Reduction of doxorubicin-induced cytotoxicity and mitochondrial damage by betanin in rat isolated cardiomyocytes and mitochondria.

Doxorubicin (DOX) is an anticancer drug which is used for treatment of several types of cancers. But the clinical use of doxorubicin is limited because of its cardiotoxicity and cardiomyopathy. Mitochondrial-dependent oxidative stress and cardiac inflammation appear to be involved in doxorubicin-induced cardiotoxicity. Betanin as a bioactive compound in Beetroot (Beta vulgaris L.) displays anti-radical, antioxidant gene regulatory and cardioprotective activities. In this current study, we investigated the protective effect of betanin on doxorubicin-induced cytotoxicity and mitochondrial-dependent oxidative stress in isolated cardiomyocytes and mitochondria. Isolated cardiomyocytes and mitochondria were treated with three concentrations of betanin (1, 5 and 10 µM) and doxorubicin (3.5 µM) for 6 h. The parameters of cellular and mitochondrial toxicity were analyzed using biochemical and flow cytometric methods. Our results showed a significant toxicity in isolated cardiomyocytes and mitochondria in presence of doxorubicin which was related to reactive oxygen species (ROS) formation, increase in malondialdehyde (MDA), increase in oxidation of GSH to GSSG, lysosomal/mitochondrial damages and mitochondrial swelling. While betanin pretreatment reverted doxorubicin-induced cytotoxicity and oxidative stress in isolated cardiomyocytes and mitochondria. These results suggest that betanin elicited a typical protective effect on doxorubicin-induced cytotoxicity and oxidative stress. It is possible that betanin could be used as a useful adjuvant in combination with doxorubicin chemotherapy for reduction of cardiotoxicity and cardiomyopathy.

Chronic subdural hematoma associated with voiding dysfunction.

We report the case of a 73-year-old male who presented with a chronic subdural hematoma that compressed the frontal lobe, an area known to be active in detrusor control, and caused contralateral hemiparesis and urgency incontinence. Urodynamically, he had a small bladder capacity and high amplitude overactive detrusor contractions with an intact sphincteric response. We concluded that the effect of intracranial lesions on voiding depends upon the site rather than the type of the pathology. Further in-depth studies are needed to clarify the effect of intracranial lesions, and accordingly the function of different brain regions and their influence on voiding.

Comparison of pulp responses to resin composites.

Diverse reports have described how various types of adhesive systems cause disastrous pulp necrosis, chronic severe inflammation or failure to stimulate any pulp reactions. This article reports on the effects of five common adhesive systems and how they compare in terms of pulp injury as measured by odontoblast survival or dentin regeneration and reactionary dentin formation. One hundred and thirty Class V pulp, non-exposed cavities were prepared in non-human primate teeth and were restored with five different adhesive systems. After a period of time between 3 and 172 days, the teeth were extracted, fixed, processed and examined histomorphometrically. Bacterial microleakage was detected with McKays stain and inflammation was categorized according to the International Organization for Standardization (ISO) criteria. The number of odontoblasts and the area of reactionary dentin were measured. Pulp reactions of all adhesive systems were generally minimal, although some systems permitted bacterial microleakage in 33% of restorations, and some other systems were associated with pulp inflammation in 22% of restorations. These observations suggest that adhesive systems provide acceptable biocompatibility, however, there is strong potential for improvement.

Histomorphometric analysis of odontoblast-like cell numbers and dentine bridge secretory activity following pulp exposure.

AIM: The purpose of this study was to collect quantitative information about the numbers and dentine bridge secretory activity of odontoblast-like cells following dental pulp exposure. METHODOLOGY: The numbers and secretory activity of odontoblast-like cells were measured histomorphometrically between 7 days and 2 years in 161 pulp-exposed nonhuman primate teeth. The area of dentine bridges and the dimensions of cavity preparations were measured. The density of odontoblast-like cells and subjacent reorganizing tissue cells were measured beneath dentine bridge formation. The presence of operative dentine debris and tunnel defects in bridges was noted. Pulp inflammation was categorized according to ISO standards. Bacteria were detected using McKay's stain. RESULTS: The area of dentine bridges was mediated by the density and secretory activity of odontoblast-like cells over time. The cell density of subjacent reorganizing tissue was found to be strongly associated with that of odontoblast-like cells. Bacterial microleakage was found to impede dentine bridge secretion by odontoblast-like cells. CONCLUSIONS: Pulp reparative activity occurs naturally beneath capping materials in the absence of bacterial microleakage. The outcome of pulp-capping treatments could be beneficially influenced by concentrating attention on limiting the width of pulp exposure, minimizing pulp injury by limiting the creation of operative debris and placing materials which prevent bacterial microleakage.

Comparison of pulp responses following restoration of exposed and non-exposed cavities.

OBJECTIVES: The purpose of this study is to compare and contrast differences of pulp responses between non-exposed and exposed cavity preparations in terms of inflammation, frequency of bacterial microleakage, odontoblast and odontoblastoid cell numbers, and tertiary dentine formation. METHODS: Class V non-exposed cavities (n=161) and exposed cavities (n=161 teeth) were prepared in non-human primate teeth. Cavities were restored with calcium hydroxide [Ca(OH)(2)], resin modified glass ionomer, or resin composite. Following extraction (7-730 days), bacteria were detected with McKays stain and pulp reactions were categorized according to ISO guidelines. Teeth were analyzed histomorphometrically and statistically using analysis of variance tests. RESULTS: Exposed cavities in comparison with non-exposed cavities were found to have more severe inflammation (p=0.0001), greater quantities of tertiary dentine (p=0.0001), and an increased frequency of bacterial microleakage (p=0.0034). The density of odontoblastoid cells beneath pulp exposed tertiary dentine was found to be 47.8% of odontoblast cell density beneath non-exposed dentine (p=0.0001). CONCLUSIONS: The restoration of exposed cavity preparations is associated with more traumatic pulp injury and repair responses. Consequently, efforts should be made to minimize iatrogenic dentine removal during cavity preparation and the creation of pulp exposures whenever possible.

New paeonilactone-A adducts formed by anaerobic incubation of paeoniflorin with Lactobacillus brevis in the presence of arylthiols.

During the course of preparing anticonvulsant paeonimetabolin-I adducts, new paeonilactone-A adducts: 9-phenylthiopaeonilactone-A, 9-(o-tolylthio)paeonilactone-A, 9-(m-tolylthio)paeonilactone-A, 9-(p-tolylthio)-paeonilactone-A and 9-(2-naphthylthio)paeonilactone-A, were obtained along with expected paeonimetabolin-I adducts by anaerobic incubation of paeoniflorin from peony roots with Lactobacillus brevis in the presence of the aromatic thiols, phenylthiol, o-tolylthiol, m-tolylthiol, p-tolylthiol and 2-naphthylthiol. The structures of these compounds were determined by spectroscopic methods including two dimensional (2D) NMR.

Biocomposition and reaction of pulp tissues to restorative treatments.

Dentistry has experienced exponential growth in the biologic and physiologic knowledge of enamel, dentin, and pulp tissues. In one decade, material development has exceeded clinical testing limits, allowing their arrival to the commercial market without proper validation. This article clarifies the enigma of acid etching; explaining and clarifying the diverse opinions and issues of material toxicity between in vitro and in vivo usage test perspectives. This article also demystifies the biology of pulp healing regarding calcium hydroxide and adhesive systems to promote dentin bridge formation. Lastly, this article provides biologically lucid pulp exposure treatment regimens with agents such as NaOCl, allowing clinicians to increase their long-term clinical success.

A comparative scanning electron microscopic study on the characteristics of demineralized dentin root surface using different tetracycline HCl concentrations and application times.

BACKGROUND: The use of demineralizing agents has been reported to enhance the degree of connective tissue attachment to denuded roots. Of the agents used, tetracycline HCI has received the most attention. METHODS: The purpose of this study was to evaluate and compare the SEM surface morphology of human root dentin following various concentrations and application times of tetracycline HCl. The surface characteristics were compared and the width of dentin tubule orifices were measured and analyzed. Twelve human teeth were collected and stored in distilled water after soft tissue removal using hand instruments. The apical third of each root was removed and remaining mid-root region was sectioned longitudinally through the root canal following removal of its cementum with a fine diamond bur. A total of 48 dentin specimens were randomly divided into 8 groups for conditioning at different tetracycline HCl concentrations, at 0, 10, 25, 50, 75, 100, 125, and 150 mg/ml. Application times for each group were 1, 3, and 5 minutes. Immediately following treatment procedures, the specimens were rinsed, fixed in GTA-PBF, dehydrated, and prepared for SEM. Each specimen was examined at 2 magnification values, representative fields photographed, and data tested by one-way ANOVA and paired t test statistical analysis. RESULTS: Our results indicate that the use of tetracycline HCl solution between 50 mg/ml and 150 mg/ml showed a statistically significant opening of dentin tubules. All tetracycline HCl groups at 1, 3, and 5 minutes show smear layer removal from the dentin surface. CONCLUSIONS: Dentin demineralization is not time dependent at all concentrations of tetracycline HCI.

Pulpotomy reconsidered: application of an adhesive system to pulpotomized permanent primate pulps.

OBJECTIVE: This study was undertaken to compare the healing response of permanent primate pulps to pulpotomy procedures following hemorrhage control and adhesive hybridization to their response after conventional treatments. METHOD AND MATERIALS: Forty-two cavities were placed throughout the dentitions of 4 adult monkeys. In 24 teeth, following mechanical bur exposure and pulpotomy, hemorrhage was controlled with application of 3% sodium hypochlorite. The cavity was rinsed and the enamel-dentin-pulp surface was restored with an adhesive system for 6 and 7 months. Calcium hydroxide, formocresol, and resin-modified glass-ionomer cement were placed as conventional treatments in 18 teeth for 70 days and cavities were sealed with resin-modified glass-ionomer cement. Following perfusion fixation, tissues were demineralized, sectioned, stained, and histologically graded using defined criteria. RESULTS: Of 24 adhesive system pulps, 10 showed no or minimal pulpal response, 1 showed an acute response, 6 showed a chronic response, 2 showed a severe response, and 5 showed compartmentalized zones of localized necrosis. Only 8 adhesive system pulps showed stained bacteria associated with inflamed tissues. Thirteen adhesive system pulps showed dentin bridging directly at the adhesive system interface. Calcium hydroxide-treated specimens showed healing and dentin formation, while resin-modified glass-ionomer cement and formocresol treatments failed to result in any bridging. Apical tissues in all adhesive-treated specimens showed normal pulps and primary odontoblasts along their entire walls. CONCLUSION: Permanent pulps without periapical radiolucencies may survive pulpotomy, provided that hemorrhage is properly controlled and the pulp-restoration interface is hybridized to exclude all microleakage.

Anticonvulsant activity of paeonimetabolin-I adducts obtained by incubation of paeoniflorin and thiol compounds with Lactobacillus brevis.

Seventeen thiopaeonimetabolin-I adducts were obtained as mixtures of diastereoisomers after incubation of paeoniflorin with Lactobacillus brevis in the presence of various thiols. The anticonvulsant activity of the adducts was investigated in mice using the maximal subcutaneous pentylenetetrazol seizure test and sodium valproate (1.5 mmol/kg) as a positive control. Thirteen adducts showed dose-dependent prolongation of latencies of clonic and tonic convulsions. Maximal protection against convulsions was effectively demonstrated by 8-(n-hexylthio)paeonimetabolin I (8) and 8-benzoylthiopaeonimetabolin I (18) at doses of 0.125 and 0.25 mmol/kg, respectively, while 100% protection was only achieved at 0.5 mmol/kg of 8-cyclopentylthiopaeonimetabolin I and 8-(p-tolylthio)paeonimetabolin I. The principal anticonvulsant activity of the diastereoisomers of 8 and 18 was attributed to their 7S-isomers [ED50 values of 0.09 and 0.12 mmol/kg, and protective indices of 5.0 and 4.0 for 8 (7S) and 18 (7S), respectively], while the 7R counterparts [8 (7R) and 18 (7R)] showed a muscle relaxation effect.

Biological basis for clinical success: pulp protection and the tooth-restoration interface.

This article provides biological and technological information that strengthens clinicians' understanding of cohesive hybridization and pulp therapy in order to support their routine use of bonding and resin systems. Utilizing cohesive systems, clinicians should experience several advantages over traditional water-soluble base and liner systems. When properly applied, cohesive hybridization of vital dentin prevents immediate postoperative hypersensitivity under all restorations and completely seals the entire tooth-restoration interface, which provides a reduction in recurrent caries.

Effects of paeoniflorin derivatives on scopolamine-induced amnesia using a passive avoidance task in mice; structure-activity relationship.

Paeoniflorin (1) and its derivatives having in common a cage-like pinane skeleton with hemiketal-acetal system, were evaluated for their effects on memory impairment induced by scopolamine in mice using a step-down type passive avoidance task. In the test session, 1 and its derivatives were intraperitoneally (i.p.) administered at doses of 0.002, 0.01, 0.02 and 0.2 mmol/kg, and 30 min later (15 min before the experiment), scopolamine (1 mg/kg, i.p.) was given. These compounds showed dose-dependent attenuation in a dose range of 0.002-0.02 mmol/kg and also enhancement of scopolamine-induced decrease in step-down latency. The effects of these compounds, except that of 2',3',4',5'-O-tetraacetyl-3-O-methylpaeoniflorin (8), followed a bell-shaped dose response profile. 8-Debenzoyl-6-deglucosyl-3-O-methylpaeoniflorin (6) showed no significant increase in the step-down latency at all tested doses. Maximum step-down latency was obtained by 3-O-methylpaeoniflorin (3) and 2',3,3',4',5'-penta-O-methylpaeoniflorin (7) (the minimal effective dose was 0.002 mmol/kg). Relative to 3, debenzoylation, as in 8-debenzoyl-3-O-methylpaeoniflorin (4), slightly increased the latency, while deglucosylation, as in 6-deglucosyl-3-O-methylpaeoniflorin (5), significantly reduced the prolongation of latency. Removal of both glucose and benzoyl moieties resulted in the loss of activity as seen in 6. These results revealed that, in addition to the cage-like pinane skeleton, the benzoyl and the glucosyl moieties are important structural elements of the paeoniflorin skeleton as its effects on scopolamine-induced amnesia.

Pulpal response to a resin-modified glass-ionomer material on nonexposed and exposed monkey pulps.

OBJECTIVE: This study evaluated the biocompatibility of a resin-modified glass-ionomer material on monkey pulps. METHOD AND MATERIALS: Standardized Class V cavities were prepared in 112 teeth distributed in six healthy adult monkeys. The resin-modified glass-ionomer cement was placed in 24 nonexposed and 36 exposed pulps according to manufacturer's instructions. ZOE was used as a control in nonexposed pulps, while calcium hydroxide was used as a control for exposed pulps. Tissues were collected at 6 to 7, 21 to 27, and 90 to 97 days. After demineralization, the teeth were serially sectioned, stained, and observed by light microscopy. RESULTS: Except for one resin-modified glass-ionomer pulp at 6 days, there were no differences between the responses of nonexposed pulps to resin-modified glass-ionomer specimens and ZOE controls. In exposed pulps, eight of 36 resin-modified glass-ionomer pulps showed various grades of inflammatory response, all associated with stained bacteria. Pulpal healing was similar in both resin-modified glass-ionomer and calcium hydroxide direct-capped exposures. Twenty-two of 26 exposed pulps restored with the resin-modified glass-ionomer cement showed dentin bridge formation at 21 and 97 days. CONCLUSION: The resin-modified glass-ionomer material exhibited acceptable biologic compatibility in exposed and nonexposed cavities.

Potent anticonvulsant paeonimetabolin-I derivatives obtained by incubation of paeoniflorin and thiol compounds with Lactobacillus brevis.

Seventeen thiopaeonimetabolin-I adducts were obtained as mixtures of diastereoisomers after incubation of paeoniflorin with Lactobacillus brevis in the presence of various thiols. Four compounds, 8-(n-hexylthio)- (8), 8-cyclopentylthio-, 8-(p-tolyl)thio- and 8-benzoylthio- (18) paeonimetabolins, showed 100% protection against pentylenetetrazole-induced convulsions at doses of 0.125, 0.25, or 0.50 mmol/kg, relative to valproic acid (100% protection at 1.5 mmol/kg). For 8 and 18, the principle anticonvulsant activity resided in the (7S)-isomers while (7R)-isomers showed muscle relaxation effects.

Biocompatibility of primer, adhesive and resin composite systems on non-exposed and exposed pulps of non-human primate teeth.

PURPOSE: To evaluate the histologic response of 332 non-exposed and 127 exposed monkey pulps applying nine adhesive systems. MATERIALS AND METHODS: Class V and Class I cavities were used in non-exposed and exposed monkey pulps at the three ISO usage time intervals. RESULTS: There were no histologic differences in pulp responses among the nine adhesive systems used in either Class V and/or Class I cavities when compared to pulp responses of Ca(OH)2 controls at the ISO time intervals. The nine adhesive systems and resin composites are non-toxic to either non-exposed or exposed pulps, being biologically compatible to pulp tissues when placed on mechanical pulp exposures following hemorrhage control with a 2.5% NaOCl and per manufacturers' directions. It is imperative that clinicians understand the biological importance of hemorrhage control as well as the technique sensitivity of hydrophilic primers in order to optimize the efficacy of adhesives for clinical success against microleakage of bacterial factors.

"True normal" TMD control subjects: a rare clinical finding.

This study evaluated the accuracy of the clinical diagnosis of patients with temporomandibular joint dysfunction symptoms compared to a group of asymptomatic volunteers. The clinical examination and history questionnaire used during the evaluation of TMD patients were less accurate evaluating asymptomatic subjects than when combined with computerized joint vibration analysis. "True normal" control subjects were rarely found when these diagnostic modalities were combined in the TMD examination process. Most of the asymptomatic subjects had subclinical signs of TMD. The small sample size is significant, especially since large numbers of subjects appear to be necessary to obtain even small numbers of "true normals."

Biocompatibility of Optibond and XR-Bond adhesive systems in nonhuman primate teeth.

This study evaluated the histologic responses of two different adhesive systems on the teeth of seven healthy adult monkeys. Class V cavities in 128 teeth were observed at 7,21 to 27, and 90 to 97 days. Statistical data showed no significant differences in pulp inflammation between the Optibond (Kerr), XR-Bond (Kerr), and IRM (Caulk) groups in pulps at the three time intervals. Some odontoblastic disruption and inflammation was seen in pulps restored with XR-Primer at the three time intervals. Pulp healing was similar in teeth treated with both direct-capped Optibond and calcium hydroxide, and there was no significant increase in pulpal inflammation with time. No abscesses or necrotic pulps were seen in any teeth. Optibond and XR-Bond adhesive systems are biologically acceptable in nonhuman primate pulp tissues.

Biocompatability of compomer restorative systems on nonexposed dental pulps of primate teeth.

This study evaluated the histologic response of total-etched and nonetched compomer restored cavity preparations. One hundred fifteen class 5 cavity preparations were placed in the teeth of four healthy adult monkeys at 7, 27, and 90 days. A 37% H3PO4 was applied for 10 seconds and rinsed in total-etched preparations. No statistical differences were seen in inflammatory reactions among total-etched or nonetched compomers at 7, 27, and 90 days. There were no statistical differences in inflammatory cell responses among all compomer systems in regard to time intervals. Pulpal responses of compomers were greater than IRM at each time period. Pulp responses were associated with stained bacteria in 32 of 89 compomer teeth. No necrotic pulps were seen in any teeth. Statistical data show a positive correlation (P < 0.05) between bacterial presence and pulpal inflammation. IRM pulps showed no inflammation or bacterial staining. Compomers are biologically compatible with pulp tissues when bacteria are excluded.

Spiroheterocyclic system. Part IV: Novel azo dye sulpha drugs of spiroheterocyclic naphthenes.

Novel azo-dyes have been synthesized by diazotization of 4-amino benzene-4'-(substituted heterocyclo) sulphonamide derivatives and coupling with 1-oxa-4-thia-spiro[4,4]nonan-2-one (I) and/or with 1-oxa-4-thia- spiro[4,5]decan-2-one (I') in acid medium to give the corresponding 3-azo-(4'-substituted benzenesulphonamido)-1-oxa-4-thia-spiro[4,4]nonan-2-one (II-IX) and/or 1-oxa-4-thia-spiro[4,5]decan-2-one (II'-IX'] as spiro-ligands. Treatment of these ligands with metal salts of iron (Fe3+), copper (Cu2+) and mercury (Hg2+) as chlorides in ethanolic solution furnished the corresponding metal chelates (IIa-c-IXa-c) and/or (II'a-c-IX'a-c). The compounds were tested in vitro for antimicrobial activity to study the structure-activity relationship.

Nitriles in heterocyclic synthesis. Part III: New sulpha drugs related to cyanopyridine derivatives.

4-Hydroxyacetophenone (1) was reacted with cinnamonitrile derivatives (2-6) to give 3-cyano-4-(substituted phenyl)-6-(p-hydroxyphenyl)-pyridines (7-11). Interaction of compounds 7-9 with 4'-substituted heterocyclo-benzenesulphonyl diazonium chloride gave the corresponding 3-cyano-4-(substituted phenyl)-6-(3'-azobenzene sulphonamido-4'-hydroxyphenyl) pyridines (12-29). The corresponding iron (III) copper (II) and mercury (II) chelates were also prepared in a 1:2 metal-to-ligand ratio. All the synthesized compounds were characterized on the basis of microanalysis, IR and 1H-NMR spectrometry.