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Biomedical subjects

A B Lansdown

Publications and source records attributed to A B Lansdown.

At least 19 recordsLinked to original sources

Experimental observations in the rat on the influence of cadmium on skin wound repair.

Wound healing in the skin depends upon the availability of appropriate trace metals as enzyme cofactors and structural components in tissue repair. The present study forms part of a series of experimental investigations to examine the influence of xenobiotic elements with no known nutritional function and which are known to compete with essential trace metals. It was designed to investigate further the importance of trace metals in wound healing as an aid to wound management and to identify mechanisms of nonhealing which constitute a major problem in human medicine. Surgically induced skin wounds in young adult male Wistar rats were exposed topically to 0.2 ml of 0.01, 0.10 or 1.0% cadmium chloride (aq.) daily for up to 10 days. Control wounds received de-ionized water only. Wounds exposed to cadmium chloride at 0.01 or 0.10% healed in a similar fashion to controls and exhibited a comparable histological profile with metallothionein distribution. Wounds receiving 1.0% cadmium chloride failed to heal or fully re-epithelialize within 7 days and animals were humanely killed. They showed a persistent mass of inflammatory cell infiltration, oedema, wound debris and aberrant epidermal cell growth. Metallothionein concentrations in the epidermis and fibroblasts of the papillary dermis increased greatly by 5 days postwounding and remained high through the observation period. Cadmium was identified in the liver, kidney and wound sites. In the wound, 1.0% cadmium chloride induced statistically significant (P > 0.001) changes in local concentrations of zinc and calcium at key stages in the healing process, and as a consequence disturbed the trace metal balance necessary for normal wound repair. Zinc levels were increased twofold after 7 days, but calcium was markedly reduced. Local changes in the distribution of metallothionein indicate interaction of cadmium and trace metal carrier proteins as a probable mechanism for impaired wound healing. The cytotoxicity of cadmium is considered to be largely responsible.

Animals↗

Sequential changes in trace metal, metallothionein and calmodulin concentrations in healing skin wounds.

Metalloenzymes have an important role in repair and regenerative processes in skin wounds. Demands for different enzymes vary according to the phase in the healing cascade and constituent events. Sequential changes in the concentrations of calcium, copper, magnesium and zinc were studied in the incisional wound model in the rat over a 10 d period. Copper levels remained low (< 10 microg/g dry weight) throughout, but calcium, magnesium and zinc increased from wounding and peaked at about 5 d at a time of high inflammation, granulation tissue formation and epidermal cell proliferation. Metal concentrations declined to normal by 7 d when inflammation had regressed, re-epithelialisation of the wound site was complete and the 'normalisation' phase had commenced. Although the wound was overtly healed by 10 d, the epidermis was still moderately hyperplastic. In view of competitive binding of trace metals at membrane receptors and carrier proteins, the ratios or balance between these trace metals was examined and the significance is discussed. Using immunocytochemistry, we demonstrated increases in metallothionein immunoreactivity as an indication of zinc and copper activity in the papillary dermis and in basal epidermal cells near the wound margin 1-5 d after wounding. This is consistent with metalloenzyme requirements in inflammation and fibrogenesis. Calmodulin, a major cytosolic calcium binding protein was highest in maturing keratinocytes and in sebaceous gland cells of normal skin; it was notably more abundant in the epidermis near the wound margin and in re-epithelialising areas at a time when local calcium levels were highest.

Animals↗

Trace metals in keratinising epithelia in beagle dogs.

The concentrations of the trace elements zinc, copper and iron and the minerals calcium and magnesium were measured in keratinising epithelia from 12 beagle dogs. The richly vascular tissues of the snout and tongue that showed parakeratotic changes, contained the highest concentrations of iron, zinc and copper. Zinc, calcium and magnesium concentrations were high in the pressure keratinisation tissue of the footpad. There was a high concentration of calcium in the nose tip. The thin skin of the back contained the lowest concentration of all five elements.

Animals↗

Silver aids healing in the sterile skin wound: experimental studies in the laboratory rat.

Incisional wounds 15 mm long were induced surgically in the back skin of young adult Wistar rats. They were sutured and used as an experimental model in the therapeutic evaluation of daily applications of 0.5 mL of silver nitrate (SN) at 0.01, 0.1 or 1.0% w/v aqueous solution, or 0.5 g silver sulphadiazine (SSD) over a 10-day period. Control wounds received deionized water only. The silver preparations were not toxic but SN did stain the hair and superficial layers of the stratum corneum. The wounds remained microbiologically clean. Wounds exposed to SN (0.1 or 1.0%) or SSD healed more rapidly than controls. From about the fourth day of treatment, we noted a more rapid exteriorization of sutures, improved wound closure and an earlier loss of scabs and wound debris. Silver treatment appeared to reduce the inflammatory and granulation tissue phases of healing and enhance epidermal repair. Silver from SN was deposited as silver sulphide in extrafollicular hair shafts and superficial aspects of the skin and wound debris but not at deeper levels. Silver uptake was four-fold higher in damaged skin than in intact tissue. SSD was absorbed by intact and wounded skin but the silver did not precipitate as silver sulphide and its localization in the tissue is not known. Uptake of silver from SN or SSD was associated with changes in the concentrations of zinc and calcium in the skin. Zinc levels were depressed during the inflammatory and proliferative phases of healing and then increased. Zinc concentrations had normalized by 10 days when wound healing was achieved. Calcium levels remained higher than normal throughout the observation period. The mechanism of action of silver in advancing wound healing in the rat is unclear. Its ability to reduce the inflammatory and granulation phases of healing, and to invoke metallothionein production and influence metal ion binding are possibly important.

Animals↗

Dermal toxicity and percutaneous absorption of cadmium in rats and mice.

Cadmium is a common contaminant in sawdust and other materials used in laboratory animal bedding. This study was conducted to assess the irritancy of a soluble cadmium compound to the skin and percutaneous absorption of the cadmium ion. Cadmium chloride solution was administered to the shaved skin of the dorsum of rats and mice daily for 10 days at concentrations of 1.0, 0.1, and 0.01% (wt/vol). Cadmium accumulated in the skin in association with approximately 6,000 ng/g in animals exposed to the high dose. Skin damage of hyperkeratosis and acanthosis with some ulcerative change was dose-related. The mitotic index in mouse skin was increased up to twofold. In rat blood, concentrations of cadmium, after 10 days of administration of a 1% concentration, were 11.65 micrograms/L, indicating percutaneous absorption. Clear evidence was seen of an accumulation of cadmium in the liver (526 ng/g) and kidney (216 ng/g), but histopathologic evidence of damage was absent, after this period at least. Concentrations of zinc were increased in the skin, probably as a consequence of local increases in metallothionein, a zinc-binding protein.

Administration, Cutaneous↗

Physiological and toxicological changes in the skin resulting from the action and interaction of metal ions.

The human environment contains more than 50 metal or metalloid elements. At least 15 are recognized as trace elements, with zinc, calcium, copper, magnesium, and iron having specific roles in skin morphogenesis and function. The present review focuses on the presumed role of metal ions in the skin, their competition for carrier proteins, and membrane receptors. Evidence presented shows that the balance of trace metal ions is critical for normal skin and repair mechanisms following injury. Xenobiotic ions can impair this balance, leading to pathological change. The skin acts as an organ of elimination of excess trace metals and xenobiotic ions from the body, but mechanisms of voidance vary for different metals. Metal ions are an important cause of allergies, and evidence is presented to show that the majority of metals or metal compounds can induce allergic changes. Except for chromium and nickel, which are among the most common human allergens, animal models have provided little information. At least cadmium, thorium, lead, chromium, nickel, beryllium, and arsenic and proven or putative carcinogens in animals or humans on the basis of cytological or epidemiological evidence. However, only arsenic exhibits a clear predilection for the skin. Other metals such as gold can induce subcutaneous sarcoma following injection, but the relevance of this observation in terms of human occupational risk is discounted.

Animals↗

An evaluation of the local reaction and biodegradation of calcium sodium alginate (Kaltostat) following subcutaneous implantation in the rat.

Kaltostat swabs were implanted subcutaneously in rats to evaluate their biodegradability and ability to evoke local tissue reactions. Implant sites were evaluated after 24 h and after 7 days, 28 days and 12 weeks. Histological sections showed no noticeable degradation of the Kaltostat within the 3 month observation period, contrary to some published reports. Following subsidence of a modest foreign body reaction, implants became embedded in thin fibrous sheaths which were infiltrated with vascular channels and fibroblasts. This study demonstrates that Kaltostat fibres are well tolerated following subcutaneous implantation in the rat model and present no obvious toxic risk or contraindication to their use as wound dressings or as haemostatic agents in general surgery.

Alginates↗

Spinal dysplasia with stump tail and hind limb paralysis in a laboratory bred cat.

A case is presented of a specified pathogen free bred cat which was apparently tail-less at birth and at three weeks of age revealed hind limb paralysis. The animal was euthanized at 4 weeks and X-radiography revealed an abnormal spinal curvature, greatly reduced caudal vertebrae and abnormal pelvic development. A small tail was dissected at post-mortem, but other abnormalities were not seen.

Animals↗

Interspecies variations in response to topical application of selected zinc compounds.

The dermal irritancy of six zinc compounds was examined in three animal models. In open patch tests involving five daily applications, zinc chloride (1% aqueous solution) was severely irritant in rabbit, guinea-pig and mouse tests, inducing epidermal hyperplasia and ulceration; aqueous zinc acetate (20%) was slightly less irritant. Zinc oxide (20% suspension dilute Tween 80), zinc sulphate (1% aqueous solution) and zinc pyrithione (20% suspension) were not overtly irritant, but induced a marginal epidermal hyperplasia and increased hair growth. Zinc undecylenate (20% suspension) was not irritant. Epidermal irritancy in these studies is related to the interaction of zinc ion with epidermal keratin. The compounds studied were not consistently bacteriostatic in the three species tested.

Administration, Topical↗

Alterations in crypt cell populations in the small intestine as an early toxic response to sub-acute ethanol administration.

Crypt cell production was examined in young male rats (Sprague-Dawley) given 1, 5 or 15% ethanol in their drinking water for up to 14 days. Ethanol 1 and 5% did not influence food and liquid consumption and growth was similar to that seen in control animals given tap water only to drink. Animals given 15% ethanol exhibited a significant reduction in food and liquid intake and showed a marked diminution in weight gain within 7 days. Ethanol consumption did not affect the length of the small bowel, but 5 and 15% concentrations inhibited cell production in the jejunum and in the distal aspect of the ileum. The relative position of the proliferative compartment, as assessed by the 50% total mitosis level, was unaltered as a result of the treatment. 1% Ethanol led to an increased mitotic rate in the jejunum after 14 days, treatment. Crypt cell production returned to normal in animals given 5% ethanol for 7 days and then a recovery period of 7 days. Mitotic inhibition resulting from ethanol ingestion is probably due to a direct effect (jejunum and proximal ileum) but systemic changes possibly contribute to changes seen in the distal ileum. The nutritional and toxicological implications of ethanol consumption are discussed.

Animals↗

Skeletal abnormality of sheep: clinical radiological and pathological account of occurrence of dwarf lambs.

Details are given of the clinical, radiological and pathological appearance of dwarf lambs. Twenty-seven of 110 lambs born were affected, occurring as singletons, twins or one of a pair of twins. All affected lambs were dead within a few minutes of birth. They were short and plump with a domed head and shortened nose, short paddle-like limbs, a narrow thorax and swollen abdomen. The defect involved chondrocyte dysplasia, producing defective endochondral ossification and the presence of abnormal cartilage in the respiratory tract. No specific genetic or environmental cause was identified.

Animals↗

Morphological variations in keratinising epithelia in the beagle.

Six keratinising epithelia in the beagle have been studied using conventional histology and fluorescence methods to identify the nature of the keratin present. Three patterns of differentiation were identified, those present in areas of hairy skin, the foot pad and the tongue and nasal tip. In the first group, the epidermis is generally thin and exhibits a low mitotic rate but the keratin formed is mature. In the foot pad and tongue, which are examples of pressure keratinisation, the epidermis is appreciably thicker because of the presence of a phospholipid-rich cornified layer. A third form of keratinisation is seen in the nasal tip and in regions of the tongue, characterised by parakeratotic changes, high phospholipid accumulation and other features reported previously in keratinising epithelia subject to prolonged hydration.

Animals↗