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PubMed2004

[Does the liver ability to regeneration decrease with age? The dynamics of functional activity of mitochondria in process of the liver regeneration].

The ability of liver of 1-, 3-, 12- and 24-month rats to mass restoration, mass gain and activity of cell energy system from 1 to 30 days after ectomy of liver medial and left lateral lowels were investigated. It was shown that the old animals did not rebate to young ones in respect of regenerant gain and exceeded them with mitochondria functional activity at the early stages of regeneration (2-24 h after operation). We detected a little lag in old rats (12 and 24 monthes) in comparison with 1-3 ones in rate of liver mass reset to corresponding age groups control level. It may be explained by the difference between young and old animals in strategy of organism homeostasis after ectomy of 2/3 liver mass. The rhythmic character of activities for the most of indices of mitochondria functional activity in liver regenerating up to 24 h with maximum at 2-3 h and 12-18 h after operation was detected. The detected rhythm was typical mostly to mitochondria of the old animals. The high functional activity of mitochondria of the old animals and on the late stages of liver regeneration was shown.

Adenosine Diphosphate↗

PubMed1991

Regeneration procedures: grafting materials, guided tissue regeneration, and growth factors.

Flap debridement, bone grafting, and guided tissue regeneration have the capacity of regenerating bone, periodontal ligament, and cementum. Alloplastic materials are used to fill periodontal defects, and healing occurs by repair. While varying amounts of new bone may form with allografts, a long junctional epithelium is usually the mode of attachment. Flap debridement has been reported to successfully treat multiple walled intrabony defects. Healing results in bone regeneration. However, there is probably a long junctional epithelium adjacent to the root. Defects treated by guided tissue regeneration have been demonstrated to heal with new cementum, periodontal ligament, and bone. Recently, growth factors have been discussed as a possible means of enhancing wound healing.

Bone Transplantation↗

PubMed1987

Cytochemical localization of calcium in mitochondria of regenerating rat adrenal cortex. A study of adrenal regeneration hypertension.

The distribution of calcium in the mitochondria of the adrenal gland was studied during development of adrenal regeneration hypertension. Electron opaque precipitate (calcium antimonate) was localized predominantly in the intercristal space within mitochondria and in cisternae of smooth endoplasmic reticulum. Stereological techniques were employed to quantitate the volume per cell of precipitate. Compared to the zona glomerulosa or zona fasciculata of controls, the volume per cell of electron opaque precipitate in mitochondria of the regenerating gland was significantly reduced at 5 and 14 days after enucleation. By 21 days, the volume of mitochondrial precipitate per cell, while more than that in zona glomerulosa cells, was less than in mitochondria from control zona fasciculata cells. As a comparison, normal rats were treated with ACTH or were hypophysectomized. ACTH-treatment did not greatly increase the precipitate associated with mitochondria in the zona fasciculata. Mitochondria in the zona fasciculata of hypophysectomized rats however showed a significant reduction in precipitate per cell correlating with a significantly reduced volume of mitochondria per cell as compared to those of control zona fasciculata cells. Giant mitochondria were observed in hypophysectomized animals. Volume of precipitate per cell associated with smooth endoplasmic reticulum was increased slightly, but significantly, as compared to that in controls treated with ACTH, whereas in hypophysectomized rats, it was decreased significantly. Adrenocortical cells arising from the zona glomerulosa and sub zona glomerulosa region differentiate to zona fasciculata cells during regeneration and may have an altered capacity to concentrate calcium. Change in intramitochondrial calcium may be correlated with the reduced formation of corticosterone from its precursor, deoxycorticosterone, thereby contributing to the pathogenesis of adrenal regeneration hypertension.

Adrenal Cortex↗

PubMed1979

Quantitative studies of the regeneration of rat myelinated nerve fibres: variations in the number and size of regenerating fibres after repeated localized freezings.

The number and size of myelinated nerve fibres were determined in the nerve to the medial head of the gastrocnemius muscles of rats whose left sciatic nerve was repeatedly frozen (one to five times at three weekly intervals). The contralateral nerve was used as a control. Results varied according to the number of freezings performed and, for a given number of freezings, according to the period of regeneration. When measurements were completed 1 month after the last of several localized freezings, the number of regenerating myelinated nerve fibres increased regularly up to the third freezing, reaching to about 220% of the control value, but no higher values were recorded after four or five freezings. The nerve fibre distribution was unimodal in all the nerves studied. The mean diameter of all myelinated fibres decreased with the number of freezings from 50% of the control value after the first to 36% after the fifth. When measurements were made 1, 3, 6, 12 and 18 months after the third and final freezing, the number of regenerating myelinated nerve fibres decreased by about 30% between the first and third month and then stabilized at 190% of the control value. Nerve fibre distribution became bimodal from the third month onwards, and the mean diameter of all myelinated fibres increased regularly. However, by the eighteenth month, the size of regenerated myelinated nerve fibres had only reached 70% of the normal contralateral value.

Animals↗

PubMed1984

[Liver regeneration and the immune system. II. Suppressor activities of lymphocytes activated in vivo by liver regeneration and their genetic control].

The lymph node cells (LNC) activated in vivo by liver regeneration following partial hepatectomy of mice (pLNC: primed lymph node cells) respond to regenerating liver cells in vitro with typical secondary immune response characteristics (as shown in Paper I). These lymph node cells activated in vivo suppress the proliferation of responder lymphocytes cultured with mitomycin C (MMC)-treated regenerating syngeneic liver cells (sMLHLR). The suppressive activity was already present in LNC 4 days after partial hepatectomy and remained unchanged for at least 16 days. These pLNC were effective not only on sMLHLR but also on syngeneic mixed lymphocyte culture (sMLR) and allogeneic mixed lymphocyte culture (MLR), of which responder cells share I-A (I-B) subregions of MHC with pLNC. The pLNC restimulated in vitro with regenerating liver cells (ppLNC: in vitro reactivated pLNC) suppress the proliferation of syngeneic responder cells in sMLR, but not of cells from congeneic mice differing from the ppLNC at a cluster of genes linked to the Ig locus. Thus the suppressive activity of pLNC is controlled by the I-A (I-B) subregions of the MHC and that of ppLNC by genes in the Ig region.

Animals↗

PubMedDate not supplied

Effects of carcinogens on regenerating and non-regenerating limbs in amphibia (review).

The effects of chemical carcinogens on regenerating and non-regenerating limbs in amphibia are reviewed. The regeneration-competent tissues show a remarkable resistance to chemical carcinogenesis. However, chemical carcinogens can induce teratogenesis when they are administered to the regeneration blastema, while normal differentiation occurs in limited cases when they are administered to the intact limbs. The regenerative capacity may be considered as the deterrent to neoplasia in these tissues.

Abnormalities, Drug-Induced↗

PubMed1984

[Liver regeneration and the immune system. 1. In vitro and in vivo activation of lymphocytes by liver regeneration].

When syngeneic lymphocytes and mitomycin C (MMC) treated regenerating liver cells prepared from a partial hepatectomized mice are cultured together, the in vitro DNA synthetic response is activated (sMLHLR: syngeneic mixed hepatectomized liver cell-lymphocyte culture). Ia+ Kupffer cells play an important role as stimulators in the responses, since the stimulating activity of regenerating liver cells is lost by the pretreatment of them with anti-Ia monoclonal antibody plus complement or the removing Kupffer cells from them. The lymphocytes are activated also in vivo during liver regeneration after a partial hepatectomy. Because, when lymphocytes prepared from hepatectomized mice are cultured with regenerating liver cells, lymphocytes are stimulated to accelerate their DNA synthesis in a typical manner of the secondary immune responses (secondary sMLHLR). In primary sMLHLR, the responder cells are mainly Lyt-1+ whereas in secondary sMLHLR they are mainly Lyt-2+. The mechanism of changing the Lyt phenotype of major responder cells from Lyt-1 to Lyt-2 during sMLHLR is discussed.

Animals↗

PubMed1978

[Regeneration of a whole worm from a small fragment of the body of Dugesia tigrina planaria following repeated removal of regenerates].

The ability of restoration of the whole worm from a small body fragment was not reduced after 8 removals of the anterior and posterior regenerates. The polarity of restoring fragments in the most cases corresponded to the initial one. Upon the colchicine effect on the restoring fragments which accompanied the repeated removal of the regenerates, a high percentage of cases of incomplete somatic embryogenesis was observed: the formation of bi- and multipolar forms. The formation of regenerates is realized by neoblasts. Upon the repeated removal of regenerates, the dedifferentiated intestine cells appear to take part in the restorative processes as well.

Animals↗

PubMed1980

Adrenal regeneration hypertension prevented by thyroidectomy: a quantitative ultrastructural study of the regenerating adrenal cortex.

Thyroparathyroidectomy (TPX) prevents adrenal regeneration hypertension (ARH) in female rats and concomitantly inhibits regeneration of the adrenal cortex. Removal of the thyroid gland plays the major role in preventing ARH inasmuch as parathyroidectomized adrenal-enucleated (PX-AE) rats became hypertensive, whereas thyroparathyroidectomized adrenal-enucleated rats (TPX-AE + PT) did not. Inhibition of adrenocortical regneration by TPX is reflected by a significant decrease in adrenal weight, volume of cortical parenchymal tissue per gland, and average cell volume at three weeks, compared with the regenerating adrenal gland in adrenal-enucleated thyroid-parathyroid-intact (AE) rats. Mitochondria in TPX-AE rats resembled closely those from zona fasciculata cells of a normal adrenal gland; stereologic techniques for electron microscopic examination confirmed that mitochondrial volume/cell and surface area of total mitochondrial membranes/cell (outer/inner membranes plus cristae) of adrenocortical cells from TPX-AE rats did not differ significantly from those of AE animals. The surface area of mitochondrial cristae of TPX-AE rats, however, was significantly greater than that of AE rats, whereas the surface area of the inner/outer mitochondrial membrane of the TPX-AE group was decreased significantly as compared with that of the AE group. The diameter of mitochondria in TPX-AE rats was larger than in the AE group, although the number of mitochondria/cell was significantly less in TPX-AE rats than in AE rats. Although TPX had no significant effect on the levels of DOC or corticosterone in the serum of quiescent AE rats as compared with TPX-AE rats, the rise in DOC in the serum after ether stress was blunted in the TPX-AE group as compared with that in the AE group. The rise in corticosterone in the TPX-AE group was comparable to that of the AE animals. Thus, partial inhibition of adrenal regeneration in TPX-AE rats in combination with a blunted rise in DOC levels in response to stress may well contribute to the prevention of ARH.

Adrenal Cortex↗

PubMed1977

Hormone control in regeneration: effects of somatostatin on appendage regeneration, blood glucose and liver glycogen in Diemictylus viridescens.

In the present communication, synthetic somatostatin, a hypothalamic factor which has a known inhibitory effect on the release of growth hormone, thyroid-stimulating hormone, prolactin, insulin and glucagon in man and other mammals, was found to have an inhibitory effect on limb and tail regeneration in adult Diemictylus viridescens, when the newts were treated with a daily dose of 3-5 or 15 microgram/animal for a period of 34 days post-amputation. At the higher dose, the animals exhibited total inhibition of appendage regeneration in a few cases and the remainder showed a considerable delay compared to the controls; none of the experimental animals reached the advanced four-digit stage achieved by the controls. Furthermore, the blood glucose and liver glycogen values in the somatostatin-treated animals were significantly lower than the control values. Mechanisms in the storage, mobilization and utilization of glucose (involving hormones) are discussed in relation to appendage regeneration in the newt and possible controls of regeneration at the level of the hypothalamus are suggested.

Animals↗

PubMed1983

Blood cells and their role in regeneration. I. Changes in circulating blood cell counts during forelimb regeneration.

The possible role of leukocytes in regeneration was examined through the evaluation of quantitative changes in circulating blood cell counts during forelimb regeneration in adult newts. Leukocyte counts declined during the first 2 weeks, then returned to preamputational levels. Thrombocytes were also depressed (40-67%) throughout the progressive stages (9-30 days). In addition, lymphocytes were reduced, especially during the preblastemic phase (less than 15 days). In contrast, neutrophils were increased immediately following wound healing and during the differentiation stages, but were otherwise unchanged. These variations appear to reflect physiological changes occurring during regeneration and are consistent with a potential role for leukocytes in regeneration.

Animals↗

PubMed2006

Gene-enhanced tissue engineering for dental hard tissue regeneration: (2) dentin-pulp and periodontal regeneration.

Potential applications for gene-based tissue engineering therapies in the oral and maxillofacial complex include the delivery of growth factors for periodontal regeneration, pulp capping/dentin regeneration, and bone grafting of large osseous defects in dental and craniofacial reconstruction. Part 1 reviewed the principals of gene-enhanced tissue engineering and the techniques of introducing DNA into cells. This manuscript will review recent advances in gene-based therapies for dental hard tissue regeneration, specifically as it pertains to dentin regeneration/pulp capping and periodontal regeneration.

Journal Article↗

PubMed1988

Production in vitro by spinal cord of growth factor(s) acting on newt limb regeneration: influence of regeneration of the nerve fibers.

In order to approach the problem of regulation of growth factor(s) production during limb regeneration in newt, we co-cultivated spinal cord segments and blastemas. First we showed that, like the sensory supply, the spinal cord possesses size-dependent mitogenic capacities for limb blastemas. A 5-mm long spinal segment enhances radiolabelled thymidine incorporation to the same extent as spinal ganglia (1.6-fold). Second, we co-cultivated blastemas with spinal segments, the nerve fibers of which were previously stimulated to regenerate (= stimulated spinal segment) or not (= non-stimulated spinal segment). Only after a 24-h coculture, do stimulated spinal segments enhance thymidine incorporation in blastemas 2-fold more than non-stimulated spinal segments. Our results suggest that during limb regeneration brachial nerves produce more growth factor(s) when regrowing, inducing the proliferation of blastema cells which in return deliver a neuronotrophic factor acting on these nerves.

Animals↗

PubMed1998

Bone regeneration after radicular cyst removal with and without guided bone regeneration.

In order to determine the degree of bone regeneration after removal of radicular cysts using guided bone regeneration (GBR), a prospective, controlled and randomized clinical study was performed. Thirty patients with radicular cysts were divided into three groups. One group, the control group (n=10 patients), was treated by enucleation and primary closure. The other two groups were treated by enucleation and primary closure but GBR was used in addition, using a resorbable membrane (n=10) and a nonresorbable membrane (n=10). The membranes were fixed with nonresorbable Memfix System screws. The residual volume and the density of the newly formed tissue was measured by computer-assisted tomography and computer-assisted digital image analysis before enucleation and three and six months postoperatively. No statistical significance was found in density and residual volume between the three treatment groups after six months. These results suggest that GBR using membranes does not contribute to increased bone regeneration.

Adult↗

PubMed2001

Presence of interleukin-4-producing cells for human bone regeneration after application of guided tissue regeneration membranes.

To study the process of bone regeneration we examined three samples of periapical regenerative tissue obtained from two patients under a guided tissue regeneration treatment in endodontic surgery by the immunohistochemical and enzyme histochemical methods. The regenerative tissue consisted of a large number of fibroblast-like cells and a small number of mononuclear cells. Fibroblast-like cells stained positively for alkaline phosphatase and osteopontin, whereas mononuclear cells stained positively for CD4. Interleukin-4-producing cells could be detected in adjacent sections. However, interferon-y-producing cells could not be detected. These findings suggest that interleukin-4-producing cells may be one of the elements associated with success in the human bone regeneration process in vivo.

Adult↗

PubMed2005

Similarities and differences between induced organ regeneration in adults and early foetal regeneration.

At least three organs (skin, peripheral nerves and the conjunctiva) have been induced to regenerate partially in adults following application of porous, degradable scaffolds with highly specific structure (templates). Templates blocked contraction and scar formation by inducing a reduction in the density of contractile fibroblasts (probably myofibroblasts) and by preventing these cells to organize themselves appropriately in the wound. In contrast, during early foetal healing, myofibroblasts were absent and wounds did not close by contraction but rather by spontaneous regeneration. The adult regenerative process has so far led to imperfect recovery of the physiological anatomy of skin (skin appendages were missing), while early foetal healing has led to apparently complete restoration. Furthermore, the mechanism of the adult regenerative process involves thwarting of myofibroblast function while, during early foetal healing, differentiation of myofibroblasts has not yet occurred. The data suggest that induced organ regeneration in the adult is the result of partial reversion to early foetal healing. If so, the adult may conceal a foetal response that may be subject to activation following application of highly active scaffolds or of other substances or cells.

Adult↗

PubMed1995

The importance of periodontal pathogens in guided periodontal tissue regeneration and guided bone regeneration.

Although guided tissue regeneration (GTR) procedures in periodontitis lesions and around endosseous dental implants represent exciting new therapeutic modalities in periodontics, these treatments can fail because of shortcomings in surgical techniques, restriction in the size and shape of the defect, anatomic features interfering with surgery, or infectious complications. Our studies show that optimal tissue regeneration cannot be expected for a nonbioabsorbable barrier membrane placed in a site infected by periodontopathic microorganisms. Our data also indicate that treatment failure is most frequent in patients who harbor high levels of periodontal pathogens and show evidence of severe periodontitis in numerous teeth. To decrease the risk of infection and to ensure proper healing, periodontal therapy should precede insertion of the barrier membrane for GTR. Recently, we have studied the effect of the pathogens on periodontal GTR and guided bone regeneration around dental implants and the results are reviewed in this article.

Biofilms↗

PubMed1992

Expression of alpha-cardiac and alpha-skeletal actin mRNAs in relation to innervation in regenerating and non-regenerating rat skeletal muscles.

The expression of alpha-cardiac and alpha-skeletal actin mRNA in regenerating muscle was examined. Changes in mRNA levels were analyzed in autografted extensor digitorum longus (EDL) muscles in rats using alpha-isoform specific synthetic oligonucleotides and beta-actin cDNA as probes. After autografting, the expression of alpha-cardiac actin mRNA was induced; concomitantly that of alpha-skeletal actin mRNA was reduced. The pattern of alpha-actin mRNA expression appeared to be similar to that seen in embryonic skeletal muscle. In order to evaluate the effects of innervation on alpha-actin mRNA expression in regenerating muscle, nerveless, standard, and nerve-intact autografted muscles were examined. More complete innervation facilitated the recovery of alpha-skeletal actin mRNA to control levels, but had little effect on the amount of alpha-cardiac actin mRNA. We found that regenerating muscle shows that embryonic pattern of alpha-actin mRNAs in the early stage and concluded that the recovery of alpha-skeletal actin mRNA expression to the adult pattern is influenced by innervation, while alpha-cardiac actin mRNA expression is nerve independent.

Actins↗