Life Extension Blood Test Super Sale

Abstracts
















WOUND HEALING
(SURGICAL WOUNDS, TRAUMA, BURNS)
(Page 4)


Printing? Use This!
Table of Contents

bar

book Aloe vera (gel) cream as a topical treatment for outpatient burns
book Necrolytic migratory erythema and zinc deficiency
book Sepsis impairs anastomotic collagen gene expression and synthesis: A possible role for nitric oxide
book Regionally different vascular response to vasoactive substances in the remodelled infarcted rat heart; Aberrant vasculature in the infarct scar
book Wound healing: The role of the mast cell as a zinc carrier
book Modulation of tendon healing by nitric oxide
book Acute protein-calorie malnutrition impairs wound healing: A possible role of decreased wound nitric oxide synthesis
book Interaction between the insulin-like growth factor family and the integrin receptor family in tissue repair processes: Evidence in a rabbit
book Dietary L-arginine in renal disease
book Serum protein and zinc levels in patients with thoracic empyema
book Arginine-enriched diets: Rationale for use and experimental data
book Protection by zinc against UVA- and UVB-induced cellular and genomic damage in vivo and in vitro
book Nutrition and wound healing
book Effect of the hydroxyl radical on fibroblast-mediated collagen remodelling in vitro
book Prevention of the inhibitory effect of intraperitoneal 5-FU on intestinal anastomosis by zinc
book Nutritional pharmacology and malignant disease: A therapeutic modality in patients with cancer
book Essential microminerals and their response to burn injury
book Effects of an arginine-glycine-aspartic acid peptide-containing artificial matrix on epithelial migration in vitro and experimental second-degree burn wound healing in vivo
book Spontaneously increased production of nitric oxide and aberrant expression of the inducible nitric oxide synthase in vivo in the transforming growth factor beta1 null mouse
book The management of lower-extremity ulcers with zinc-saline wet dressings versus normal saline wet dressings
book Glutamine homologues and derivatives: A limiting factor in current artificial nutrition?
book Nitric oxide is necessary for a switch from stationary to locomoting phenotype in epithelial cells
book The effect of an arginine-glycine-aspartic acid peptide and hyaluronate synthetic matrix on epithelialization of meshed skin graft interstices
book Nutritional intake and status of clients in the home with open surgical wounds.
book High-dose Vitamin-C therapy for extensive deep dermal burns.


bar



Aloe vera (gel) cream as a topical treatment for outpatient burns

Heck E.; Head M.; Nowak D.; et al.
Dept. Surg., Univ. Texas Hlth Sci. Cent., Dallas, Tex. USA
Burns (England), 1981, 7/4 (291-294)

The objectives in the use of topical agents in burn therapy are bacterial control and relief of pain. In this study a commonly discussed 'home remedy' now commercially available is compared with a widely used prescription agent in the control of bacterial flora in outpatient burn wounds. Additionally, the study examines healing times in the two groups for any demonstrated effect.



Necrolytic migratory erythema and zinc deficiency

Sinclair S. A.; Reynolds N.J.
N.J. Reynolds, Department of Dermatology, Royal Victoria Infirmacy, Queen Victoria Road, Newcastle upon Tyne NE1 4LP United Kingdom
British Journal of Dermatology (United Kingdom), 1997, 136/5 (783-785)

Necrolytic migratory erythema (NME) is an uncommon condition classically associated with high plasma levels of circulating glucagon and a glucagonoma. We report a patient with cirrhosis who showed clinical and histological features of NME. Investigation revealed normal glucagon levels without evidence of glc supplementation resulted in rapid and complete resolution of the eruption.



Sepsis impairs anastomotic collagen gene expression and synthesis: A possible role for nitric oxide

Thornton F.J.; Ahrendt G.M.; Schaffer M.R.; Tantry U.S.; Barbul A.
Dr. A. Barbul, Department of Surgery, Sinai Hospital of Baltimore, 2401 W. Belvedere Ave., Baltimore, MD 21215 USA
Journal of Surgical Research (USA), 1997, 69/1 (81-86)

Although intra-abdominal sepsis is known to impair colon healing by inhibiting anastomotic collagen synthesis, the effect of systemic sepsis on this process is unknown. Endotoxins and cytokines associated with sepsis induce nitric oxide synthesis both systemically and locally within colonic tissue. We hypothesized that systemic sepsis impairs colonic healing and examined a possible correlation with nitric oxide expression. Male Sprague- Dawley rats received intraperitoneal injections of either saline (sham group) or Escherichia coli endotoxin (lipopolysaccharide 1 mg/100 g body weight) at Times - 24 and - 12 hr (LPS group). All animals underwent laparotomy and left colonic anastomosis at Time 0. At 24 and 96 hr postlaparotomy rats were sacrificed, the anastomoses excised, and (3H)-proline incorporation into protein measured as an index of total new protein synthesis (TNP). Digestion with purified collagenase yielded incorporation into the collagen fraction (CDP). Additional sham and LPS-treated rats were sacrificed at 24, 72, and 120 hr, the anastomoses excised, and nitric oxide synthase activity in the tissue measured by the conversion of (3H)-arginine to (3H)citrulline in an ex vivo culture system. Finally, sham and LPS rats were sacrificed at 120 hr for measurement of colon anastomotic bursting pressure. Systemic sepsis significantly impaired new collagen synthesis in anamotic tissue at 24 hr compared to control samples (P < 0.02). No difference was noted at 96 hr. TNP synthesis was similar in both groups at 24 or 96 hr. Northern blot analysis confirmed a significant decrease in Type I and Type III collagen mRNA expression at 24 hr in septic rats. Anastomotic bursting pressure was also decreased in the septic group (P < 0.003). Sepsis elevated nitric oxide synthase activity in anastomotic tissue 24 hr postanastomosis, when compared to sham tissue (P < 0.0001). These data suggest that systemic endotoxin induces nitric oxide synthesis at the anastomotic site. The simultaneous dysregulation of collagen gene expression and synthesis with decreased anastomotic strength suggests a possible regulatory role for nitric oxide in gastrointestinal healing.



Regionally different vascular response to vasoactive substances in the remodelled infarcted rat heart; Aberrant vasculature in the infarct scar

Kalkman E.A.J.; Van Haren P.; Saxena P.R.; Schoemaker R.G.
R.G. Schoemaker, Department of Pharmacology, Faculty Medicine and Health Sciences, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam Netherlands
Journal of Molecular and Cellular Cardiology (United Kingdom), 1997, 29/5 (1487-1497)

Remodelling after myocardial infarction (MI) is associated with vascular adaption, increasing vascular capacity of non-infarcted myocardium, and angiogenesis in the infarcted part during wound healing and scarring. We investigated regional vascular reactivity in the infarcted rat heart. Transmural infarction of the left ventricular free wall was induced by coronary artery ligation. After 3 weeks, regional flow during maximal vasodilation (nitroprusside, NPR) and submaximal vasoconstriction (arginine-vasopressin, AVP) were studied in buffer-perfused hearts. The main findings were

(1) a reduced vasodilator response (NPR) in the viable part of the left ventricular free wall, where hypertrophy was most pronounced, resulting in reduced maximal tissue perfusion of the myocardium bordering the scar (19.7 plus or minus 0.6 v 25.7 plus or minus 1.2 ml/min.g), whereas peted regions was preserved.

(2) A 54% lower vasodilator response (NPR) and a 25% stronger vasoconstriction (AVP) in scar tissue compared to viable parts of MI hearts. Microscopy showed thicker walls of resistance arteries in scar tissue than in viable parts of MI hearts or in sham hearts, morphometrically substantiated by two- to three-fold greater wall/lumen ratios. These data indicate a deviant response of scar vessels of MI hearts, and in the non-infarcted part, a reduced coronary reserve in the most hypertrophied region. Whereas the former may be caused by different vessel structure, the reduced vasodilator reserve of the spared part of the left ventricular free wall may indicate vasodilation at rest due to insufficient vascular growth. Thus, the most hypertrophied region would be at the highest risk of further ischemic damage.



Wound healing: The role of the mast cell as a zinc carrier

Hardjowasito W.; Basuki A.
Dr. W. Hardjowasito, Department of Surgery, Saiful Anwar General Hospital, Medical Faculty Brawijaya University, Jln JA Suprapto 2, Malang 65111 Indonesia
Asian Journal of Surgery (Hongkong), 1997, 20/1 (42-46)

The role of mast cells in wound healing in a racial group of Proto Malay people living in Timor, Indonesia was studied. The relationship between fine scar formation after cleft lip reconstruction surgery, the growing evidence of micronutrient zinc deficiency in the region and an unusual number of mast cells distributed in the skin compared with a racial group of Deutero Malay people living in Malang, East Java, Indonesia was explored. It has been suggested that a possible role of mast cells, in a zinc deficient area, is that they accumulate zinc to compensate for the deficiency and to provide the necessary amount for better wound healing. Further investigations are still under way to give a more sound understanding of mast cells as zinc carriers.



Modulation of tendon healing by nitric oxide

Murrell G.A.C.; Szabo C.; Hannafin J.A.; Jang D.; Dolan M.M.; Deng X.-H.; Murrell D.F.; Warren R.F.
Australia
Inflammation Research (Switzerland), 1997, 46/1 (19-27)

Nitric oxide (NO.) is a small, diffusible free radical that is generated from L-arginine by a family of enzymes, collectively termed the nitric oxide synthases. We investigated the role of NO. in tendon healing. NO. synthase activity and immunoreactivity was absent in un-injured rat Achilles tendon. After surgical division there was a five-fold increase in NO. synthase activity and immunoreactivity within the healing tendon at day 7, with a return to near baseline levels at day 14. Inhibition of NO. synthase activity with oral administration of Nomega-nitro-L-arginine methyl ester (L-NAME) resulted in a significant reduction in cross-sectional area (30% at day 7, p < 0.01, 50% at day 15, p < 0.001) and failure load (24% at day 7, p < 0.01) of the healing Achilles tendon constructs. Rats fed the same regimen of the enantiomer of L-NAME, (D-NAME) had normal tendon healing. These results indicate that nitric oxide synthase is induced during tendon healing and inhibition of nitric oxide synthase inhibits this tendon healing.



Acute protein-calorie malnutrition impairs wound healing: A possible role of decreased wound nitric oxide synthesis

Schaffer M.R.; Tantry U.; Ahrendt G.M.; Wasserkrug H.L.; Barbul A.
USA
Journal of the American College of Surgeons (USA), 1997, 184/1 (37-43)

BACKGROUND: Nitric oxide is synthesized in wounds. Systemic inhibition of wound nitric oxide synthesis decreases wound collagen accumulation and wound mechanical strength. The role of nitric oxide during impaired healing is not known. In a model of impaired wound healing induced by acute protein- calorie malnutrition, we correlated wound healing parameters with wound nitric oxide synthesis.

STUDY DESIGN: One group of Sprague-Dawley rats was rendered acutely malnourished by restricting its food intake to 50 percent of the food intake of an ad libitum-fed control group. Wound collagen accumulation and types I and III collagen gene expression were measured 10 days postwounding in subcutaneously implanted polyvinyl alcohol sponges. Nitric oxide synthesis was determined in wound fluid and in supernatants of wound cell cultures.

RESULTS: Animals with acute protein-calorie malnutrition lost 10.4plus or minus0.8 percent, while controls gained 17.5plus or minus1.2 percent of their original body weight. Protein-calorie malnutrition reduced sponge hydroxyproline contents (995plus or minus84 compare with 1,580plus or minus109 microg/100 mg sponge, p<.001), indicating diminished wound collagen accumulation. Gene expression of type III, but not type I, collagen was decreased in wounds of protein- calorie malnutrition animals. Nitrite/nitrate and citrulline concentrations in wound fluid (p<.01) and in wound cell supernatants (p<.001) were also lower in protein-calorie malnutrition animals, indicating a net decrease in nitric oxide production.

CONCLUSIONS: Impaired wound collagen accumulation caused by protein-calorie malnutrition may be a reflection of reduced nitric oxide synthesis within the wound.



Interaction between the insulin-like growth factor family and the integrin receptor family in tissue repair processes: Evidence in a rabbit

Galiano R.D.; Zhao L.L.; Clemmons D.R.; Roth S.I.; Lin X.; Mustoe T.A.
USA
Journal of Clinical Investigation (USA), 1996, 98/11 (2462-2468)

We have determined previously that IGF-I is dependent on the presence of IGF binding protein-1 (IGFBP-1) to act as a wound healing agent. We sought to determine the mechanism whereby IGFBP-1 is able to enhance IGF-I bioactivity. As IGFBP-1 binds both the alphleft arrow over right arrowbeta1 integrin as well as IGF-I in vitro, we asked which of the following interactions were important: (a) the ability of IGFBP- 1 to interact with an integrin receptor, and/or (b) the binding of IGF-I by IGFBP-1. We used an IGF-1 analogue (des(1-3)IGF-I) with a > 100-fold reduction in affinity for IGFBP-1 as well as an IGFBP-1 mutant (WGD-IGFBP-1) which does not associate with the alphleft arrow over right arrowbeta1 integrin to selectively abrogate each of these interactions. We also tested the ability of IGFBP-2, a related bies not associate with integrin family members, to enhance IGF-I bioactivity. Full- thickness dermal wounds were created on rabbit ears; various combinations of native IGF-I, native IGFBP-1, native IGFBP-2, and their respective analogues/mutants were applied to each wound. Wounds were harvested 7 d later for analysis. Only native IGF-I in combination with native IGFBP-1 was effective as a wound healing agent, enhancing reepithelialization and granulation tissue deposition by 64plus or minus5 and 83plus or minus12% over controls (P = 0.008 and 0.016, respectively). The same doses of IGF-I/WGD-IGFBP-1, des(1-3)IGF- I/IGFBP-1, and IGF-I/IGFBP-2 were ineffective. We propose that IGF-I physically interacts with IGFBP-1 and that IGFBP-1 also binds to an integrin receptor, most likely the alphleft arrow over right arrowbeta1 integrin. This interaction is unique to IGFBP-1 as the closely related IGFBP-2 had no effect, a finding consistent with its inability to bind to integrin receptors. Our results suggest that activation of both the IGF-I receptor and the alphleft arrow over right arrowbeta1 integrin is required for IGF-I to stimulate wound healing.



Dietary L-arginine in renal disease

Peters H.; Noble N.A.
Division of Nephrology, Univ. of Utah School of Medicine, Salt lake City, UT 84132 USA
Seminars in Nephrology (USA), 1996, 16/6 (567-575)

The amino acid L-arginine is a substrate for at least three products involved extensively in tissue injury and fibrosis. L-arginine is metabolized to L-proline, a major constituent of the collagen that makes up fibrotic extracellular matrix. L-arginine is a precursor for polyamines, which are required for proliferative responses characteristic of many renal diseases. L-arginine is also the sole substrate for generation of nitric oxide (NO) which, produced in large quantities by macrophages, has been implicated in tissue injury. On the other hand, NO produced in small quantities endothelium is a critical vasodilator. Given the importance of elevated intraglomerular pressure in renal injury, it is perhaps not surprising that dietary L-arginine supplementation increases NO generation and is beneficial in reducing intraglomerular pressure and subsequent disease. Other data, based on the therapeutic effects of low protein diets, have suggested that L- arginine restriction limits NO-mediated glomerular injury and greatly reduces matrix accumulation, consistent with the idea that limitation of substrate effectively diminishes injurious NO levels, polyamine synthesis, and collagen production.



Serum protein and zinc levels in patients with thoracic empyema

Balkan M.E.; Ozgunes H.
Department of Thoracic Surgery, Ataturk Chest Dis./Surgical Ctr., 8 06280 Kecioren, Ankara Turkey
Biological Trace Element Research (USA), 1996, 54/2 (105-112)

The element Zn is the metal component or activator of many important enzymes. The tissue concentrations and activities of Zn metalloenzymes direct the rate of protein and nucleic acid syntheses, thereby influencing tissue growth and reparative processes. Most of the serum Zn is normally bound to circulating proteins. Low serum Zn concentrations might result from depletion of Zn-binding proteins. Serum protein and Zn concentrations have been reported to be depressed in patients with acute and chronic diseases. We compare the serum protein and Zn values of patients with thoracic empyema (n = 20) with those of a control group (n = 20). The values obtained in the empyema group were significantly lower than those in the control group before the study. Test group administered 220 mg zinc sulfate (ZnSO4. 7H2O) over 20 d and there was a significant increase in the values for serum protein and Zn after the oral administration of the zinc sulfate.



Arginine-enriched diets: Rationale for use and experimental data

Cynober L.; Vasson M.-P.; Aussel C.
Laboratoire de Biochimie, Biologie Moleculaire et Nutrition, UFR de Pharmacie, 28, place Henri-Dunant, 63001 Clermont-Ferrand Cedex 1 France
Nutrition Clinique et Metabolisme (France), 1996, 10/2 (89-95)

Since the pioneering work of Rose who classified arginine as a non- essential amino acid, subsequent works have revealed that arginine can become an essential amino acid in stress situations. In septic rats, arginine- enriched nutrition (either enteral or parenteral) improves nitrogen balance and total body and liver protein synthesis. In addition, arginine stimulates growth hormone and insulin secretion. The most remarkable action of arginine is certainly that exerted on cellular immunity. This action concerns thymus and extra-thymus areas. Finally, arginine favours wound healing improves host defenses in cancer and slows tumour growth. The pharmacological action of arginine probably depends upon various mechanisms: its action on immunity may be mediated by the synthesis of nitric oxide and polyamines (via ornithine synthesis). The effect on wound healing may be related to proline synthesis. The effects on nitrogen metabolism may be linked to growth hormone secretion. These observations form the rationale for the administration of arginine- enriched diets to injured patients.



Protection by zinc against UVA- and UVB-induced cellular and genomic damage in vivo and in vitro

Record I.R.; Jannes M.; Dreosti I.E.
CSIRO Division of Human Nutrition, Gouger St, Adelaide, SA 5000 Australia
Biological Trace Element Research (USA), 1996, 53/1-3 (19-25)

For many years, zinc salts have been used both topically and orally to treat minor burns and abrasions as well as to enhance wound repair in man and animals. In this study we describe the protective effects of zinc against UV- induced genotoxicity in vitro and against sunburn cell formation in mouse skin in vivo. Cultured skin cells from neonatal mice showed a dramatic increase in the number of micronuclei as a result of UVA and UVB irradiation. Inclusion of zinc at 5 microg/mL in the medium significantly reduced the frequency of micronuclei and of micronucleated cells. In hairless mice, topical application of zinc chloride for 5 consecutive days or a single application 2 h prior to UV exposure reduced the number of sunburn cells in the epidermis as did application of zinc 1 h after exposure. Application 2 h after irradiation also tended to have a protective effect, although there was a large variation between animals. It is proposed that an influx of zinc can protect epidermal cells against some of the more delayed effects of UV-induced damage.



Nutrition and wound healing

Collins C.M.
Care of the Critically Ill (United Kingdom), 1996, 12/3 (87-90)

Nutrition is an important factor in the outcome of clinical conditions, including injury. Although many micronutrients are essential factors in the healing process, there is little clinical proof that deficiency states delay wound healing. However, global nutrition support has been demonstrated to reduce the development of non-wound complications that indirectly prolong wound healing. Specific nutrients may have additional immunomodulatory influences that positively affect wound healing.



Effect of the hydroxyl radical on fibroblast-mediated collagen remodelling in vitro

Arisawa S.; Arisawa T.; Ohashi M.; Nitta Y.; Ikeya T.; Asai J.
Second Dept. of Internal Medicine, Nagoya University School of Medicine, Tsurumacho, Nagoya 466 Japan
Clinical and Experimental Pharmacology and Physiology (Australia), 1996, 23/3 (222-228)

It has been reported that free radicals prevent wound healing. However, the mechanism of this effect is not yet clear. We attempted to clarify the influence of hydroxyl radicals on wound healing in vitro. We used an ascorbate-copper ion system (ACS) to produce hydroxyl radicals in accordance with variables of time elapsed and concentration of copper ion. The effects of hydroxyl radical on fibroblast-mediated collagen remodelling, cell viability, the functions of fibroblasts and collagen fibrils were studied. With a copper ion concentration of 100 micromol/L ACS significantly reduced contraction, while 10 micromol/L stimulated contraction. Hydrogen peroxide (H2O2) was employed in observing these findings. ACS did not influence cell viability, the expression of alpha2beta1 integrin and cellular fibronectin, or the cytoskeletal organization of fibroblasts involving actin until 3 h. A concentration of ACS at 10 micromol/L of copper ion induced the polymerization of collagen after 30 min, while ACS at 100 micromol/L induced collagen degradation, this finding was also established by using H2O2. Collagen reduced the amount of formaldehyde produced by trapping hydroxyl radical with dimethyl sulfoxide. Our findings suggest that collagen is denatured by scavenging the hydroxyl radical before fibroblasts are damaged, so that the radical may influence the remodelling of collagen.



Prevention of the inhibitory effect of intraperitoneal 5-FU on intestinal anastomosis by zinc

Tumer A.R.; Kama N.A.; Muftuoglu S.F.; Dener C.; Tumer L.; Dagdeviren A.
4 Cerrahi Servisi, Ankara Numune Hastanesi, Ankara Turkey
Turkish Journal of Gastroenterology (Turkey), 1996, 7/1 (72-81)

Today adjuvant therapy using early postoperative intraperitoneal chemotherapy, is particularly appropriate treatment to prevent the local and regional recurrence in resectable colon cancers. Intraperitoneal 5-Fluorouracil (5-FU) is the most preferable agent for this purpose. The aim of this study is to determine the effect of Zn against the inhibitory effect of 5-FU on the healing of colonic anastomosis. In 5-FU treated group, average bursting pressure (p:0.048) and hydroxyproline levels were significantly decreased (p:0.015). In only Zn treated group, average bursting pressure was significantly increased (p:0.02) whereas hydroxyproline levels showed no correlation with the control group (p:0.560). In both 5-FU and Zn treated groups average bursting pressure had statistically significant correlation only with the 5-FU treated group (p:0.014). In this group hydroxyproline levels were increased as well (p:0.014). The histological observations showed that 5-FU impaired the healing of colonic anastomosis with the appearance of necrotic tissue at the anastomosis region. However the 5-FU and Zn groups appeared to be nearly completely epithelialized and also the number of fibroblasts were increased while necrotic ti much as in the 5-FU treated group. We conclude that Zn addition modulates healing of colonic anastomosis by counteracting the negative effect of 5-FU.



Nutritional pharmacology and malignant disease: A therapeutic modality in patients with cancer

Heys S.D.; Gough D.B.; Khan L.; Eremin O.
Surgical Nutrition/Metabolism Unit, University of Aberdeen, Medical School Buildings, Foresterhill, Aberdeen AB9 2ZD United Kingdom
British Journal of Surgery (United Kingdom), 1996, 83/5 (608-619)

It is now established that certain nutrients have a significant effect on cellular metabolism and growth, tissue repair and regeneration, and modulation of host defences. So far, however, potential clinical benefits have been difficult to demonstrate. Nevertheless, the use of nutrients in combinations seems to have promise and may be associated with a reduction in infectious complications and length of hospital stay. Nutritional pharmacology in the future may be able to improve tumour response to chemotherapy and may minimize the metabolic effect of cachexia.



Essential microminerals and their response to burn injury

Gamliel Z.; DeBiasse M.A.; Demling R.H.
Journal of Burn Care and Rehabilitation (USA), 1996, 17/3 (264-272)

Certain microminerals, named because of their minute quantities in the body, are essential components for maintaining homeostasis involving, in particular, metabolism, immune defenses, and wound healing. In general, these trace elements are characterized by having multiple roles and by demonstrating deficiency syndromes that are complex and difficult to diagnosis. The response of the microminerals to injury, especially burn injury, is not well defined. The purpose of this article is to describe the known roles of the trace elements and the effect of burn injury on circulating and tissue levels. As will be noted, much less is known regarding the impact of trace elements' changes on the injury process than the role of these elements in the normal state. In addition, the amount of trace elements needed for the stress changes after injury are, for the most part, undefined.



Effects of an arginine-glycine-aspartic acid peptide-containing artificial matrix on epithelial migration in vitro and experimental second-degree burn wound healing in vivo

Mertz P.M.; Davis S.C.; Franzen L.; Uchima F.-D.; Pickett M.P.; Pierschbacher M.D.; Polarek J.W.
Dermatology/Cutaneous Surgery Dept., University of Miami Sch. of Medicine, 1600 NW 10th St., Miami, FL 33136 USA
Journal of Burn Care and Rehabilitation (USA), 1996, 17/3 (199-206)

Cells central to dermal tissue repair such as dermal fibroblasts and keratinocytes interact with arginine-glycine-aspartic acid (RGD)-containing proteins of the extracellular matrix such as fibronectin. It has been shown that synthetic peptides containing this RGD sequence can also support cell attachment and migration in vitro. We therefore set out to test whether the use of these peptides, when formulated as a synthetic RGD-peptide matrix consisting of peptide complexed with hyaluronic acid, would have an effect on the rate of epithelial migration and hounds. Evaluation consisted of measuring the extent of epithelial outgrowth from human dermal explants and the epithelization of experimental second-degree burn wounds in pigs. We show here that the RGD-peptide matrix supports epithelial sheet migration from explants in a dose-dependent manner. In second-degree burn wounds in pigs, wounds treated with daily applications of the RGD peptide matrix under occlusion resurfaced at a significantly faster rate (day 7 = 57% completely epithelized) than wounds treated with hyaluronic acid under occlusion (day 7 = 13% completely epithelized, p < 0.01), occlusion alone (day 7 = 13% completely epithelized, p < 0.01), or air exposed (day 7 = 0% completely epithelized, p < 0.001). Histologic examination showed that wounds treated with the RGD-peptide matrix also had thicker epithelial covering and greater granulation tissue deposition than occluded, air-exposed, and hyaluronate-treated wounds. These data therefore show that the use of RGD-peptide matrix induces faster explant epithelial migration and results in faster healing of experimental second-degree burns.



Spontaneously increased production of nitric oxide and aberrant expression of the inducible nitric oxide synthase in vivo in the transforming growth factor beta1 null mouse

Vodovotz Y.; Geiser A.G.; Chesler L.; Letterio J.J.; Campbell A.; Lucia M.S.; Sporn M.B.; Roberts A.B.
Laboratory of Chemoprevention, National Institutes of Health, Building 41, Bethesda, MD 20892 USA
Journal of Experimental Medicine (USA), 1996, 183/5 (2337-2342)

Transforming growth factor beta1 null mice (TGF-beta1(-/-)) suffer from multifocal inflammation and die by 3-4 wk of age. In these mice, levels of nitric oxide (NO) reaction products in serum are elevated approximately fourfold over levels m controls, peaking at 15-17 d of life. Short-term treatment of TGF-beta1(-/-) mice with N(G)-monomethyl-L-arginine suppressed this elevated production of NO. Expression of inducible NO synthase (iNOS) mRNA and protein is increased in the kidney and heart of TGF-beta1(-/-) mice. These findings demonstrate that TGF-betaerred from mechanistic studies o n the control of iNOS expression by TGF-beta1 in vitro.



The management of lower-extremity ulcers with zinc-saline wet dressings versus normal saline wet dressings

Rittenhouse T.
911 Medical Arts Building, 327 N. Washington Avenue, Scranton, PA 18503 USA
Advances in Therapy (USA), 1996, 13/2 (88-94)

Zinc-saline wet dressings were compared to normal-saline wet dressings for the management of lower extremity ulcers in a pilot study of 28 elderly patients. Although both study groups were comparable at baseline, the data suggest that the use of zinc-saline wet dressings creates a wound environment that is associated with trends toward faster healing and enhanced rates of epithelialization, as well as significantly more efficient wound management than the normal-saline controls. These data are presented in light of the requirement for maintaining a moist, acidic environment within a wound in order to permit the best possible healing and remodeling.



Glutamine homologues and derivatives: A limiting factor in current artificial nutrition?

Pesty F.; Sultan F.
Braun Medical S.A., 204 Avenue du Marechal Juin, 92107 Boulogne Cedex France
Nutrition Clinique et Metabolisme (France), 1996, 10/1 (7-17)

Glutamate, aspartate, arginine and glutamine can represent a third to half of the protein content in food and are the most amino acids rapidly cleared from plasma after IV administration. However, their abundance is limited in artificial nutrition. Along with alpha-ketoglutarate, ornithine, asparagine, oxalo-acetate, they can be defined as glutamine homologues and derivatives (GHD). Chemically, they share the same C4 and C5 carbons skeletons. GHD are biochemically interchangeable, but their synthesis from other substrates is quantitatively very limited and costly in energy. Thus, muscular proteolysis becomes the main source of GHD in the post-operative state. They play an important role in all processes requiring rapid cell division: wound healing, preservation of gut integrity, immune response, and growth in childhood. In addition, they participate in detoxication and neurotransmission in the brain. Experimental and clinical data suggest considering GHD content as a decisive criterion when choosing an amino acid solution for parenteral nutrition and probably also for enteral regimens. In human nutrition, they could be at least as efficient as glutamine, whose presence in parenteral mixtures is precluded by its poor stability. Enhanced supply for GHD can be achieved with glutamine dipeptides or ornithine alpha-ketoglutarate supplementation.



Nitric oxide is necessary for a switch from stationary to locomoting phenotype in epithelial cells

Noiri E.; Peresleni T.; Srivastava N.; Weber P.; Bahou W.F.; Peunova N.; Goligorsky M.S.
Dept. of Medicine, SUNY at Stony Brook, Stony Brook, NY 11794-8152 USA
American Journal of Physiology - Cell Physiology (USA), 1996, 270/3 39-3

The restitution of epithelial integrity is accomplished in part by cell migration. Studying this process, we have found that nitric oxide (NO) release from migrating epithelial BSC-1 cells displayed a biphasic response to the inflicted wounds; an initial transient release of NO is followed by a delayed sustained elevation. Whereas the constitutive endothelial NO synthase (NOS) did not show any spatial or temporal changes associated with wounding, the inducible NOS became expressed 3 h after wounding and showed higher abundance at the edges of epithelial wounds. L-Arginine (L-Arg) or NO-donor, S-nitroso-N-acetyl-DL-penicillamine, exerted motogenic effect in epithelial and endothelial cells. Inhibition of NOS with N(G)-nitro-L-arginine methyl ester (L-NAME) or a selective knockout of inducible NOS with antisense oligodeoxynucleotides reduced the rate of spontaneous or epidermal growth factor (EGF)-induced BSC-1 cell migration. Migrating cells showed the polarized expression of NOS, suggesting a head-to-rear NO gradient. Several growth factors (EGF, insulin-like growth factor I, hepatocyte growth factor, and fibroblast growth factor) were motogenic for BSC-1 cells, but this effect was abrogated by pretreatment with L-NAME. We conclude that endogenous NO production is a prerequisite for BSC-1 cell migration. A vectorial NO release may be essential for the spatially and temporally coordinated reciprocal phenomena that occur at the leading and trailing edge of locomoting epithelial cells. Although the exact mode of NO action remains uncertain, it is conceivable that the production of NO serves as a cellular switch from the stationary to the locomoting epithelial phenotype.



The effect of an arginine-glycine-aspartic acid peptide and hyaluronate synthetic matrix on epithelialization of meshed skin graft interstices

Cooper M.L.; Hansbrough J.F.; Polarek J.W.
FIBROGEN, 772 Lucerne Dr., Sunnyvale, CA 94086 USA
J Burn Care Rehabil 1996 Mar-Apr;17(2):108-16

Keratinocytes and fibroblasts interact with proteins of the extracellular matrix such as fibronectin and vitronectin through RGD (arginine-glycine- aspartic acid) cell-attachment sequences. This study evaluated the ability of a provisional synthetic matrix composed of an RGD peptide and hyaluronic acid to accelerate the epithelialization of the interstices of meshed, human, split-thickness skin when placed on full-thickness wounds of athymic mice. Full-thickness skin defects, sparing the panniculus carnosus, were created on athymic mice and 3:1 meshed, human skin was placed on them. The grafts had four central, isolated interstices, which epithelialized by migration of human keratinocytes. Conditions were either the addition to the wound of the synthetic matrix or a matrix of hyaluronic acid alone. The time to closure of the graft interstices was decreased (p < 0.02) in the wounds treated with the RGD peptide-hyaluronic acid provisional matrix. The resultant epithelium of the closed interstices was significantly thicker 8 days after surgery for the RGD-treated wounds. Basement membrane proteins (laminin and type IV collagen) were also found to be present at the dermoepidermal junction earlier in the RGD-treated wounds. These results imply that use of the RGD peptide conjugate to effect-cell-matrix interactions may have clinical significance in the field of wound healing.



Nutritional intake and status of clients in the home with open surgical wounds.

Stotts NA, Whitney JD
J Community Health Nurs 1990;7(2):77-86

The purpose of this study was to determine (a) whether the nutritional intake of patients at home with wounds healing by secondary intention was adequate to support healing, and (b) the nutritional status of these patients. Nineteen subjects with a mean age of 65.3 years were accrued. Of the 17 subjects for whom nutritional intake data were available, 16 had insufficient caloric intake to support healing and over half had less than the Recommended Daily Allowance (RDA) of protein. Using the RDA as a conservative measure of vitamin and mineral need with injury, Vitamin-C intake was decreased in approximately one third of the subjects, while all but one had decreased zinc intake. Over two thirds of the subjects reported a decrease from their usual weight and all the subjects measured had triceps skin fold (TSF) and mid-arm muscle circumference (MAMC) which were below the first and second Health and Nutrition Examination Surveys (HANES I & II) median. Mean serum albumin of the sample was below normal. The nutritional intake of these patients needs increased attention. Community health nurses (CHNs) need to assess nutritional status and monitor the intake of patients with wounds. Future research needs to address why intake is decreased and test strategies to increase oral intake.



High-dose Vitamin-C therapy for extensive deep dermal burns.

Matsuda T, Tanaka H, Shimazaki S, Matsuda H, Abcarian H, Reyes H, Hanumadass M
Hektoen Institute for Medical Research, Chicago, Illinois.
Burns 1992 Apr;18(2):127-31

We studied the haemodynamic effects of antioxidant therapy with high-dose Vitamin-C administration (170 mg/kg/24 h) in guinea-pigs with 70 per cent body surface area deep dermal burns. The animals were divided into three groups of six animals each. Group 1 was resuscitated with Ringer's lactate solution according to the Parkland formula; group 2 with 25 per cent of the Parkland formula with Vitamin-C; and group 3 with 25 per cent of the Parkland formula without Vitamin-C. There were no significant differences in heart rates or in blood pressures between the groups throughout the 24-h study period. Group 3 showed significantly higher haematocrit values at 3 h postburn and thereafter as compared with those of group 2. The cardiac output values of group 2 were significantly higher than those of group 3, but equivalent to those of group 1. The water content of the burned skin in group 2 was significantly lower than that in the other groups, indicating that increased postburn capillary permeability was minimized by the administration of Vitamin-C. With adjuvant high-dose Vitamin-C administration, we were able to reduce the 24-h resuscitation fluid volume from 4 ml/kg/per cent burn to 1 ml/kg/per cent burn, while maintaining adequate cardiac output.