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Biomedical subjects

B Reed

Publications and source records attributed to B Reed.

At least 37 records · Page 2Linked to original sources

Effects of high levels of fluoride on bone formation: an in vitro model system.

In order to develop an in vitro model for the study of the effects of different agents on biomineralization, a three-dimensional cell culture system was investigated at different levels of fluoride. Rat fetal osteoblasts were seeded onto collagen discs and maintained in a culture medium for 40 days. Results showed that, at 40 days, the cultured matrices had a Ca:P ratio, mineral content and Fourier transform infrared (FTIR) spectrum that were close to those seen for normal rat bone. Viable cells, observed by light microscopy, were present in the matrix at 40 days. The formation of a mineralized matrix in this experimental set-up provided a model for exploring in vitro the effects of high levels of fluoride on bone. The fluoride content of the mineral formed in the cultures showed a dose-dependent increase in fluoride content with time. Also, an increase in the crystallinity of the apatite in the presence of fluoride, was observed by FTIR. The Ca:P ratio and percentage mineral by weight showed no apparent differences among the groups. The three-dimensional model used for this study has the potential to be a powerful tool in the study of time-dependent effects of drugs and other factors on osteoblast cell functions and subsequently on matrix mineralization.

Animals↗

Treating a patient with the Werner syndrome and osteoporosis using recombinant human insulin-like growth factor.

OBJECTIVE: To assess the safety and effect of recombinant human insulin-like growth factor 1 (rhlGF-1) on measures of bone metabolism in a human model of age-related osteoporosis. DESIGN: 6-month prospective case study. SETTING: General clinical research center. PATIENTS: 1 patient with the Werner syndrome, a low serum IGF-1 level, and osteoporosis. INTERVENTION: Daily subcutaneous administration of rhIGF-1 for 6 months. MEASUREMENTS: Serum alkaline phosphatase, osteocalcin, type I procollagen C-peptide and urinary hydroxyproline, calcium, and pyridinoline cross-links as measures of bone metabolism and radial shaft, femoral neck, and lumbar bone masses. RESULTS: Serum osteocalcin and type I procollagen C-peptide increased during rhIGF-1 therapy (P < 0.05). Twenty-four hour urinary calcium, hydroxyproline, and pyridinoline cross-links were also higher after treatment than they were before treatment (P < 0.05). During 6 months of treatment, the bone mineral density of the L2 to L4 vertebrae increased 3%; this value exceeded the coefficient of variation of this measurement. Bone density at the femoral neck and radial shaft changed by less than the coefficient of variation of these measurements. No significant changes in serum glucose values or other adverse effects of treatment were noted. CONCLUSIONS: Treatment with rhIGF-1 increased both bone formation and resorption in a patient with the Werner syndrome, a low baseline serum IGF-1 level, and established osteoporosis. Because lumbar bone mass increased without evidence of bone loss in the appendicular skeleton, a net increase in bone formation (formation greater than resorption) may have been responsible.

Adult↗

The pharmacokinetics and absorption of recombinant human relaxin in nonpregnant rabbits and rhesus monkeys after intravenous and intravaginal administration.

Recombinant human relaxin (rhRlx) is being developed as a potential cervical ripening agent to be applied intravaginally or intracervically prior to parturition. The pharmacokinetics and absorption of rhRlx were determined in nonpregnant female rabbits and rhesus monkeys after intravenous bolus (iv) and intravaginal administration of 0.1 mg/kg; additionally, rabbits were dosed with 0.5 mg/kg intravaginally. In rabbits (n = 6), mean (+/- SD) peak concentrations following iv bolus administration were 1554 +/- 296 ng/mL. The weight-normalized clearance (CL/W) was 5.9 +/- 0.4 mL/min/kg, initial volume of distribution (V1/W) was 57 +/- 9 mL/kg, and volume of distribution at steady state (Vss/W), assuming central compartment elimination, was 240 +/- 20 mL/kg. Vss/W could be as large as 2000 +/- 400 mL/kg without this assumption. The estimated amounts of rhRlx absorbed in rabbits following intravaginal administration of 0.1 and 0.5 mg/kg (n = 5/dose) were 3.1 +/- 1.4 and 0.7 +/- 0.3%, respectively; peak concentrations were 600 +/- 297 and 1066 +/- 584 pg/mL, respectively. In rhesus monkeys (n = 5) after iv administration, peak concentrations were 971 +/- 277 ng/mL; CL/W was 4.1 +/- 0.6 mL/min/kg, V1/W was 78 +/- 25 mL/kg, and Vss/W, assuming central compartment elimination, was 690 +/- 220 mL/kg. The upper limit for Vss/W was 1600 +/- 200 mL/kg when no assumptions were made regarding site (compartment) of elimination. After intravaginal administration (n = 6), two monkeys had undetectable rhRlx concentrations throughout the 48-hr sampling interval; one monkey had only one sample containing measurable rhRlx (51 pg/mL) at 24 hr; and three monkeys absorbed < 2% of the 0.1 mg/kg dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Genetic similarity of Candida albicans strains from vaginitis patients and their partners.

The moderately repetitive sequence Ca3 was used to fingerprint strains of Candida albicans isolated from vulvovaginal infections of 10 women and strains isolated from their male partners. The Dendron software package was then used to compare the DNA fingerprints of these strains with those of vaginal commensals from women from the same geographical locale, vaginal commensals from women from a different geographical locale, and commensals from male partners of asymptomatic women from the same geographical locale. The results demonstrate that, in the majority of cases (8 of 10), strains from symptomatic patients and their partners are either identical or more similar to each other than to other strains, infecting strains do not represent a group genetically distinguishable from vaginal commensal isolates from women from the same geographical locale, and both infecting strains and commensals from individuals in the test locale can be distinguished from commensals obtained in another geographical locale. The results also suggest that women with vaginal infections are responsible for strain replacement in their male partners.

Adult↗

Human seminal relaxin is a product of the same gene as human luteal relaxin.

Unlike that of other species, which have only one gene encoding relaxin, the human genome contains two nonallelic genes for relaxin, designated H1 and H2, which encode markedly different relaxin peptides. Whereas human relaxin gene H2 is selectively expressed in the ovary, no ovarian expression of gene H1 has been detected. Since relaxin is actively produced in the human male, it is possible to postulate divergent gene expression of relaxin in the male and female. We examined this question directly through the structural determination of human seminal relaxin and its comparison with the structure of human luteal relaxin. Partially purified relaxin, prepared from pooled human seminal plasma which had been delipidated by extraction with acid acetone and hexane, subjected to two cycles of HPLC and an additional purification step by ion-exchange chromatography, was further purified by immunoaffinity chromatography, using a monoclonal antibody to the H2 relaxin A chain which cross-reacts with synthetic H1 relaxin, followed by an additional HPLC step performed on a C4 reverse-phase column. The recovered, purified relaxin was then analyzed by N-terminal gas-phase sequencing and fast atom bombardment mass spectroscopy for determination of the amino acid sequence and molecular ions of the A and B chains, respectively. The results demonstrate that the structure of the predominant relaxin in human semen plasma is derived from the product of the H2 gene, consisting of a N-terminal pyroglutamic acid A-24 A chain and a mixture of B-26 and B-27 B chains. With the exception of degradation of the seminal relaxin B chain C-terminus, this structure is identical to the structure of human luteal relaxin. Therefore, both human seminal and luteal relaxin are products of the H2 gene.

Amino Acid Sequence↗

Effect of cooking methods on the mutagenicity of food and on urinary mutagenicity of human consumers.

The effects of cooking methods on the in vitro mutagenicity of individual foods, the in vitro mutagenicity of meals containing those foods, and the mutagenic exposure of human volunteers following consumption of the meals were examined using Ames bacterial strain TA98 with S-9 metabolic activation. Three methods of food preparation--boiling, baking and frying/flame-broiling--were compared. With meats, frying or broiling resulted in higher in vitro mutagenicity (10- to 50-fold) than did baking or boiling, whereas for carbohydrates, eggs or vegetables mutagenicity did not vary markedly with cooking method. The observed (experimental) mutagenic activity of the meals was quite similar to their calculated (predicted) mutagenicity, obtained by summing the mutagenicity of the individual foods in the meal. The close agreement between experimental and predicted mutagenicity indicated that components of the meal did not interact in either a synergistic or inhibitory manner. The mutagenicity of fried flame-broiled meals was approximately 10-fold greater than the mutagenicity of baked or broiled meals, which were similar in mutagenicity. The mutagenicity of human urine following consumption of the meals was related to the in vitro mutagenicity of the meals themselves. The in vitro mutagenicity of meals is markedly affected by the cooking method used to prepare them and the mutagenicity of the diet may be reflected in the mutagenicity of body fluids.

Adult↗

Teratological assessment of exposure to time-varying magnetic field.

A teratological assessment was performed using rats that were exposed to an alternating magnetic field. The magnetic field had a sawtooth waveform similar to that produced by video display terminals (VDTs). Female rats were exposed 2 weeks prior to and throughout pregnancy at a rate of 7 h/day. Three intensities of magnetic field (5.7, 23 or 66 microT) were used. All of these field intensities were much greater than those to which VDT users are exposed. A slight but statistically significant decrease in maternal lymphocyte count for the highest intensity field was found as compared with the control group. However, the lymphocyte count was within the normal range, and the observed changes in hematological parameters were considered mild. No other maternal or fetal parameters that were examined showed a significant difference for any of the three field intensities. Where minor variations in skeleton development were observed they were known to be the common "noise" that appears in every teratological evaluation.

Animals↗

Effects of MHz ultrasound on electrical pain threshold perception in humans.

An electrode system was developed consisting of two 8 mm long 0.2 mm diameter silver-coated copper wires arranged parallel to each other 8 mm apart and held in contact with the skin by means of an acoustically transparent plastic adhesive tape. This system was attached to the upper arms of young adult volunteers who increased the voltage of the rectangular electrical pulses supplied to the electrodes until a reproducible sharp prickling pain sensation was perceived. A one inch diameter physiotherapy transducer was positioned over the electrode site so that ultrasound could be administered throughout the measurement period. The experiments were performed single blind to eliminate any subjective bias on the part of the volunteers. Preliminary experiments established that highly reproducible (+/- 3 to 4%) pain threshold perception values could be obtained, and that these values were not affected by changes in (a) the duration of the "on" time of the electrical pulses between 1.5 and 48 ms, (b) the contact pressure between the transducer and the electrode site, (c) the time interval between successive threshold measurements (providing that an unacceptable level of oedema was not produced around the electrodes), and (d) whether or not a test measurement was preceded by a control. Ultrasound exposure via a direct contact technique consistently produced a statistically significant (p less than 0.05) decrease in the perception threshold for electrical pain. This effect usually developed within 30-60 s and its magnitude increased both with increasing intensity (rising to 20.7 +/- 0.57% at an SATA intensity of 0.43 W/cm2 at 1.1 MHz) and with increasing frequency at the same ultrasonic intensity. Delivering the same amount of ultrasonic energy in the form of 2 ms bursts at several different peak intensities produced exactly the same reduction in pain threshold perception. These results indicate a thermal interaction mechanism, and similar threshold changes could be obtained by heating or cooling the electrode site by nonacoustic means. The inclusion of a thermocouple junction between the electrode wires showed that temperature increases of up to 10 degrees C could be produced when the transducer was in direct contact with the tape over the electrodes. The volunteers were not aware of these temperature increases which were primarily caused by heating of the transducer face. If the temperature of the skin surface is kept constant by interposing a thermostatted water path between the transducer and the electrode system, then similar ultrasound exposures had no detectable effects upon the electrical pain perception threshold.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Orthodontic relapse, apical root resorption, and crestal alveolar bone levels.

This investigation examined the relationship of postorthodontic treatment relapse to crestal alveolar bone support and root resorption. Thirty-six persons having completed the retention phase of orthodontics at least 10 years earlier were divided into two groups based on the amount of relapse crowding of the mandibular anterior teeth. Eighteen subjects (relapse group) exhibited 2 mm or more of mandibular anterior relapse crowding and 18 subjects (nonrelapse group) exhibited no mandibular anterior relapse crowding. At time of recall, full-mouth series of periapical and bitewing radiographs were obtained as well as lateral cephalometric films to allow comparison with similar lateral cephalometric films obtained at pretreatment and retention time points. The radiographs were examined to assess three parameters: root resorption, crestal alveolar bone levels, and changes in the position and angulation of the maxillary incisors. The subjects in the relapse group had undergone longer periods of treatment and exhibited a greater prevalence of root resorption; they also displayed significantly greater crestal alveolar bone level distances, indicating greater loss of bone support than that observed in the nonrelapse group. The distances that teeth were translated seemed to affect the extent of root resorption and crestal bone loss with smaller amounts of tooth translation seemingly more prone to demonstrate tissue loss. The findings of this investigation suggest there may be a relationship between orthodontic relapse and the parameters of increased root resorption and decreased crestal alveolar bone levels.

Adult↗

Octachlorostyrene: a 90-day toxicity study in the rat.

This study was designed to provide information on the subchronic toxicity of octachlorostyrene (OCS), a demonstrated environmental pollutant in fish from the Great Lakes of North America and the Norwegian coast in Europe. Groups of 15 male and 15 female rats were administered OCS mixed in the diet at 0.05, 0.5, 5.0, 50, or 500 ppm for 13 weeks. Increased liver weights were observed in male and female rats fed 50 ppm OCS and higher, while enlarged kidney and spleen were noted in the highest dose groups. Hepatic microsomal enzyme induction occurred at 5.0 ppm OCS and higher for the males and 50 ppm and higher for the females. The chemical produced serum biochemical changes at concentrations as low as 5.0 ppm. OCS treatment resulted in hematological disturbances starting with the 0.5-ppm dose group. Dose-dependent histological changes were observed in the thyroid, kidneys, and liver of the treated animals. OCS residues accumulated in a dose-related fashion in the liver and fat of treated animals. These results indicate that OCS produced toxic effects at low levels of exposure and accumulated in the tissues of rats.

Adipose Tissue↗

Periodontal response after tooth movement into intrabony defects.

The present study was undertaken since conflicting evidence exists regarding the effect of such tooth movement on levels of connective tissue attachment. Localized intrabony pockets were produced around isolated incisors in four rhesus monkeys. The root surfaces were planned to the level of the bone at the base of the angular bony defects. An oral hygiene regime was begun and continued for the remainder of the study. The experimental teeth were moved orthodontically into, and through, the original area of the intrabony defect. Two months after cessation of active tooth movement, block specimens were removed for histologic analysis. Control specimens comprised those teeth with induced periodontal defects, but without tooth movement. In specimens not subjected to tooth movement, angular bony defects were present and epithelium lined the root surface to the apical extent of instrumentation. The alveolar bone adjacent to the orthodontically moved teeth no longer had angular defect morphology. On the pressure side, epithelium lined the root surface, was interposed between root surface and bone and terminated at the apical limit of root instrumentation. On the tension side, the crest of the bone was located apical to the level of root planing, and epithelium lined the instrumented portion of the root surface. It was concluded that orthodontic tooth movement into intrabony periodontal defects was without effect upon the levels of connective tissue attachment.

Alveolar Process↗