Synthesis and evaluation of long-acting D-penicillamine derivatives.

This study extends the use of two lathyrogens, ss-aminopropionitrile (BAPN) and D-penicillamine (DPA) from daily systemic or local-topical administration to long-time acting agents. This was achieved by converting the hydrophilic drugs into lipophilic derivatives. The synthesis of functional derivatives of DPA consisted in esterification with methyl-, hexyl-, or benzyl alcohols in the presence of thionylchloride.

Single intratumoral injection of long-acting benzyl ester of D-penicillamine inhibits the growth of melanoma tumor in mice.

Using a murine model of melanoma we tested the effect of D-penicillamine administered in repetitive, daily injections, or as a single large dose injected either in saline or in a biodegradable polymer. We also studied the effect of a single intratumoral injection of benzyl-ester-D-penicillamine on the growth of the tumor. Daily injections of the drug or its administration in a polymer or benzyl-ester of D-penicillamine were all significantly inhibitory.

Inhibition of breast adenocarcinoma growth by intratumoral injection of lipophilic long-acting lathyrogens.

Prevention of the formation of crosslinks and/or disintegration of already formed collagen fibrils in the tumor by known lathyrogens, beta-aminopropionitrile or D-penicillamine, may result in the weakening of tumor support, decreasing angiogenesis and promoting tumor regression. This paper reviews our studies with a single intratumoral injection of lipophilic lathyrogens and others, using a systemic administration to investigate the effect of both lathyrogens. Details of our experimental results are also given.

Effects on wound healing of zinc oxide in a hydrocolloid dressing.

Background: Zinc oxide incorporated in gauze enhances healing of chronic wounds in humans and experimental pig wounds.

Objective: The purpose of this study was to examine the effects of zinc oxide added to a hydrocolloid dressing on the healing of surgical wounds in domestic pigs.

Methods: Forty partial-thickness wounds (2.

The effect of single shock waves on the vascular system of artificially perfused rabbit kidneys.

Extracorporeally-perfused rabbit kidneys were exposed to five shock waves at 14 kV on the XL1 Dornier experimental lithotripter (Dornier Medical Systems, Inc., Germering, Germany). While the perfusion flow rate was kept constant, the arterial perfusion pressure was recorded to assess changes in vascular resistance.

Collagen fibers as a temporary scaffold for replacement of ACL in goats.

ACL substitutes made of braided or plied purified collagen fibers and cross-linked with hexamethylenediisocyanate were implanted into a total of 14 adult goats to achieve resorption within 8 to 10 months. Two types of collagen fiber prostheses differing in degree of collagen purification were tested. The implants were harvested 2 to 11 months postimplantation, tested for mechanical strength, and evaluated by morphological methods.

Effect of surgical manipulation of polytetrafluoroethylene grafts on microstructural properties and healing characteristics.

The effects on graft healing of alterations in the microstructure of polytetrafluoroethylene (PTFE) grafts induced by surgical instruments have not been fully elucidated. This study evaluates changes in the structural and physical properties of PTFE grafts resulting from the intentional application of commonly used surgical instruments and the influence of these changes on cellular ingrowth. The extent of cellular ingrowth into intact (10, 30, and 60 microns unreinforced and 30 microns reinforced [R]) and structurally compromised PTFE grafts (30 reinforced and 60 microns nonreinforced) implanted subcutaneously in Sprague-Dawley (n = 14) rats was evaluated at 7 and 21 days.

Use of an antibiotic-bonded graft for in situ reconstruction after prosthetic graft infections.

We have developed an infection resistant vascular prosthesis by bonding rifampin to Dacron grafts with the use of a collagen matrix release system. The purpose of this study was to determine the efficacy of this antibiotic-bonded graft in resisting infection after an in situ reconstruction of a previously infected prosthetic bypass. Eighty-three adult mongrel dogs underwent implantation of a 3 cm untreated Dacron graft into the infrarenal aorta.

Influence of shock waves on fracture healing.

During the last decades the influence of physical factors on fracture healing has been widely described. With the use of shock waves for the treatment of urolithiasis, a new mechanical medium has been introduced into medicine. For the first time the influence of shock waves on fracture healing was studied in rats.

Effects of electrocautery on midline laparotomy wound infection.

This study compared the healing of midline fascial incisions made with either scalpel or electrocautery and inoculated with Escherichia coli in 57 Sprague-Dawley rats. At 7 days, tensile strength was significantly less when incisions were made with electrocautery than with a scalpel. Additionally, would strength was inversely related to the concentration of the inoculum of E coli.

Prevention of graft infection by use of prostheses bonded with a rifampin/collagen release system.

The objective of this study was to test the efficacy of bonding rifampin to double-velour Dacron grafts with collagen to prevent graft sepsis. Fifty 6.0 mm Dacron grafts (length 5.

Inert wound dressing is not desirable.

Four Yorkshire piglets were inflicted with a total of 92 split-thickness wounds 4.8 cm2 in area and 400 microns deep. The wounds were treated with eight dressing regimens under the same experimental design.

Vitamin E reduction of lipid peroxidation products in rats fed cod liver oil and ethanol.

The purpose of this study was to investigate the effects of vitamin E supplementation on ethanol- and cod liver oil-induced lipid peroxidation. Adult male rats received diets containing ethanol, cod liver oil and supplemented with vitamin E for 28 days. Following treatment, hepatic conjugated dienes, lipid fluorescence, and exhalation of ethane were measured as indices of lipid peroxidation.

Efficacy and duration of antistaphylococcal activity comparing three antibiotics bonded to Dacron vascular grafts with a collagen release system.

Type 1 collagen, minimally cross-linked, was used to bind one of three antibiotics (amikacin, chloramphenicol, or rifampin) to double-velour Dacron grafts to develop a prosthesis resistant to infection. Six millimeter disks of graft were placed in separate flasks (specific for each antibiotic) containing albumin in saline and continuously agitated. At daily intervals the solution was changed, and paired graft samples were removed and placed on a blood agar plate confluently streaked with bacteria.

Enhancement of re-epithelialization with topical zinc oxide in porcine partial-thickness wounds.

We investigated the effect of locally applied zinc on the healing of partial-thickness skin wounds in the domestic pig using two zinc compounds (zinc oxide and zinc sulfate) in two different vehicles (a gauze compress and a collagen sponge). The rate of re-epithelialization was determined morphometrically 48 and 64 hr after infliction of standardized square wounds (4.8 cm2 and 400-microns deep) with an electrokeratome.

The effect of vitamin E (alpha-tocopherol) supplementation on hepatic levels of vitamin A and E in ethanol and cod liver oil fed rats.

Eight groups of 5 rats were fed 8 differing liquid diets with and without ethanol, cod liver oil and/or increased levels of vitamin E. Hepatic levels of vitamins A and E were determined following the 28-day feeding time. Ethanol consumption decreased the levels of hepatic vitamin E (p less than 0.

Effect of electrocautery on wound healing in midline laparotomy incisions.

The effect of electrocautery on midline fascial wound healing was studied in 108 Sprague-Dawley rats. Midline wound tensile strength was significantly reduced in fascia incised with the coagulation current compared with the cutting current or scalpel. In addition, tissue necrosis and inflammation as well as adhesion formation between the incision and abdominal viscera were more extensive in animals with incisions made using coagulation current.

A comparison of parallel versus perpendicular placement of retention sutures in abdominal wound closure.

A new technique for placement of retention sutures is described. Twenty-five rats underwent midline laparotomy incision. The control group was closed with traditional placement of through-and-through retention sutures placed in a perpendicular direction to the wound.

Occlusion of the vas deferens in dogs with a biocompatible hydrogel solution.

The surgically exposed vasa deferentia of 21 dogs were injected, under visual inspection, with Hypan N-90 acrylic hydrogel (50-150 microL). The hydrogel was deposited inside the vas lumen via a 22-gauge Teflon intercatheter. The solution gelled within 120 seconds.

Effect of shock waves on the healing of partial-thickness wounds in piglets.

During the last 20 years, the role of various physical factors in wound healing has been widely studied and recognized. With the use of shock waves for the treatment of urolithiasis, a new mechanical medium has been introduced into medicine. The influence of shock waves on the reepithelialization of partial-thickness wounds was studied in four Yorkshire piglets by a quantitative morphometric method.

Antibiotic irrigation and the formation of intraabdominal adhesions.

The efficacy of antibiotic peritoneal lavage in the prevention of postoperative infection is controversial. The role of intraperitoneally administered cefazolin and tetracycline in the formation of adhesions was studied in the rodent model. Thirty-two rats were divided into 3 groups.

Transport of beta-aminopropionitrile through intact skin or scar tissue.

A lathyrogen, [C14]aminopropionitrile (beta APN), was administered to 34 rats either in K-Y jelly or saline vehicles onto intact shaven skin or onto a healed splinted deep excision wound. The dynamics of beta APN transport and content in the skin or repair tissue was observed after 2, 5, 8, and 24 hr of topical administration. The repair tissue quickly absorbed the lathyrogen and reached maximum at the 2-hr sampling.

Use of cross-linked bovine pericardium as a disc replacement in the rabbit temporomandibular joint.

Chemically purified bovine pericardial membrane, highly cross-linked with monomeric glutaraldehyde, was implanted in the TMJ area in ten adult rabbits in place of partially excised discs. Sham controls had the temporal aspect of the TMJ scraped with a scalpel. After 3 months, the whole TMJ area was processed for morphologic and scanning electron micrographic (SEM) evaluation.