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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.
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