Search

Sleep is critical for brain development and synaptic plasticity. In male wild-type mice, chronic sleep restriction during development results in long-lasting impairments in behavior including hypoactivity, decreased sociability, and increased repetitive behavior. Disordered sleep is characteristic of many neurodevelopmental disorders. Moreover, the severity of behavioral symptoms is correlated with the degree of disordered sleep. We hypothesized that chronic developmental sleep restriction in a mouse model of fragile X syndrome (FXS) would exacerbate behavioral phenotypes. To test our hypothesis, we sleep-restricted Fmr1 knockout (KO) mice for 3 h per day from P5 to P52 and subjected mice to behavioral tests beginning on P42. Contrary to our expectations, sleep restriction improved the hyperactivity and lack of preference for social novelty phenotypes in Fmr1 KO mice but had no measurable effect on repetitive activity. Sleep restriction also resulted in changes in regional distribution of myelin basic protein, suggesting effects on myelination. These findings have implications for the role of disrupted sleep in the severity of symptoms in FXS.

Sleep abnormalities are prevalent in autism spectrum disorders (ASD). Moreover, the severity of ASD symptoms are correlated with the degree of disturbed sleep. We asked if disturbed sleep during brain development itself could lead to ASD-like symptoms, particularly behavioral manifestations. We reasoned that sleep is known to be important for normal brain development and plasticity, so disrupted sleep during development might result in changes that contribute to behavioral impairments associated with ASD. We sleep-restricted C57BL/6J male mice [beginning at postnatal day 5 (P5) and continuing through P52] 3 h per day by means of gentle handling and compared the data with a stress group (handled every 15 min during the 3-h period) and a control group (no additional handling). From P42–P52, we assessed the behavioral effects of sleep-restriction in this pre-recovery phase. Then, we allowed the mice to recover for 4 weeks and tested behavior once again. Compared to the control group, we found that sleep restricted-mice had long-lasting hypoactivity, and impaired social behavior; repetitive behavior was unaffected. These behavior changes were accompanied by an increase in the downstream signaling products of the mammalian target of rapamycin pathway. These data affirm the importance of undisturbed sleep during development and show that, at least in this model, sleep-restriction can play a causative role in the development of behavioral abnormalities. Assessing and treating sleep abnormalities in ASD may be important in alleviating some of the symptoms.

Chemical modification of banana starch (Musa paradisiaca L.) with the degradation products of virgin and bottle waste of polyethylene terephthalate was carried out in situ. The modified starch was characterized by FTIR and NMR, which allowed proposing three chemical structures. SEM micrographs showed that the morphology of the modified starch granule is directly related with mass ratio of Starch/PET and type of PET used in the reaction. The crystallinity of the modified starch decreased up to 92.6% and 62.5% using bottle waste and virgin PET, respectively, according to XRD diffractograms. TGA analysis showed that the starch degradation temperature decreased by 12 °C. Modified starch films were elaborate and its electrical conductivity was found to be 2.9 times compared to that of native starch. The starch/PET film presented the highest value in the mechanical property of elongation at break compared to the starch-only film. The modified starch film was degraded above 80% by aqueous hydrolysis., (Copyright © 2021. Published by Elsevier Ltd.)

Background/objective: Preconditioning has been considered promising for the treatment of ischemic flaps. In this study, the therapeutic effect of postconditioning was compared with that of preconditioning during ischemia/reperfusion (I/R) injury, and a role of inducible nitric oxide synthase (iNOS) in postconditioning treatment was also explored., Methods: Sixty rats were randomly divided into four groups with 15 rats in each group. Ischemic injury was induced in a rat's gracilis muscle flap model. Preconditioning and postconditioning were performed respectively on the flaps in the pre-con group and the post-con group. No treatment was given to the flaps in the control group, and flaps without I/R injury were used as a sham control. Muscle viability ratio, histology, and gene expression of iNOS were examined at different time intervals (3, 12, and 18 h)., Results: A significantly higher survival ratio was observed in both the pre-con group (78.98 ± 3.39, 62.74 ± 3.7, and 54.42 ± 4.45 %) and the post-con group (77.42 ± 4.14, 59.74 ± 6.67, and 49.52 ± 4.13 %) than the control group (45.22 ± 3.69, 42.44 ± 3.76, and 33.2 ± 3.29 %) at 3, 12, and 18 h postoperatively (P < 0.05). There was no statistical difference between the pre-con group and the post-con group (P > 0.05). Histological examination showed delayed and attenuated tissue damage in both the pre-con group and the post-con group when compared to that of the control group. A higher expression of iNOS was observed in both the pre-con group and the post-con group than the control group and the sham group (P < 0.05)., Conclusions: Significant improvement of flap survival could be achieved by both preconditioning and postconditioning treatments; however, better protection could be provided by preconditioning. The higher expression of iNOS may play an important role in the therapeutic effect of postconditioning during I/R injury.

We describe a case of mutual transpositional transfers of toe and thumb in an attempt to restore the aesthetic appearance of the thumb with a deformity of the nail. The reconstructed thumb with the skin-nail flap from the great toe gave an excellent result both aesthetically and functionally, and the nail grew normally. The donor site of the great toe that was covered with the skin-nail flap from the thumb healed satisfactorily. This is another option for donor site management, the results of which are good, but the indications are under discussion.

Background: The goals of this study were to review the outcome of the surgical procedure and hospitalization associated with meningomyelocele repair, and to examine the results of different closure strategies., Methods: Eighty-three consecutive patients having surgery for meningomyelocele over a ten year period form the basis of this study. Thirty-two closures with a mean defect size preoperatively of 11.5 cm(2) were performed by the neurosurgeon (ADP), and fifty-one closures with a mean defect size of 28.4 cm(2) by the plastic surgeon (MFA)., Results: Defects up to 12 cm(2) were closed with local advancement fasciocutaneous flaps. As defect size increased, latissimus muscle flaps were added in 30 (36%) and gluteus muscle in 16 (19%). In recent years, 18 patients (21.6%) with a mean defect of 29 cm(2) were treated with overlapping of deepithelialized fasciocutaneous flaps to add an additional layer of coverage to the dural closure. There were 9 major complications, 6 requiring reoperation. There were 10 minor wound failures managed conservatively. Mean hospital stay was 24.2 days. Re-operation increased length of stay to 45 days (p < 0.0001). Minor wound problems added 6 days to mean hospital stay. Wound failure did not correlate with either defect size or closure technique. Thoracic location was associated with increased wound failure (p < 0.05). Use of a shunt did not increase morbidity. All closures remained durable after discharge., Conclusions: Location in the thoracic area predicts major wound failure and need for reoperation. Wound complications significantly increase hospital stay. The use of a variety of techniques to achieve multi-layered closures leads to durable coverage for defects of all sizes., (Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Purpose: The goal of this study was to evaluate the 4-year minimum (5.5-y average) results of trapeziectomy and ligament reconstruction using a modified Thompson technique with the abductor pollicis longus tendon for the primary treatment of advanced-stage basal joint arthritis (Eaton stages III and IV)., Methods: We evaluated 25 thumbs in 18 patients after ligament reconstruction arthroplasty for surgical treatment of advanced thumb basal joint arthritis. Treatment consisted of piecemeal excision of the entire trapezium, ligament reconstruction and interposition using the abductor pollicis longus tendon, and 8 weeks of K-wire immobilization of the thumb metacarpal. We evaluated range of motion, lateral pinch, tip pinch, grip strength, and outcomes questionnaires including the Arthritis Impact Measurement Scales 2 Short Form before and at an average of 5.5 years after surgery., Results: Seventeen of 18 patients reported excellent or good relief of pain and were satisfied with their operation, and all of the patients would have the operation again. Of the 25 thumbs, 24 adducted fully into the plane of the palm and opposed to the fifth metacarpal head. Preoperative and postoperative strength comparisons demonstrated an average increase in grip, key pinch, and tip pinch strength of 14%, 12%, and 6%, respectively. The outcomes data demonstrated noteworthy improvement in writing, buttoning a shirt, turning a key/lock, and arthritis pain categories., Conclusions: This technique restored a stable, pain-free thumb that yielded excellent strength and motion at an average of 5.5 years after the procedure. Compared with published reports of techniques that use hematoma distraction or harvest of all or part of the flexor carpi radialis tendon, this modified Thompson technique has similar pain relief, satisfaction, and motion but had less improvement in strength, which might have resulted from differences in the studied samples., (Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

The arterialized venous flaps are highly regarded in microsurgical and reconstructive surgeries based on advantages of ease of design and harvest without the need to perform deep dissection, no sacrifice of a major artery at the donor site, no limitation of the donor sites, and less donor-site morbidity. Many experimental investigations and clinical applications have been reported. However, their survivals are still inconsistent, and survival mechanisms remain controversial. In this review, we update the existing problems, experimental studies for survival mechanisms, clinical practices, and methods developed to improve their survivals.

The purpose of this experimental study is to investigate the improvement in flap survival of prearterialization with delay procedure in venous flaps in rats. The transverse superficial inferior epigastric flap was utilized. Forty-six rats were randomized into four groups: group 1 as arterialized venous flaps, group 2 as venous flaps of prearterialization with delay procedure, group 3 as arterial perfusion venous flap, and group 4 as venous perfusion venous flap. Direct observation, histological analysis, and vascular perfusion examination by Indian ink injection were performed for flap assessment. The percentage of flap survival was 41.6 +/- 2.4%, 98.0 +/- 1.8%, 89.5 +/- 1.0%, and 11.3 +/- 0.8% in these four groups, respectively. Significant differences were noted between groups ( P < 0.05) except for between group 2 and group 3 ( P > 0.05). Vascular perfusion studies revealed that the Indian ink filled the entire flaps of group 2 in comparison with partially filled flaps in other groups. Histological examination showed more small vessels were observed through all layers of the flaps as well as dilated superficial veins in group 2 than those in other groups. In conclusion, prearterialization with delay procedure can improve the viability of the flap, and this method may be a strategy for flap prefabrication based on the venous network., (Copyright Thieme Medical Publishers.)

In microsurgical flap procedures, creation of an arteriovenous fistula (AVF) is a technique of vein grafting where the vein graft is connected to recipient vessels as a flow-through loop prior to harvest and inset of the flap. Controversy exists whether this technique can be used as a 2-stage procedure with the loop and flap transfer accomplished in sequential operations or if the loop and flap transfer should be performed in a single operation. We performed 12 consecutive 1-stage AVF-flap procedures, with 1 flap failure. We combined this series with previously published reports to compare outcomes of 1-stage and 2-stage procedures. We found no significant difference in flap outcomes or complication rates between the 2 strategies. We conclude from our experience and this analysis that single-stage AVF-flap procedures are the optimum application of this technique.

The radial forearm flap has been used for reconstruction of the cervical esophagus most often as a patch or for circumferential repair of short defects (less than 5 cm). In the following three cases, the radial forearm flap was used to reconstruct circumferential cervical esophageal defects ranging from 5 to 12 mm in length. These procedures were successfully carried out in three patients in whom the intraoperative defect was unexpectedly large or the intra-abdominal viscera harvest would have been difficult. These patients had reliable esophageal function 8 to 24 months after surgery. We conclude that the radial forearm flap can be used for reconstruction of large circumferential defects of the cervical esophagus.

In cases of severe macromastia, the free nipple graft technique has been the traditional alternative to pedicle transposition. Distress over nipple survival in large reduction mammaplasty and long pedicle transposition is largely responsible for this.A retrospective investigation of the records of 142 reduction mammaplasty patients was carried out to determine whether nipple survival or overall complication rates were significantly different in patients undergoing larger (>1500 g per side) as compared with smaller reductions (< 1500 g per side). The 2 patient groups were compared with respect to mild or severe complications. Data were analyzed using Fisher exact test and 2-sample t tests. A P value of < 0.05 was considered statistically significant. No patient in either group had total nipple loss. There were no statistically significant differences in major or minor complications between the 2 groups. In our experience, the inferior pedicle, Wise pattern reduction is a reliable and predictable method of reduction, appropriate for all breast sizes and pedicle lengths.

We investigated the changes in the properties of water when exposed to sunlight for 40 days. We hypothesize and prove that solar irradiation to water entraps electromagnetic radiation as potential energy, which becomes kinetic energy in various systems. It is postulated that photochemically-induced energy transfers, associated with individual spectral emission of visible spectrum of solar light, exert diverse influences on biological systems. Bottles of distilled water, individually wrapped in spectral-colored cellophane were exposed to sunlight and compared to an unwrapped bottle to determine chemical and physical changes as well as modifications of biological properties. Each bottle of water was named according to the color of cellophane paper with letter E (stands for exposed) as a prefix with (E-violet, E-indigo, E-blue, E-green, E-yellow, E-orange, and E-red). E-control (without wrap) was exposed to polychromatic sunlight. This study addresses two main issues viz., the chemical and physical changes in E-water and its effect on biological activities. Chemical and physical composition analysis using inductively coupled plasma atomic emission spectrometry; physical conductance by a Wheatstone Bridge type conductivity meter; osmolarity by a vapor pressure osmometer; and, salt solubility profile of 10% sodium bicarbonate were determined. Furthermore, testing the effect of E-waters on human lymphocyte proliferation, mosquito larvae hatching and seed germination determined the functional role of solar radiation through specific spectrum/s of visible light on various biological processes. We found that water exposed to visible spectral emissions of sunlight had an altered elemental composition, electrical conductance, osmolarity and salt-solubility, as well as differences in bio-modulatory effects. A gradual increase in leaching of Boron from E-violet to E-red was noted. E-indigo showed maximal increase in electrical conductance and maximal salt solubility of sodium bicarbonate. E-blue inhibited phyto-hemagglutinin-induced immune cell proliferation and mosquito larvae hatching. E-orange stimulated root elongation in seed germination. We conclude that 40-day exposure of water to specific solar spectrum changes chemical and physical properties and influences on biological activity.

In Eastern cultures, such as India, it is traditionally recommended that women but not men cover their heads while working in the scorching sun. The purpose of this pilot study was to determine whether there was any scientific basis for this cultural tradition. We examined the differential cytotoxic effects of ultraviolet A light (UVA) on an established T cell line treated with female and male sex hormones. CD4+ Jurkat T cells were plated in 96 well plates at 2 x 106 cells/ml and treated with 17beta-estradiol (EST) or testosterone (TE). These cells were irradiated by UVA light with an irradiance of 170 J/cm2 for 15min at a distance of 6 cm from the surface of the 96-well plate. Controls included cells not treated with hormones or UVA. The effects of EST and TE were investigated between 1 and 20 ng/mL. Cytotoxicity by fluorescein-diacetate staining and COMET assay generating single strand DNA cleavage, tail length and tail moment measurements were examined. The effect of estrogen (5ng/mL) on apoptosis and its mediators was further studied using DNA laddering and western blotting for bcl-2 and p53. We found that EST alone, without UVA, enhanced Jurkat T cell survival. However, EST exhibited a dose-related cytotoxicity in the presence of UVA; up to 28% at 20 ng/ml. TE did not alter UVA-induced cytotoxicity. Since TE did not alter cell viability in the presence of UVA further damaging studies were not performed. COMET assay demonstrated the harmful effects of EST in the presence of UVA while EST without UVA. had no significant effect on the nuclear damage. Apoptosis was not present as indicated by the absence of DNA laddering on agarose gel electrophoresis at 5ng/ml EST or TE +/- UVA. Western blot showed that estrogen down regulated bcl-2 independently of UVA radiation while p53 was down regulated in the presence of UVA treatment. EST and TE have differential effects on UVA-induced cytotoxicity in Jurkat T-lymphocyte which suggested that women may be more susceptible to the harmful effects of solar irradiation than men.

The induction of endogenous vascular endothelial growth factor (VEGF) production in the skin flap with ischemic injury and the effect of exogenous VEGF on survival of the ischemic skin flap were studied in rats. A dorsal flap model (3x10 cm(2)) was used in this study. In Part I, biopsies were taken from the flap at 2.5, 5.5, and 8.5 cm distances from the distal edge at 0, 6, 12, and 24 h after the flaps were sutured. Malonyldialdehyde (MDA) and VEGF(165) protein level were measured. In Part II, exogenous VEGF (1 microg/ml) was injected subdermally into the flaps in 14 rats before the flaps were replaced. Flaps that received a saline injection were used as the controls. The skin paddle survival was measured on postoperative day five. The results showed that the MDA level in the distal part of the flap significantly increased at 24 h postoperatively when compared to MDA in other parts of the flap. However, VEGF levels in the distal part of the flap significantly decreased when compared to the middle part of the flap. Subdermal injection of exogenous VEGF to the distal area of the flap could significantly improve survival of the distal flap (89% of total skin paddle) when compared to the control, which had a 64% mean percent survival. We conclude that production of endogenous VEGF protein is significantly increased in the skin flap with mild ischemia, but decreased in the flap with severe ischemia. Administration of exogenous VEGF could significantly enhance survival of ischemic flaps.

The effects of static electromagnetic fields (SEFs) on MG-63, a human osteoblast cell-line, were investigated. We examined proliferation, proline uptake and gene expression in an SEF approximately 1/728th the intensity of those previously reported. Cells were placed within an SEF apparatus (average field intensity of 0.618mT) with appropriate controls. Proliferation was measured by 3H-thymidine incorporation and showed a 34% decrease in cells exposed to SEF (P = .0001; N = 3). Proline, a major component of collagen necessary for bone formation by osteoblasts, incorporation was reduced 37% (P = 0.006; N = 3). Reverse-transcription-polymerase chain reaction revealed that collagen I, alkaline phosphatase, parathyroid hormone-receptor, and osteocalcin mRNA's were down regulated with the low intensity SEF. Exposure to very low SEFs affects the MG-63 osteoblasts in a manner that may be detrimental to bone formation.

Aeromonas hydrophila infection has been described as the cause of necrotizing fasciitis in patients with suppressed immune systems, burns, or trauma in an aquatic setting. We report a case in which severe necrotizing fasciitis involving hand, arm, chest, and lateral side of trunk, along with toxic shock, developed after the patient was bitten by a venomous snake. Mixed aerobic and anaerobic bacteria, including A hydrophila, were isolated from the wound culture. The patient was treated with antivenom, a diuretic regimen, broad spectrum antibiotics, and 18 separate surgical procedures. After the application of skin grafts, the wound completely healed. This case illustrates that a venomous snakebite may result in infection with A hydrophila and can cause severe necrotizing fasciitis. Early and aggressive surgical intervention should be implemented as soon as the necrotizing fasciitis is diagnosed.

It has been observed previously that a hematoma affects skin flap survival adversely through free radical action. The current study was undertaken to determine whether similar mechanisms are operative in skin grafts. The experiment was divided into two parts. During part I, 2 x 2 cm2 split-thickness skin grafts (STSGs) were harvested from 18 Fischer rats and were divided randomly into three groups (each consisted of six grafts), and incubated with plasma, blood, and blood plus 70 mg deferoxamine for 48 hours respectively. Tissue samples were assayed for lipoperoxidation (malondialdehyde [MDA]), superoxide dismutase (SOD), and nitric oxide synthase (NOS). During part II, 36 STSGs were harvested and were divided randomly into three groups. The grafts were incubated as in part I for 48 hours. The STSGs were then affixed to the same dimension recipient beds created on the back of 36 inbred rats. Survival was evaluated 7 days postoperatively. The results showed that there was no significant difference in MDA and NOS levels between each incubated graft group in part I. Only the SOD level in both grafts incubated with plasma and blood plus deferoxamine were significantly higher than the grafts over blood alone (p < 0.05). During part II, there was no significant difference of the average STSG survival percentage between the groups incubated with blood and blood plus deferoxamine (35.8 +/- 6.5% and 52.0 +/- 9.5%). The survival percentage of the group incubated with plasma was 81.8 +/- 7.3%, which was significantly higher than the other two groups (p < 0.01). The authors concluded that unlike a distal flap model, the pathological importance of free radicals in survival of the STSG over a hematoma is insignificant. A more likely hypothesis, as suggested by others, is that a hematoma serves as a barrier preventing angiogenesis.

Rigid fixation has been used over the past 20 years for the long-lasting correction of traumatic and congenital craniofacial defects. It has been noted that the use of plates and screws can result in the migration of the hardware through the skull to the inner cerebral cortex where it embeds in the dura. In addition, there is controversy concerning the safety of using titanium plates in the pediatric population. We report here on an 8-year-old boy who presented to our clinic with a chronic headache after rigid craniofacial fixation using titanium plates 7 years before.

The potential for hyperbaric oxygen therapy (HBO) to decrease the untoward effects of a secondary ischemic event was studied in the rat superficial epigastric flap model. The secondary venous ischemic flap was created by cross-clamping the vascular pedicles for 2 h. Twenty-four hours later, the flap was reelevated and the venous pedicle was occluded for 5 h. Thirty-two rats were divided into three groups. In experimental group 1, animals received HBO treatment immediately prior to the initial flap elevation and ischemia at 2 atmosphere pressures for 90 min. In experimental group 2, the rats underwent a similar course except for a second 90-min HBO course immediately prior to the secondary venous occlusion. The rats without HBO therapy were used as controls. The results showed that all control flaps were nonviable at 1 week by clinical inspection and fluorescein injection. Complete flap survival occurred in 20% of group 1 flaps and 30.8% of group 2 flaps. Partial flap survival occurred in the rest of the flaps in these two groups, with mean survival areas of 48% and 55%, respectively. In conclusion, HBO treatments significantly increase the survival of flaps subjected to a secondary ischemia, even if administered before the primary ischemia. Administering HBO prior to secondary venous ischemia was marginal, which may be due to the effect of O(2) given by HBO not lasting longer than 5 h., (Copyright 2002 Wiley-Liss, Inc.)

In total, 41 consecutive patients with "idiopathic carpal tunnel syndrome" and abnormal electrophysiologic findings who underwent carpal tunnel release were studied prospectively. The focus of this investigation was the evaluation of the levels of specific chemical mediators within the serum and flexor tenosynovium of these patients. Blood was collected from these patients within 1 week prior to carpal tunnel release, and flexor tenosynovium was obtained at time of surgery. Specimens were then analyzed to determine the levels of interleukins 1 and 6, prostaglandin E(2) (PGE(2)), and malondialdehyde bis diethyl acetal. These values were compared to those of controls who had no evidence of carpal tunnel syndrome. A significant increase was noted in the serum malondialdehyde and tenosynovial levels of malondialdehyde, interleukin 6, and prostaglandin PGE(2) compared to controls. The elevated levels of these biologic factors and the absence of interleukin 1 elevation support a noninflammatory ischemia-reperfusion etiology for so-called "idiopathic carpal tunnel syndrome" that causes progressive edema and fibrosis of the tissues within the carpal canal. These findings correlate with previous histopathology reports. We believe that "idiopathic carpal tunnel syndrome" is an "-osis" not an "-itis.", (Copyright 2002 Wiley-Liss, Inc. MICROSURGERY 22:378-385 2002)

The effect of exogenous vascular endothelium growth factor (VEGF) on the survival of the distal skin paddle with early pedicle division was studied in a rat tubed pedicle flap model. In part I, tubed pedicle skin flaps were created on the backs of 14 rats. The pedicle was divided after an interval of 3, 4, 5 or 7 days, and the survival area of each distal skin paddle was measured 5 days after the pedicle was divided. The percentages of survival were 0, 24.9%, 89.9% and 100%, respectively. In part II, tube flaps were created in 20 rats. In the experimental group, 2 ml of VEGF (50 microg ml(-1)) was injected into the recipient bed during tube flap creation in each rat. In the control group, 2 ml of saline was given. The tubed pedicle was divided 4 days after creation. The mean survival area of the distal skin paddle in the group treated with VEGF was 7.32 +/- 1.36 cm(2) (80.91%) at 5 days after pedicle division, which was of statistical significance when compared with the survival in the control group of 2.70 +/- 1.89 cm(2) (27.9%). The histology showed angiogenesis at the skin paddle-recipient bed interface following VEGF injection. These results demonstrate that the subcutaneous administration of VEGF into the recipient bed of the tube flap transfer can induce angiogenes is at the junction between the donor and the recipient bed, and improve skin paddle survival with early pedicle division., (Copyright 2002 The British Association of Plastic Surgeons.)

Motor vehicle collisions are second only to altercations as the most common cause of mandible fractures. This article details in a retrospectively studied group the incidence of isolated mandible fractures and associated injuries in patients who were involved in motor vehicle collisions. This group consisted of 148 patients with mandible fractures listed in the University of Mississippi's trauma registry during the past 5 years. In almost all patients, associated injuries occurred with mandible fractures that were caused by motor vehicle collisions, with an incidence of 99.3 percent. Facial and head lacerations and facial fractures were the leading associated injuries, occurring in more than half of the patients who had a mandible fracture. Closed head injury is the major life-threatening associated injury and cause of mortality. The life-threatening injuries occurred in 64.8 percent of patients in this study. The mortality rate in this group of patients was 8.1 percent. These data suggest that mandible fractures from motor vehicle collisions should never be viewed as an isolated injury but rather as part of a spectrum of significant and sometimes life-threatening injuries that require thorough trauma evaluation at the time of presentation.

Both smooth muscle cells and endothelial cells play an important role in vascular wound healing. To elucidate the role of fructose-1,6-diphosphate, cell proliferation and cell migration studies were performed with human endothelial cells and rat smooth muscle cells. To mimic blood vessels, endothelial and smooth muscle cells were used in 1:10, 1:5, and 1:1 concentrations, respectively, mimicking large-, mid-, and capillary-sized blood vessels. Cell migration was studied with fetal bovine serum-starved cells. For cell proliferation assay, cells were plated at 30-50% confluency and then starved. The cells were incubated for 48 h with fructose-1,6-diphosphate at (per ml) 10 mg, 1 mg, 500 microg, 250 microg, 100 microg, and 10 microg, pulsed with tritiated-thymidine and incubated with 1 N NaOH for 30 min at room temperature, harvested, and counted. For migration assay, confluent cells were starved, wounded, and incubated for 24 h with same concentrations of fructose-1,6-diphosphate as in proliferation assay. The cells were fixed and counted. Smooth muscle cell proliferation was inhibited by fructose-1,6-diphosphate at 10 mg/ml. In the xenograft models of 1:10, 1:5, and 1:1 fructose-1,6-diphosphate inhibited proliferation at 10 mg/ml. In migration studies 10 mg fructose-1,6-diphosphate per ml was inhibitory to both cell types. In large-, mid-, and capillary-sized blood vessels, fructose-1,6-diphosphate inhibited proliferation of both cell types at 10 mg/ml. At the individual cell level, fructose-1,6-diphosphate is nonstimulatory to proliferation of endothelial cells while inhibiting migration, and it acts on smooth muscle cells by inhibiting both proliferation and migration.

The Zucker fat rat inherits obesity and hyperinsulinemia, exhibits insulin resistance, and is, therefore, a model of adult onset, or type II, diabetes. The purpose of this study was to determine if excision of fat depots from the infant Zucker (fa+/fa+) rat would affect growth, fat cell number, hyperinsulinism, and hyperlipidemia. In the experimental design, 10 percent of the total body weight (inguinal and interscapular depots) was excised at 6 weeks of age from 18 fat and 18 lean (fa+/fa-) litter mates, with 18 fat and 18 lean rats serving as nonoperated controls. At intervals, serum glucose, insulin, cholesterol, and triglycerides were measured. Initially, the operated fat group was significantly (p < 0.01) lighter than the nonoperated group. By 9 weeks postoperatively, the operated fat rat group had regained weight and continued to grow at the same rate as the nonoperated fat rats because of intra-abdominal fat depots. Lipectomy had no effect on growth rate of the lean rat group. Although lipectomy caused no consistent change in serum glucose or insulin levels, it caused a significant decrease in lipid levels. For example, the operated fat rats had a reduction in cholesterol from 876 to 171 mg/dl by 15 weeks postoperatively, and serum cholesterol persisted at about 50 percent of the nonoperated group throughout the rest of the study (38 weeks postoperatively). Even a greater reduction in triglyceride levels occurred, for example, from 7415 to 1082 mg/dl at 24 weeks postoperatively. Lipectomy did not cause a change in lipid levels in the lean group. It is concluded that the lipectomy in the Zucker fat group is an excellent model to evaluate the effects of changes in fat cell number on lipid metabolism.

Optic nerve compression is one of the complications in craniofacial surgery and blepharoplasty. We have shown previously that acute and chronic nerve compression produce significant tissue injury in rat sciatic nerve. In the present study the optic nerve was evaluated for possible ischemia/reperfusion injury after acute compression in an animal model. Male New Zealand White rabbits were used in the experiment. The optic nerve was subjected to 2-hour compression followed by reperfusion for 1 hour. Nerve compression was established by banding the optic nerve with silastic tubing. The compressed optic nerve was assayed for malondialdehyde, an indicator of lipid peroxidation, measured as thiobarbituric acid reactive substances (TBARS). The TBARS levels increased significantly to 2.5 times normal, from 37+/-6 pmoles per milligram tissue (N=6) to 90+/-12 pmoles per milligram tissue dry weight (N=5) in the compressed/reperfused nerve (p < 0.05). Much of these increases were prevented by treatment with deferoxamine, an iron chelator and antioxidant. The results indicate that optic nerve is injured by acute compression followed by reperfusion. The nerve compression injury appears to be due to reactive oxygen species and can be ameliorated by treatment with free radical scavengers.

Cell injury by oxidative stress is an important mechanism for renal epithelial cell destruction. This study observed the protective effect of turmeric and its constituents on H2O2-induced injury. Turmeric consists of a water soluble turmerin and lipid soluble curcumin with potent antioxidant properties. Confluent LLC-PK1 cells were labelled with 3H-arachidonic acid at 0.1 microCi/ml over 18 h and then further labelled with 51Cr. Turmeric ( 100 microg/ml-0.1 microg/ml), turmerin (800 ng/ml-0.8 ng/ml), curcumin (100 microg/ml-0.1 microg/ml), vitamin E (100 microM) and 21-aminosteroid (20 microM) were added and incubated for 3 h at 37 degrees C in 24-well plate. The adherent cells were washed and incubated for 3 h with 1.5 mM H2O2 at 37 degrees C. 3H-arachidonic acid release, 51Cr release and lipid peroxidation by the thiobarbituric acid reaction was determined. Turmeric ( 100 microg/ml) and curcumin (100 microg/ml, 10 microg/ml) gave as much protection as did vitamin E in both chromium release assay and lipid degradation while Turmeric (100 microg/ml) and curcumin (100 microg/ml) gave comparable inhibition of lipid peroxidation. Turmerin and 21-aminosteroid showed no protection. These findings provide evidence that turmeric and curcumin provide protection against oxidative stress in a renal cell line.

This study evaluated the capacity of diabetic rats to recover the ability to walk after nerve repair or nerve graft of the posterior tibial nerve at thigh level. Functional recovery of the posterior tibial nerve was evaluated by walking track analysis during regeneration in streptozotocin-induced diabetic rats. Surgical procedures were performed 8 weeks after induction of diabetes. The nerve repair was epineurial. The nerve graft was a 1.5 cm segment orthotopically replaced. There was no significant difference in functional recovery between normal and diabetic rats for both the nerve repair and nerve graft groups at 6, 12, and 24 weeks after nerve reconstruction. It is concluded that the presence of diabetes is not a contraindication for nerve reconstruction.

Nitric oxide (NO) under basal conditions is an important regulator of vascular tone. Under ischemic conditions, however, NO can combine with superoxide anion to produce the damaging hydroxyl free radical. The current project observes the effect of inhibiting NO production (L-Nitro-amino-methyl-arginine, L-NAME) on flaps rendered ischemic by secondary (2 degrees) venous obstruction. Eighty rats had 3 x 6 cm skin flaps based on the epigastric vessels. Primary (1 degree) ischemia was produced by arteriovenous occlusion for 2 hours; (2 degrees) venous ischemia was induced by clamping the vein, alone for either 3 or 5 hours. Thirty minutes prior to 2 degrees ischemia, rats received either L-NAME (30 mg/kg) or saline buffer. Flap survival was assessed 7 days later and Chi-square analysis was used. At 3 hours of ischemia, treatment improved survival from 55% to 85% (P < 0.05). Treatment also improved survival at 5 hours of ischemia from 5% to 35% (P < 0.04). Although under resting conditions, NO is a potent vasodilator, during 2 degrees venous obstruction it may contribute to flap necrosis.

The effects of tissue expansion on free flap tolerance and metabolic response to secondary ischemia were evaluated. A total of 178 male syngeneic Lewis rats were used: 28 in perfusion study and 75 donor and 75 recipient animals in flap survival study. Animals were organized in three experimental groups: control, sham operation, and expansion group. Sham group animals had the expander implanted but not insufflated. After 4 weeks of tissue expansion, 3 x 5-cm epigastric free flaps were transplanted to recipient animals. Twenty-four hours later, secondary ischemia was produced by 3-hour venous occlusion. Flap survival, perfusion, and enzyme activities were determined. Pre-expanded skin flaps had an increase in perfusion of approximately 700% as measured by fluorescein levels compared with control flaps (p < 0.001) and demonstrated a better success rate (76%) compared with those of the control (40%) (p < 0.05) and sham (28%) groups (p < 0.05). Glutathione peroxidase, glutathione reductase, and glucose 6-phosphate dehydrogenase of the antioxidant defense systems significantly increased in skin in both the sham and the expansion groups. In response to secondary ischemia, the control and sham groups exhibited a decrease in enzyme activities of the glutathione redox cycle, whereas the expansion group showed no significant changes from the elevated baseline activities. Tissue expansion improved flap tolerance to secondary ischemia by increasing flap circulation and probably by augmenting tissue metabolic response to oxidative stress.

Nerve compression causes injury by local ischemia and direct mechanical distortion. Peripheral nerves in diabetes mellitus are more prone to injury than those of nondiabetics. We sought to determine whether reperfusion-induced, oxygen-derived free radical injury occurs in peripheral nerves subjected to acute compression in normal and chronically diabetic rats. Female Sprague-Dawley rats weighing 250 to 275 g (N = 347) were divided into two groups: normal and streptozocin-induced diabetics. A total of 187 normal and 160 diabetic nerves were analyzed. After 8 weeks of untreated hyperglycemia, the sciatic nerves of normal and diabetes mellitus rats were subjected to one of three operations: a sham operation, 24-hour compression alone, and 24-hour compression followed by 1-hour reperfusion (CR). Nerve compression was established by banding the right sciatic nerve with a Silastic tubing, 1 cm long and 0.62 mm internal diameter, which was secured with 6-0 nylon suture. In the CR group, after 24 hours of compression, the tubings were released for 1 hour to permit reperfusion. Nerve tissue within the zone of compression underwent biopsy examination and was frozen for subsequent analysis. Blood flow to the nerve was quantified by injecting fluorescein (10 mg/kg intravenously) 10 minutes before harvest and measuring tissue levels fluorometrically. Compression with the Silastic tubing significantly reduced neural blood flow by 75%. Blood flow improved but failed to return to baseline levels after tubing release in diabetes mellitus nerves while perfusion returned to baseline in non-diabetes mellitus nerves. Nerve homogenate was assayed for malonyldialdehyde, an indicator of lipoperoxidation, as well as enzymes of cellular defense and glucose metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of 21-aminosteroid, a lazaroid (U74389F), on tissue injury after secondary ischemia was evaluated in 3 x 5 cm island skin flaps in male Sprague-Dawley rats (n = 30). Primary ischemia was produced by arteriovenous occlusion for 1 hour. Eighteen hours later, secondary ischemia was inflicted by 4-hour venous occlusion. The treatment group received intravenous lazaroid (3 mg/kg) 30 minutes before the start of secondary ischemia. The control group received the same volume of citrate buffer vehicle using the same route and schedule. Skin-flap survival was an all-or-none phenomenon and assessed at 7 days after secondary ischemia. Malondialdehyde (MDA) content was measured to determine the occurrence of lipid peroxidation. Myeloperoxidase (MPO) activity was assayed to assess the degree of neutrophil infiltration. Treatment with this lazaroid significantly improved the survival rate from 0 percent (0 of 13) to 53 percent (9 of 17) (p < 0.01). Malondialdehyde content was 62 +/- 10 (mean +/- SEM, n = 4) pmol/mg dry weight in normal skin. Malondialdehyde increased by 3 times normal in the flaps destined to survive and by 13 times in the flaps destined to undergo necrosis (p < 0.001). Myeloperoxidase activity was negligible in normal skin. At the end of secondary ischemia, the flaps destined to survive exhibited a high myeloperoxidase activity. The flaps destined to necrosis showed the enzyme activity 2.2 times more than surviving flaps (p < 0.01). The results suggest that the lazaroid U74389F may improve survival by attenuating neutrophil infiltration and by reducing lipid peroxidation.

We have studied the recovery of microvascular function in ischemic epigastric skin flaps by characterizing the regional hemodynamics in the axial and random portions of double- and single-pedicle island skin flaps in the rat. Blood flows were measured with radiolabeled microspheres 1 day after bipedicle flaps were elevated and at 4 hr, 72 hr, and 1 week after ligation of one of the pedicles. These hemodynamic measurements were correlated with assessments of angiogenesis and skin necrosis performed by lectin histochemistry and histopathology. Twenty-four hours after the skin flap elevation, the mean blood flow was 0.26 ml.min-1.g-1. After the ligation of one pedicle, the blood flow in the axial portion of the skin flap was unchanged at 4 hr (0.22 ml.min-1.g-1), declined insignificantly at 72 hr (0.15 ml.min-1.g-1), and remained normal at 1 week. In the random portion of the skin flap very little collateral blood flow was present at 4 hr (0.06 ml.min-1.g-1) and 72 hr (0.09 ml.min-1.g-1). Blood flow in the random skin flap returned to normal by 1 week (0.27 ml.min-1.g-1). Reelevation of the skin flap at 1 week caused an insignificant decline (10%) in total blood flow to the skin flap. Skin necrosis was detected histologically at 72 hr only in the lateral portion of the random skin flap, where blood flow was less than 0.03 ml.min-1.g-1. Increased areas of lectin binding to vascular endothelium were seen in the subdermal layers of the skin flap by 1 week, presumably due to angiogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

There is ample evidence of the involvement of free radicals in mediating skin flap necrosis. Dimethyl sulfoxide (DMSO) is a well-tolerated, safe drug that is a powerful scavenger of the hydroxyl free radical. The current study investigated the effect of DMSO on the survival of 9 x 4 cm skin flaps based on the epigastric vessels subjected to primary venous occlusion. Forty-seven skin flaps were elevated and the epigastric vein was occluded by a microvascular clamp for 8 hours. Group 1 received DMSO (1.5 gm/kg) intraperitoneally at reperfusion. Group 2 received saline solution, group 3 received DMSO at reperfusion and every day for 5 days, group 4 received DMSO preoperatively and then as in group 3, and group 5 was the saline solution control for groups 3 and 4. DMSO did not increase percent flap survival when given as a single dose at reperfusion (40.6% +/- 42.7%) compared with saline solution (33.7% +/- 41.2%). When DMSO was continued in the postoperative period, group 3 (86.2% +/- 25.8%) and group 4 (78.0% +/- 32.5%) had significantly better survival than the saline solution control group (32.6% +/- 39.8%) (p < 0.01 and p < 0.03, respectively). There was no significant difference between groups 3 and 4. DMSO administered at reperfusion and postoperatively for 5 days significantly increased flap survival. It is hypothesized that this occurs through scavenging deleterious free radical species. This effect may have clinical significance.