Retardation Of Healing Research Articles

Bioactive poly(salicylic acid)-poly(citric acid) scaffolds improve diabetic wound repair via regulating HIF-1α, Nrf2 and macrophage.

Diabetic wounds environment is over-oxidized, over-inflammatory, leading to difficulties in regenerating blood vessels, and retardation of healing in diabetic wounds. Therefore, diabetic wounds can be treated from the perspective of scavenging oxidative free radicals and reducing the level of inflammation. Herein, we report a bioactive poly(salicylic acid)-poly(citric acid) (FPSa-PCG) hydrogel for diabetic wound repair. The FPSa-PCG hydrogel shows abilities of antioxidation, anti-inflammation, and regulation of macrophage phenotype. The FPSa-PCG hydrogel showed good biocompatibility, and obtain the abilities of promotion of macrophages migration, reduction of ROS generation, suppression of the M1-type macrophage polarization. FPSa and PCG could synergistically enhance the angiogenesis through upregulating the mRNA expression of HIF1Α, VEGF, and CD31 in endothelial cells and reduce the ROS level of macrophages through upregulating the mRNA expression of Nrf2. The in vivo diabetic wound model confirmed the promoting effect of FPSa-PCG hydrogel on wound closure in diabetes. The further studies found that FPSa-PCG hydrogel could induce the CD31 protein expression in the subcutaneous tissue and inhibit the TNF-a protein expression. This work shows that the simple composition FPSa-PCG hydrogel has a promising therapeutic potential in the treatment of diabetic wounds.

Relationship between calcinosis cutis in epidermal necrolysis and caspofungin, a physicochemical investigation

Epidermal necrolysis (EN) is a rare life-threatening condition, usually drug-induced and characterised by a diffuse epidermal and mucosal detachment. Calcinosis cutis is reported in various skin diseases, occurring preferentially with tissue damage, but has never been described in EN. Clinical, biological and histopathological characteristics of three patients were retrospectively obtained from medical charts. Immunohistochemistry of classical osteogenic markers was used to explore the pathogenesis of the calcifications; their chemical composition was determined by μFourier transform infra-red (μFTIR) spectroscopy and their localization and morphology by field-emission scanning electron microscopy (FE-SEM). In a recent letter, part of the results of this investigation has been already presented. In this contribution, we have added original data to this previous letter. We have investigated a set of biopsies corresponding to patients who presented atypical healing retardation due to calcinosis cutis. Through FE-SEM observations at the nanometre scale, we describe different areas where are present voluminous calcifications at the surface, submicrometre spherical entities within the papillary dermis and then large “normal” fibres. FE-SEM observations show clearly that “large” calcifications are the result of an agglomeration of small spherical entities. Moreover, micrometre scale spherical entities are the results of an agglomeration of nanometer scale spherical entities. Finally, the last set of data seems to show that the starting point of the calcifications process is “distant” from the epidermis in part of the dermis which appears undamaged. Regarding the chemical composition of large calcifications, different μFTIR maps which underlined the presence of calcium-phosphate apatite have been gathered. Moreover, histopathology indicates that these pathological calcifications are not induced following a trans-differentiation of the skin cells into an osteochondrogenic phenotype. The association of caspofungin administration, known to induce in vitro intracellular calcium influx, and inflammation, induced by EN, known to favor dystrophic calcifications in various inflammatory skin diseases, could explain this never-before reported occurrence of calcinosis cutis.

Curettage versus Zinc Oxide Eugenol as a Treatment Modality in Patients with Dry Socket

Dry socket (DS) is a very common complication of dental extraction. Although it is due to healing retardation, pain is the most important symptom in DS. Variant studies discussed many treatment methods for pain alleviation, but with wide controversy regarding the efficacy. Zinc oxide eugenol (ZOE) is an old treatment depends on the obtunding neurotoxic properties of eugenol. Zinc oxide eugenol was recommended by many authors; however, there is no general recommendation. Curettage was an accepted treatment method by some authors, but was contraindicated by others. The literature does not provide enough comparative data of two or more agents. In the current comparative study, forty patients with DS were randomly divided into two equal groups. In Group I, curettage was performed to remove the superficial layer of the bone of the extraction socket. A gauze pack was placed over the socket for 20 minutes. For group II a brief saline irrigation of the extraction socket was followed by lightly packing with a cotton pellet impregnated with fresh mix of ZOE. The current study demonstrated that curettage is more efficient than ZOE with regards to the required total treatment period and the number of the needed analgesic tablets.

Bio‐nanomechanics: Revealing the Role of Epithelial Mechanics and Macrophage Clearance during Pulmonary Epithelial Injury Recovery in the Presence of Carbon Nanotubes (Adv. Mater. 52/2018)

In article number 1806181, Dedy Septiadi, Barbara Rothen-Rutishauser, and co-workers develop an in vitro wound healing assay based on extensive photobleaching-induced apoptosis to study repair response of lung epithelial tissue after injury. The result reveals the importance of epithelial mechanics (i.e., cell pushing), phagocytic activity of macrophages during the repair, and retardation of healing upon cell exposure to carbon nanotubes.

Involvement of small G protein RhoB in the regulation of proliferation, adhesion and migration by dexamethasone in osteoblastic cells.

Long-term exposure to therapeutic doses of glucocorticoids (GCs) results in bone remodeling, which frequently causes osteoporosis and fracture healing retardation because of the abnormality of osteoblastic proliferation and differentiation. The mechanisms of GCs’ effect on osteoblasts are largely unknown. In this present study, we found that dexamethasone (Dex) could induce the expression of the small G protein, RhoB, in mRNA and protein levels in the osteoblast-derived osteosarcoma cell lines MG-63. The up-regulation of RhoB mRNA by Dex mainly occurs at posttranscriptional level by increasing its mRNA stability through PI-3K/Akt and p38 mitogen-activated protein kinase signaling pathways. Over-expression of RhoB in MG-63 cells magnified while down-regulation of RhoB level by RNA interference impaired Dex-induced growth inhibition but not differentiation. What’s more, over-expression of RhoB mimicked the effect of Dex on cell adhesion and migration. And interfering RhoB expression partially suppressed Dex-induced pro-adhesion and anti-migration in MG-63 cells. In conclusion, these results indicate that RhoB plays an important role in the pathological effect of Dex on osteoblastic growth and migration, which is a part of the mechanisms of GCs’ adverse effect on bone remodeling.

Stress and Traumatic Brain Injury Elicit Similar Cytokine Responses in Blood and Liver

Mildtraumatic brain injury (mTBI) is a major health issue comprising aheterogeneous and complex array of pathologies. Little is understood about the mechanisms of secondary injury in the evolution of damage after mTBI; however an apparent hepatic‐neural communication may generate a systemic inflammatory response (SIR). A stress‐mediated release of cortisol and catecholamines can enhance the SIR, leading to immunological dysfunction causing a retardation of healing in brain and systemic infrastructure. This study investigated the role of the SIR after TBI in male Wistar rats (N=129) that were subjected to one of four different procedures: mild TBI, moderate TBI, stress with mild TBI, or stress with sham TBI. Stress was generated using immobilization‐restraint tubes for 2 hours per day for the 4 days prior to injury. TBI was induced using a 500g weight‐dropmethod (from 100cm height for mild injury; and 120cm for moderate injury). Rats were sacrificed 6 hours, 48 hours, or 14 days after TBI or sham procedure. Serum corticosterone remained significantly elevated at 14‐days post‐injury. In order to correlate circulating inflammatory responses with liver specific responses, a panel of cytokines(e.g. IL6, TNFα, IFNγ, etc.) and SIR‐associated proteins (e.g. VEGF, TIMP, ICAM, etc.) were analyzed in liver tissue as well as in serum. Overall, we detected few differences in cytokine expression across the various experimental procedures or time‐pointsin serum or liver tissue (e.g. liver IFNγ at 48hr A.U.: modTBI 0.43±0.19;mildTBI 0.48±0.11; mildTBI w/stress 0.52±0.15; shamTBI w/stress 0.36±0.10; p=0.88). Thus, it appears that the SIR may not play a significant role in mild TBI pathology, specifically as it pertains to common circulating and hepatic cytokine pathways. Funded by USAMRMC. Author views not official US Army or DoDpolicy.

Effect of Subcutaneous Epinephrine/Saline/Local Anesthetic Versus Saline-Only Injection on Split-Thickness Skin Graft Donor Site Perfusion, Healing, and Pain

The technique for split-thickness skin graft harvest varies among surgeons. Even though there is scientific evidence that the subcutaneous injection of modified tumescent solution reduces blood loss during burn surgery, the technique has not been unanimously adapted because of, in part, fear of healing retardation. This study prospectively examines the effect of tumescent injection on donor site perfusion, healing, and pain. Ten burn patients in need of grafting with a need for two distinctly different donor sites were included. During the grafting procedure, the two donor areas were randomly assigned to receive either modified tumescent solution or warm sterile saline solution subcutaneously before skin graft harvest with a dermatome. Perfusion, pain, pruritus, and donor site healing were measured, and a follow-up evaluation on scar quality was performed. Baseline perfusion on day 1 was significantly less in the donor site injected with modified tumescent solution (62.26 vs 95.71 perfusion units; P = .031), whereas the response to heat was similar in both sites. The physiologic response to injury (hyperemia) on days 2 and 3 was not suppressed in the modified tumescent group. Pain reported on day 1 was 2.38/10 in the tumescent site and 3.38/10 in the saline site (P = .21). On all other days, measurements showed no difference between the two sites. Donor sites healed in an average of 16.1 days with modified tumescent solution and in 16.4 days with saline. Late follow-up showed no difference in scar quality. The subcutaneous injection of modified tumescent solution before split-thickness donor site harvest has no adverse effect on donor site perfusion past day 1 or donor site healing. The addition of a local anesthetic may decrease pain for 24 hours postoperatively, but the difference in this study group was not significant. This technique should be universally recommended.

Induction of Adhesion-dependent Signals Using Low-intensity Ultrasound

In multicellular organisms, cell behavior is dictated by interactions with the extracellular matrix. Consequences of matrix-engagement range from regulation of cell migration and proliferation, to secretion and even differentiation. The signals underlying each of these complex processes arise from the molecular interactions of extracellular matrix receptors on the surface of the cell. Integrins are the prototypic receptors and provide a mechanical link between extracellular matrix and the cytoskeleton, as well as initiating some of the adhesion-dependent signaling cascades. However, it is becoming increasingly apparent that additional transmembrane receptors function alongside the integrins to regulate both the integrin itself and signals downstream. The most elegant of these examples is the transmembrane proteoglycan, syndecan-4, which cooperates with α5β1-integrin during adhesion to fibronectin. In vivo models demonstrate the importance of syndecan-4 signaling, as syndecan-4-knockout mice exhibit healing retardation due to inefficient fibroblast migration1,2. In wild-type animals, migration of fibroblasts toward a wound is triggered by the appearance of fibronectin that leaks from damaged capillaries and is deposited by macrophages in injured tissue. Therefore there is great interest in discovering strategies that enhance fibronectin-dependent signaling and could accelerate repair processes. The integrin-mediated and syndecan-4-mediated components of fibronectin-dependent signaling can be separated by stimulating cells with recombinant fibronectin fragments. Although integrin engagement is essential for cell adhesion, certain fibronectin-dependent signals are regulated by syndecan-4. Syndecan-4 activates the Rac1 protrusive signal3, causes integrin redistribution1, triggers recruitment of cytoskeletal molecules, such as vinculin, to focal adhesions4, and thereby induces directional migration3. We have looked for alternative strategies for activating such signals and found that low-intensity pulsed ultrasound (LIPUS) can mimic the effects of syndecan-4 engagement5. In this protocol we describe the method by which 30 mW/cm2, 1.5 MHz ultrasound, pulsed at 1 kHz (Fig. 1) can be applied to fibroblasts in culture (Fig. 2) to induce Rac1 activation and focal adhesion formation. Ultrasound stimulation is applied for a maximum of 20 minutes, as this combination of parameters has been found to be most efficacious for acceleration of clinical fracture repair6. The method uses recombinant fibronectin fragments to engage α5β1-integrin, without engagement of syndecan-4, and requires inhibition of protein synthesis by cycloheximide to block deposition of additional matrix by the fibroblasts., The positive effect of ultrasound on repair mechanisms is well documented7,8, and by understanding the molecular effect of ultrasound in culture we should be able to refine the therapeutic technique to improve clinical outcomes.

Induction of Adhesion-dependent Signals Using Low-intensity Ultrasound

In multicellular organisms, cell behavior is dictated by interactions with the extracellular matrix. Consequences of matrix-engagement range from regulation of cell migration and proliferation, to secretion and even differentiation. The signals underlying each of these complex processes arise from the molecular interactions of extracellular matrix receptors on the surface of the cell. Integrins are the prototypic receptors and provide a mechanical link between extracellular matrix and the cytoskeleton, as well as initiating some of the adhesion-dependent signaling cascades. However, it is becoming increasingly apparent that additional transmembrane receptors function alongside the integrins to regulate both the integrin itself and signals downstream. The most elegant of these examples is the transmembrane proteoglycan, syndecan-4, which cooperates with α5β1-integrin during adhesion to fibronectin. In vivo models demonstrate the importance of syndecan-4 signaling, as syndecan-4-knockout mice exhibit healing retardation due to inefficient fibroblast migration1,2. In wild-type animals, migration of fibroblasts toward a wound is triggered by the appearance of fibronectin that leaks from damaged capillaries and is deposited by macrophages in injured tissue. Therefore there is great interest in discovering strategies that enhance fibronectin-dependent signaling and could accelerate repair processes.The integrin-mediated and syndecan-4-mediated components of fibronectin-dependent signaling can be separated by stimulating cells with recombinant fibronectin fragments. Although integrin engagement is essential for cell adhesion, certain fibronectin-dependent signals are regulated by syndecan-4. Syndecan-4 activates the Rac1 protrusive signal3, causes integrin redistribution1, triggers recruitment of cytoskeletal molecules, such as vinculin, to focal adhesions4, and thereby induces directional migration3. We have looked for alternative strategies for activating such signals and found that low-intensity pulsed ultrasound (LIPUS) can mimic the effects of syndecan-4 engagement5. In this protocol we describe the method by which 30 mW/cm2, 1.5 MHz ultrasound, pulsed at 1 kHz (Fig. 1) can be applied to fibroblasts in culture (Fig. 2) to induce Rac1 activation and focal adhesion formation. Ultrasound stimulation is applied for a maximum of 20 minutes, as this combination of parameters has been found to be most efficacious for acceleration of clinical fracture repair6. The method uses recombinant fibronectin fragments to engage α5β1-integrin, without engagement of syndecan-4, and requires inhibition of protein synthesis by cycloheximide to block deposition of additional matrix by the fibroblasts., The positive effect of ultrasound on repair mechanisms is well documented7,8, and by understanding the molecular effect of ultrasound in culture we should be able to refine the therapeutic technique to improve clinical outcomes.

Laser photobiostimulation of wound healing: Reciprocity of irradiance and exposure time on energy density for splinted wounds in diabetic mice

We have used a 660 nm laser diode in genetic diabetic mice to stimulate the healing of wounds covered with a Tegaderm HP dressing that causes a retardation of contraction (splinted wounds). The influence of irradiance (power density) on wound healing has been examined with the same energy dose delivered to the wounds. This energy dose caused maximal stimulation of healing in a previous study. A circular excisional wound was made on the left flank of diabetic mice using a 5-mm skin punch, and covered with a Tegaderm HP dressing. Four different treatments were tested: Treatment 1, not irradiated (control); treatment 2, 100 mW, 20 seconds; treatment 3, 50 mW, 40 seconds; treatment 4, 25 mW, 80 seconds. Treatments were given daily for 7 days. The irradiances for treatments 2, 3, and 4 were estimated to be 233-313, 116-156, and 58-78 mW/cm(2), respectively. In total, 53 mice were used. Wounds were harvested on day 14 and healing assessed from hematoxylin-eosin stained sections examined by light microscopy. The wounds were splinted in 42 of the mice, and splinting caused a retardation of healing. The findings showed that wound healing was stimulated to a similar extent by treatments 2, 3, and 4 and occurred mainly by reepithelization and granulation tissue formation. The laser parameters used represent an energy dose of 2.0 J per irradiation and, for an estimated area of irradiation of 32-43 mm(2), corresponds to an energy density of 4.7-6.3 J/cm(2). Irradiation 660 nm with irradiances estimated to be 233-313, 116-156, and 58-78 mW/cm(2) and an estimated energy density of 4.7-6.3 J/cm(2) each day for 7 days stimulated healing to a similar extent in splinted wounds of diabetic mice.

Laser photobiostimulation of wound healing: Defining a dose response for splinted wounds in diabetic mice

We have used a 660 nm, 80 mW laser diode in genetic diabetic mice to stimulate the healing of wounds covered with a Tegaderm HP dressing that causes a retardation of contraction (splinted wounds). The purpose of our study was to examine the effects of irradiating the wounds for different time intervals in order to determine a dose response relationship. A circular excisional wound was made on the left flank of diabetic mice using a 5-mm skin punch, and covered with a Tegaderm HP dressing. Mice were allocated to four groups in which wounds were irradiated 660 nm, 80 mW for 0, 10, 20, or 40 seconds each day for 7 days. In total, 51 mice were used. Wounds were harvested on day 14 and the healing assessed from hematoxylin-eosin stained sections examined by light microscopy. The wounds were splinted in 40 of the mice, and splinting caused a retardation of healing. The findings for the four treatments showed that irradiation for 20 second/day for 7 days brought about the greatest extent of healing. The wounds healed mainly by re-epithelization and granulation tissue formation. This duration of irradiation represents an energy dose of 1.6 J per irradiation and, for an estimated area of irradiation of 32-43 mm², corresponds to an energy density of 3.7-5.0 J/cm². Irradiation with 660 nm, 80 mW at an energy density of 3.7-5.0 J/cm² each day for 7 days caused the maximal stimulation of healing in splinted wounds of diabetic mice.

Efficacy of a Helicase-Primase Inhibitor in Animal Models of Ocular Herpes Simplex Virus Type 1 Infection

The aim of this study was to evaluate the effect of BAY 57-1293, a helicase-primase inhibitor, on herpes simplex virus type 1 (HSV-1) reactivation in mice and its efficacy on established disease in rabbits. BALB/c mice latent for McKrae-strain HSV-1 were reactivated via heat stress, treated with BAY 57-1293, and their corneas were swabbed for virus or the trigeminal ganglia (TG) obtained for quantification of viral DNA. New Zealand white rabbits were infected and treated topically or orally in comparison with trifluridine or valacyclovir. Oral BAY 57-1293 suppressed reactivation in HSV-1-infected mice and reduced the viral load in TG up to four orders of magnitude. In the rabbits, the therapeutic efficacies of topical BAY 57-1293 and trifluridine were similar. Once-daily oral BAY 57-1293 was significantly more effective than valacyclovir and as effective as twice a day topical trifluridine. BAY 57-1293 may be more effective than valacyclovir, without the cytotoxicity or potential healing retardation seen with trifluridine. Oral BAY 57-1293 may be a substitute for eye drops as an effective treatment for herpetic keratitis and might be useful in treating stromal keratitis and iritis, as well as preventing recurrences of ocular herpes.

Increased Lengthening Rate Decreases Expression of Fibroblast Growth Factor 2, Platelet-Derived Growth Factor, Vascular Endothelial Growth Factor, and CD31 in a Rat Model of Distraction Osteogenesis

The rate of lengthening has a profound impact on bone regeneration during distraction osteogenesis. Rapid distraction can delay or completely inhibit union, whereas distracting too slowly may lead to premature consolidation. However, the mechanisms responsible for retardation of healing due to rapid distraction have not been elucidated. This study explored whether rapid distraction alters the expression of certain angiogenic growth factors, in particular, fibroblast growth factor 2 (FGF-2), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-AA), and subsequent new vessel formation as evidenced by platelet endothelial cellular adhesion marker expression (CD31), an indicator of vascular budding. Unilateral femoral lengthenings were performed in 60 male Sprague-Dawley rats using a protocol that involved a 7-day latency period and distraction rates of either 0.5 (slow distraction) or 1.5 mm/d (fast distraction) for a total of 7.0 mm of lengthening. Animals were euthanized on postoperative days 8, 10, 12, 14, and 21 (n = 6 per time point and distraction rate). Expression of FGF-2, VEGF, PDGF-AA, and CD31 was characterized immunohistochemically. Cellular staining of FGF-2, PDGF-AA, VEGF, and CD31 was reduced on days 8 to 12 in the regenerate of the fast-distraction animals compared with the slow-distraction animals. Staining of all growth factors was weak on days 14 and 21 at the slow rate and absent at the fast rate. Regardless of time point, a similar spatial localization of growth factor expression was observed at the 2 rates of distraction. The reduced expression of angiogenic growth factors and CD31, a marker of new vessel formation, indicates that the angiogenic cascade and new vessel formation required for effective bone healing is disrupted at a distraction rate of 1.5 mm/d in a rat model of limb lengthening. Delayed bone healing with rapid distraction may be due in part to decreased cellular signaling required for angiogenesis. It may be possible to improve bone healing at increased distraction rates with the appropriately timed administration of growth factors.

Retardation of wound healing by procaine.

Lignocaine has previously been shown to retard wound healing; the retardation is directly related to the concentration of the drug used and is enhanced by the addition of adrenaline. The study described in this paper aimed to determine whether procaine has a similar effect and, if so, whether the effect of sterile water alone and of procaine in various concentrations on the tensile strength of skin wounds in rats. 5 and 7 days after operation. At 5 days sterile water had produced a significant retardation of wound healing. All concentrations of procaine produced significant retardation of healing at 5 days and adrenaline enhanced this effect. By 7 days the effect was greatly diminished and only those rats injected with 2 per cent procaine with adrenaline had significantly weaker wounds. The study suggests that 2 per cent procaine with adrenaline is better avoided and even when lower concentrations are used sutures should be retained for 7 days.

Proteinase-activated receptors 1 and 4 counter-regulate endostatin and VEGF release from human platelets

The roles of proteinase-activated receptors (PARs) in platelet functions other than aggregation are not well understood. Among these is the release of factors that regulate the process of angiogenesis, such as endostatin and VEGF, which, respectively, inhibit and promote angiogenesis. PAR1 and PAR4 are expressed on the surface of human platelets and can be activated by thrombin. In the present study, we have attempted to determine the roles of PAR1 and PAR4 in regulating release of endostatin and VEGF from human platelets. Aggregation and endostatin release could be elicited by a specific PAR4 agonist (AYPGKF-NH(2)). The PAR4 agonist concentration dependently suppressed VEGF release. A selective PAR1 agonist (TFLLR-NH(2)) induced platelet aggregation and VEGF release but suppressed endostatin release. Thrombin did not affect endostatin or VEGF release. However, in the presence of a selective PAR1 antagonist (SCH79797), thrombin stimulated endostatin release and suppressed VEGF release. Conversely, in the presence of a selective PAR4 antagonist (transcinnamoyl-YPGKF-NH(2)), thrombin stimulated VEGF release. In vivo, treatment of rats with established gastric ulcers with a PAR1 antagonist each day for 1 wk resulted in a significant retardation of healing. We conclude that PAR1 and PAR4 counter-regulate the release of endostatin and VEGF from platelets. These protease-activated receptors could therefore play a crucial role in regulating angiogenesis and in turn could regulate the processes of wound healing and tumor growth.

FTIR Spectroscopic Investigation of Mineral Structure of Streptozotocin Induced Diabetic Rat Femur and Tibia

Diabetes mellitus (DM) can be accepted as a heterogenous multi organ disorder that can affect various systems of the human body. Disorders include retinopathy, neuropathy, cardiomyopathy, musculoskeletal abnormalities such as diminished bone formation and bone healing retardation. Low bone mineral density is often mentioned as a complication for patients with insulin dependent diabetes mellitus (type I DM). Streptozotocin (STZ) induced diabetic rats are good models for investigation of the complications of insulin dependent diabetes. In the present study, the effects of STZ induced diabetes on the mineral environment of rat bones namely femur and tibia were studied by Fourier transform infrared (FTIR) spectroscopic technique. The results revealed that mineral crystal sizes increased and carbonate content decreased for diabetic femur and tibia. These changes can be due to the formation of osteoporosis which is widely seen in diabetic patients.

Improvement and retardation of wound healing: effects of pharmacological agents in laboratory animal studies.

Impaired wound healing is an important problem; retardation of healing may be induced by endogenous and/or exogenous factors and treatments capable of ameliorating these effects are needed. The effects of solutions containing light ichthyol or povidone iodine, of ointments containing zinc oxide (ZO) and/or cod liver oil (CLO), and of a polyurethane-hydrogel foam wound dressing were examined on healing of full-thickness murine skin wounds impaired by systemic dexamethasone. The effects of the ointments were also studied on murine skin ulceration induced by subcutaneous sodium dodecyl sulphate solution. Light ichthyol at 1% and 2% but not at 5% and 10%, povidone iodine at 1% and the foam accelerated impaired healing. The ointments containing ZO or CLO accelerated healing of impaired full-thickness wounds and of ulcerated skin; ZO and CLO were synergistic. These studies demonstrate the value of murine models in the evaluation of agents employed in veterinary wound dressings.

Use of Granulated Sugar to Pressure Sores

In the case of severely injured or weak patients, one of the most difficult problems to physicians is the management of pressure sores. It is generally known, however, that severely injured deep pressure sores extended to the bones are cured only by surgical treatment.On the other hand, it has been reported that sugar promotes granulation of tissues and thus cures wounds. We examined the effect of sugar mixed with povidone-iodine or silver-sulfadiazine ointment on the deep pressure sores of Grade 3/4 (Shea 1975). Within the first week of sugar therapy, the color of the ulcers turned to fresh pink, thus indicating that the circulation of the sore and its surrounding were improved. Then the ulcers gradually disappeared and filled with pink granulation tissue. However, long-term application of povidone-iodine sugar sometimes caused infection with Pseudomonas aeruginosa, resulting in retardation of healing. Use of silver-sulfadiazine sugar cured the infection and promoted granulation of tissues. Finally the ulcers were covered with skin. But duration of the therapy depended upon the degree of the sores as well as of the conditions of patients. Thus, it seems that sugar therapy is a useful means for the treatment of severe pressure sores.

Effect of irradiation-timing on the initial socket healing in rats

The effect of a single dose of 1500 R on early postextraction socket healing was studied in jaws of rats. A severe delay in healing was found in animals irradiated 2 weeks prior to extraction. Retardation of healing to a lesser degree was demonstrated in sockets irradiated immediately after exodontia.

The effects of extraperiosteal and subperiosteal dissection. II. On fracture healing.

The effects of subperiosteal and extraperiosteal dissection on the healing of tibial osteotomies were studied in fourteen rabbits killed three weeks after the osteotomy. Of the tibiae exposed subperiosteally, 71 per cent healed; of those exposed extraperiosteally, only 7 per cent had solid union. The first group had a significantly lower level of hydroxyproline in the callus and higher values for breaking load, breaking strength, and absorption of energy to failure. In ten animals that also had muscle transection at the osteotomy site, the rate and type of healing was similar whether no dissection, subperiosteal dissection, or extraperiosteal dissection had been done, but the callus showed lower calcium levels and higher hydroxyproline levels than in either of the groups with muscle trauma. This implies retardation of healing caused by muscle injury. Our data suggest that in the absence of muscle damage, subperiosteal dissection results in earlier healing than does extraperiosteal dissection. Muscle transection markedly retards healing; then, after transection, neither type of dissection appears to retard healing more than the other.