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Biomedical subjects

E Seifter

Publications and source records attributed to E Seifter.

At least 55 records · Page 3Linked to original sources
PubMed1981

Impaired wound healing in streptozotocin diabetes. Prevention by supplemental vitamin A.

Goodson and Hunt showed that wound healing is impaired in streptozotocin (Sz) diabetic rats; we speculated that this impairment results from defective early inflammatory responses to wounding. Because we had shown that supplemental vitamin A stimulates the early inflammatory response to wounding in nondiabetic rats, we studied the effect of supplemental vitamin A on wound healing in rats with Sz-induced diabetes. Male Sprague-Dawley rats were fed a commercial rat chow containing twice the amount of vitamin A recommended by the NRC for healthy rats. The rats ate and drank (tap water) ad libitum. Two-thirds of the rats were injected (intravenously) with Sz 60 mg/kg body weight. All of these rats became diabetic (hyperglycemia greater than 350 mg/dl, hyperphagic, polydipsic, polyuric, glycosuric greater than 2%). Seven days later, half of the Sz-injected rats were continued on the chow (Group 2) while the other half (Group 3) were switched to the chow supplemented with 150,000 units of vitamin A/kg chow. The next day, all were wounded (7 cm skin incisions and s.c. polyvinyl alcohol sponge implants). Similarly wounded saline injected nondiabetic rats ingesting the unsupplemented chow served as controls (Group 1). The wounds of Group 2 rats healed poorly compared to Group 1 (breaking strength of skin incisions, 308 +/- 19 g vs 584 +/- 23 g, p less than 0.001; hydroxyproline of the sponge reparative tissue, 0.87 mg vs 2.40 mg/100 mg sponge p less than 0.001). Supplemental vitamin A (Group 3) did not affect the hyperglycemia, hyperphagia, polydipsia or glycosuria, but increased the breaking strengths of the incisions of the diabetic rats (468 +/- 40 g, p less than 0.001), and the sponge hydroxyproline (2.38 mg/100 mg sponge, p less than 0.001). In another experiment, in which the wounding and start of supplemental vitamin A were delayed until 28 days after streptozotocin administration (50 mg/kg body weight), similar results were obtained. Streptozotocin diabetes also caused a decrease in the cross-linking of reparative collagen as judged by the ratio of breaking strengths of skin incisions before and after formalin fixation. Supplemental vitamin A did not influence this defect. Sz also caused peripheral lymphocytopenia, adrenal hypertrophy and thymic involution which responded to the supplemental vitamin A. Based upon experimental data and theoretical considerations we conclude Sz diabetes causes two defects in wound healing: a) quantitatively (reduction in reparative collagen accumulation) and b) qualitative reduction in the degree of cross-linking of reparative wound collagen. The action of supplemental vitamin A in correcting the impaired wound healing, adrenal enlargement, thymic involution and lymphocytopenia of Sz-diabetic rats is independent of an effect on their disturbed carbohydrate metabolism.

Animals↗
PubMed1981

Burn sepsis: bacterial interference with Pseudomonas aeruginosa.

The pathogenicity of several strains of Pseudomonas aeruginosa for burned rats (3 degrees scald burns, 20% body surface) following topical application of the bacteria to the burn within 1 hour after burning was established. Following this, it was demonstrated that purposeful infection of such 3 degrees scald burns of rats by a strain of Ps. aeruginosa of low virulence (JB-77) protects the rats from the lethal effect of subsequent (48-hour) topical contamination of the burn by a highly virulent strain of Ps. aeruginosa (VA-134) (p less than 0.001). This finding was confirmed in a similar experiment beginning with germfree rats. When the challenge with the highly virulent Ps. aeruginosa strain was 24 hours (rather than 48 hours) after the burning and topical contamination of the burn with the low virulence strain of Ps. aeruginosa, there was little protection (p N.S.). When burned rats were given the low virulence strain of Ps. aeruginosa by gavage right after burning, there was not protection to subsequent (48 hours) challenge by topical application of the highly virulent strain of Ps. aeruginosa to the burn (11/12 vs 12/12 dying). Our finding that purposeful infection of a 3 degrees burn of rats (conventional and also germfree) by a strain of Ps. aeruginosa of low virulence protects from the lethal effect of subsequent (48-hour) topical contamination of the burn by a highly virulent strain of Ps. aeruginosa is due, we believe, to direct bacterial interference between the two strains of pseudomonas.

Animals↗
PubMed1981

Chemical debridement of burns: mercaptans.

Experiments were conducted using non-enzymatic chemical agents (with emphasis on certain mercaptans), alone, in conjunction with enzymatic agents and/or other nonenzymatic chemicals for debridement of burns. Both in vitro (rats, pigs, humans) and in vivo (rats, pigs) tests were carried out. N-acetylcysteine, penicillamine and cysteine ethyl ester in low to moderate concentrations accelerate the debriding action of bromelain (an enzymatic preparation from pineapple stems) and in higher concentrations, N-acetylcysteine and penicillamine (cysteine ethyl ester was not tested) cause ready separation of the burn eschar from the underlying tissue before solubilization of the eschar is complete (rat) or has occurred (pig). Debridement of 3 degree burns of rats is complete within 4-6 hours; the take of immediately applied syngeneic skin grafts is complete and permanent. This is first time rapid debridement of 3 degree burns permitting immediate successful skin grafting has been accomplished with known defined chemicals. In pigs there is softening of the 3 degree burn eschar by N-acetylcysteine but little, if any, dissolution of the eschar. However, mechanical separation of the eschar from the underlying tissue is accomplished readily with a wooden throat stick with no bleeding. There is a change in color of the superficial layer of the underlying subcutaneous tissue from yellow-light brown to dark brown-black. The debrided areas begin to granulate promptly. The healing of deep dermal burns of pigs is hastened by the application of N-acetylcysteine for a day (beginning 24 hours after burning) while the healing of moderately deep dermal burns is not modified. Unburned skin is not damaged. There is no apparent systemic toxicity associated with the use of N-acetylcysteine for debridement of 10-15% b.s.a. 3 degree burns of rats or 15-20% b.s.a. 3 degree burns of pigs. Major emphasis has been on N-acetylcysteine because of the potential adverse secondary effect of penicillamine and cysteine ethyl ester; N-acetylcysteine is readily metabolized. The use of a keratolytic agent prior to the application of N-acetylcysteine hastens the latter's action. Sulfamylon and sulfadiazine can be used with N-acetylcysteine without interfering with its debriding action. The effects of the mercaptans are likely due largely to their ability to depolymerize connective tissue proteoglycans and proteins, especially at the interface between living and dead tissue.

Acetylcysteine↗
PubMed1981

Granulopoiesis associated with the C3HBA tumor in mice.

Female C3H/HeJ mice were inoculated with syngeneic breast adenocarcinoma cells (C3HBA). A progressive neutrophilia developed as the tumors grew. A linear relationship was demonstrated between the tumor diameter and the extent of the neutrophilia. Local tumor excision caused a rapid fall (3 days) in the neutrophil count. Media conditioned with tumor cells, normal mouse kidney, and bone marrow of normal or tumor-bearing mice were prepared. Tumor cell-conditioned medium was found to have marked stimulating activity for granulocytic colony formation of mouse bone marrow cells. Sera from tumor-bearing mice also had colony-stimulating activity. This finding strongly suggested that the neutrophilia was caused by the release of a neutrophil-stimulating factor from the tumor.

Adenocarcinoma↗
PubMed1978

White cell involvement in the inflammatory, wound healing, and immune actions of vitamin A.

Stress or injury-induced phenomena, such as impaired wound healing and immune depression, may be related to impaired function of certain leukocyte populations. Since vitamin A prevents some aspects of stress, we studied its effect on various white cell populations in normal and injured rats. Supplemental vitamin A (150,000 IU/kg chow) to normal rats resulted in marked increases in thymic weight and lymphocytes without any effct on adrenal weight. The basal chow contains 13,700 IU vitamin A per kg. In rats subjected to moderately severe injury (dorsal wounding or unilateral femoral fracture), supplemental vitamin A greatly diminished the thymic involution observed in chow-fed controls and delayed or minimized the accompanying adrenal hypertrophy. In uninjured rats, supplemental vitamin A induced in three to four days a temporary circulatory leukocytosis characterized by lymhocytosis, monocytosis, and a relative neutropenia. These changes in the blood picture persisted one day after femoral fracture. On the second and third day postfracture the lymphocyte and neutrophil values returned to normal while the monocytosis persisted. Polyvinyl alcohol sponges implanted next to the fracture site demonstrated that supplemental vitamin A consistently increased the number of white blood cells migrating into the wound area and showed significantly larger numbers of monocytes/macrophages. These data suggest that vitamin A influences the numbers and nature of white cells involved in immune, inflammatory, and wound healing processes. In addition to the known antiglucocorticoid activity of vitamin A, these effects may represent a direct beneficial action of dietary vitamin A supplements for stressed and injured animals.

Adrenal Glands↗
PubMed1978

Arginine: an essential amino acid for injured rats.

The influence of arginine supplements on growth and healing of skin incisional wounds was studied in rats fed either a chemically defined diet lacking arginine or a laboratory chow containing 1.8% arginine. Rats fed the arginine-free diet grew more poorly than did arginine-supplemented rats (1.8 vs. 7.0 gm/day) in the preoperative period. After operation arginine-deficient animals grew very poorly (1 gm/day), while arginine-supplemented rats gained 4.3 gm/day. Arginine-deficient animals showed impaired wound healing, as judged by the breaking strengths of their incisions 10 days after wounding (228 vs. 293 gm for the arginine-supplemented rats). Arginine-deficient rats also showed decreased collagen deposition in a specific wound site, as indicated by the decreased content in hydroxyproline in sponge granulomas (2.5 vs. 4.2 mg/100 mg. of sponge for the arginine-supplemented rats). In rats fed commercial chow, 1% arginine decreased the postoperative weight loss associated with injury (0.7 vs. 5.2 gm) in one experiment and improved wound strength in two experiments (312 vs. 188 gm in one experiment and 309 vs. 246 gm in another). Arginine also increased hydroxyproline deposition in a specific wound area (5.5 vs. 4.1 mg in one experiment and 3.1 vs. 1.9 mg. in another). It is concluded that arginine has two roles in wounded animals. It is essential for the synthesis of the increased amounts of reparative collagen required for wound healing, and it decreases some of the negative aspects of the metabolic responses to injury. These are thought to be associated with an arginine-induced growth hormone release.

Animals↗
PubMed1977

Effects of enviromental temperature and femoral fracture on wound healing in rats.

Femoral fracture, unilateral and bilateral, impaired the healing of dorsal skin incisions and formation of reparative granulation tissue in subcutaneously implanted polyvinyl alcohol sponges judged histologically and by breaking strengths and hydroxyproline contents, respectively, 1 week after injury in pair-fed rats kept at 22 degrees C. When rats were transferred to a room at 30 degrees C immediately after skin incision and sponge implants, with or without unilateral fracture, no differences in healing were observed between the two groups. Rats with skin incision, sponge implants, and either femoral fracture or sham-fracture excreted more urinary nitrogen than preoperatively when kept at 22 degrees. Counterpart groups transferred to a 30 degrees room right after operation excreted less urinary nitrogen than preoperatively, but because of lower food intakes postoperatively, the ratio of urinary nitrogen to food intake nitrogen was increased. With equivalent food intakes, pair-fed rats with fracture kept at 22 degrees postoperatively lost more weight and excreted more nitrogen than corresponding rats transfered to a 30 degrees room.

Animals↗
PubMed1977

Lipid metabolism in regressing rat corpora lutea of pregnancy.

Lipid accumulation is a hallmark of corpus luteum regression and we characterized lipids stored in rat corpora lutea of pregnancy between days 21 and 24 post coitum, the period of luteolysis. A 10-fold rise in lutein triglyceride concentrations occurred between days 21 and 24, which represented the major alteration in luteal lipid metabolism during luteolysis, coinciding with the appearance of numerous lipid droplets in the luteal cells. The fatty acid composition of luteal triglycerides was altered between days 20 and 23 in a pattern consistent with the influx of blood triglyceride fatty acids. No evidence for increased de novo fatty acid synthesis by luteal tissue between days 21 and 24 post coitum was obtained using in vitro methods. [14C]Acetate incorporation into lipids declined between days 16 and 24 and label was preferentially introduced into long chain polyunsaturated fatty acids. Rates of tritium incorporation into fatty acids from tritiated water were relatively low. [14C]Glucose was predominantly incorporated into the glycerol moiety of luteal lipids and incorporation of label into this fraction was augmented between days 21 and 23 post coitum. The incorporation of [14C]palmitate into triglycerides of luteal tissue during in vitro incubation also increased between days 21 and 23. In vitro lactate production, [14C]glucose oxidation, and [14C-palmitate oxidation to 14CO2 increased significantly during this time. We conclude that specific biochemical alterations occur in regressing corpora facilitating uptake and storage of blood glyceride fatty acids as triglycerides. The physiological significance of this triglyceride accumulation remains to be elucidated.

Acetates↗