Therapeutic activity of chlorhexidine-poloxamer antiseptic gel on wound healing in rats: a preclinical study.

Despite the progress in curative and preventive medicine, skin lesions after injuries or surgical interventions are still a big problem. The aim of wound care is to get damaged tissues to heal as soon as possible. A gel-forming material helps to maintain proper humidity in the wound and promotes the healing process. For this purpose, a healing gel containing the active substance chlorhexidine based on poloxamer was prepared. The aim of this study was to assess in vivo the therapeutic efficacy of chlorhexidine-poloxamer gel in treatment of wounds caused experimentally and inoculated with bacteria, and the effect of an antiseptic gel applied on a healthy rat skin. Wistar albino rats were selected for these studies. The effect of an antiseptic gel on the healing excision and incision wounds, as well as the irritating effect on the healthy skin were assessed. Cross-sectional full-thickness specimens from each group were collected at the end of the experiment to assess the histopathological alterations. Chlorhexidine-poloxamer gels accelerate the healing of infected skin wounds because the active ingredient chlorhexidine remains at the application site, and systemic effects are avoided. Moreover, chlorhexidine-poloxamer gels are easy to use because they can be easily washed off from the wound surface by water. The present study has revealed that chlorhexidine-poloxamer gels promote healing of full-thickness skin wounds without skin irritation. This makes it possible to plan further clinical trials in the target species.

Efficacy of Topical Therapy with Newly Developed Terbinafine and Econazole Formulations in the Treatment of Dermatophytosis in Cats.

In the field of veterinary dermatology dermatophytosis is one of the most frequently occurring infectious diseases, therefore its treatment should be effective, convenient, safe and inexpensive. The aim of this study was to evaluate the efficacy of newly developed topical formulations in the treatment of cats with dermatophytosis. Evaluation of clinical efficacy and safety of terbinafine and econazole formulations administered topically twice a day was performed in 40 cats. Cats, suffering from the most widely spread Microsporum canis-induced dermatophytosis and treated with terbinafine hydrochloride 1% cream, recovered within 20.3±0.88 days; whereas when treated with econazole nitrate 1% cream, they recovered within 28.4±1.14 days. A positive therapeutic effect was yielded by combined treatment with local application of creams and whole coat spray with enilconazole 0.2% emulsion "Imaverol". Most cats treated with econazole cream revealed redness and irritation of the skin at the site of application. This study demonstrates that terbinafine tended to have superior clinical efficacy (p<0.001) in the treatment of dermatophytosis in cats compared to the azole tested.

The development of an outcomes management system for acute medical rehabilitation.

In 1993, Continental Medical Systems, Inc. (CMS), a provider of comprehensive medical rehabilitation, developed the Total Outcomes and Prediction Program (TOPP) to measure and evaluate key medical rehabilitation outcomes, quality indicators, and patient satisfaction at its 37 acute rehabilitation hospitals. The broad purposes of TOPP are to manage patient treatment, improve the cost-effectiveness of care, and provide outcomes reporting for managed care and other interested parties. The challenge was to develop a system which could measure, evaluate, and report medical rehabilitation patient outcomes in a way that could be easily understood by multiple audiences, including payers, accrediting organizations, physicians, patients and families, case managers, and CMS clinical staff. Using data from the Uniform Data System for Medical Rehabilitation database, CMS created descriptive outcomes reports for each hospital and for the corporation overall, including performance statistics, outcomes report cards, and quality report cards. These initial reports, as well as updates, quarterly reports, and special ad hoc requests, provide CMS corporate and hospital staff with statistically valid and reliable information to manage the outcomes of medical rehabilitation treatment. TOPP has assisted CMS with meeting accreditation standards for outcomes management and measurement and has been used in managed care contract negotiations. Future TOPP efforts will integrate resource use data, medical acuity and outcomes from acute, subacute, and outpatient rehabilitation levels into CMS' outcomes reporting system.

The effects of epileptic cortical activity on the development of callosal projections.

The effect of epileptic neural activity on the postnatal development of the corpus callosum was studied. Epileptiform activity was induced in the visual cortex of postnatal rabbits by continuous infusion of penicillin. Callosal projections of the occipital cortex were studied in rabbits aged at least 4 weeks. In these penicillin-exposed rabbits, the visual callosal projections extended through most of area 17 in a projection pattern characteristic of neonatal rabbits, rather than being restricted to a narrow callosal zone at the lateral border of area 17, as they usually are by this age. The results indicate that epileptic cortical activity stabilizes immature callosal projections which are normally eliminated during development. The maintenance of such immature and non-specific projections in the mature CNS may interfere with normal cortical functions and could underlie the cognitive deficits which have been observed following childhood epilepsy.

Visual callosal projections in the adult ferret.

The laminar and tangential organization of visual callosal projections of areas 17 and 18 were investigated in the adult ferret, using histochemical methods to visualize axonally transported horseradish peroxidase (HRP). Normal adult ferrets were given injections of HRP throughout one visual cortex or had gelfoam soaked in HRP applied to the transected corpus callosum. The ferret callosal cell distribution has a greater tangential extent in area 18 than in area 17. In addition, the radial organization of callosal cells in areas 17 and 18 differs: three times as many infragranular cells are present in area 18 than in area 17, although the number of supragranular cells is similar for both areas 17 and 18. Since the projections of alpha retinal ganglion cells are reported to be exclusively contralateral in the ferret (Vitek et al., 1985), callosal projections may make a major contribution to the binocularity of neurons in area 18.

Transcallosally evoked responses in the visual cortex of normal and monocularly enucleated rabbits.

In visual cortex of normal adult rabbits, callosal projections are restricted to a 2 mm wide band at the area 17/18 border. In adult rabbits which are monocularly enucleated (ME) on the day of birth, the callosal zone extends 4 mm into the medial region of area 17 in the cortex ipsilateral to the remaining eye. In this study, the function of these anomalous callosal projections in ME rabbits was investigated using electrophysiological techniques. A microelectrode was placed in the visual cortex ipsilateral to the enucleated eye at the 17/18 border, bipolar stimulating electrodes were placed in a homotopic location in the contralateral cortex, and averaged evoked responses (AERs) to stimulation were recorded. The stimulating electrodes were then moved mediolaterally in 1 mm steps, and the AERs were recorded for each location of the stimulating electrodes. In the normal rabbit, a maximal short latency evoked response was recorded when the stimulating electrodes were at a location homotopic to the recording electrode. When the stimulating electrodes were moved a distance of 1 mm or more from this optimal position, this short latency response was either absent or dramatically decreased in amplitude, reflecting the precise topographic pattern of the normal callosal projection. In contrast, in ME rabbits, a consistent response was evoked at the 17/18 border when the stimulating electrodes were moved as much as 3 mm medial to the homotopic position. Since antidromically activated responses and both pre- and postsynaptic orthodromically activated responses contribute to the AER, recordings were also made from single cells in some animals.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of monocular enucleation on visual topography in area 17 in the rabbit.

The effects of neonatal monocular enucleation on the topographic representation of the ipsilateral visual field in the visual cortex of the rabbit were investigated, using electrophysiological recordings of multi-unit activity in area 17. Topography of receptive fields was determined in normal adult rabbits, adult rabbits monocularly enucleated on the day of birth and adult rabbits monocularly enucleated as adults. In normal rabbits and in adult enucleates, the projection from the ipsilateral eye is represented by a strip of cortex extending approximately 2 mm from the 17/18 border. In neonatal enucleates, the width of the area of cortex in which the projection from the ipsilateral eye is represented was approximately twice as large as normal. Visual topography was normal in the superior-inferior axis but was distorted in the nasotemporal axis. Our data suggest that the abnormal topography observed in the visual cortex of neonatally enucleated rabbits may play a major role in shaping the abnormal visual callosal projections observed in these animals. In addition, our data indicate that, following neonatal monocular enucleation, developmental abnormalities in the topography of geniculocortical projections can occur independently of any alteration in the retinogeniculate projection patterns.

Organization of callosal connections in the visual cortex of the rabbit following neonatal enucleation, dark rearing, and strobe rearing.

The organization of visual callosal projections was studied in (1) normal adult rabbits; (2) adult rabbits which had undergone monocular enucleation (ME) or binocular enucleation (BE) at birth; and (3) adult rabbits which had been deprived of normal visual experience during development by dark rearing (DR) or strobe rearing (SR). Previously published observations (Murphy and Grigonis, Behav Brain Res 30:151, 1988) on callosal organization in adult rabbits in which retinal ganglion cell activity was eliminated during development by intraocular tetrodotoxin (TTX) injections, are also summarized for comparison with these data. The tangential extent of the callosal cell zone was significantly larger than normal in DR, TTX, and ME rabbits, was unchanged in BE rabbits, and was significantly reduced in SR rabbits. An analysis of the laminar distribution of the callosal cells revealed a significant increase in the percentage of callosal cells in lamina IV in ME, DR, and TTX animals. Measurements of density of callosal cells showed a significant increase in the density of the callosal projection in ME and SR rabbits and a decrease in density in BE rabbits compared with normal. The data suggest that the mechanisms involved in the development of the tangential and laminar organization of the callosal cell zone are different. In addition, the data suggest that the mechanisms involved in the maintenance of callosal projections are different from the mechanisms involved in the elimination of callosal projections during development. The effects of these developmental manipulations on callosal organization in other mammals are reviewed and compared with the effects in rabbits. The data suggest that species differences in the degree of maturity of the visual system at birth and in the extent of callosal development at the time of eye opening, may underlie species differences in the effects of these manipulations on the organization of visual callosal projections during development.

Postnatal development of the visual corpus callosum: the influence of activity of the retinofugal projections.

Visual callosal projections were studied in normal adult rabbits, and in adult rabbits in which normal development was manipulated by monocular enucleation on the first or seventh postnatal day, or by abolition of retinal physiological activity by repeated application of tetrodotoxin (TTX) beginning on postnatal day 7. Animals given control vehicle injections, and animals enucleated on postnatal day 7 did not differ from normal in the tangential extent of their callosal zone which is limited to the lateral one-third of area 17. In contrast, animals enucleated on the day of birth and animals given TTX vitreous injections beginning on postnatal day 6-7 are similar in that the tangential extent of their callosal cell zone extends approximately through the lateral two-thirds of area 17. The results suggest that different mechanisms underly the effects of removal of the eye, and abolition of retinal activity, and that the critical period for the effective manipulation of these two mechanisms is different.

The development of orientation and direction selectivity in the rabbit visual cortex.

The postnatal development of orientation and direction selectivity of single cells was examined in the primary visual cortex of rabbits. The percentage of cells which were orientation-selective reached adult levels by day 30, whereas the proportion of cells which were direction-selective did not reach adult levels until day 60. Differences in the time course of development of orientation and direction selectivity, together with data previously reported on differences in the effects of deprivation on orientation and direction selectivity, suggest that (1) different mechanisms underly the organization of orientation and direction selectivity and (2) the critical periods for the effects of deprivation on orientation and direction selectivity reflect the different time course of the normal development of these two response properties.

The effects of ablation of visual cortex in neonatal rabbits on the organization of retinothalamic and retinopretectal projections.

Primary visual cortex was ablated unilaterally in neonatal rabbits. Following a survival of 2-4 months, retrograde degeneration of the dorsal lateral geniculate nucleus (LGd) was assessed, and reorganization of retinofugal pathways was studied using methods of anretrograde transport of [3H]proline or of horseradish peroxidase. A complete lesion of primary visual cortex resulted in complete retrograde degeneration of the LGd with no sparing of any class of neurons. The terminations of retinofugal axons in the pretectum and thalamus were compared with those observed in normal animals. No major reorganization of ipsilateral retinofugal projections was observed in either the thalamus and pretectum ipsilateral to the ablated cortex, or in the thalamus and pretectum contralateral to the ablated cortex. However, contralateral retinofugal projections to the thalamus and to the pretectum ipsilateral to the ablated cortex were significantly different from normal. In the thalamus, the projections to the lateral posterior nucleus were expanded in area and increased in density. In the pretectum, the projections to the rostral pretectal areas were greatly increased in area, especially in the region of the olivary pretectal nucleus and posterior pretectal nucleus. However, the density of these projections was not increased relative to normal. Consideration of these results in relation to other published data on the anatomical consequences of neonatal visual cortex lesions, both in mammals which show behavioral sparing following neonatal visual cortex lesions and in mammals which, like the rabbit, show no behavioral sparing, suggests that: (1) behavioral sparing may correlate with patterns of survival or death of neurons in the thalamus and retina; and (2) reorganization of retinofugal pathways is not necessarily associated with behavioral sparing.

The effects of neonatal monocular enucleation on the organization of ipsilateral and contralateral retinothalamic projections in the rabbit.

Autoradiographic methods were used to compare the ipsilateral and contralateral retinothalamic projections in pigmented Dutch-Belted rabbits that had neonatal monocular enucleation with the projections found in normally reared rabbits. In the normal adult rabbit, there is dense label throughout the dorsal lateral geniculate nucleus (LGd) except for a decreased label density in the region corresponding to the ipsilateral input. Following neonatal monocular enucleation, the contralateral projection fills in the part of the LGd corresponding to the ipsilateral input. Our data indicate that following monocular enucleation, two processes occur: an arrest of the segregation process and an expansion of the contralateral projection into the space normally containing the terminals of the ipsilateral projection. In addition, this filling in of the terminal space occurs relatively rapidly and is completed by day 14. No changes, however, were observed in the ipsilateral projection to the LGd. Unlike the LGd, the ventral lateral geniculate nucleus and the intergeniculate leaflet showed increases in the size of the ipsilateral projection region, and no changes in the contralateral projection. The present findings suggest that there may be different mechanisms governing whether alterations in the distribution of retinothalamic projections will occur in either the ipsilateral or contralateral nucleus.

The pretectal nucleus lentiformis mesencephali of Rana pipiens.

The pretectal nucleus lentiformis mesencephali (nLM) of Rana pipiens was investigated with autoradiographic, horseradish peroxidase (HRP), and Golgi techniques. Retinal afferents to nLM originate primarily from the central retina. The primary projection is contralateral with a small ipsilateral component. Following optic nerve transection and HRP impregnation, contralateral retinal afferents show a restricted, dense core of HRP label in the superficial portion of the nucleus with sparser HRP label in the surround. Ipsilateral retinal afferents arborize throughout nLM, except in the dense-core region. Additional afferents to nLM originate from the ipsilateral tectum, the nucleus rotundus, the mesencephalic pretectal gray, the contralateral nLM, and the nucleus of the basal optic root. Afferents from the accessory optic system arborize only in the dense-core region, following HRP injections into the nucleus of the basal optic root, while afferents from the mesencephalic pretectal gray arborize in all parts of nLM except the dense core. Afferents from the tectum and anterior thalamus appear to arborize throughout the nucleus without discernible pattern. The lamination of afferent terminals in nLM was correlated with Nissl-stained cytoarchitectural material in which the majority of large neurons cluster around the dense core of nLM. Three types of neurons occur in nLM: large neurons (25-micron dia.), fusiform neurons (12.5-micron dia.), and stellate neurons (10-micron dia.). Additionally, two cell groups outside nLM which send dendrites into the nucleus were observed: cells of the posterior lateral nucleus and cells of the posterior thalamic pretectal gray. Both large and fusiform neurons project to the deep layers of the optic tectum as well as to the ventral rhombencephalon superficial to the abducens nucleus. While a small number of fusiform neurons project to the nucleus of the basal optic root, the stellate neurons appear to be intrinsic to nLM. The anuran nLM strongly resembles the nucleus of the optic tract in mammals in terms of the site of origin of its retinal afferents, lamination of afferent terminations, its central connections, and its demonstrated involvement in horizontal optokinetic nystagmus.

Photomechanical responses of visual receptors in the retina of the bullfrog (Rana catesbeiana).

All photoreceptor types in the bullfrog (Rana catesbeiana) retina exhibit changes of position within the receptor layer, depending upon the state of retinal adaptation, and the season in which the displacement was measured. The most light-adapted position of each photoreceptor type following monochromatic adaptation was not related specifically to the lambda-max of its own photopigment. In general, however, the response profiles were similar for photoreceptors having the same lambda-max. The red rod, accessory member of the double cone, green rod and the miniature cone showed similar response profiles, while the single cone and the principal member of the double cone showed similar patterns of movement as a function of adapting wavelength. The response profiles for the short and middle lambda-max photoreceptors obtained in summer months appeared similar to the action spectrum of the retinal pigment epithelium (RPE) as previously described by Liebman and co-workers. Seasonal differences were also found. The observed photomechanical response profiles may be determined by complex interactions between adjacent photoreceptors, as well.

Decrease in metacontrast masking following adaptation to flicker.

Selective adaptation was used to explore the characterisitcs of a metacontrast masking stimulus which contribute to its effectiveness in masking the test stimulus. Subjects adapted for 10 s to a configuration like the masking stimulus that was either continuously on or flickering. Following this they viewed a metacontrast presentation and estimated the brightness of the test stimulus. Prior adaptation to a continuously present stimulus did not appreciably affect metacontrast masking; however, masking was greatly reduced following adaptation to flickering stimuli. These results are consistent with recent models of metacontrast masking based on transient and sustained visual channels.