Stem cells of the corneal epithelium lack connexins and metabolite transfer capacity.

The stem cells of the corneal epithelial lineage are confined to the basal cell layer of the limbus, a vascularized outer corneal rim. These slow cycling cells of great proliferative potential maintain the corneal epithelial mass. Since cell-cell communication plays an important role in development and differentiation, we conducted a comparative examination of the expression of two corneal connexins, C x 43 and C x 50, and the tracer transfer capacity of the limbal and corneal epithelia using the scrape loading technique. C x 43 is abundantly expressed in the basal cell layer of the epithelium covering the cornea, but is essentially absent from the mouse, human, neonatal rabbit, and chicken limbal epithelium. In the adult rabbit the limbal epithelium displays an overall weak C x 43 immunoreactivity, but C x 43-free isolated basal cells can be distinguished. C x 50 is expressed throughout the corneal epithelium of the three mammalian corneas, but is not detectable in the limbus. Scrape loading experiments in the rabbit yielded results which were consistent with the immunohistological findings; limbal epithelium lacked tracer (lucifer yellow) transfer capacity, strongly suggesting the absence of functional gap junctions. Altogether, our results demonstrate the incompetence of stem cells for gap junction-mediated cell-to-cell communication. This property may reflect the need of these unique cells to maintain a distinct intracellular environment.

Alterations in connexin expression and cell communication in healing corneal epithelium.

PURPOSE: The aim of this study was to examine cell-to-cell metabolite transfer and connexin distribution in the rabbit corneal epithelium, in the stationary state, and during wound healing. METHODS: Rabbit corneas were wounded with a surgical tool, producing a 3-mm-wide elongated debridement. Corneas were allowed to heal in vivo for up to 45 hours. Monoclonal antibodies against connexins Cx 26, Cx 32, Cx 43, and Cx 50 were used to stain cryostat sections. Cell-to-cell metabolite transfer capacity was assessed by a modification of the scrape-loading technique using lucifer yellow as the organic ion tracer. RESULTS: The rabbit corneal epithelium contains Cx 43 and Cx 50, localized in the cell's plasma membrane, as shown previously for other species. Cx 26 and Cx 32 are not detectable. Tracer transfer occurred in both basal and suprabasal cell layers. After wounding, the migrating epithelial monolayer lacked Cx 43 and Cx 50. This change was apparent 6 hours after injury and persisted until complete wound closure (approximately 24 hours). The Cx 50 membrane stain was increased elsewhere, in particular in the transition zone between monolayered and multilayered epithelium. Consistent with the expression changes, migrating cells displayed no or minimal cell-to-cell tracer transfer, whereas in the periphery of the wound, tracer transfer was enhanced in comparison to the control specimen. CONCLUSIONS: Corneal epithelial healing involves biphasic changes in the expression of connexins and cell-to-cell communications. These alterations may be critical for the optimization of the healing response.

[The pharmacodynamic and hypotensive efficacy of proxodolol in an acute drug test on hypertension patients]. / Farmakodinamika i gipotenzivnaia éffektivnost' proksodolola v usloviiakh ostrogo lekarstvennogo testa u bol'nykh gipertonicheskoi bolezn'iu.

The antihypertensive efficacy and hemodynamic effects of the new hybrid (beta-, alpha-) adrenoceptor blocking agent proxodolol were studied in 74 patients with mild, moderate, and severe arterial hypertension who received a single dose of 10, 20, or 40 mg. Oral and intravenous proxodolol showed a significant dose-dependent antihypertensive action which was independent of the type of hemodynamics and manifested itself by decreasing cardiac output.

[The pharmacodynamics of proxodolol when administered once and in a course of doses to patients with stenocardia of effort]. / Farmakodinamika proksodolola pri odnokratnom i kursovom naznachenii bol'nym stenokardiei napriazheniia.

The effects of placebo and proxodolol, a new hybrid (beta-, alpha-) adrenoblocking agent, on exercise tolerance, hemodynamics and the conduction system were compared in 28 patients with coronary heart disease, Functional Class II-III exercise-induced angina pectoris at rest and during bicycle ergometric exercise test. Proxodolol was shown to exert a significant dose-dependent antianginal effect without producing any negative effect on atrioventricular and intraventricular conduction.

[Surgical treatment of tuberculosis of non-pulmonary localization]. / Khirurgicheskoe lechenie tuberkuleza vnelegochnoi lokalizatsii.

Experiments in 86 rabbits and observation of 360 patients have shown the antibacterial therapy to be of limited use for the treatment of non-pulmonary tuberculosis. It was found that the antibacterial therapy failed to result in healing the caseous-destructive foci and to cure turebculosis of kidneys, bones, joints, female genitals and lymph nodes. It is considered to be a reason for surgical procedures according to principles of the focal surgery on non-pulmonary tuberculosis elaborated by P. G. Kornev and his school.