Bone wound healing after maxillary molar extraction in ovariectomized aged rats

Epididymal and testicular spermatozoa have been used widely for ICSI among men with obstructive azoospermia and NOA. New aspiration and biopsy techniques are available, and several sperm preparation methods have been described to isolate sperm. Most samples have sufficient sperm for cryopreservation. Accordingly, clinicians must sort through these new procedures to develop treatment plans that best suit their practices. In the future, other methods will be developed, and clinicians will have to critically review them prior to use.     

Nutrition and wound healing

This paper reviews evidence that suggests malnutrition exists among the sick population in hospital and at home, a situation that has not improved in 20 years. It examines the consequences of malnutrition in broad terms and its effect on wound healing. The role of specific nutrients for wound healing is discussed, and finally the barriers which prevent nurses from delivering adequate patient nutrition are exposed.     

General principles of wound healing

Wound healing is a complex process involving different biologic and immunologic systems. Despite improvements in diagnostics and therapy, wound failures remain a clinical problem. The approach to a nonhealed wound is an interdisciplinary challenge that should not be underestimated. Better understanding of the complex wound-healing cascade helps our approach to wound healing and its possible failure. Manipulations of the involved immunologic features offer future therapeutic strategies.     

Nutritional aspects of wound healing

The nutritional aspects of wound healing include completing a nutritional assessment, estimating a patient's nutrient needs, and evaluating options for medical nutrition therapy. Some key nutrients involved in wound healing are discussed and their food sources described.     

Specific nutritional factors in wound healing

Provision of a nutritionally complete diet provides the optimum environment for recovery and healing. Clinical research and experience suggest that several nutritional factors may be associated with impaired wound healing, including vitamin C, vitamin A, vitamin E, zinc, protein, and individual amino acids. Studies have shown that supplementing specific nutrients to patients who are not clinically deficient has little effect on pressure ulcer healing. Inexpensive, nontoxic nutritional supplements may not harm the patient, however, some nutritional supplements are expensive or potentially toxic. Before routine use of these nutrients can be justified, further research is required.     

The importance of nutrition in wound healing

Nursing Standards recent Focus on Nutrition campaign raised some uncomfortable issues about nurses' knowledge of wound healing. We continue the theme here, with a review of the importance of good nutrition for effective wound healing.     

Nitric oxide regulates wound healing

Nitric oxide (NO) synthesis occurs during wound healing, but its role has not been defined. To study the effect of NO on wound repair, S-methyl isothiouronium (MITU, a competitive inhibitor of NO synthase) was administered at a dose of 10, 50, and 100 mg/kg body weight/day, using intraperitoneally implanted miniosmotic pumps. Groups of 10 male Balb/C mice underwent a dorsal skin incision and polyvinyl alcohol sponges were inserted subcutaneously. The animals were sacrificed 10 days postwounding and wound breaking strength and hydroxyproline content of sponges, an index of reparative collagen deposition, were determined. Some sponges were used to harvest wound fluid and infiltrating cells, which were then incubated overnight with or without 1 mM MITU. Nitrite and nitrate, stable end products of NO, were measured in wound fluid and in wound cell culture supernatants. Continuous intraperitoneal infusion of MITU significantly decreased wound fluid nitrite/nitrate concentrations in a dose dependent manner (P < 0.01). Inhibition of wound NO synthesis by 100 mg MITU/kg/day was paralleled by lowered wound collagen accumulation (P < 0.01) and wound breaking strength (P < 0.01). In vitro NO synthesis by wound cells obtained from animals treated with 100 mg MITU/kg/day was not significantly different from controls (12.6 +/- 1.2 vs 10.7 +/- 0.6 nmole NO2 + NO3/microgram DNA), reflecting the reversible inhibition of NO synthase by MITU. However, NO production was equally inhibited in wound infiltrating cells by the in vitro addition of MITU (83% vs 85%, respectively). These data suggest that nitric oxide synthesis is critical to wound collagen accumulation and acquisition of mechanical strength.     

Angiogenesis in wound healing and tumor metastasis

Formation of new blood vessels is essential for several physiological and pathological events, e.g. embryogenesis, wound healing and tumor growth and metastasis. In order to increase the insight into the mechanisms of angiogenesis we have visualized the different components of the microvasculature in human wounds and tumors by immunohistochemistry on the light and electronmicroscopic level. For this purpose, antibodies recognizing distinct markers for human endothelial cells, pericytes and basal lamina were used on freshly frozen or paraformaldehyde-fixed tissue samples. In terms of efficacy, the PAL-E antigen is highly specific for blood vessel endothelium. Its sensitivity is less than other endothelial markers, such as von Willebrand factor and CD 31, as it is not expressed in arterioles. Within the context of the microvasculature alpha-smooth muscle actin and the HMW-MAA chondroitin sulphate proteoglycan are useful markers for pericytes. Type IV Collagen and Laminin can be visualized consistently in the microvascular basal lamina. During the formation of granulation tissue in wound healing a heterogeneity of the expression of endothelial and pericyte markers is found. In the least matured zone in granulation tissue of decubitus lesions and experimental skin wounds microvessels already contained both endothelial cells and pericytes, suggesting a role for both cell types in the early steps of angiogenesis. Regarding the tumor microvasculature, antibodies to von Willebrand factor often failed to stain capillaries, that did show expression of the other endothelial markers studied. Broad staining in pericytes was found for the HMW-MAA chondroitin sulphate proteoglycan. In contrast, these cells only locally expressed alpha-smooth muscle actin. Staining of the basal lamina components Type IV Collagen and Laminin within tumors was not restricted to the microvasculature. Therefore, antibodies recognizing endothelial markers, particularly PAL-E and BMA 120, are preferable as tools to visualize the tumor microvasculature. In accordance with the situation in granulation tissue of wound healing the broad presence of pericytes in the microvasculature of human tumor suggests an involvement of this cell type in tumor angiogenesis. Recent immunohistochemical studies on human tumor lesions indicated that a high number of microvessels adjacent to the tumor as a measure of tumor angiogenesis is an unfavorable prognostic factor in cutaneous melanoma, mammary carcinoma and non-small cell pulmonary carcinoma. This new application of immunohistochemistry represents a valuable, clinically relevant adjunct to the repertoire of the surgical pathologist.     

The conjunctiva in corneal epithelial wound healing

BACKGROUND/AIMS: During the healing of corneal epithelial wounds with limbal involvement, conjunctival epithelium often migrates across the denuded limbus to cover the corneal surface. It is believed that, over a period of time, conjunctival epithelium covering the cornea assumes characteristics of corneal epithelium by a process referred to as conjunctival transdifferentiation. The purpose of this study was to examine, clinically, the fate of conjunctival epithelial cells covering the cornea and to assess the healing of corneal epithelial wounds when the conjunctival epithelium was removed or actively prevented from crossing the limbus and extending onto the cornea. METHODS: 10 patients with conjunctivalisation of the cornea were followed for an average of 7.5 months. Five patients in this group had their conjunctival epithelium removed from the corneal surface and allowed to heal from the remaining intact corneal epithelium. In another four patients with corneal epithelial defects, the conjunctival epithelium was actively prevented from crossing the limbus by mechanically scraping it off. RESULTS: The area of cornea covered by conjunctival epithelium appeared thin, irregular, attracted new vessels and was prone to recurrent erosions. Conjunctivalisation of the visual axis affected vision. Removal of conjunctival epithelium from the cornea allowed cells of corneal epithelial phenotype to cover the denuded area with alleviation of symptoms and improvement of vision. It was also established that migration of conjunctival epithelium onto corneal surface could be anticipated by close monitoring of the healing of corneal epithelial wounds, and prevented by scraping off conjunctival epithelium before it reached the limbus. CONCLUSION: This study shows that there is little clinical evidence to support the concept that conjunctival transdifferentiation per se, occurs in humans. "Replacement" of conjunctival epithelium by corneal epithelial cells may be an important mechanism by which conjunctival "transdifferentiation" may occur. In patients with partial stem cell deficiency this approach can be a useful and effective alternative to partial limbal transplantation, as is currently practised.     

Effect of microamperage stimulation on the rate of wound healing in rats: a histological study

BACKGROUND AND PURPOSE: This study examined cutaneous wound healing after microamperage stimulation (MS). SUBJECTS: Twelve female Sprague-Dawley rats were studied. METHODS: The treatment (wound reduction) group (n = 6) received 100 microA of current at 0.3 Hz on a 50% duty cycle for 2 hours a day for 14 days. The control group (n = 6) received the same handling and electrode placement, but no current was applied. Wound size was measured daily following each treatment. Histological analysis included measurement of epithelial thickness, vascularity, and fibroblast density from tissue sections taken at the end of the experiment. RESULTS: An analysis of variance showed no significant difference between the two groups with respect to the change in wound size over the 14 treatment days. A series of t tests showed no significant differences between the groups for any of the histological measurements. CONCLUSION AND DISCUSSION: The results of this study do not support the hypothesis that MS accelerates acute cutaneous wound healing.     

Expression of Wnt genes in early wound healing

The effects of ambient temperature (22 degrees C/10 degrees C) and season (summer/winter) on anuran skin allograft and xenograft rejection was tested in frogs (Rana temporaria and R. esculenta) and toads (Bufo bufo, Bombina variegata, and Bombina bombina). Mean graft survival times were significantly prolonged at the low temperature in a species-specific manner, the edible frog (R. esculenta) being the most sensitive and the common toad (Bufo bufo) relatively resistant. Allografts were more temperature-dependent than xenografts; in the latter case, temperature sensitivity was specific to each donor-host combination. Rejection of second-set grafts in R. esculenta was accelerated both in warmth and in cold, but second-set grafts were less temperature-sensitive than sensitizing ones. Both in summer and in winter, R. esculenta rejected allografts promptly at 22 degrees C but slowly at 10 degrees C. In both seasons, Bombina variegata kept at 22 degrees C rejected allografts in a chronic manner. This indicates that amphibian transplantation immunity depends on the donor-host genetic disparity and ambient temperature but is independent of season.     

Three-dimensional observation of wound temperature in primary healing

In a group of 30 patients the temperature in the epigastric region was followed pre-operatively for four days. After upper medial laparotomy the temperature of the wound and its surroundings was followed during eight post-operative days. Thus every examinee was a control to himself. The temperature was measured on AGA 780 thermovision system. The advantages of thermovision in observing temperature in primary healing are manifold. The method is painless, non-contact, thereby decreasing the risk of contamination from outside, gives an absolutely accurate image of temperature over a larger or smaller area, and analysis of the thermogram is relatively simple. The defining of the healing process as thermal change in intensity, extensiveness and time is, in essence, three-dimensional. It gives the possibility of accurate indirect observation of biochemical and chemico-physical changes in the wound and its surroundings.     

Fetal tissue repair and wound healing

The fibrosis and scar formation that characterize adult wound healing are also the cause of clinical problems; scar contracture, hypertrophic scar, and pulmonary and hepatic fibrosis are only a few examples. Studies of fetal wound healing can provide an insight into the initiation and regulation of a scarless repair process akin to regeneration. Studies of fetal repair have already suggested mechanisms that might favorably alter adult healing. Topical application of hyaluronic acid to wounds in adult diabetic rats leads to enhanced epithelial migration. It has been recognized that the addition of TGF-beta to fetal wounds causes an adultlike healing response with fibrosis and inflammation. A subsequent study using neutralizing antibody to TGF-beta in adult wounds showed enhanced healing with a more normal dermal architecture with fewer macrophages, fewer blood vessels, and less collagen. As our understanding of regenerative tissue repair increases, the opportunities to modulate adult fibrotic conditions should expand.     

Lymphocyte function in wound healing and following injury

BACKGROUND: Injury activates a cascade of local and systemic immune responses. METHODS: A literature review was undertaken of lymphocyte function in wound healing and following injury. RESULTS: Lymphocytes are not required for the initiation of wound healing, but an intact cellular immune response is essential for a normal outcome of tissue repair. Injury affects lymphocyte immune mechanisms leading to generalized immunosuppression which, in turn, increases host susceptibility to infection and sepsis. Although the exact origin of post-traumatic immunosuppression remains unknown, stress hormones and immunosuppressive factors, such as inflammatory cytokines, prostaglandin E2 and nitric oxide, affect lymphocyte function adversely. Post-traumatic impairment of T lymphocyte immune function is reflected in decreased lymphocyte numbers, as well as altered T cell phenotype and activity. Antibody-producing B lymphocytes are variably affected by injury, probably secondary to alterations of T lymphocyte function, as a result of their close interaction with helper T cells. Therapeutic modulation of the host immune response may include non-specific and specific interventions to improve overall defence mechanisms. CONCLUSION: Early resuscitation to restore lymphocyte function after injury is important for tissue repair and the prevention of immunosuppression.