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Biomedical subjects

G Ksander

Publications and source records attributed to G Ksander.

6 recordsLinked to original sources
PubMed1993

Occurrence and localization of transforming growth factor-beta (TGF-beta 1, beta 2) during rabbit skin development.

The expression of (TGF beta-1) and (TGF beta-2) in adult, fetal, and neonatal rabbit skin has been analyzed by immunohistochemistry. Samples were collected from the backs of fetal rabbits (23 and 30 days of gestation), newborn rabbits (1 day post-partum) and adult pregnant and nonpregnant rabbits. Forty samples were studied. To identify TGF-beta two antibodies were used: (RAB4) and (CL-B1/29). TGF-beta 1 and TGF-beta 2 displayed distinct distribution and intensity of staining at different stages of development. TGF-beta 1 was present in fetal skin (23 days of pregnancy) expressing abundant staining in cells within epidermis, dermis and hypodermis. Fetal skin (30 days of pregnancy) exhibited weak staining for TGF-beta 1; only isolated dermal cells in close proximity to hair follicles and sweat glands expressed intracellular staining. Newborn rabbit skin showed low expression for TGF-beta 1, around hair follicles and sweat glands. In contrast adult pregnant and non-pregnant rabbit skin exhibited abundant staining for TGF-beta 1 in epidermis, papillary dermis, around hair follicles, sweat glands, and blood vessels, no difference was observed among pregnant and non-pregnant rabbits. TGF-beta 2 was detected in all specimens and the distribution and intensity of staining were similar to those found for TGF-beta 1 in all groups. Our findings demonstrate that the expression of TGF-beta 1 and TGF-beta 2 is intense during early stages of rabbit skin development when morphogenesis is taking place and skin appendages are being formed; and less intense when these structures are formed and skin growth predominates. These results suggest an important role for TGF-beta 1 and TGF-beta 2 in rabbit skin development, probably regulating morphogenesis and growth.

Aging↗
PubMed1991

Inhibition of thromboxane synthetase potentiates the antihypertensive action of an angiotensin-converting enzyme inhibitor by a prostaglandin-dependent but kinin-independent mechanism.

Mean arterial pressure (BP) was measured in conscious, spontaneously hypertensive rats (SHR). Oral administration of the angiotensin I-converting enzyme inhibitor (ACEI) CGS 16617 significantly lowered BP. In contrast, the thromboxane synthetase inhibitor (TxSI) CGS 12970 lacked an antihypertensive action in SHR. When administered concurrently, the TxSI significantly potentiated the antihypertensive actions of the ACEI. Inhibition of thromboxane synthetase did not potentiate the antihypertensive actions of metoprolol or verapamil, indicating that a specific interaction exists between a TxSI and an ACEI. The antihypertensive actions of CGS 16617 also were potentiated by the cyclooxygenase inhibitor indomethacin, a result suggesting that CGS 12970 may enhance the action of CGS 16617 by inhibiting the action of vasoconstrictor prostaglandins produced after administration of an ACEI. The potentiation of the antihypertensive actions of CGS 16617 by CGS 12970 remained unaffected by either the kallikrein inhibitor aprotinin or a bradykinin receptor antagonist. Thus, although the interaction between an ACEI and a TxSI is a prostaglandin-dependent mechanism, it is not mediated by endogenous kinins. Inhibition of thromboxane synthetase significantly stimulated renin release and significantly attenuated the pressor response to exogenously administered angiotensin II. An increase in the dependency of BP upon the renin-angiotensin system and attenuation of the vascular actions of angiotensin II may serve to explain the potentiation of the antihypertensive action of ACEI after inhibition of thromboxane synthetase. The interaction between ACEI and TxSI was not restricted to SHR, because a TxSI potentiated the actions of an ACEI in both normotensive and deoxycorticosterone acetate/Na hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Injectable cross-linked collagen with improved flow properties.

Aqueous suspensions of glutaraldehyde cross-linked fibrillar collagen and non-cross-linked fibrillar collagen were examined by rheometry, particle size analysis, and microscopic techniques. Although cross-linked collagen suspensions were similar to non-cross-linked suspensions by microscopic and size analyses, they differed in rheometric properties. Concentric cylinder Couette flow, shear creep, uniaxial creep, and porous bed flow all revealed that cross-linked collagen was more resistant to deformation and flow than non-cross-linked collagen. These results were in agreement with in vivo dermal implantation studies, both in pig and human; i.e., compared to non-cross-linked collagen, the cross-linked formulation was more difficult to inject into tissue and did not spread uniformly, sometimes giving rise to palpable lumps or large masses evident in histological sections. When hyaluronic acid was blended with cross-linked collagen to achieve a final hyaluronate concentration of 5 mg/mL, there was a significant improvement in ease of injection into tissue. Rheometry on blends of hyaluronate and cross-linked collagen demonstrated that the blend required lower forces to achieve deformation and flow, compared to cross-linked collagen alone. Particle size analysis on the blend showed a reduction in fiber aggregate dimensions, compared to cross-linked collagen alone.

Animals↗
PubMed1988

The influence of heparin on the wound healing response to collagen implants in vivo.

The biologic response to fibrillar collagen (collagen) and fibrillar collagen plus heparin (collagen/heparin) implants have been compared in the rat subcutaneous and guinea pig dermal wound models. The reconstituted bovine dermal collagen implants were injected subcutaneously in rats at concentrations ranging from 18 to 30 mg/ml and in volumes ranging from 0.5 to 1.0 ml. The biologic response to the collagen implants alone was characterized by a transient invasion of a modest number of inflammatory cells within the first three days of implantation that was followed by limited fibroblast invasion into the peripheral 1/3 of the implant during the course of the next three to four weeks. Occasionally, blood vessels were observed to invade the peripheral regions of the implant. The degree (number) and extent (depth) of cell invasion were inversely related to initial collagen implant concentration. Addition of heparin (0.3-20 micrograms/mg collagen) to these implants resulted in a significant dose-dependent increase in the degree and extent of fibroblast invasion. Radiolabeling studies showed that the collagen and collagen/heparin implants were cleared from the subcutis at identical rates. Implantation of these formulations in a guinea pig dermal wound model was also performed, using a semi-occlusive wound dressing (Opsite) to maintain the implant in the wound site. The fibrillar collagen implant alone was pushed upward by developing granulation tissue at the base of the wound and served as a support for epidermal cell migration, proliferation, and differentiation as wound closure proceeded. The implant was slowly invaded and turned over as granulation tissue developed from the base and margins of the wound bed. The inclusion of heparin in these implants resulted in a significantly different pattern of wound healing. The collagen/heparin implants histologically presented a more broken-up or porous appearance following implantation, which was associated with a greater degree of penetration of developing granulation tissue into the implant itself as compared to the collagen implants. Radiolabeling studies revealed that clearance rates of implants with and without heparin from wound sites were similar, as noted in the rat subcutis. Laser doppler flowmetry studies suggested that the heparin--containing implants were more vascular than control wound sites or sites treated with collagen alone.

Animals↗
PubMed1988

Difficulties in laser Doppler measurement of skin blood flow under applied external pressure.

During the course of a study of skin blood flow under applied external pressure, it became apparent that decreasing blood flow by loading the skin surface reveals problems that are fundamental to the method of laser Doppler flowmetry. These problems have to do with the fact that the laser Doppler is extremely sensitive to red cell motion of any kind, whether associated with the ordered red cell motion of blood flow or the random red cell motion associated with changes in temperature or vessel occlusion. This effect becomes increasingly important whenever blood flow is compromised (a situation of considerable clinical significance), since the random portion of the signal then becomes significant in comparison with the diminished blood flow. Experiments have been conducted in living animals and with stationary drops of blood which clearly show the importance of these effects with regard to the interpretation of laser Doppler signals. Significant laser Doppler flow signals were repeatedly observed after manipulations which could reasonably be expected to reduce blood flow to zero.

Animals↗