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PubMed1999

A bioactive glass particulate in the treatment of molar furcation invasions.

BACKGROUND: Procedures for the treatment of molar furcation invasion defects range from open flap debridement, apically repositioned flap, hemisection, tunneling or extraction, to regenerative therapies. METHODS: The results of surgical therapy consisting of the clinical parameters of probing depth and bleeding on probing were compared in 15 patients with moderate to advanced adult periodontitis. Each patient received surgical therapy consisting of regenerative therapy using bioactive glass compared to open flap debridement alone in human mandibular molar furcation defects. RESULTS: The results of therapy were statistically significant in the defects treated with the bioactive glass. CONCLUSIONS: This study revealed the benefits of bioactive glass in the treatment of Class II furcation defects regarding the clinical parameters of probing depth reduction and the reduction in bleeding on probing.

Adult↗

PubMed2001

Effects of pretreatment clinical parameters on bioactive glass implantation in intrabony periodontal defects.

BACKGROUND: The various methods for regeneration of periodontal tissue that have been developed can be classified into guided tissue regeneration and bone implantation. Since the implantation materials have shown both deficiencies and merits, dentists have begun exploring the bioactive glass first used in plastic surgery. This paper examines the effectiveness of this new material on periodontal intrabony defects. METHODS: Clinical effects of bioactive glass implantation in intrabony periodontal defects were evaluated 6 months after surgery in 38 intrabony defects from 38 patients with chronic periodontitis. Twenty-one experimental defects received bioactive glass implantation (test group), while 17 control defects were treated with a flap procedure only (control group). The criteria for comparative observation were preoperative and postoperative probing depth (PD), clinical attachment level (CAL), bone probing depth (BPD), and gingival recession. RESULTS: Reductions in PD were observed in both groups (P<0.01). The reduction in PD was significantly greater in the test group when preoperative PD exceeded 7 mm (P<0.01). Improvements in CAL were also observed in both groups (P<0.01), with the test group showing significantly greater gains (P<0.05). In those cases where preoperative CAL was less than 7 mm, there was no statistically significant difference between the two groups. Reduction in BPD was observed in both groups, with the test group showing significantly greater reduction (P <0.01). There was no significant difference in BPD change, however, when preoperative BPD was < or =7 mm. Significantly greater reduction of BPD in the test group was observed when intrabony defect depth was >4 mm (P <0.05). Significant improvements in PD, CAL, and BPD were noted in the test group when the crestal involvement exceeded 100 degrees. Correlation test between various clinical parameters indicated that greater changes in PD and CAL in the test group were observed when preoperative CAL was large (P<0.001), and greater changes in PD (P<0.05), CAL (P<0.01), and BPD (P<0.05) were noted when preoperative BPD was large. Correlation between crestal involvement and CAL change was noted only in the control group (P<0.01). High correlations were observed between PD changes and CAL changes and between CAL changes and BPD changes in both groups. CONCLUSIONS: Use of a bone substitute in a flap operation resulted in significantly greater improvements in CAL and BPD over flap operation alone and seemed to have positive effects in postoperative PD, CAL, and BPD in those cases with more severe preoperative CAL and BPD.

Adult↗

PubMed2003

Bioabsorbable membrane and bioactive glass in the treatment of intrabony defects in patients with generalized aggressive periodontitis: results of a 12-month clinical and radiological study.

BACKGROUND: Guided tissue regeneration can be achieved using membranes. In recent years, some evidence has been provided that bioactive glass is also capable of supporting the regenerative healing of periodontal lesions. The aim of this clinical and radiological prospective study was to compare the effectiveness of a bioabsorbable membrane and a bioactive glass in the treatment of intrabony defects in patients with generalized aggressive periodontitis. METHODS: Twelve patients (9 females, 3 males) with generalized aggressive periodontitis were enrolled in the study. The investigations were confined to 1- to 3-walled intrabony defects with a depth > or = 4 mm and with preoperative probing depths > or = 7 mm. Teeth with furcation involvement were excluded. Fifteen of the total 30 defects were treated with the membrane (RXT group) and 15 with the bioactive glass (PG group). Allocation to the groups was randomized. The clinical parameters plaque index (PI), gingival index (GI), probing depth (PD), bleeding on probing (BOP), gingival recession (GR), clinical attachment level (CAL), and mobility were recorded prior to surgery as well as 6 and 12 months after surgery. Intraoral radiographs were taken in standardized paralleling technique at baseline and 12 months after the surgery. Following digitization, changes in the distances from the alveolar crest (xCA) to the defect base (xBD) and from the CEJ (xCEJ) to the xCA were determined. Statistical analysis was based on Kolmogorov-Smirnov test, Wilcoxon signed-ranks test, analysis of covariance, and Spearman's bivariate correlation analysis. RESULTS: After 12 months, a reduction in PD of 4.0 +/- 2.1 mm (P < 0.001) and a gain in CAL of 3.4 +/- 2.3 mm (P < 0.001) was registered in the RXT group. There was a slight increase in GR by 0.6 +/- 1.5 mm (P = 0.074). In the PG group, a reduction in PD of 3.8 +/- 1.9 mm (P < 0.001) and a gain in CAL of 2.8 +/- 1.9 mm (P < 0.001) was recorded, whereas GR increased by 1.0 +/- 1.4 mm (P = 0.007). The 6-month results did not differ significantly from the stated values. Radiographically, the defects (xCA to xBD) were found to be filled by 57.2 +/- 33.5% (P = 0.001) in the RXT group and by 50.5 +/- 22.8% (P = 0.001) in the PG group. Crestal resorption (xCEJ to xCA) was 6.1 +/- 34.5% (P = 0.910) in the RXT group and 15.1 +/- 39.7% (P = 0.433) in the PG group. Only the change in gingival recession after 12 months was significantly greater (P = 0.031) in the PG group, with -1.0 +/- 1.4 mm, compared to the RXT group, with -0.6 +/- 1.5 mm. Changes in the other clinical and radiological parameters showed no significant differences. The attachment gain correlated negatively with the preoperative PI (r = -0.574; P = 0.004) and with BOP after 6 months (r = -0.315; P = 0.021). CONCLUSIONS: Highly significant improvements in the parameters PD, CAL, and xCA-xBD were recorded after 6 and 12 months, respectively, with both regenerative materials. A good standard of oral hygiene and inflammation-free periodontal tissue in the postoperative phase improved the treatment outcome.

Absorbable Implants↗

PubMed2006

Bioabsorbable membrane and bioactive glass in the treatment of intrabony defects in patients with generalized aggressive periodontitis: results of a 5-year clinical and radiological study.

BACKGROUND: The aim of this clinical and radiological prospective 5-year study was to compare the long-term effectiveness of a bioabsorbable membrane and a bioactive glass in the treatment of intrabony defects in patients with generalized aggressive periodontitis. METHODS: Sixteen patients (11 women and five men) with generalized aggressive periodontitis were enrolled in the study. The investigations were confined to 1- to 3-walled intrabony defects with a depth >/=4 mm and with preoperative probing depths (PDs) >/=7 mm. Teeth with furcation involvement were excluded. Twenty-two of the defects were treated with the membrane (RXT group) and 20 with the bioactive glass (PG group). Allocation to the two groups was randomized. The clinical parameters plaque index (PI), gingival index (GI), PD, bleeding on probing (BOP), gingival recession (GR), clinical attachment level (CAL), and tooth mobility were recorded before surgery and at 6 months and every year for 5 years after surgery. Intraoral radiographs were taken using a standardized paralleling technique at baseline and every year for 5 years. Statistical analysis was based on Kolmogorov-Smirnov and Wilcoxon signed-rank tests, analysis of covariance, and Spearman's bivariate correlation analysis. RESULTS: After 5 years, a reduction in PD of 3.6 +/- 0.8 mm (P = 0.016) and a gain in CAL of 3.0 +/- 2.0 mm (P = 0.01) were registered in the RXT group. There was a slight increase in GR by 0.6 +/- 1.4 mm (P = 0.334). In the PG group, a reduction in PD of 3.5 +/- 1.4 mm (P = 0.01) and a gain in CAL of 3.3 +/- 2.1 mm (P = 0.01) were recorded, whereas GR increased by 0.2 +/- 1.7 mm (P = 0.525). The 1-, 2-, 3-, and 4-year results did not differ significantly from the 5-year results. Radiographically, the defects (the point on the proximal surface of the defective tooth at which the projected alveolar crest intersected the root surface [xCA] to the most coronally located point at the proximal surface of the tooth on the defect side up to which the periodontal ligament space still displayed a uniform width [xBD]) were found to be filled by 47.5% +/- 38.3% (P = 0.001) in the RXT group and by 65.0% +/- 50.5% (P = 0.001) in the PG group. Crestal resorption (the most apical point of the enamel at the proximal surface of the tooth on the defect side [xCEJ] to the xCA) was 19.0% +/- 30.2% (P = 0.374) in the RXT group and 12.3% +/- 38.6% (P = 0.647) in the PG group. The xCEJ to the xBD was significantly more in the PG group (28.4 +/- 24.6 versus 7.3 +/- 21.8, P = 0.048). A good standard of oral hygiene and inflammation-free periodontal tissue in the postoperative phase improved the treatment outcome. No dependence of attachment gain was found on the tooth type, number of walls involved in the defects (r = 0.075; P = 0.319), or intraoperative depth (r = 0.114; P = 0.307). CONCLUSIONS: Highly significant improvements in the parameters PD and CAL were recorded after 5 years with both regenerative materials. Radiographically, the defects (the xCED to the xBD) were found to be filled significantly more in the bioactive glass group. A good standard of oral hygiene and inflammation-free periodontal tissue in the postoperative phase improved the treatment outcome.

Absorbable Implants↗

PubMed2005

Paradoxical role of cytochrome P450 3A in the bioactivation and clinical effects of levo-alpha-acetylmethadol: importance of clinical investigations to validate in vitro drug metabolism studies.

OBJECTIVE: Levo-alpha-acetylmethadol (LAAM, levacetylmethadol) is a long-acting opioid agonist used for the prevention of opioid withdrawal. LAAM undergoes sequential N-demethylation to norLAAM and dinorLAAM, which are more potent and longer-acting than LAAM. Hepatic and intestinal microsomal N-demethylation in vitro is catalysed mainly by cytochrome P450 (CYP) 3A4; however, the role of CYP3A in LAAM disposition in humans in vivo is unknown. This investigation tested the hypothesis that CYP3A induction (or inhibition) would increase (or decrease) LAAM metabolism and bioactivation and, thus, clinical effects. It also related changes in LAAM disposition during enzyme inhibition or induction to any changes in pharmacological effect. METHODS: Healthy volunteers (n = 13) completed the three-way, randomised, balanced crossover study. Subjects received oral LAAM (0.25 mg/kg) after CYP3A induction (rifampicin [rifampin]), inhibition (troleandomycin) or nothing (controls). Plasma and urine LAAM, norLAAM and dinorLAAM were determined by electrospray high-performance liquid chromatography/mass spectrometry (HPLC/MS). Dark-adapted pupil diameter change from baseline (miosis) was the LAAM effect measure. Results were analysed by noncompartmental methods and by a combined pharmacokinetic/pharmacodynamic model. RESULTS: Compared with controls, CYP3A induction (or inhibition) decreased (or increased) plasma LAAM concentrations and mean area under the plasma concentration-time curve from time zero to infinity (AUC(infinity) 199 +/- 91 [control] versus 11.3 +/- 4.0 [rifampicin] and 731 +/- 229 ng . h/mL [troleandomycin]; p < 0.05), and increased (or decreased) median formation clearances of norLAAM (1740 versus 14 100 and 302 mL/h/kg; p < 0.05) and dinorLAAM (636 versus 7840 and 173 mL/h/kg; p < 0.05). Surprisingly, however, CYP3A induction (or inhibition) decreased (or increased) mean plasma metabolite AUC from 0 to 96 hours (AUC(96)) [norLAAM + dinorLAAM] (859 +/- 241 versus 107 +/- 48 and 1185 +/- 179 ng . h/mL; p < 0.05) and clinical effects (mean miosis AUC(96) 128 +/- 40 versus 22.5 +/- 14.9 and 178 +/- 81 mm . h; p < 0.05). Clinical effects were best correlated with plasma norLAAM concentrations. CONCLUSION: CYP3A mediates human LAAM N-demethylation and bioactivation to norLAAM and dinorLAAM in vivo. Paradoxically, however, CYP3A induction decreased and inhibition increased LAAM active metabolite concentrations and clinical effects. This suggests a CYP3A-mediated metabolic pathway leading to inactive metabolites, which predominates over CYP3A-dependent bioactivation. These results highlight the need for clinical investigations to validate in vitro drug metabolism studies.

Administration, Oral↗

PubMed2003

Food-derived bioactive peptides--opportunities for designing future foods.

Dietary proteins are known to carry a wide range of nutritional, functional and biological properties. Nutritionally, the proteins are a source of energy and amino acids, which are essential for growth and maintenance. Functionally, the proteins contribute to the physicochemical and sensory properties of various protein-rich foods. Furthermore, many dietary proteins possess specific biological properties which make these components potential ingredients of functional or health-promoting foods. Many of these properties are attributed to physiologically active peptides encrypted in protein molecules. Particularly rich sources of such peptides are milk and egg, but they are also found in meat of various kinds as well as many plants. These peptides are inactive within the sequence of parent protein and can be released during gastrointestinal digestion or food processing. Depending on the amino acid sequence, these peptides may exert a number of different activities in vivo, affecting, e.g., the cardiovascular, endocrine, immune and nervous systems in addition to nutrient utilization. There is increasing commercial interest in the production of bioactive peptides from various sources. Industrial-scale production of such peptides is, however, hampered by the lack of suitable technologies. Bioactive peptides can also be produced from milk proteins through fermentation of milk, by starters employed in the manufacture of fermented milks or cheese. In particular, antihypertensive peptides have been identified in fermented milk, whey and ripened cheese. A few of these peptides have been commercialised in the form of fermented milks. There is a need to develop technologies which retain or even enhance the activity of bioactive peptides in food systems. Also, it is essential to study the optimum utilization of such peptides during passage through the gastrointestinal tract.

Egg Proteins↗

PubMed2006

Bioactivation and hepatotoxicity of nitroaromatic drugs.

Certain drugs containing a nitroaromatic moiety (e.g., tolcapone, nimesulide, nilutamide, flutamide, nitrofurantoin) have been associated with organ-selective toxicity including rare cases of idiosyncratic liver injury. What they have in common is the potential for multistep nitroreductive bioactivation (6-electron transfer) that produces the potentially hazardous nitroanion radical, nitroso intermediate, and N-hydroxy derivative. These intermediates have been associated with increased oxidant stress and targeting of nucleophilic residues on proteins and nucleic acids. However, other mechanisms including the formation of oxidative metabolites and mitochondrial liability, as well as inherent toxicokinetic properties, also determine the drugs' overall potency. Therefore, structural modification not only of the nitro moiety but also of ring substituents can greatly reduce toxicity. Novel concepts have revealed that, besides the classical microsomal nitroreductases, cytosolic and mitochondrial enzymes including nitric oxide synthase can also bioactivate certain nitroarenes (nilutamide). Furthermore, animal models of silent mitochondrial dysfunction have demonstrated that a mitochondrial oxidant stress posed by certain nitroaromatic drugs (nimesulide) can produce significant mitochondrial injury if superimposed on a genetic mitochondrial abnormality. Finally, there may be mechanisms for all nitroaromatic drugs that do not involve bioactivation of the nitro group, e.g., AHR interactions with flutamide. Taken together, the focus of research on the hepatic toxicity of nitroarene-containing drugs has shifted over the past years from the identification of the reactive intermediates generated during the bioreductive pathway to the underlying biomechanisms of liver injury. Most likely one of the next paradigm shifts will include the identification of determinants of susceptibility to nitroaromatic drug-induced hepatotoxicity.

Benzophenones↗

PubMed2003

Neuropeptide conversion to bioactive fragments--an important pathway in neuromodulation.

Biosynthetic pathways for the formation of neuroactive peptides and the processes for their inactivation include several enzymatic steps. In addition to enzymatic processing and degradation, several neuropeptides have been shown to undergo enzymatic conversion to fragments with retained or modified biological activity. This has most clearly been demonstrated for e.g. opioid peptides, tachykinins, calcitonin gene-related peptide (CGRP) as well as for peptides belonging to the renin-angiotensin system. Sometimes the released fragment shares the activity of the parent compound. However, in many cases the conversion reaction is linked to a change in the receptor activation profile, i.e. the generated fragment acts on and stimulates a receptor not recognized by the parent peptide. This review will describe the characteristics of certain neuropeptide fragments having the ability to modify the biological action of the peptide from which they are derived. Focus will be directed to the tachykinins, the opioid peptides, angiotensins as well as to CGRP, bradykinin and nociceptin. The kappa opioid receptor selective opioid peptide, dynorphin, recognized for its ability to produce dysphoria, is converted to the delta opioid receptor agonist Leu-enkephalin, with euphoric properties. The tachykinins, typified by substance P (SP), is converted to the bioactive fragment SP(1-7), a heptapeptide mimicking some but opposing other effects of the parent peptide. The bioactive angiotensin II, known to bind to and stimulate the AT-1 and AT-2 receptors, is converted to angiotensin IV (i.e. angiotensin 3-8) with preference for the AT-4 sites or to angiotensin (1-7), not recognized by any of these receptors. Both angiotensin IV and angiotensin (1-7) are biologically active. For example angiotensin (1-7) retains some of the actions ascribed for angiotensin II but is shown to counteract others. Thus, it is obvious that the activity of many neuroactive peptides is modulated by bioactive fragments, which are formed by the action of a variety of peptidases. This phenomenon appears to represent an important regulatory mechanism that modulates many neuropeptide systems but is generally not acknowledged.

Animals↗

PubMed2004

The role of cytochrome P450 in cytotoxic bioactivation: future therapeutic directions.

The cytochrome P450s are an essential group of enzymes involved in metabolism of drugs, foreign chemicals, arachidonic acid, cholesterol, steroids and other important lipids. The cytochrome P450 enzyme system is responsible for much of the phase I metabolism of chemotherapeutic agents. At the simplest level the detoxification properties of the cytochrome P450s are used to help clear a cytotoxic before it results in serious irreversible toxicity to the patient while at other levels the cytochrome P450s are involved to varying extents in drug bioactivation. This metabolism primarily occurs in organs and tissues of the body known to express cytochrome P450 ubiquitously (i.e. liver and gastrointestinal tract), but there is also evidence to suggest that it occurs within the tumor microenvironment due to localized, tumor specific expression of certain P450 isoforms. Several of today's currently prescribed cytotoxics (e.g. cyclophosphamide and tamoxifen) undergo systematic bioactivation by cytochrome P450, which often results in toxicity to the patient. The realization that many tumors have differential cytochrome P450 expression when compared to the corresponding normal tissue has allowed the rational design of the next generation of cytotoxic around cytochrome P450 enzymology. Several new agents now entering clinical trials (e.g. Phortress and AQ4N) are specifically designed to exploit tumor cytochrome P450, resulting in local bioactivation of the cytotoxic at the tumor site. Specific activation of pro-drugs by isoforms whose expression or particular catalytic activity is limited to cancer cells offers the possibility of truly targeted chemotherapy with minimized systemic toxicity.

Animals↗

PubMed2004

The oxazolomycins: a structurally novel class of bioactive compounds.

Oxazolomycin, first isolated in 1985, is a novel bioactive compound, exhibiting potent antiviral, antibacterial and cytotoxic activity, and is now known to be the parent of a wider class of compounds. The broad-spectrum activity of oxazolomycin has been attributed to its protonophoric properties. This review outlines the isolation, structural determination, biosynthesis, bioactivity, biological mode of action and synthesis of all members of this compound class. Significantly, the oxazolomycins appear to offer not only a completely novel chemotype as a bioactive lead structure, but also a chemotype, which also exhibits an unusual biological mode of action.

Anti-Bacterial Agents↗

PubMed2002

Behaviour of moderately differentiated osteoblast-like cells cultured in contact with bioactive glasses.

Bioactive glasses have been shown to stimulate osteogenesis both in vivo and in vitro. However, the molecular mechanisms underlying this process are still poorly understood. In this study, we have investigated the behaviour of osteoblast-like cells (MG63), cultured in the presence of bioglass particles. Three types of granules were used: 45S5 bioactive glass, 45S5 granules preincubated in tris buffer and 60S non-reactive glass, used as control. Phase contrast microscopy permitted step-by-step visualization of cell cultures in contact with the particles. Ultrastructural observations of undecalcified sections revealed direct contacts of the cells and an electron-dense layer located at the periphery of the material. Protein synthesis was evaluated biochemically and showed a gradual increase throughout the culture time in the three types of cultures. Alkaline phosphatase was detected in situ, in clusters of packed cells either in contact with the material or in the background cell layer. Semi-quantitative RT-PCR analysis of the main osteoblastic markers showed that gene expression was maintained in all three cultures. The fact that osteocalcin was not detected, supports the fact that the MG63 cell line is composed of less differentiated osteogenic cells rather than mature osteoblasts. We also demonstrated for the first time in this cell line, the expression of Msx-2, Dlx-3 and Dlx-7 homeogenes, known to regulate in vivo foetal skeletogenesis as well as adult skeletal regeneration. However, no significant differences could be recognised in the expression pattern of bone markers between the three types of cultures. Yet these preliminary results indicate that bioactive glasses provided a suitable environment for the growth and proliferation of osteoblasts in vitro, since no drastic changes in phenotype expression of pre-osteoblasts was noted.

Journal Article↗

PubMed1984

Hepatic metabolism and bioactivation of mycotoxins and plant toxins.

The intoxication of livestock from ingested feed contaminated with naturally occurring toxicants is of great economic importance. Certain toxicants require enzymatic bioactivation before harmful effects are exhibited. In the liver, the cytochrome P-450 dependent mixed function oxidase (MFO) system normally metabolizes foreign compounds (xenobiotics) into more polar, more excretable and less toxic metabolites. During metabolism of aflatoxins and pyrrolizidine alkaloids (PA), oxidized metabolites are highly reactive with cellular components and are more toxic than the parent compounds. Hepatic bioactivation is of considerable importance because active metabolites are formed directly within the tissues of the animal. In addition, the MFO system has only limited specificity and is dependent on many factors including diet, age, sex, species and environmental influences. The interrelationship of these factors on aflatoxicosis and pyrrolizidine alkaloidosis are often responsible for the chronic nature and difficult etiology of these diseases. A better understanding of the factors affecting metabolism and bioactivation of these toxicants may lead to the development of techniques for protecting animals that are subjected to contaminated feeds.

Aflatoxins↗

PubMed1996

Recent studies on mechanisms of bioactivation and detoxification of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific lung carcinogen.

This article reviews recent advances in the biochemistry and molecular biology of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific pulmonary carcinogen believed to be involved in the induction of lung cancer in smokers. Several aspects of NNK bioactivation are addressed, including identification of its metabolites in laboratory animals and humans, cytochrome P450 enzyme involvement in its metabolic activation, DNA and protein adduct formation, biological significance of the major DNA adducts formed, and mutations in oncogenes from tumors induced by NNK. Collectively, the presently available data provide a reasonably clear picture of NNK bioactivation in rodents, although there are still important gaps in our mechanistic understanding of NNK-induced tumorigenesis. The studies in rodents and primates have facilitated development of methods to assess NNK bioactivation in humans, which will be applicable to studies of lung cancer susceptibility and prevention.

Animals↗

PubMed1982

Bioactivation of halogenated hydrocarbons.

Halogenated hydrocarbons are an economically and toxicologically important group of chemicals. These compounds may produce toxic effects after metabolism to stable, but toxic, products or to reactive, electrophilic intermediates. The biotransformation reaction may involve oxidative or reductive reactions or may proceed with no change in oxidation state. The bioactivation reactions are catalyzed most frequently by cytochrome P-450-dependent monooxygenases, but glutathione S-transferases may also catalyze bioactivation reactions. Detailed reaction mechanism studies are useful in understanding the biotransformation and bioactivation pathways of halogenated hydrocarbons.

Biotransformation↗

PubMed1998

Estrogen and progestin bioactivity of foods, herbs, and spices.

In this study we report on the content and bioactivity of plant (phyto) estrogens and progestins in various foods, herbs, and spices, before and after human consumption. Over 150 herbs traditionally used by herbalists for treating a variety of health problems were extracted and tested for their relative capacity to compete with estradiol and progesterone binding to intracellular receptors for progesterone (PR) and estradiol (ER) in intact human breast cancer cells. The six highest ER-binding herbs that are commonly consumed were soy, licorice, red clover, thyme, tumeric, hops, and verbena. The six highest PR-binding herbs and spices commonly consumed were oregano, verbena, tumeric, thyme, red clover and damiana. Some of the herbs and spices found to contain high phytoestrogens and phytoprogestins were further tested for bioactivity based on their ability to regulate cell growth rate in ER (+) and ER (-) breast cancer cell lines and to induce or inhibit the synthesis of alkaline phosphatase, an end product of progesterone action, in PR (+) cells. In general, we found that ER-binding herbal extracts were agonists, much like estradiol, whereas PR-binding extracts, were neutral or antagonists. The bioavailability of phytoestrogens and phytoprogestins in vivo were studied by quantitating the ER-binding and PR-binding capacity of saliva following consumption of soy milk, exogenous progesterone, medroxyprogesterone acetate, or wild mexican yam products containing diosgenin. Soy milk caused a dramatic increase in saliva ER-binding components without a concomitant rise in estradiol. Consumption of PR-binding herbs increased the progestin activity of saliva, but there were marked differences in bioactivity. In summary, we have demonstrated that many of the commonly consumed foods, herbs, and spices contain phytoestrogens and phytoprogestins that act as agonists and antagonists in vivo.

Alkaline Phosphatase↗

PubMed2002

[High bioactive material-bone graft in bone defect healing]

OBJECTIVE: To assese the value and clinical significance of bioactive material-hydroxyapatite (HA) combined with TGF-beta1 in bone defect healing. METHODS: The applicability of bioactive material-HA granules combined with TGF-beta1 (group A) as a substitute for bone graft was observed in SD rat model. The results were compared with those of HA granules (Group B) and ungrafted bone defect (Group C). RESULTS: Group A demonstrated the highest level of type I collagen mRNA during healing period. CONCLUSION: The bioactive material-HA combined with TGF-beta1 can efficiently bond to ongrowing new bone comparing to HA granules.

Journal Article↗

PubMed2001

Neutrophil proteinase 3-mediated induction of bioactive IL-18 secretion by human oral epithelial cells.

IL-18, a potent IFN-gamma-inducing cytokine, is expressed by various nonimmune cells as well as macrophages, suggesting that it has important physiological and immunological roles. The present study focused on the mechanism of active IL-18 induction from human oral epithelial cells. The epithelial cells and the cell lines constitutively express IL-18 mRNA and the 24-kDa precursor form of IL-18. Bioactive IL-18 exhibiting IFN-gamma-inducing activity was detected in the supernatant of the cells on costimulation with neutrophil proteinase 3 (PR3) and LPS for 24 h after IFN-gamma-priming for 3 days. An active 18-kDa form of IL-18 was detected in lysate and supernatant of the cells only after the above treatment and the induction was inhibited by cycloheximide and by serine proteinase inhibitors. After the treatment, lactate dehydrogenase activity was not detected in the cell culture supernatant, and PR3 was detected only in the membrane and not in cytoplasm fractions of the cells. Caspase-1 was not detected in the cells even after the treatment and the IL-18 induction was not inhibited by a caspase-1 inhibitor. These results suggest that the PR3-mediated induction of bioactive IL-18 secretion from oral epithelial cells in combination with LPS after IFN-gamma-priming occurred via a caspase-1-independent pathway, and provide new insight into the possible involvement of a neutrophil proteinase in the induction of bioactive IL-18 in oral inflammation such as periodontitis.

Adult↗

PubMed1996

Bioactive metabolites of EM574 and EM523, erythromycin derivatives having strong gastrointestinal motor stimulating activity.

Two motilides, EM574 (N-demethyl-N-isopropyl-8,9-anhydroerythromycin A 6,9-hemiacetal) and EM523 (N-demethyl-N-ethyl-8,9-anhydroerythromycin A 6,9-hemiacetal) have strong gastrointestinal motor stimulating (GMS) activity. When administered orally to dogs, these agents showed strong GMS activity, but their plasma levels were very low and the metabolites which have been determined so far using the radio-labeled compounds show only weak GMS activity. The findings suggested that unknown bioactive metabolites might be responsible for the GMS activity. From the liver of dogs given EM574 intravenously, two bioactive metabolites, EM574 P1 and P2, were isolated by solvent extraction and chromatography as detected by contractile activity. They both showed the same UV spectra as EM574 and the molecular ion peaks at m/z 760 (MH+) and 602 (MH(+)-cladinose) in the FAB-MS. From 2D-NMR experiments, the structures of EM574 P1 and P2 were unveiled to be the 15- and 14-hydroxyl derivatives of EM574, respectively. EM523 P1 and P2 were also isolated in the same procedure. In order to prepare these bioactive metabolites, EM574 and EM523 were converted enzymatically with dog liver homogenates in the presence of co-enzymes to give the corresponding P1 and P2. The structures of the metabolites are shown in Fig 1. They exhibited stronger contractile activity in vitro and GMS activity in vivo than the parent compounds.

Animals↗