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PubMed1990

Regeneration of teat canal keratin in lactating dairy cows.

This study was designed to determine the regeneration rate of teat canal keratin in two groups of 10 lactating Holstein cows. The weight of keratin obtained upon successive collections of keratin was determined. Intervals between successive collections were varied between 8 and 72 h. Following initial collection, the quantity of keratin removed was regenerated within 1 to 2.5 d. The rate of keratin regeneration per teat was approximately 1.5 mg of wet weight or .6 mg of dry weight per 24 h. The concentration (microgram lipid/mg keratin, wet weight) of lipid in keratin samples collected during regeneration was almost twice that present initially or after regeneration was complete. With the exception of free cholesterol, composition (%) of lipid components of keratin did not differ between samples collected initially, those collected early in the process of regeneration, and those collected after the mass of keratin removed had been replaced. Although data suggest that keratin matures during the process of regeneration, maturation appears complete by the time mass of keratin is fully regenerated. Additionally, the quantity of keratin recovered at initial sampling was inversely correlated with milk production. We hypothesize that as milk production increases, more keratin is lost during milking.

Animals↗
PubMed1989

Regeneration in the rat optic nerve after cold injury.

In order to examine nerve regeneration under conditions in which the basal laminae of the glial limiting membranes (GLM) and blood vessels were preserved intact, the intraorbital segment of adult rat optic nerve was frozen locally. During the next 3 months, degenerative and regenerative changes in axons and glial cells were observed by light and electron microscopy. On the day after treatment, all the myelinated and unmyelinated axons in the central zone of the lesion were damaged. The astrocyte endfeet of the GLM as well as the blood vessels were extensively disrupted, while their basal laminae were preserved apparently intact as a continuous sheet. Three days after treatment, regenerating axons appeared in the central zone of the lesion. They contained various numbers of clear and dense-cored vesicles as well as some smooth endoplasmic reticulum. The regenerating axons gradually increased in number, especially beneath the pial and perivascular surfaces of the lesion, where an abundance of regenerating axons was found 3 months after treatment. A few of these axons were abnormally remyelinated by oligodendrocytes. In addition to this axonal regeneration through the intraoptic nerve compartment, fine regenerating axons were seen growing out through GLM into the pial connective tissue 3 weeks after treatment. Astrocyte endfeet of the GLM became irregular in contour, protruding in a fern-leaf fashion into the pial connective tissue. Fine naked axons grew out through these protrusions and subsequently increased in number, vigorously growing in large bundles both proximally and distally along blood vessels in the pial connective tissue. Bundles of regenerating axons extended as much as 1.5 mm from the site of the lesion 3 months after surgery. These bundles were covered by thin processes of pial or arachnoidal non-neuronal cells, and the regenerating axons remained unmyelinated. The above findings indicate that under well-nourished conditions, adult mammalian optic nerve exhibits considerable regenerative ability.

Animals↗
PubMed1989

Dopamine antagonist speeds up tail regeneration in lizards exposed to continuous darkness: evidence for prolactin involvement.

In earlier studies, we demonstrated that continuous light (LL:LD, 24:0) stimulated tail regeneration whereas continuous darkness (DD:LD, 0:24) and pinealectomy depressed the same in the Gekkonid lizard, Hemidactylus flaviviridis, and, furthermore, exogenous prolactin significantly enhanced the regeneration process in lizards kept in 0:24 LD. However, the regeneration process in animals exposed to 24:0 LD was unaffected by the dopamine agonist, bromocriptine. This study with pimozide, an antipsychotic drug, and a potent dopamine receptor antagonist was conducted to ascertain whether the dopaminergic regulation of prolactin release is operative in lizards, as in mammals, and to provide further evidence for prolactin involvement in regenerative growth. Once daily intraperitoneal injection of 50 micrograms/kg pimozide to H. flaviviridis, 5 days prior to tail autotomy and 50 days thereafter, stimulated the regeneration process in lizards exposed to 0:24 LD. The initiation of regeneration, the total length of new growth (regenerate) produced by Day 50, and the total percentage replacement of the lost (autotomized) tails at the end of 50 days of experimentation were all significantly enhanced in pimozide-treated animals as compared with their counterparts injected with 0.6% sterile saline; in fact, better than saline-injected controls exposed to 24:0 LD of 638 lux intensity. The daily growth rate was also enhanced in pimozide-treated lizards. Interestingly, the pattern of regeneration as well as the final regenerate of pimozide-treated lizards were similar to those observed earlier in ovine prolactin-treated animals exposed to similar experimental photoperiodic schedules.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2026

Genome-Wide Identification of the LdARF Gene Family in Lilium davidii var. unicolor and Transient Functional Analysis of LdARF17 in Bulblet Regeneration.

Auxin response factors (ARFs) are key transcriptional regulators of the auxin signaling pathway and play important roles in plant organogenesis and regeneration. However, the functions of ARF family genes in lily scale-derived bulblet regeneration remain largely unclear. In this study, 24 LdARF genes were identified from the genome of Lilium davidii var. unicolor. Phylogenetic analysis revealed that LdARF proteins showed evolutionary conservation with ARF homologs from other monocot species. Genome-wide identification, phylogenetic analysis, and expression profiling revealed functional divergence among LdARF genes during scale-derived bulblet regeneration. Among them, LdARF17 exhibited a distinct regeneration-associated expression pattern, characterized by rapid induction after scale excision and sustained high expression during subsequent bulblet initiation and formation. Subcellular localization analysis demonstrated that LdARF17 is localized in the nucleus. Transient overexpression of LdARF17 significantly promoted bulblet regeneration and was associated with increased expression of auxin-responsive and regeneration-related genes, including IAA14, LBD16, and LBD29. These findings suggest that LdARF17 acts as a positive regulator of lily scale regeneration and may influence auxin-responsive transcriptional processes associated with early cell proliferation, providing new insights into the molecular mechanisms underlying vegetative regeneration in lilies.

Auxin response factor↗
PubMedDate not supplied

Bone regeneration: new findings and potential clinical applications.

Bone is a biologically privileged tissue in that it has the capacity to undergo regeneration as part of a repair process. Fracture healing is the most common and recognizable form of bone regeneration, but several other examples of bone regeneration have been observed in humans, suggesting that the ability to regulate bone regeneration as a therapeutic tool should be possible. Historically, efforts at limb lengthening have led to procedures for regenerating bone, such as the method of Ilizarov. This procedure, known as distraction osteogenesis, has applications in a variety of skeletal conditions, including the restoration of large skeletal defects, the transport of bone in cases of severe trauma with bone loss, and the correction of skeletal deformities. Fibrodysplasia ossificans progressiva is an example of how an abnormal metabolic condition can be viewed as evidence for the capacity of humans to regenerate large amounts of bone if the cellular and molecular signaling events are altered. Elucidation of the cellular and molecular basis for bone regeneration in humans - particularly the role of the human genome in relation to the expression of various growth factors and cytokines, such as the bone morphogenetic proteins - offers great potential for the treatment of orthopaedic conditions. Development of specific bone morphogenetic proteins as therapeutic substances to induce bone regeneration in patients is well under way. As methods for enhancing fracture healing, distraction osteogenesis, and other procedures are refined, the development of protein- and gene-based therapies for regulating bone formation should lead to a new era of orthopaedic practice.

Bone Morphogenetic Proteins↗
PubMed1999

Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons and recovery of forelimb function.

Adult mammalian CNS neurons do not normally regenerate their severed axons. This failure has been attributed to scar tissue and inhibitory molecules at the injury site that block the regenerating axons, a lack of trophic support for the axotomized neurons, and intrinsic neuronal changes that follow axotomy, including cell atrophy and death. We studied whether transplants of fibroblasts genetically engineered to produce brain-derived neurotrophic factor (BDNF) would promote rubrospinal tract (RST) regeneration in adult rats. Primary fibroblasts were modified by retroviral-mediated transfer of a DNA construct encoding the human BDNF gene, an internal ribosomal entry site, and a fusion gene of lacZ and neomycin resistance genes. The modified fibroblasts produce biologically active BDNF in vitro. These cells were grafted into a partial cervical hemisection cavity that completely interrupted one RST. One and two months after lesion and transplantation, RST regeneration was demonstrated with retrograde and anterograde tracing techniques. Retrograde tracing with fluorogold showed that approximately 7% of RST neurons regenerated axons at least three to four segments caudal to the transplants. Anterograde tracing with biotinylated dextran amine revealed that the RST axons regenerated through and around the transplants, grew for long distances within white matter caudal to the transplant, and terminated in spinal cord gray matter regions that are the normal targets of RST axons. Transplants of unmodified primary fibroblasts or Gelfoam alone did not elicit regeneration. Behavioral tests demonstrated that recipients of BDNF-producing fibroblasts showed significant recovery of forelimb usage, which was abolished by a second lesion that transected the regenerated axons.

Animals↗
PubMedDate not supplied

Liver regeneration and restoration of liver function after partial hepatectomy: the relation of fibrosis of the liver parenchyma.

BACKGROUND/AIMS: Patients who survive partial hepatectomy sometimes have unsatisfactory liver regeneration and restoration of liver function. Although the extent of resection should be adjusted to attain favorable liver regeneration and restoration of liver function, a guiding principle for this has not been established. METHODOLOGY: Seventy patients with hepatic tumors associated with liver disorders of various severity who underwent hepatectomy were studied. We calculated the removal rate of the liver and the regeneration rate of the remnant liver using computed tomography. The liver function was investigated using ICG R-15 (retention rate of indocyanine green). Liver disorder was classified into 4 groups, according to the severity of fibrosis. RESULTS: The regeneration rates of the remnant liver indicated a significant decline in patients with severe fibrosis. In the no fibrosis and mild fibrosis groups, an increased removal rate was associated with increased regeneration rate, and post-operative ICG R-15 improved with time. However, in the moderate fibrosis and severe fibrosis groups, an increased removal rate was not associated with increased regeneration rate, and post-operative ICG R-15 showed no change or became worse with time. CONCLUSIONS: Severe fibrosis of the liver parenchyma is associated with poorer regeneration of the remnant liver leading to poor restoration of post-operative liver function. The severity of fibrosis is useful as a predictive factor for liver regeneration and restoration of liver function after partial hepatectomy.

Adult↗
PubMed2000

Differential modification of myosin heavy chain expression by tenotomy in regenerating fast and slow muscles of the rat.

We have examined the effect of tenotomy on the expression of myosin heavy chains (MyHC) in regenerating fast and slow skeletal muscles. Degeneration/regeneration of the left soleus and plantaris of Wistar male rats was induced by an injection into the muscle belly of a myotoxin (snake venom: Notechis scutatus scutatus). MyHC isoform content of regenerating plantaris and soleus muscles were studied 21 days after muscle injury using an electrophoretic technique. Tenotomy of the regenerating plantaris (mechanical underload) did not alter its MyHC expression (P > 0.05). In contrast, tenotomy of the regenerating soleus increased its relative levels of MyHC-2b (P < 0.05) and MyHC-2x/d (P < 0.01), and decreased its relative level of MyHC-1 (P < 0.01). Tenotomy of the synergistic gastrocnemius (overload) tended to decrease the relative level of MyHC-2b in regenerating plantaris (P < 0.07). The effect of tenotomy of the synergistic gastronecmius on the regenerating soleus was different: a decrease in the relative levels of MyHC-1 (P < 0.05) and an increase in the relative level of MyHC-neonatal (P < 0.01). In conclusion, and in contrast to a regenerating slow muscle, a change of mechanical loading by tenotomy did not seem to markedly alter the expression of mature MyHC phenotype in a fast regenerating muscle.

Animals↗
PubMed2000

"Pumping the regenerate": an evaluation of oscillating distraction osteogenesis in the rodent mandible.

Mandibular distraction osteogenesis (DO) has become an important technique to lengthen the hypoplastic mandible and to reconstruct osseous defects after ablative surgery. The hallmark of successful DO is the creation of new bone within the distraction gap. Several anecdotal reports have described alternating compressing and lengthening protocols (i.e., "pumping the regenerate") to augment regenerate bone formation. The purpose of this experiment was to analyze formally the effects of an alternating compression/distraction protocol with a traditional distraction protocol. Ten adult male rats underwent unilateral mandibular osteotomy with placement of a custom distractor. After a latency period of 5 days, distraction was initiated at a rate of 0.25 mm twice daily. Animals in the control group (N = 5) were distracted to a length of 5.0 mm for 10 days at a rate of 0.25 mm twice daily. In contrast, animals in the experimental group (N = 5) were distracted to a length of 2.5 mm (at a rate of 0.25 mm twice daily) for 5 days, then compressed 1.0 mm for a 2-day period, and redistracted to a length of 5.0 mm. Regenerate cross-sectional area was evaluated by computed tomography performed after 5 weeks of consolidation. Gross examination and histological analysis were performed by a panel of experienced reviewers. Radiological as well as histological analysis of regenerate cross-sectional area demonstrated no significant differences between experimental (i.e., "pumped") and control groups. Both groups demonstrated excellent regenerate bone formation with no evidence of fibrous union. This study represents the first attempt to investigate the anecdotal technique of pumping the mandibular regenerate. The authors have demonstrated that pumping the regenerate leads to no substantial differences in radiological or histological appearance of regenerate bone formation.

Animals↗
PubMed2000

Partial hepatectomy and laparoscopic-guided liver biopsy in rhesus macaques (Macaca mulatta): novel approach for study of liver regeneration.

BACKGROUND AND PURPOSE: Although valuable information has been gained using a rodent partial hepatectomy model to assess liver regeneration, the ability to apply this research to humans remains uncertain. Thus, liver regeneration was assessed in a non-human primate, the rhesus macaque (Macaca mulatta). METHODS: One animal underwent 60% hepatectomy, a second animal underwent 30% hepatectomy, and control surgery (cholecystectomy) was performed on two separate animals. Laparoscopic-guided liver biopsy was performed on days 1, 2, 7, 14, and 30 after surgery. Changes in hemoglobin concentration and alanine transaminase activity were assessed, and liver regeneration was evaluated by measuring the expression of Ki-67. RESULTS: All animals survived surgery and laparoscopy. Substantial liver regeneration was induced in the animal that underwent 60% hepatectomy. Excellent tissue specimens were obtained via laparoscopic-assisted liver biopsy. CONCLUSIONS: Sixty percent partial hepatectomy in rhesus macaques appears to be an excellent model for the study of hepatocellular regeneration. The procedure was safe, and effectively induced liver regeneration. In addition, laparoscopic-guided liver biopsy allows observation of changes in the liver remnant as regeneration develops, and provides excellent tissue specimens for analysis. Thus, this rhesus macaque partial hepatectomy model will allow further characterization of liver regeneration in a species closer to humans.

Animals↗
PubMed1975

Abnormal regeneration of hydra induced with vinblastine sulfate.

The effect of vinblastine sulfate on the regeneration of hydra was examined. When the three segments of hydra (fore, mid, and hind segments) were treated with 0.01% vinblastine sulfate immediately after separation, transferred to normal culture medium, and observed for 7 days, various types of abnormal regeneration were observed, especially in the regenerates from the mid segments. Other segments of hydra did not reveal any abnormal pattern of regeneration, although incomplete regeneration or no regeneration of the segments was seen in the advanced period of the treatment. In the case of treatment of the three segments with 0.01% vincristine sulfate, no abnormal regeneration was seen, in spite of marked inhibition of regeneration which was observed in the advanced period of the treatment.

Culture Media↗
PubMedDate not supplied

A role for effectors of cellular immunity in epimorphic regeneration of amphibian limbs.

Immune modulation of regeneration of amphibian appendages is suggested, but not proven, by previous studies. Earlier studies have not demonstrated effects of treatments on both epimorphic regeneration and immune responses or restoration of regeneration by specific reversal of immunomodulation. Cyclosporin A (CsA) and interleukin-2 (IL-2) were used in this study to demonstrate the effects of immune suppression and its reversal, on allograft rejection and forelimb regeneration. When administered alone, CsA suppressed rejection of skin allografts and induced a dose-dependent retardation of regeneration. IL-2, administered alone, did not affect allograft rejection or regeneration. However, when combined with CsA, IL-2 abrogated or reversed effects of CsA on both allograft rejection and forelimb regeneration, in a dose-dependent manner. The selective focus of CsA's action and the ability of IL-2 to overcome and reverse these effects strongly suggest that T-lymphocytes participate in or contribute to expression of epimorphic regeneration of amphibian appendages. Further studies are required to better characterize this role.

Animals↗
PubMed1976

[Histological aspects of posttraumatic regeneration].

A number of histological aspects (regeneration capacity, origins of regeneration, means of reparation) are discussed on the example of the reparative regeneration of the adrenal cortex. The adrenal cortex is found to possess high regeneration capacity after a traumatic injury of the organ. Realization of this capacity is dependent on general and local conditions, the character and the volume of the injury and the degree of involvment of cambial zones being of substantial significance. Among these zones are the glomerular zone and the external part of the bundle zone, whose proliferating cells are the source of the reparative regeneration of the cortical substance. The reparation of the functioning mass of the adrenal cortex is performed by the type of regenerative hypertrophy or the reparative regeneration depending on the character of the trauma. After the first type, the division of cells and their differentiation occur within the limits of the available structural elements, after the second type- of the newly formed ones. Both types are evolutionally conditioned and are definitely similar eather to postnatal growth and physiological regeneration (regenerative hypertrophy), or to the embryonic histogenesis of the definitive adrenal cortex (reparative regeneration).

Adrenal Cortex↗
PubMedDate not supplied

The effect of trimetazidine on liver regeneration after partial hepatectomy under hepatic blood inflow occlusion.

BACKGROUND/AIMS: It has been shown that hepatic blood inflow occlusion impairs liver regeneration. Our aim in this study was to investigate the effect of trimetazidine, known as an anti-ischemic and anti-oxidant agent, on liver regeneration after hepatic blood inflow occlusion. METHODOLOGY: Sprague-Dawley rats were randomized into three groups. Rats in group 1 underwent 65% hepatectomy. Rats in group 2 and 3 were subjected to 15 minutes of hepatic blood inflow occlusion during 65% hepatectomy. Rats were treated with saline (in group 1 and 2) or trimetazidine (in group 3) 30 minutes before operation. Serum level of aspartate transaminase, wet to dry liver weight ratio, and liver injury score in light microscopy were studied for the evaluation of liver injury. Liver regeneration was evaluated by PCNA-labeling index (the percentage of hepatocytes staining for proliferating cell nuclear antigen), mitotic index (the percentage of mitotic hepatocytes), and liver regeneration rate (the percentage of initial liver weight). RESULTS: Rats in group 2 and 3 had significantly higher serum aspartate transaminase level, wet to dry liver weight ratio and injury score than those in group 1 on day 1 posthepatectomy. Except for serum aspartate transaminase level on day 4, these parameters were significantly higher in group 2 than in group 1 and 3 on day 1 and 4. PCNA-labeling index and mitotic index were significantly less in group 2 and 3 than in group 1 on day 1. In contrast to liver regeneration rate, both indices in group 2 were significantly less than those in group 3 on day 1. There were no differences in regeneration parameters between the groups on day 4. Survival rate was significantly higher in group 3 than in group 2. CONCLUSIONS: Fifteen minutes of hepatic blood inflow occlusion caused an injury in the remnant liver, impaired liver regeneration, and decreased survival rate after partial hepatectomy. However, pretreatment with trimetazidine reduced liver injury, and improved liver regeneration and survival rate. For situations where hepatic blood inflow occlusion is planned in major liver resection, trimetazidine pretreatment would be useful strategy to improve postoperative outcome.

Animals↗
PubMedDate not supplied

In vitro induction of cytochrome P450 enzymes in hepatocytes isolated from the regenerating rat liver.

Partial hepatectomy results in the loss of cytochrome P450 enzymes. During regeneration, the levels of cytochrome P450 activities, apoproteins and mRNA are reduced. Our present study investigated CYP1A, CYP2E1 and CYP3A induction in the cells of rat liver regenerating for 1, 3, 7, or 14 days. Hepatocytes were isolated from regenerating liver of hepatectomized rats and treated with enzyme inducers: 3-methylcholanthrene, imidazole and dexamethasone. CYP1A enzymes of the cells isolated from regenerating liver were inducible by 3-methylcholanthrene. The rate of induction of the cells from 3-day regenerating liver by 3-methylcholanthrene was three times higher than that of the hepatocytes of sham-operated rats. Dexamethasone caused about two- or three-fold stronger elevation of CYP3A in the cells of 1-, 3- and 7-day regenerating liver than in hepatocytes of sham-operated animals. However, the degree of CYP2E1 induction by imidazole was the same (about 2.5-fold) at each regenerating time as it was detected in the hepatocytes of sham-operated animals. In conclusion, the inducibility of the cells was retained at each regenerating time, but the degree of induction showed some differences.

Animals↗
PubMed2004

[Liver regeneration after hepatectomy].

It is well known that the normal liver has enormous regenerative capacity. Despite years of effort by numerous investigators, there is still uncertainty about the signals of liver regeneration. Computed tomography (CT) is the most useful tool because it accurately measures human liver volume. Comparing the differences in regeneration after major resection of normal and injured livers, normal livers reached plateau levels within 1 to 2 months regardless of the extent of resection, whereas regeneration was retarded in injured liver. Human liver regeneration is influenced by the extent of resection. In biliary cancer, liver regeneration terminates when the liver has regained about three-quarters of its original size in about 1 year. The clinical significance of the observation that liver regeneration is an incomplete process is unclear. However, the strong correlation observed between body surface area and regenerated liver volume suggests that liver regeneration is a process of restoration of the liver to a volume suitable for body size. In living related-donor liver transplantation there is a tendency for the size of the transplanted liver to converge to the standard liver volume, regardless of whether the initial liver-graft volume was smaller or larger than the standard liver volume.

Animals↗
PubMedDate not supplied

[Analysis of the expression pattern of regulatory genes Pax6, Prox1, and Six3 during regeneration of eye structures in the newt].

We studied tissue-specific expression of homeobox genes Pax6, Prox1, and Six3 during regeneration of the retina and lens. In the native retina, mRNA of Pax6, Prox1, and Six3 was predominantly localized in ganglion cells and in the inner nuclear layer of the retina. Active Pax6, Prox1, and Six3 expression was detected at early stages of regeneration in all proliferating neuroblasts forming the retinal primordium. Low levels of Pax6, Prox1, and Six3 mRNA were revealed in depigmented cells of the pigment epithelium as compared to the proliferating neuroblasts. At the intermediate stage of retinal regeneration, the distribution of Pax6, Prox1, and Six3 mRNA was diffuse and even all over the primordium. During differentiation of the cellular layers in the course of retinal regeneration, Pax6, Prox1, and Six3 mRNA was predominantly localized in ganglion cells and in the inner part of the inner nuclear layer, which was similar to the native retina. An increased expression was revealed in the peripheral regenerated retina where multipotent cells were localized. The dual role of regulatory genes Pax6, Prox1, and Six3 during regeneration of eye structures has been revealed; these genes controlled cell proliferation and subsequent differentiation of ganglion, amacrine, and horizontal cells. High hybridization signal of all studied genes was revealed in actively proliferating epithelial cells of the native and regenerating lens, while the corneal epithelium demonstrated a lower signal. Pax6 and Prox1 expression was also revealed in single choroid cells of the regenerating eye.

Animals↗
PubMedDate not supplied

[Resources of regeneration in planarians].

We studied the intensity of blastema growth in operated planarians at an early stage of regeneration as a function of the following factors: area of regenerate and its function and number of regeneration foci (volume of regeneration). There was no direct dependence between the intensity of regeneration and the size of regenerating fragment, as well as the volume of regeneration. Some specific features of the early stage of regeneration have been described, which suggest its determinate character. The behavior of neoblasts during formation of blastemas with different localization is discussed.

Animals↗