Cadexomer-iodine ointment shows stimulation of epidermal regeneration in experimental full-thickness wounds.

The use of iodine in wound healing is still controversial. Both wound healing-stimulating effects and toxic effects leading to impaired wound healing have been reported. In order to study the direct effects of iodine on wound healing without interference of infectious pathogens, we investigated wound-healing parameters in noninfected experimental full-thickness wounds in the pig. Topical iodine treatment with an ointment consisting of a combination of iodine and cadexomer (modified starch), was compared with cadexomer ointment, the vehicle without iodine, and with treatment with saline. Treatment lasted for 30 days, followed by 30 days of wound assessment. The rate of epithelialization, wound contraction, systemic iodine absorption and several immunohistochemical markers were evaluated. All 36 wounds healed without macroscopic signs of wound infection and reepithelialized within 21 days. During the first 9 days of treatment, wounds treated with cadexomer-iodine ointment showed significantly more epithelialization than the wounds treated with either cadexomer or saline. In addition, the epidermis of wounds treated with cadexomer-iodine ointment had significantly more epithelial cell layers from day 12 to day 30, and these wounds stained for chondroitin sulphate proteoglycans in the newly formed basement membrane zone, which was not observed with the other treatments. No negative effects of cadexomer-iodine ointment on the formation of granulation tissue, neovascularization or wound contraction were observed. During the treatment systemic iodine absorption was physiologically acceptable. These results showed that treatment with cadexomer-iodine-containing ointment had positive effects on epidermal regeneration during the healing of full-thickness wounds in the pig compared with ointment alone or saline treatment.

The anti-inflammatory agent alpha-trinositol exerts its edema-preventing effects through modulation of beta 1 integrin function.

Edema formation in acute inflammation can be induced through lowering of interstitial fluid pressure (Pif) and seems to involve dynamic beta 1 integrin-mediated interactions between dermal cells and extracellular matrix fibers. The present experiments investigate the role of beta 1 integrins in the control of Pif. The anti-inflammatory drug alpha-trinositol (1,2,6-D-myo-inositol trisphosphate) stabilizes Pif in acute inflammation. Pretreatment with 5 mg IV alpha-trinositol in pentobarbital-anesthetized rats inhibited the lowering in Pif and the edema formation induced by subdermal injection of anti-beta 1 integrin IgG. This stabilization of the beta 1 integrin function in vivo was paralleled by effects of alpha-trinositol on contraction of fibroblast-populated three-dimensional collagen lattices in vitro. alpha-Trinositol was additive to the known stimulatory effect of platelet-derived growth factor-BB on the final gel size in the collagen gel contraction assay. Furthermore, alpha-trinositol counteracted the inhibitory effect of anti-beta 1 integrin Fab fragments on collagen gel contraction. Finally, subdermal injection of dibutyryl-cAMP (db-cAMP) induced increased negativity of Pif to the same extent as did anti-beta 1 integrin antibodies, and in vitro db-cAMP reduced the ability of fibroblasts to contract collagen gels. The latter effect was opposed by alpha-trinositol. The data demonstrate that alpha-trinositol modulates beta 1 integrin function and may do so via intracellular pathways in turn affecting the function and/or cell surface expression of beta 1 integrins and suggest that alpha-trinositol can serve as a tool to study integrin function. Furthermore, the data indicate that the collagen contraction assays may provide important information of the control of Pif in vivo.

alpha-Trinositol decreases lung edema formation after smoke inhalation in an ovine model.

Inhalation injury is a dominant cause of mortality in thermally injured individuals. After acute lung injury induced by smoke inhalation, lung lymph flow (QL) increased and pulmonary microvascular reflection coefficient to protein (sigma) decreased. alpha-Trinositol (PP56, 1D-myo-inositol 1,2,6-trisphosphate) can decrease edema formation after thermal injury. We therefore tested the hypothesis that alpha-trinositol could decrease the pulmonary edema noted with inhalation injury. Seven days after surgical preparation, sheep were insufflated with smoke from burning cotton towels. The alpha-trinositol group (n = 8) were treated with alpha-trinositol (2 mg/kg + 3.5 mg.kg-1 x h-1). The sham group (n = 7) received an equal volume of 0.9% NaCl. The sham group showed a large increase in QL (9.3 +/- 1.7 to 54.1 +/- 8.8 ml/h) and a decrease in sigma (0.79 +/- 0.03 to 0.48 +/- 0.03) 24 h after smoke inhalation. alpha-Trinositol attenuated the increase in QL (8.1 +/- 1.2 to 25.6 +/- 6.9 ml/h) and the decrease in sigma (0.76 +/- 0.03 to 0.60 +/- 0.03) noted with smoke inhalation. alpha-Trinositol thus decreased the changes in pulmonary microvascular permeability and transvascular fluid flux noted with inhalation injury.

Reversal of cadmium-induced hypertension by D-myo-inositol-1,2,6-trisphosphate.

The aim of this experiment was to test whether a chelating agent, D-myo-inositol-1,2,6-trisphosphate (PP56), could reverse cadmium-induced hypertension. Four groups of weanling female Long-Evans rats received ad libitum a rye-based, metal-poor diet and deionized water fortified with essential metals for 15 mo from the time of weaning. A control group received neither cadmium nor chelating agent. A second group had 0.1 ppm cadmium added to their water from weaning through mo 5. A third group had 60 ppm PP56 added to their water for mo 6-10. The fourth group had 0.1 ppm cadmium added to their water from weaning through mo 5 and 60 ppm PP56 from mo 6-10. All groups were followed without either cadmium or PP56 for mo 11-15. At approximately monthly intervals, systolic pressure was measured by the indirect tail cuff method in unanesthetized rats. Chronic cadmium feeding induced the expected hypertension, with an average increase in systolic pressure of about 15 mm Hg; the pressor effect persisted with little change for the 10 mo after cadmium was withdrawn. PP56 completely reversed the cadmium-induced hypertension, and the inhibition persisted for 5 mo after PP56 was withdrawn. PP56 by itself had no demonstrable depressor effect.

Influence of age and artificial vaginal stimulation on fertility in female bank voles (Clethrionomys glareolus).

Female bank voles mated when 30-50 days old showed only 20-25% fertility at the first mating, but fertility increased to about 80% in animals greater than 100 days of age at the first mating. Young females subjected to artificial cervical stimulation after the completion of a normal mating showed a much higher fertility than normally mated controls (76 compared with 29%). The reason for the low fertility therefore appears to be that young females require more stimulation to activate the corpora lutea than is normally received at a mating.

Influence of sexual experience and social environment on fertility and incidence of mating in young female bank voles (Clethrionomys glareolus).

Between 30 and 40 days of age, female bank voles were kept singly, in female pairs, separated from an adult male by a wire mesh, or paired with a vasectomized male. At Day 40 they were paired with adult intact males. Fertility at the first mating was low (22-25%), but if the females had previously mated with the vasectomized male fertility of the subsequent mating with the intact male was significantly increased (63%). Sterile matings therefore had a priming effect on the females, and could be important for the development of puberty in wild females. Only 55-59% of the females without contact with males between Days 30 and 40 mated with the fertile male. Contact with a male through a wire mesh increased the proportion to 80% and co-habitation with a vasectomized male to 94%. In the last group, mating also occurred at a younger age.

Effect of limited and complete mating on ovaries and adrenals in band voles, Clethrionomys glareolus.

Complete mating of voles induced ovulation and large and healthy CL were formed. By 4 days after mating adrenal weight was twice that in unmated animals. Limited amounts of mating (i.e. 1-3 intromissions) induced ovulation, but the resulting CL were small and short-lived and no adrenal hypertrophy was seen. If limited mating was followed by mechanical genital stimulation, large CL and adrenal hypertrophy were induced. Mechanical genital stimulation alone induced ovulation (mostly small CL) in some females, but not adrenal hypertrophy. It is concluded that adrenal hypertrophy after mating in the bank vole is controlled by a neuroendocrine reflex mechanism separate from that controlling ovulation, but related to that controlling luteal function.

Delayed implantation in lactating bank voles, Clethrionomys glareolus.

The time of blastocyst implantation in lactating and non-lactating female bank voles was studied. In primiparous females implantation started 4 days and 9-11 h after mating. A delayed implantation of at least 1 1/2 days was found in lactating, multiparous females when compared to non-lactating, multiparous and primiparous females.