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Biomedical subjects

S M Levenson

Publications and source records attributed to S M Levenson.

At least 37 records · Page 2Linked to original sources

Zone II flexor tendon repair: effects of vitamins A, E, beta-carotene.

Ninety-six adult Leghorn chickens each had the flexor profundus tendon in each middle toe sharply divided in Zone II with immediate repair (pentobarbital, ketamine anesthesia). Animals were then randomly assigned to receive unsupplemented standard chick chow or the chow supplemented with vitamin A (150,000 IU/kg chow), Vitamin E (1000 IU/kg chow), or beta-carotene (90 mg/kg chow). Eight animals from each of the four groups were examined at 7, 30, or 45 days post repair. After sacrifice, in situ composite wound breaking strength was measured in the amputated toe by constant speed tensiometry. Vitamin A-supplemented animals demonstrated breaking strength more than double that of control at each postoperative test day, while those animals receiving supplemental Vitamin E had breaking strength less than half that of control at Day 7 and Day 45. These results are statistically significant. Tensiometry curves differed markedly at all time points among the groups: Vitamin A curves being broader, higher, and having more spikes. These differences in the tensiometry curves, both qualitative and quantitative, may be due to differences in intrinsic tendon healing or to differences in adhesion formation or a combination of both. beta-Carotene supplementation had modest effect. We conclude that supplemental dietary vitamin A increases the breaking strength of composite tendon wounds and that supplemental dietary vitamin E decreases it.

Animals↗

Supplemental vitamin A prevents the tumor-induced defect in wound healing.

To test our hypothesis that supplemental vitamin A would mitigate the impaired healing that occurs in tumor-bearing animals, six groups of C3H mice, eight per group, eating a standard commercial mouse chow ad libitum that supports normal growth, reproduction, and longevity were innoculated with 200,000 C3HBA cells. When tumors measured approximately 6 mm in diameter, the mice were anesthesized and wounded (dorsal skin incisions and subcutaneous polyvinyl alcohol sponges). Twenty-four hours later, two groups (one continued on the chow and the other started on the chow supplemented with 150,000 IU vitamin A/kg chow) underwent local tumor irradiation; two groups, one ingesting the chow, the other the vitamin A supplemented chow, were started on cyclophosphamide therapy; two groups, one ingesting the chow, the other the vitamin A supplemented chow, received neither local tumor irradiation nor cyclophosphamide therapy. An additional two groups ingesting the chow, one group neither innoculated with tumor nor wounded, the other wounded by not innoculated, served as controls. Wound breaking strength and sponge reparative collagen accumulation (assessed by hydroxyproline proline measurement) were used as indicators of wound healing. The mice were killed 12 days after wounding. Tumor presence decreased wound breaking strength and sponge hydroxyproline content; these effects were largely negated by supplemental vitamin A. Local tumor irradiation diminished the adverse effect of tumor on sponge reparative collagen content but to a lesser extent than the supplemental vitamin A. Supplemental vitamin A added to the irradiation effect on healing but irradiation did not add to the vitamin A effect. Cyclophosphamide, a systemic radiomimetic anti-tumor agent, did not alter the impaired wound healing of the tumor-bearing mice. Supplemental vitamin A mitigated the impaired wound healing in the cyclophosphamide-treated tumor-bearing mice. Supplemental vitamin A also moderated the effects of wounding, tumor, and tumor therapies (local irradiation and cyclophosphamide) on the increase in adrenal size, leukopenia, thrombocytopenia, and thymic involution (except the last was not moderated in the cyclophosphamide-treated tumor-bearing rats). The splenic enlargement in the untreated tumor-bearing wounded rats and in those treated with cyclophosphamide was lessened by supplemental vitamin A. We hypothesize that these anti-stress effects of vitamin A underlie, in part, its action in mitigating the impaired wound healing of tumor-bearing mice, including those treated by local irradiation or cyclophosphamide. These findings have implications for the care of patients with malignant tumors.

Animals↗

Effects of maternal marijuana and cocaine use on fetal growth.

To investigate the effects on infants of the use of marijuana and cocaine during pregnancy and to compare the importance of urine assays with that of interviews in ascertaining drug use, we prospectively studied 1226 mothers, recruited from a general prenatal clinic, and their infants. On the basis of either interviews or urine assays conducted prenatally or post partum, 27 percent of the subjects had used marijuana during pregnancy and 18 percent had used cocaine. When only positive urine assays were considered, the corresponding values were 16 percent and 9 percent, respectively. When potentially confounding variables were controlled for in the analysis, the infants whose mothers had positive urine assays for marijuana, as compared with the infants whose mothers were negative according to both interviews and urine assays, had a 79-g decrease in birth weight (P = 0.04) and a 0.5-cm decrement in length (P = 0.02). Women who had positive assays for cocaine, as compared with nonusers, had infants with a 93-g decrease in birth weight (P = 0.07), a 0.7-cm decrement in length (P = 0.01), and a 0.43-cm-smaller head circumference (P = 0.01). To compare our findings with those of other investigators who did not use urine assays, we repeated the analyses, considering only self-reported use of marijuana (23 percent) and cocaine (13 percent). There were no significant associations between such use as determined by interviews alone and any of the measures of outcome. We conclude that the use of marijuana or cocaine during pregnancy is associated with impaired fetal growth and that measuring a biologic marker of such use is important to demonstrate the association.

Adolescent↗

Impaired liver regeneration in the analbuminemic rat.

Albumin has been implicated as both an inhibitor and a stimulator of liver regeneration. We examined the rate of liver regeneration following partial hepatectomy in rats which are genetically analbuminemic. Adult male analbuminemic and Sprague-Dawley control rats underwent either a 70% partial hepatectomy or a sham operation. Twenty-four hours postoperatively, rats were injected iv with tritiated thymidine and the liver remnants were resected 1 hr later. Liver weight, protein and DNA contents, and the rate of tritiated thymidine incorporation into DNA were determined. The rate of DNA synthesis in control sham-operated rats was greater (P less than 0.05) than that of analbuminemic rats. Following partial hepatectomy, there was a statistically significant (P less than 0.01) increase in DNA synthesis in control rats; no significant increase was noted in the analbuminemic rats. No significant differences in liver remnant weight or protein and DNA contents were noted between control and analbuminemic sham-operated or partially hepatectomized rats. Our data suggest that albumin plays a role in the regulation of DNA synthesis in both the resting and the regenerating liver and it may be essential in maintaining a normal rate of liver regeneration.

Albumins↗

Repeal of the Massachusetts seat belt law.

In November 1986, the Massachusetts mandatory seat belt use law repealed in a referendum by a 53 per cent to 47 per cent vote. In an anonymous random digit telephone survey of 1,046 adults in Massachusetts in summer 1986, while the law was in effect, 61 per cent of respondents had said they would vote in favor of the law. A post-repeal follow-up of 80 per cent of these persons revealed initial supporters and opponents of the law were equally likely to vote, but 15 per cent of the summer supporters switched their opinions and voted for repeal, compared to only 4 per cent of summer opponents who switched. In addition, a separate survey of 167 households that had refused to answer the summer survey indicated that survey nonrespondents were more likely to vote against the law than for it. Those opposing the law saw it as an infringement on personal liberty and believed it was not effective in reducing injury and death.

Choice Behavior↗

Cocaine use during pregnancy: prevalence and correlates.

Cocaine use during pregnancy was assessed by interviews and urine assays obtained prenatally and immediately postpartum from 679 urban women enrolled in prenatal care. Of these, 17% were found to have used cocaine at least once during pregnancy. Eight percent had urine assays positive for cocaine metabolites using the enzyme-mediated immunoassay technique with a cut-off of 300 ng/mL of benzoylecgonine. Of the cocaine users, 24% denied use at the time of the interview and were identified solely by urine assay. Cocaine users were significantly (P less than .01) less likely than nonusers to be married, Hispanic, or black born outside of the United States and were less well nourished. Users reported significantly (P less than .01) more sexually transmitted diseases, prior low birth weight infants, spontaneous and elective abortions, and greater use of alcohol, cigarettes, marijuana, opiates, and other illicit drugs during pregnancy. Because cocaine use is correlated with many potential risk factors, large sample sizes and multivariate statistical techniques are needed to determine whether cocaine use during pregnancy poses an independent risk for adverse neonatal outcomes.

Boston↗

Supplemental dietary tyrosine in sepsis and acute hemorrhagic shock.

Previous studies showed that dopamine and norepinephrine levels in rat brain are reduced following stress and that rats fed supplemental tyrosine do not exhibit these reductions. We hypothesized that dietary supplementation with tyrosine would enhance resistance to acute hemorrhagic shock and sepsis by increasing substrate (tyrosine) availability for catecholamine synthesis. Rats were fed either a standard rat chow (6.8 g of tyrosine per kilogram of chow), which supports normal growth, fertility, and longevity, or the same chow supplemented with 10 g of tyrosine per kilogram of chow. Seven days later, the rats underwent cecal ligation and perforation while under intraperitoneal pentobarbital anesthesia. There was a significant increase in survival in the tyrosine-supplemented group. Similarly, in another experiment, tyrosine-supplemented rats were able to tolerate acute fulminant hemorrhagic shock better than were nonsupplemented control animals.

Acute Disease↗

Effect of supplemental vitamin A on colon anastomotic healing in rats given preoperative irradiation.

We studied the effect of dietary supplementation with vitamin A on the healing of colon anastomoses in irradiated bowel. Rats were divided into two groups. Those in the first group were fed a standard chow diet and those in the second group were fed the same diet supplemented with 150 IU vitamin A/g of chow. The rats were maintained on their respective diets throughout the experiment. After 7 days, half the rats in each group underwent abdominal irradiation (200 rads). Seven days later, all of the rats underwent distal colon division and anastomosis under pentobarbital anesthesia. All rats were killed 7 days postoperatively, the colons excised, and bursting strength and hydroxyproline determinations performed on both the anastomotic segment and a normal proximal segment of adjacent colon. There was a significant decrease in the bursting strength at the colon anastomosis (p less than 0.02) and in the collagen content (p less than 0.02) after preoperative irradiation. This effect was mitigated by dietary vitamin A supplementation.

Animals↗

Effect of dietary supplementation with vitamin A on arterial healing in rats.

The effect of dietary supplementation with vitamin A on the healing of rat aortas was studied. Rats were divided into two groups: rats fed a standard chow and rats fed the chow supplemented with 150 IU vitamin A palmitate/g diet. Seven rats from each group were fed with the above diets for 7 days, killed with ether, and the abdominal aorta excised and assayed for hydroxyproline content and collagenase activity. Ten rats from each group were fed for 7 days on the above diets and then underwent a longitudinal aortotomy which was sutured with prolene sutures under pentobarbital anesthesia. The rats were maintained on their respective diets for 7 days and then killed with ether, their abdominal aorta was excised and both the segment with the arteriotomy and the adjacent distal normal segment were analyzed for hydroxyproline content and collagenase activity. Seven rats from each group were fed with the above diets and then underwent transverse division of the abdominal aorta and reanastomosis using nylon sutures under pentobarbital anesthesia. Rats were maintained on their respective diets throughout the postoperative period. Seven days later, all rats were killed with ether and the bursting strength of the aortic anastomoses was measured. The results showed that vitamin A supplementation in non-operated animals had no significant effect on aortic hydroxyproline content or collagenase activity. In rats undergoing longitudinal aortotomy and suture, there was a significant increase in hydroxyproline content both at the healing arteriotomy and at the adjacent non-wounded aorta in the vitamin A-supplemented group. There was also a significant increase in bursting strength of the healing aortic anastomosis in the vitamin A-supplemented rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Wound healing in normal and analbuminemic (NAR) rats.

It has been suggested by several investigators that hypoalbuminemia results in impaired wound healing. In most studies, however, hypoalbuminemia is a manifestation of malnutrition or underlying liver disease. In this study, we examined the effect of isolated hypoalbuminemia on wound healing. Analbuminemic (NAR) rats which are Sprague-Dawley mutants with trace levels of plasma albumin due to a defect in albumin synthesis were studied. Adult NAR and Sprague-Dawley rats (n = 10 each) underwent a 7 cm dorsal skin incision and implantation of a polyvinyl alcohol sponge subcutaneously under pentobarbital anesthesia. Seven days postoperatively all rats were killed with ether, the wounds were excised, and breaking strength was measured. Sponge hydroxyproline content was determined colorimetrically. There were no significant differences in wound breaking strength (fresh or formalin fixed) or sponge collagen content between the Sprague-Dawley and analbuminemic rats. We conclude that isolated hypoalbuminemia has no detrimental effect on would healing in rats.

Animals↗

Replacement of liver function in rats by transplantation of microcarrier-attached hepatocytes.

Isolated hepatocytes, harvested from normal rat livers by portal vein collagenase perfusion, can be attached to collagen-coated dextran microcarriers and transplanted by intraperitoneal injection into rats. Survival and function of the transplanted hepatocytes have been demonstrated in mutant rats lacking bilirubin-uridine diphosphate glucuronosyltransferase activity (Gunn strain) and rats with inherited lack of plasma albumin (Nagase analbuminemia rat strain). This simple technique promises to be useful in the treatment of acute liver failure in humans.

Animals↗

Effect of cimetidine on wound healing in rats.

Cimetidine, an H-2 antagonist, is one of the most commonly prescribed drugs and is used in the management of peptic ulcer disease and prevention of stress ulcerations following major trauma or operations. It has been shown that histamine has a stimulatory effect on wound healing which is believed to be mediated through H-2 receptors. We hypothesized that cimetidine would have an inhibitory effect on wound healing. Fifty-two adult rats were divided into two groups: Group A was placed on a standard chow and Group B was given chow supplemented with cimetidine (300 mg/Kg diet), a dose equivalent to that clinically used in man and effective in inhibiting gastric hypersecretion in the rat. Ten days later, all rats underwent a dorsal skin incision under pentobarbital anesthesia and implantation of a polyvinyl alcohol sponge subcutaneously. Animals were maintained on their respective diets. Rats were killed with ether five and ten days postoperatively, the wounds were excised and breaking strength measured. Sponge hydroxyproline content was measured. No significant difference in breaking strength or sponge hydroxyproline content was found between the two groups. We thus conclude that cimetidine has no effect on wound healing in rats when used in doses equivalent to the clinical dose in man.

Animals↗

Survival, organization, and function of microcarrier-attached hepatocytes transplanted in rats.

Hepatocytes harvested by collagenase perfusion of rat liver were attached to collagen-coated microcarriers and injected intraperitoneally into congeneic or allogeneic bilirubin-UDP-glucuronosyltransferase (EC 2.4.1.17)-deficient (Gunn) rats or allogeneic analbuminemic (NAR) rats. Five days later, the microcarriers were observed to have formed conglomerates chiefly on the anterior surface of the pancreas. Scanning electron microscopy showed hepatocytes attached to the granular collagen-coated surface of the microcarriers and newly formed connective tissue. Light microscopy revealed that the microcarriers formed a lattice with the collagen tissue; hepatocytes were seen within this lattice or on the surface of the microcarriers. Hepatocyte plasma membranes were nucleoside-diphosphatase (NDPase)-positive. Newly formed blood islands, blood vessels containing erythrocytes and leukocytes and NDPase-positive endothelium were observed in close proximity to the hepatocytes and fibroblasts. Transmission electron microscopic examination showed hepatocytes with microvilli and nucleoid-containing peroxisomes with catalase activity. Hepatocytes were present for up to 2 months in congeneic recipients, the longest period of observation after transplantation. After normal microcarrier-attached hepatocytes were transplanted into allogeneic Gunn rats, bilirubin glucuronides were present in bile for 6 days. When congeneic Gunn rat recipients were used, bilirubin glucuronides were present in bile throughout the study (28 days); this was accompanied by reduction of serum bilirubin concentrations to nearly normal levels. After injection of normal hepatocytes into allogeneic NAR rats, plasma albumin concentration progressively increased for 6 days and then declined. In NAR recipients which were immunosuppressed with cyclosporin A, peak plasma albumin levels were reached in 14 days and persisted nearly at that level throughout the study (28 days).

Animals↗

New method of hepatocyte transplantation and extracorporeal liver support.

A technique has been developed by the authors that allows hepatocyte attachment on collagen-coated microcarriers resulting in prolonged hepatocyte viability and function both in vivo and in vitro. Rat hepatocytes were obtained by portal vein collagenase perfusion. Intraperitoneally transplanted microcarrier-attached normal hepatocytes into congeneic Gunn rats were functioning 3-4 weeks later, as shown by the presence and persistence of conjugated bilirubin in recipient bile, sustained decrease in serum bilirubin, uptake of Tc99m-DESIDA, and morphologic criteria. Intraperitoneal transplantation of normal microcarrier-attached hepatocytes into genetically albumin deficient rats (NAR) resulted in marked increase in plasma albumin levels (6 days without and 21 days with Cyclosporin A immunosuppression). Microcarrier-attached hepatocytes transplanted after 2 weeks of storage at -80 C into congeneic Gunn rats were viable and functional as assessed by criteria outlined above. An extracorporeal liver perfusion system was developed using the microcarrier-attached hepatocytes that was capable of synthesizing and conjugating bilirubin and synthesizing liver-specific proteins.

Animals↗

The effect of vitamin E on experimentally induced peritoneal adhesions in mice.

Previous studies in our laboratory demonstrated that dietary supplementation with vitamin A enhances peritoneal adhesion formation in mice. Other researchers have shown that vitamin E antagonizes some effects of vitamin A in various systems, eg, wound healing. We investigated our hypothesis that dietary supplementation with vitamin E would decrease peritoneal adhesion formation. Adult mice were divided into the following groups: group 1, which ate a standard chow containing 65 IU of vitamin E per kilogram diet (twice the National Research Council's recommended daily allowance for normal mice); and group 2, which ate the same chow supplemented with vitamin E at 300 IU/kg diet (a nontoxic level). Following peritoneal ligation, all mice were killed on the tenth postoperative day and their peritoneal cavities examined for the presence and extent of adhesions. There was a statistically significant decrease in the incidence and degree of adhesions in the vitamin E-supplemented animals; these data supported our hypothesis.

Animals↗

Effect of dimethyl sulfoxide and glycerol on acute bowel ischemia in the rat.

After a 30 minute period of superior mesenteric artery occlusion in adult rats, there was a significant decrease in peritoneal inflammatory reaction, ileus, peritoneal adhesion formation, and histologically proved bowel wall necrosis in animals given intravenous dimethyl sulfoxide at the end of the ischemic period. In contrast, control rats given normal saline solution intravenously demonstrated severe inflammatory reaction, ileus, hemorrhagic peritoneal fluid, extensive adhesion formation, and areas of bowel wall necrosis. Intravenous glycerol did not have the beneficial effect seen with dimethyl sulfoxide. Neither compound was effective when given intraperitoneally. We conclude that intravenous dimethyl sulfoxide has a significant protective effect in rats with acute intestinal ischemia due to the superior mesenteric artery occlusion in the rat.

Animals↗

Vitamin A and retinoic acid: induced fibroblast differentiation in vitro.

The role of vitamin A in wound healing and fibroplasia has been studied extensively in vivo but the mechanism(s) of its action has not been established. In this study the effect of vitamin A and retinoic acid on fibroblast growth and collagen accumulation in vitro was examined. Vitamin A and retinoic acid added to Balb 3T3 mouse fibroblasts in tissue culture resulted in induction of cell differentiation as manifested by a decrease in cell growth rate, enhanced collagen accumulation, and morphologic differentiation. The results of this in vitro study suggest that the stimulatory in vivo effect of vitamin A and retinoic acid on collagen accumulation and fibroplasia in healing wounds is due in a major way to fibroblast differentiation and enhanced collagen synthesis.

Animals↗