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Biomedical subjects

A Ignatius

Publications and source records attributed to A Ignatius.

16 recordsLinked to original sources
PubMed2000

[In vitro cell behavior of human osteoblasts after physiological dynamic stretching].

The cell activity of human bone derived cell cultures was studied after mechanical stimulation by cyclic strain at a magnitude occurring in physiologically loaded bone tissue. Monolayers of subconfluently grown human bone derived cells were stretched in rectangular silicone dishes with cyclic uniaxial movement along their longitudinal axes. Strain was applied over two days for 30 min per day with a frequency of 1 Hz and a strain magnitude of 1000 mustrain. Cyclic stretching of the cells resulted in an increased proliferation (10-48%) and carboxyterminal collagen type I propeptide release (7-49%) of human cancellous bone derived osteoblasts while alkaline phosphatase activity and osteocalcin release were significantly reduced by 9-25% and 5-32% respectively. These results demonstrate that cyclic strain at physiologic magnitude leads to an increase of osteoblast activities related to matrix production while those activities which are characteristic for the differentiated osteoblast and relevant for matrix mineralization are decreased.

Adult↗
PubMed2000

Dynamic cell stretching increases human osteoblast proliferation and CICP synthesis but decreases osteocalcin synthesis and alkaline phosphatase activity.

The cell activity of human-bone-derived cell cultures was studied after mechanical stimulation by cyclic strain at a magnitude occurring in physiologically loaded bone tissue. Monolayers of subconfluently grown human-bone-derived cells were stretched in rectangular silicone dishes with cyclic predominantly uniaxial movement along their longitudinal axes. Strain was applied over two days for 30 min per day with a frequency of 1 Hz and a strain magnitude of 1000 microstrain. Cyclic stretching of the cells resulted in an increased proliferation (10-48%) and carboxyterminal collagen type I propeptide release (7-49%) of human-cancellous bone-derived osteoblasts while alkaline phosphatase activity and osteocalcin release were significantly reduced by 9-25 and 5-32%, respectively. These results demonstrate that cyclic strain at physiologic magnitude leads to an increase of osteoblast activities related to matrix production while those activities which are characteristic for the differentiated osteoblast and relevant for matrix mineralization are decreased.

Alkaline Phosphatase↗
PubMed1997

[Resorbable bone cements].

Bone cements are used to treat compression fractures, fill bone defects and improve implant fixation in osteoporotic patients through reinforcement of weak bone. When the fracture repair is complete the bone cement ideally should degrade. In general, calcium-phosphate bone cements are biodegradable and can fulfill this temporary function. Several research groups have developed calcium-phosphate bone cements in the last years which have a chemical structure similar to that of the apatite of bone. However the conditions for processing the cement intraoperatively, as well as the mechanical properties and degradation characteristic of the various products show great variations. Clinical long-term studies have not yet been reported so far. Whether these new types of bone cements fulfill all the requirements for clinical application is still not certain and remains to be determined in future studies.

Absorption↗
PubMed1996

Comparative animal study of three ligament prostheses for the replacement of the anterior cruciate and medial collateral ligament.

Three different ligament prostheses (Leeds-Keio, Gore-Tex and a prototype of Aramid) were implanted in sheep knee joints replacing the anterior cruciate ligament and the medial collateral ligament. After 1 yr the knees were explanted and their biomechanical properties were assessed by a drawer test and tensile tests of the implants. Additionally the ligament replacements, the synovial membrane and the lymph nodes were inspected histologically. For each type of prosthesis partial or total ruptures occurred. None of the operated joints regained normal stability and stiffness. Anterior knee stability was best for the Gore-Tex treated group and worst for those joints that received a Leeds-Keio implant. The stiffness and rupture strength were highest for the Gore-Tex prostheses. Histologically the strongest intra-articular inflammatory response was observed in the Gore-Tex treated joints. Inside the drill tunnels the severest foreign body reaction was found for the Aramid prostheses. Gore-Tex fibres often showed good bony integration. Wear particles formed from all prostheses and caused small granulomas and mild synovities. The results suggest that none of the tested materials represent an ideal solution for ligament replacement. Relatively good stability does not guarantee good biocompatibility and vice versa. This suggests that ligament prostheses should be applied only in salvage cases.

Animals↗
PubMed1996

Early, full weightbearing with flexible fixation delays fracture healing.

Secondary fracture healing is known to be accelerated by the process of periosteal callus formation that can be induced by flexible fracture fixation in connection with loading of the injured extremity. The purpose of this study was to compare the healing of experimental fractures of long bones in sheep under early weightbearing with that of fractures under delayed, steadily increasing weightbearing. Differences in the quality of fracture healing were described by biomechanical (rigidity of fracture, indentation stiffness of callus) and histologic methods. Prevention from early, full weightbearing resulted in a higher flexural rigidity of the fracture, an increased mechanical stiffness of the callus tissue, and an enhanced bone formation at the healing front. Although early loading of a fresh fracture initiated an enormous amount of periosteal callus, the healing of the osteotomy was significantly delayed, and the quality of the newly formed tissue was reduced as compared with fractures with a reduced loading situation. A reduction of load transfer by delaying full weightbearing is advantageous for the healing of fractures stabilized with flexible fixation systems.

Animals↗
PubMed1995

Radiation biochemistry of the chicken embryo: DNA synthesis and DNA degradation following X-irradiation.

Chicken embryos were X-irradiated with a dose of 8 Gy. At a developmental stage of 15 days, desoxyribonucleic acid (DNA) synthesis, nucleoid sedimentation, viscosity of the alkaline cell lysates and DNA fragmentation were examined in brain and/or liver cells. Further studies aimed at the appearance of acid-soluble nucleic acid metabolites in the allantoic fluid. Complementary investigations comprised the in vitro activities of a DNase I and a DNase II of liver and brain cells as well as of the allantoic fluid of X-irradiated embryos. It could be shown for the first time that, following acute X-irradiation of the chicken embryo, the inhibition of DNA synthesis is accompanied by at least two enzymatic DNA degradation phases. The early phase comprises a period of 6 (-12) h, whereas the second phase lasts, with organ-specific peculiarities, > or = 24 h. During the early period, some apoptotic phenomena are seen, whereas at the later stages of radiation response signs of necrolysis become evident. The excretion of DNA metabolites, probably oligonucleotides, in the allantoic fluid is enhanced following X-irradiation > 2 Gy and may be used as an additional parameter of the overall radiation damage. Therefore, the chicken embryo may be regarded as a radiobiological and possibly toxicological alternative to laboratory animals with respect to the nucleic acid metabolism.

Allantois↗
PubMed1994

The in vitro influence of sulfated bis-lactobionic acid amides on O6-alkylguanine-DNA alkyltransferase, DNase I, nucleic acid synthesis and chromatin structure.

The influence of four sulfated bis-lactobionic acid amides (BLAA) of molecular weights between 2388 and 2514 on O6-alkylguanine-DNA alkyltransferase (AT), DNase I and nucleic acid synthesis as well as on nucleoid sedimentation and the viscosity of alkaline lysates of chicken embryo cells was studied in vitro. The activities of AT and DNase I were inhibited by BLAA in a dose-dependent manner. Depending on the polyanion used, concentrations depleting AT activity by 50% ranged between 3.5 and 7.0 microM, whereas BLAA concentrations of almost 250-320 microM were needed to halve DNase I activity. At concentrations above 8 microM, BLAA decreased scheduled DNA synthesis in a dose-dependent fashion whereas RNA synthesis remained unchanged even at the highest BLAA concentrations used (2 mM). In chicken embryo brain cells BLAA exerted a biphasic effect on the nucleoid sedimentation and the viscosity of alkaline cell lysates reflecting a decrease in chromatin compactness at lower BLAA concentrations (10-100 microM) and an increase in chromatin compactness at higher polyanion concentrations (> or = 200 microM). The remarkably high sensitivity of the nuclear enzyme AT deserves further investigation in regard to the fate of the polyanions within cells and tissues.

Animals↗
PubMed1993

Toxicological studies with primary cultures of chick embryo cells: DNA fragmentation under the influence of DNase I-inhibitors.

Chicken embryo brain and liver cells in vitro exhibited spontaneous DNA fragmentation as determined by viscometry of alkaline cell lysates. Ca2+ and Mg2+ enhanced, while Zn2+, the Ca2+ chelator ethylenglycol-bis(beta-aminoethyl-ether)-N,N,N'-tetraacetic acid (EGTA), spermine and--to a lesser extent--spermidine and Hoechst 33,258 inhibited spontaneous DNA fragmentation. Under the same conditions chromatin condensation, as assessed by nucleoid sedimentation, increased. Exposure of chicken embryo cells to various genotoxic agents, i.e. doxorubicin, bleomycin, methyl methanesulfonate, thiyl radicals, H2O2, UV light, and X-rays, increased DNA fragmentation in a dose dependent manner. Zn2+ or EGTA diminished DNA fragmentation in cells exposed to bleomycin, thiyl radicals, H2O2 and UV light. An apparent sensitisation to X-irradiation has been observed in Zn2+ or EGTA-pretreated cells. It is suggested by the present investigations that, with agent specific peculiarities, apoptotic phenomena are implicated when nucleotoxicity is assessed in chicken embryo cells by physico-chemical short-term tests in vitro.

Animals↗
PubMed1992

Poly(ADP-ribose)polymerase-activity of chicken embryo cells exposed to nucleotoxic agents.

Poly(ADP-ribose)polymerase (PARP)-activity was assessed in vitro from the incorporation of the adenosine-diphosphate-ribose moiety of 14C-NAD+ in the acid-insoluble cell fraction. When compared to mammalian (rat) cells, chicken embryo cells exhibit an almost three- to fourfold higher constitutive PARP-activity and an about two- to threefold lower chromatin compactness as evidenced by viscometry of alkaline cell lysates and nucleoid sedimentation. X-irradiation, bleomycin and H2O2 activated PARP. Hyperthermia (43 degrees C), doxorubicin, ethidium bromide and novobiocin resulted in an inhibition of the enzyme activity. Even at the highest doses used, UV-light, monofunctionally alkylating agents and the bisbenzimide Hoechst 33258 remained without significant effects. It is suggested that, with respect to DNA-and/or chromatin-interactive agents, the chicken embryo PARP-test may be complementary to the results of morphological and biochemical studies.

Animals↗
PubMed1992

DNA damage and repair in chick embryo cells following X-irradiation in vitro as compared to mammalian cells--biochemical and physico-chemical investigations.

Brain cells (b-cells) and liver cells (l-cells) of the chicken embryo and thymic cells (t-cells) of the rat were X-irradiated in vitro at doses of 1.25-50 Gy. When compared to t-cells, b- and l-cells exhibited 1) a lower stimulation of poly (adenosine diphosphate-ribose) transferase and unscheduled DNA synthesis following X-irradiation, 2) an almost fivefold higher inhibition of semiconservative DNA synthesis, 3) a less condensed chromatin, 4) about fourfold higher threshold doses with regard to significant effects on nucleoid sedimentation and viscometry of alkaline cellular lysates, and 5) an apparently two- to threefold lower DNA repair during a 30 min post-exposure repair period. The results suggest that the lower radiation sensitivity of chicken embryo cells is attributable to an initial mechanism of DNA repair and/or DNA protection which may be closely connected to minor chromatin compactness and higher intrinsic activities of repair enzymes.

Animals↗
PubMed1992

A short-term test for nucleotoxicity that uses chick embryo cells treated in vitro and in vivo--physico-chemical and biochemical investigations.

1. In vitro, some nucleotoxic or potentially nucleotoxic agents were tested with freshly isolated liver and brain cells from chick embryos as well as with thymic cells of the rat. 2. In vivo, chicken embryos were exposed to X-rays, methyl methanesulfonate, methyl nitrosourea, triethylene thiophosphoramide, and dimethylnitrosamine. 3. The toxic effects were determined by viscometry of alkaline cell lysates, nucleoid sedimentation, scheduled (SDS) and unscheduled (UDS) DNA synthesis and/or RNA synthesis. 4. The dose-effect curves obtained in vitro show that directly acting genotoxic agents are detected by the embryonic cells with equal or comparable sensitivity as by mammalian cells. 5. In vivo, genotoxicity is reflected by a decrease in alkaline lysate viscosity, nucleoid sedimentation and SDS and an increase in UDS. 6. From the present results it is suggested that chick embryo cells offer a simple, rapid and inexpensive short-term nucleotoxicity test for directly acting agents, the main disadvantage being the innate inability to biotransform indirectly acting agents.

Animals↗
PubMed1992

Influence of suramin on some DNA-directed enzymes and primary cultures of chicken embryo and rat cells.

The influence of suramin on O6-alkylguanine-DNA alkyltransferase (AT), DNase I and poly(adenosine diphosphate ribose)polymerase (PADPR) as well as on primary cultures of rat and chick embryo cells was examined by using some short-term tests. AT and DNase I were inhibited by suramin in a dose-dependent manner (DE50 = 65 and 100 micrograms/ml, respectively). PADPR activity was increased over a concentration range of 40-320 micrograms/ml. At concentrations above 40 micrograms/ml suramin decreased scheduled and unscheduled DNA synthesis. At doses of below 20 micrograms/ml the substance slightly stimulated unscheduled DNA synthesis in embryonic cells. Suramin enhanced nucleoid sedimentation and diminished the viscosity of alkaline cell lysates. From the present results it is concluded that suramin, at clinically relevant concentrations, is able to interact with enzyme systems which are critical to important nuclear functions and to interfere--in a cell specific manner--with histones and/or matrix proteins, resulting in greater chromatin compactness.

Animals↗
PubMed1992

Effect of gyrase inhibitors on some eukaryotic short-term test systems. DNase I in vitro nucleic acid synthesis and DNA repair in primary cultures of chicken embryo and rat cells.

DNase I activity was diminished by ciprofloxacin (CFL), nalidixic acid, norfloxacin, and ofloxacin in a dose-dependent manner, the MIC's (minimal significantly inhibiting concentrations) being 3.2, 2.8, 2.4, and 7.6 micrograms/ml, resp., in phase I-reaction (increase in DNA hyperchromicity) and 21, 20, 55, and 56 micrograms/ml, resp., in phase II-reaction (formation of acid-soluble products). The Line-weaver-Burk plots indicated inhibition by substrate (phase I) and uncompetitive inhibition (phase II). The decrease in scheduled DNA synthesis by CFL showed MIC's of 270, 100, 1000, and 850 micrograms/ml in chicken embryo brain (B) and liver (L) cells and in rat thymic (T) and splenic (S) cells, resp. With regard to ribonucleic acid synthesis, MIC values of 82, 82, 12.5, and 48 micrograms/ml CFL were determined, resp. Within a concentration range of 25-1600 micrograms/ml, no principal differences existed between the 4-quinolones used. In T-cells, DNA repair as induced by X-irradiation or UV-light and determined by nucleoid sedimentation was inhibited by CFL (greater than 100 micrograms/ml). The present results demonstrate biological effects of 4-quinolones on eukaryotic systems at remarkably low concentrations. In this context, the possibility of interactions with DNA catabolizing enzyme systems and synergistic effects with DNA/chromatin-damaging agents should be considered further.

Animals↗
PubMedDate not supplied

Oestrogen treatment of tall girls: effect decreases with age.

Fifty-nine tall girls were treated with oestrogen to reduce final height, starting at the ages of 9.1 to 16.2 years. We assessed the result of this treatment by comparison with matched controls. The epiphyseal bone age at the start of therapy, the final height, the Bayley-Pinneau (BP) and Roche-Wainer-Thissen (RWT) predictions of final height, and the errors in both predictions were evaluated. The matched pairs were divided into three groups according to bone age at the start of treatment; I less than 10.5 (n = 16), II 10.5-12.0 (n = 22) and III greater than 12.0 years (n = 21). The mean (SD) intrapair reduction of height for these groups was 9.7 (4.0) cm, 4.3 (4.3) cm and 3.5 (3.2) cm, respectively, according to BP predictions and 6.3 (4.3) cm, 3.4 (3.0) cm and 1.2 (3.3) cm according to RWT predictions. No method of predicting height is accurate for tall girls and simultaneous predictions may differ greatly. Close agreement between the BP and RWT predictions does not indicate greater accuracy. The earlier therapy is started, the greater is the effect. Young girls need psychosocial support with therapy.

Adolescent↗
PubMedDate not supplied

O6-alkylguanine-DNA alkyltransferase in the chick embryo during development.

In the whole embryo, O6-alkylguanine-DNA alkyltransferase (AT) activity increased until day 9 of development and declined sharply after day 13. AT activity of the liver was greatest between day 12 and day 20 and decreased fast after hatching. In the brain, AT activities reached a maximum at day 17 and 18 and declined sharply after hatching. At two developmental stages with different AT activities (day 10 and day 17) DNA alkylation in the brains was estimated 6, 12, 24 and 48 h after administration of N-methyl-N-nitrosourea in ovo by viscometric measurement of DNA fragmentation. The high AT activities of the chicken embryo brain at the 17th day of development correlated with minor DNA fragmentation following a repair period of 12-24 h. It is suggested that the high basal level of AT in the chick embryo might have a protective function against the persistence of the genotoxic lesion O6-methylguanine during development.

Aging↗