (Th2) cytokines (IL-4 and IL-10). The mechanisms responsible for this effect are not clear. We used a T-dependent antigen to study both the effect of burn injury on antigen-specific Th functions in vivo and the effect of anti-IL-10 antibody on these functions. METHODS: Male A/J mice were anesthetized and given a 25% scald burn or a sham burn. On day 0 all mice were immunized with 100 micrograms trinitrobenzene sulfonic acid (TNP) haptenated ovalbumin (TNP-OVA) in complete Freund's adjuvant. Mice (10 per group) were given 250 micrograms monoclonal rat antimurine IL-10 antibody (anti-IL-10 MAB) or control rat immunoglobin G (IgG) on day 0 and 100 micrograms anti-IL-10 MAB or IgG on day 2. On day 10 the mice were killed to obtain serum and spleen cells. TNP-specific serum antibody isotype titers were determined by enzyme-linked immunosorbent assay (ELISA). Splenocyte proliferation and cytokine-production in response to TNP-OVA or to anti-CD3 MAB were determined by tritiated thymidine incorporation and by ELISA, respectively. RESULTS: Burn injury resulted in depressed levels of the TNP-specific IgG2a antibody isotype (Th1 dependent), whereas TNP-specific IgG1 and IgE (Th2 dependent) levels were not decreased in burn versus sham burn mice. Anti-IL-10 MAB but not IgG restored the IgG2a response. Burn injury also resulted in reduced TNP-OVA-specific proliferation of splenocytes, whereas anti-CD3 proliferation was equivalent in burn and sham mice. TNP-OVA-specific IL-2 and IFN-gamma production were significantly reduced by burn injury. Anti-IL-10 MAB restored TNP-OVA-specific proliferation and antigen-specific IL-2 and interferon-gamma production by splenocytes from burn mice. CONCLUSIONS: Burn injury induces the loss of antigen-specific Th1 cell function, and IL-10 acts as a trigger to down-regulate Th1 activity after injury.

Animals↗