Prevention of enamel demineralization after tooth bleaching by bioactive glass incorporated into toothpaste.

BACKGROUND: The aim of this study was to determine the effects of bleaching on the structure of the enamel layer of teeth and the potential of the commercial bioactive glass NovaMin® in two different toothpastes to remineralize such regions of the enamel. Three aspects were considered: the extent and nature of the alterations in the enamel after application of the bleaching agents; the extent of remineralization after application of two commercial toothpastes containing bioactive glass; and whether or not there were differences between the toothpastes in terms of their effectiveness in promoting remineralization. METHODS: Bleaching agent based on 16% carbamide peroxide was applied to the enamel surface of freshly extracted human molars for 8 minutes, once a day for 7 days. After the bleaching cycles, the enamel surface was analysed by SEM and EDX. RESULTS: The results obtained in the study lead to the conclusion that application of 16% carbamide peroxide causes distinct morphological changes to the enamel surface which vary from mild to severe. Subsequent treatment with either of the toothpastes containing the bioactive glass NovaMin® resulted in the formation of a protective layer on the enamel surface, consisting of bioactive glass deposits, with only slight differences between the two brands. Application of these dentifrices also caused increases in the Ca and P content of the enamel layer, returning it to that of undamaged enamel. CONCLUSIONS: Remineralizing toothpastes should be used after bleaching, in order to repair any damage to the mineral tissue caused by these procedures.

Melanocortin-4 receptor activation stimulates hypothalamic brain-derived neurotrophic factor release to regulate food intake, body temperature and cardiovascular function.

In the present study, we aimed to investigate the neuromodulatory role played by hypothalamic brain-derived neurotrophic factor (BDNF) in the regulation of acute cardiovascular and feeding responses to melanocortin-4 receptor (MC4R) activation. In vitro, a selective MC4R agonist, MK1, stimulated BDNF release from isolated rat hypothalami and this effect was blocked by preincubation with the MC3/4R antagonist SHU-9119. In vivo, peripheral administration of MK1 decreased food intake in rats and this effect was blocked by pretreatment with an anti-BDNF antibody administered into the third ventricle. When anorexia was induced with the cannabinoid-1 receptor (CB1R) antagonist AM251, the anti-BDNF antibody did not prevent the reduction in food intake. Peripheral administration of MK1 also increased mean arterial pressure, heart rate and body temperature. These effects were prevented by pretreatment with the anti-BDNF antibody whereas the intracerebroventricular administration of BDNF caused changes similar to those of MK1. These findings demonstrate for the first time that activation of MC4R leads to an acute release of BDNF in the hypothalamus. This release is a prerequisite for MC4R-induced effects on appetite, body temperature and cardiovascular function. By contrast, CB1R antagonist-mediated anorexia is independent of the MC4R/BDNF pathway. Overall, these results show that BDNF is an important downstream mediator of the MC4R pathway.

A clinical evaluation of ophthalmic assessment in children with sensori-neural deafness.

BACKGROUND: Since 1991, children with sensori-neural deafness and their families within Southern Derbyshire have been supported by a multiagency approach to their diagnosis and management. RESULTS: One hundred and twenty-two children were seen at the Child Development Centre for an holistic assessment, and 110 of these children have had an ophthalmic assessment, of whom 48 (43.6%) were found to have ophthalmic abnormalities. These included 43 children (39.1%) with refractive errors, ranging from mild to severe. Of 82 children with uncomplicated deafness, 26 (31.7%) had refractive errors. The prevalence of ophthalmic problems was higher than the prevalence in hearing school children in the literature and in local pre-school children. There were six cases of Usher syndrome. Twenty-one children had more than one eye defect. The findings indicate that deaf and hearing impaired children are two to three times more likely to develop ophthalmic abnormalities than their hearing peers, which makes early detection of paramount importance. An important local outcome has been the establishment of guidelines for ophthalmic assessment to include assessment of vision and screening for Usher syndrome by electro-physiological testing at aged 7 years and above. Screening has been completed to date in 78 children with congenital sensori-neural deafness. CONCLUSIONS: Sensitive and efficient ophthalmic assessment and management are essential for all deaf and hearing impaired children and national guidelines need to be established for both assessment of vision and screening for Usher syndrome, based on further evaluated research.

Vitamin E deficiency and metabolic deficits in neuronal ceroid lipofuscinosis described by bioinformatics.

The mnd mouse, a model of neuronal ceroid lipofusinosis (NCL), has a profound vitamin E deficiency in sera and brain, associated with cerebral deterioration characteristic of NCL. In this study, the vitamin E deficiency is corrected using dietary supplementation. However, the histopathological features associated with NCL remained. With use of a bioinformatics approach based on high-resolution solid and solution state 1H-NMR spectroscopy and principal component analysis (PCA), the deficits associated with NCL are defined in terms of a metabolic phenotype. Although vitamin E supplementation reversed some of the metabolic abnormalities, in particular the concentration of phenylalanine in extracts of cerebral tissue, PCA demonstrated that metabolic deficits associated with NCL were greater than any effects produced from vitamin E supplementation. These deficits included increased glutamate and N-acetyl-L-aspartate and decreased creatine and glutamine concentrations in aqueous extracts of the cortex, as well as profound accumulation of lipid in intact cerebral tissue. This is discussed in terms of faulty production of mitochondrial-associated membranes, thought to be central to the deficits in mnd mice.

A randomised controlled trial of the efficacy of supervised toothbrushing in high-caries-risk children.

Scottish children have one of the highest levels of caries experience in Europe. Only 33% of 5-year-old children in Dundee who developed caries in their first permanent molars by 7 brushed their teeth twice a day. High-caries-risk children should benefit if they brush more often with fluoridated toothpaste. The aim of this clinical trial was to determine the reduction in 2-year caries increment that can be achieved by daily supervised toothbrushing on school-days with a toothpaste containing 1,000 ppm fluoride (as sodium monofluorophosphate) and 0.13% calcium glycerophosphate, combined with recommended daily home use, compared to a control group involving no intervention other than 6-monthly clinical examinations. Five hundred and thirty-four children, mean age 5.3, in schools in deprived areas of Tayside were recruited. Each school had two parallel classes, one randomly selected to be the brushing class and the other, the control. Local mothers were trained as toothbrushing supervisors. Children brushed on school-days and received home supplies. A single examiner undertook 6-monthly examinations recording plaque, caries (D(1) level), and used FOTI to supplement the visual caries examination. For children in the brushing classes, the 2-year mean caries increment on first permanent molars was 0.81 at D(1) and 0.21 at D(3) compared to 1.19 and 0.48 for children in the control classes (significant reductions of 32% at D(1) and 56% at D(3)). In conclusion, high-caries-risk children have been shown to have significantly less caries after participating in a supervised toothbrushing programme with a fluoridated toothpaste.

Clinical and pathophysiologic correlates of 1064-nm Nd:Yag laser treatment of reticular veins and venulectasias.

BACKGROUND: The goal of sclerotherapy, laser therapy, and intense pulsed-light therapy is to produce long-term, cosmetically significant elimination of disfiguring leg veins. This study examines the histologic and clinical effects of using a 1064-nm Nd:YAG laser system on lower extremity vessels. DESIGN: A single treatment using the following parameters: wavelength, 1064 nm (multiple synchronized pulsing); spot size, 6 mm; pulse duration, 14 milliseconds (single pulse); and fluence, 130 J/cm(2). SETTING: Private dermatology practice. PATIENTS: Thirteen women (mean age, 38.5 years) with blue venulectasia, 0.5 to 1.5 mm in diameter (class 2), and reticular veins, 1.5 to 3.0 mm in diameter (class 3), on the thighs. MAIN OUTCOME MEASURES: Examination of treated and untreated areas by 2 masked observers using macrophotography (1, 2, 3, and 6 months after treatment), Doppler, and optical chromatographic changes. Findings from three 2-mm punch biopsies from treated (immediately and 4 weeks after treatment) and untreated sites. Routine histologic examination; special stains (for elastic and connective tissue and for mucopolysaccharides); and immunohistochemical analysis for expression of the heat shock protein hsp70, tie2 (an endothelial cell-specific receptor tyrosine kinase), and transforming growth factors beta1 and beta2. RESULTS: Eight patients (62%) manifested 75% to 100% clearing of treated vessel surface area. Treated areas revealed perivascular hemorrhage, thrombi, fragmentation and homogenization of elastic fibers, and eosinophilia of vessel walls. Expression of hsp70 and transforming growth factor beta was increased in treated vessels. CONCLUSIONS: Our data confirm the effectiveness of 1064-nm Nd:YAG laser treatment in clearing dilated lower extremity veins, probably by heat-induced vessel damage and subsequent fibrosis. Maintenance of clearing was achieved for up to 6 months. However, the presence of recanalized thrombi in some of the specimens suggests the potential for long-term vessel reappearance.

Pain perception and utility: a comparison of the syringe and computerized local injection techniques.

Thirty patients received maxillary infiltration and mandibular inferior alveolar nerve block injections with both a traditional syringe and a computerized system, the Wand. Patients noted their preference for either system and rated their injection pain and postoperative discomfort on a ten-point scale for each type of injection. Mean injection discomfort ratings with the Wand were lower than with the syringe but were not statistically significant. Reduced postoperative discomfort using the Wand for the inferior alveolar nerve block was significant. Both of the dentists in the study and those patients who stated a preference favored the Wand system.

Long-term photoepilation using a broad-spectrum intense pulsed light source.

BACKGROUND: The goal of laser or flashlamp photoepilation is to produce long-term, cosmetically significant hair removal. We document the long-term efficacy achieved with an intense pulsed light source for photoepilation. DESIGN: Prospective study comparing long-term results of single vs multiple treatments, and effects of anatomic site and skin type on efficacy of photoepilation with a device emitting broad-spectrum, noncoherent (nonlaser) radiation from 550- to 1200-nm wavelengths, in macropulses divided into 2 to 5 minipulses. SETTING: Private dermatology practice. PATIENTS: Thirty-four patients (8 men, 26 women) with hirsutism. INTERVENTIONS: Parameters for the study were wavelength of 615 to 695 nm, pulse duration of 2.6 to 3.3 milliseconds, fluence of 34 to 42 J/cm(2), 10 x 45-mm exposure field, and application of 1 degrees C cooling gel. MAIN OUTCOME MEASURES: Hair removal efficiency, calculated as percentage ratio of the number of hairs present compared with baseline counts, and patient satisfaction questionnaire completed at last follow-up. RESULTS: The mean hair removal efficiency achieved was 76% after a mean of 3.7 treatments. More than 94% of the sites reached mean hair removal efficiency values greater than 50%. Hair removal efficiency was not significantly related to skin type, hair color, anatomic site, or number of treatments. Side effects were mild and reversible and occurred in a minority of patients (hyperpigmentation in 3 and superficial crusting in 2). CONCLUSIONS: Our data document the long-term clinical efficacy of intense pulsed light source-induced hair removal in light and dark skin phenotypes. Maximal photoepilation was achieved from the initial 1 to 3 treatments; only a small added benefit was seen after more treatments.

Combined HPLC, NMR spectroscopy, and ion-trap mass spectrometry with application to the detection and characterization of xenobiotic and endogenous metabolites in human urine.

The direct coupling of HPLC with NMR spectroscopy has been extended by splitting the HPLC eluent after conventional UV detection and sending part to a NMR spectrometer and part to an ion-trap mass spectrometer in a "triplehyphenated" HPLC-NMR-MS system. Combined UV, 1H NMR, and positive-ion electrospray MS detection was achieved in the continuous-flow mode using whole human urine from a subject dosed with acetaminophen. By means of HPLC-NMR-MS, the structural information available from the complementary spectroscopic techniques provided rapid confirmation of the identity of the acetaminophen glucuronide and sulfate metabolites, together with a number of endogenous metabolites. In particular, the HPLC-NMR-MS approach allowed the unequivocal identification of phenylacetylglutamine in human urine, an endogenous metabolite not previously observed in 1H NMR spectra of urine because of extensive overlap with resonances from other metabolites. The analytical advantages and complementarity of NMR and MS techniques in direct hyphenation with HPLC are discussed. The new technique of HPLC-NMR-MS will provide the scope for more comprehensive and fully automated analysis of biofluids and other complex mixtures than was previously available from single hyphenation of these instruments.

Silicone gel and octamethylcyclotetrasiloxane (D4) enhances antibody production to bovine serum albumin in mice.

The purpose of the present study was to determine whether components of silicone breast implants [silicon (polydimethylsiloxane) oil, silicone gel, and octamethylcyclotetrasiloxane (D4)] potentiate the antibody response to bovine serum albumin (BSA) in mice. Seventy A/J mice were divided into seven groups which received the following: group I--phosphate buffer solution (PBS); group II--20 centistoke (cs) silicone oil; group III--50% silicone gel homogenized in silicone oil; group IV--incomplete Freunds' adjuvant (IFA); group V--IFA mixed with an equal volume of silicone oil; group VI--D4; and group VII--IFA mixed with an equal volume of DA. Each 0.1 mL of treatment material(s) was mixed or emulsified with an equal 0.1-mL volume of 250 micrograms/mL BSA in PBS solution. Antibodies to BSA were measured using an enzyme-linked immunosorbent assay. Our study demonstrates for the first time that both D4 and the silicone gel potentiate antibody production to BSA in mice. Histopathologic evaluation of the injection sites reveals granulomas for mice injected with IFA and D4 preparations. Whether D4 or silicone gel acts as an adjuvant against self-antigens has yet to be determined.

Silicone gel and octamethylcyclotetrasiloxane potentiate antibody production to bovine serum albumin in mice.

Earlier studies, in the rat, have shown that silicone gel acts as a potent adjuvant for antibody production against bovine serum albumin (BSA). The purpose of the present study is to determine whether components of the silicone breast implant (silicone oil, silicone gel, and octamethylcyclotetrasiloxane [D4]) potentiate the antibody response to BSA in mice. Groups of ten A/J mice received a single subcutaneous injection of 0.1 ml of BSA emulsified with the following: a) silicone preparations, b) incomplete Freund's adjuvant, or c) saline alone. Antibodies to BSA were measured using an enzyme-linked immunosorbant assay. The results indicate that both D4 and the silicone gel potentiate antibody production to BSA in mice. Known adjuvants have been shown to induce autoimmune syndromes in animal models. Whether silicones can act in a similar mechanism is still unclear.

Gastro-intestinal availability of aluminium from tea.

The in vitro speciation of aluminium (Al) in black tea infusion (pH 4.8) was assessed using 3000, 10,000 and 30,000 Da cut-off ultrafilters, and the effect of adding human gastric juice (pH 2.3) and then raising the pH to 6.5 were also studied. 78% Al in the tea infusion passed through the 3000-Da ultrafilter; this percentage increased to more than 90% with the addition of gastric juice at pH 2.3, but then reduced to approximately 5% when the incubate was adjusted to pH 6.5. The breakdown of tea-derived polyphenols to low molecular weight phenols in vivo was measured using high-resolution 1H nuclear magnetic resonance spectroscopic analysis of ileostomy effluent, but there was no evidence of low molecular weight breakdown products from the polyphenols of ingested tea in this effluent. These results suggest that only a small proportion of Al in tea is potentially available for absorption throughout the small bowel. It may be misleading to estimate systemic Al absorption from tea drinking simply from total urinary aluminium excretion as has been done previously.

Synthesis and anticonvulsant activity of enaminones.

A new series of novel enaminones has been synthesized from cyclic beta-dicarbonyl precursors which were condensed with morpholine, pyrrolidine, phenethylamine, hydrazines, substituted benzyl amines, and substituted anilines. These compounds were subsequently evaluated for anticonvulsant activity in a variety of anticonvulsant models by the National Institute of Neurological and Communicative Disorders and Stroke and in our laboratory. Several of these compounds exhibited potent anticonvulsant activity with a remarkable lack of neurotoxicity. The most active analog, methyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxo-cyclohex-3-en-1-oate++ + (27), was protective in the maximal electroshock (MES) seizure test in the rat with an oral ED50 of 5.8 mg/kg with no toxicity noted at doses up to 380 mg/kg, thus providing a protective index (TD50/ED50) of greater than 65.5. A similar protective index for 27 was noted upon intraperitoneal (ip) administration in mice. The anticonvulsant effect of 27 occurred within 15 min of administration and the compound remained active beyond 4 h. Compound 27 was also active in the rat corneal kindled model. The application of Free-Wilson analysis to structure-activity correlation in this series is discussed.

Calcium, the renin-aldosterone system, and the hypotensive response to nifedipine.

Ionic, hormonal, and blood pressure responses to a single oral dose of the calcium channel blocker nifedipine were assessed in 25 essential hypertensive subjects. When grouped according to their renin-sodium profile, low renin subjects had a greater hypotensive response to nifedipine (change in diastolic blood pressure -20.0 +/- 1.4 vs -6.4 +/- 1.0%; p less than 0.005) than did high renin hypertensive subjects. The initial level of serum ionized calcium predicted the blood pressure response to nifedipine (r = 0.70, p less than 0.001), as did the initial plasma renin activity (r = 0.65, p less than 0.005). Nifedipine induced a transient rise in serum ionized calcium (from 2.22 +/- 0.02 to 2.28 +/- 0.02 mEq/L; p less than 0.01), while plasma renin activity was consistently elevated compared with initial values at 30 (p less than 0.01), 60 (p less than 0.01), and 120 (p less than 0.05) minutes after drug administration. By comparison, plasma aldosterone levels did not rise and even declined at 30 (p less than 0.01), 60 (p less than 0.05), and 120 (p less than 0.05) minutes after nifedipine. These results suggest that low renin hypertension is more critically dependent on extracellular calcium than are higher renin forms and demonstrate that levels of serum ionized calcium, plasma renin activity, or both may predict the sensitivity of blood pressure to calcium channel blockade. Lastly, calcium may play a pivotal role in vivo in coupling renin stimulation to adrenal aldosterone responses.

Calcium metabolism in essential hypertension: relationship to altered renin system activity.

Hypertensive disease is associated with various abnormalities of calcium metabolism although how these abnormalities relate to the elevated pressure remains unclear. Based on the use of renin-sodium profiling, we have defined heterogeneous deviations in circulating levels of ionized calcium and magnesium as well as of the calcium-regulating hormones parathyroid hormone, calcitonin, and 1,25-dihydroxyvitamin D (1,25D), which parallel similar deviations in plasma renin activity. Essential hypertensive subjects with a profile of low renin, lower ionized calcium, and elevated 1,25D respond best to the calcium channel blocker nifedipine, demonstrate an enhanced sensitivity to the blood pressure effects of dietary salt loading, and have significantly lower blood pressures in response to oral calcium supplementation. Hypertensive subjects with the opposite metabolic profile--higher renin activity, higher serum ionized calcium, and lower 1,25D levels--are relatively insensitive to the blood pressure effects of either dietary salt loading or nifedipine, and show no significant hypotensive response to calcium supplements. Altogether, these alterations of calcium ionic and hormonal metabolism suggest that the hormonal control of calcium metabolism is linked to renin system activity as well as to the pathophysiology of the hypertensive process.

Calcium metabolism and the renin-aldosterone system in essential hypertension.

Despite recent appreciation of a role for calcium in clinical hypertension, evidence at present is conflicting. Thus, certain studies suggest increased calcium availability may be associated with increased levels of blood pressure, while others suggest that a calcium deficiency may contribute to the pathogenesis of hypertensive disease. Our own group has thus far demonstrated deviations of circulating levels of ionized calcium and of magnesium in essential hypertension, linked with concurrent deviations in the activity of the renal pressor hormone, renin. Furthermore, calcium metabolic indices may predict and even determine dietary sodium sensitivity in hypertension, as well as the blood pressure responsiveness to antihypertensive drug therapy. Moreover, oral calcium supplementation may itself possess antihypertensive actions in specifically targeted renin subgroups of essential hypertensive subjects. Altogether, these results link calcium metabolism, renin system activity, and the pathogenesis of hypertensive disease. It may ultimately be calcium-regulating hormones, which determine cellular disposition of calcium, rather than circulating levels of calcium itself, that mediate the blood pressure and possibly even the renin deviations observed among differing hypertensive individuals.

X-ray microanalysis of proximal and distal tubule cells in the mouse kidney, and the influence of cadmium on the concentration of natural intracellular elements.

Quantitative X-ray microanalysis of frozen freeze-dried sections of mouse cortex have been used to determine the concentrations of Na, Mg, P, S, Cl, K, Ca and Cd in normal mice and those subjected t 0.7 mumol of cadmium chloride in two subcutaneous injections. These injections result in tissue levels of approximately 100 mg Cd/kg dry weight (less than 1 mM) in whole kidney when analysed by atomic absorption spectrometry. There were distinct and characteristic differences -- 'fingerprints' -- in the elemental composition of both cytoplasm and mitochondria in proximal and distal tubules of normal mice that were distributed by the cadmium treatment. The most significant effect of the cadmium injections was a highly significant increase in the sulphur content of the cytoplasm and mitochondria of distal tubules and a loss in concentration of Mg, P, Cl, K, and particularly Na, from the mitochondria. These results are discussed in the light of current concepts of metallothionein induction (metallothionein is a sulphur-rich protein that acts to bind, amongst other metals, cadmium) and the lack of damage observed in the distal tubules.

Effect of fermentation and formalin preservation on the protein component of bovine colostrum.

Colostrum was inoculated with Streptococcus lactis or yogurt culture or preserved with .1% (vol/vol) formalin in two separate experiments. All preparations then were stored at ambient temperature for 24 days. With increasing storage time, a larger proportion of the total colostrum nitrogen was not precipitated in 10% (wt/vol) trichloroacetic acid. By day 24, this represented 30 to 35% for the fermented samples and 10 to 15% for the formalin preserved samples. The majority of this nonprecipitable nitrogen was amino acids and small peptides. Most of the nitrogen in colostrum even after 24 days of storage should be nutritionally useful to the calf because even the nonprecipitable portion is amino acids and peptides.

Chemical changes in bovine colostrum preserved with formalin or by fermentation.

Fresh bovine colstrum from second and third milkings postpartum was inoculated with either a yogurt culture or Streptococcus lactis or preserved with .1% formalin in two separate experiments. There was a rapid decrease in pH of the fermented samples which corresponded to decreased lactose concentrations and increased lactate and titratable acidity. Titratable acidity in the fermented colostrums increased further after 10 days from the production of volatile fatty acids, but pH did not decrease. The pH of the yogurt fermentations in Experiment 2 decreased to 3.8, and the continued increase in titratable acidity was from lactic acid rather than volatile fatty acids. The lowest pH of all other fermentations was 4.1. The extent of metabolism of the formalin-preserved colostrum was much less than for the colostrum fermented by either culture.