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Molar incisor hypomineralization (MIH) is an endemic pediatric disease with an unclear pathogenesis. Considering that saliva controls enamel remineralization and that MIH is associated with higher saliva flow rate, we hypothesized that the protein composition of saliva is linked to disease. To test this, we enrolled 5 children aged 6–14 years with MIH showing at least one hypersensitive molar and 5 caries-free children without hypomineralization. Saliva samples were subjected to proteomic analysis followed by protein classification in to biological pathways. Among 618 salivary proteins identified with high confidence, 88 proteins were identified exclusively in MIH patients and 16 proteins in healthy controls only. Biological pathway analysis classified these 88 patient-only proteins to neutrophil-mediated adaptive immunity, the activation of the classical pathway of complement activation, extracellular matrix degradation, heme scavenging as well as glutathione -and drug metabolism. The 16 controls-only proteins were associated with adaptive immunity related to platelet degranulation and the lysosome. This report suggests that the proteaneous composition of saliva is affected in MIH patients, reflecting a catabolic environment which is linked to inflammation. [ABSTRACT FROM AUTHOR]

Copyright of HNO is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: We sought to determine the dose-response effects of extended-release (ER) dexmethylphenidate (d-MPH) and ER mixed amphetamine salts (MAS) on objective measures of sleep. Methods: This was an 8-week, double-blind, placebo-controlled, randomized, two period, crossover study of youth with attention-deficit hyperactivity disorder (ADHD) as confirmed by the Kiddie Schedule for Affective Disorders for School-Age Children-Present and Lifetime version (K-SADS-PL). Children aged 10-17 years were recruited from clinical practice, colleague referrals, and flyers. Participants were randomized to initially receive either d-MPH or MAS. During each 4-week drug period, children received three dose levels (10, 20, and 25/30 mg) in ascending order, with placebo substituted for active medication in a randomized fashion during 1 week of the study. After 4 weeks, participants were switched to the alternative medication for another 4 weeks of treatment. The main outcome measure was sleep duration as measured by actigraphy. Children, parents, and researchers were blinded to drug, dose, and placebo status. Results: Sixty-five participants met the inclusion criteria and were enrolled in the study. Of these, 37 participants with sufficient sleep data for analysis were included. Sleep schedule measures showed a significant effect for dose on sleep start time ( F(1,36) = 6.284; p < 0.05), with a significantly later sleep start time when children were receiving 20- or 30-mg doses, compared with placebo ( p < 0.05). A significant dose effect was found on actual sleep duration ( F(1,36) = 8.112; p < 0.05), with significantly shorter actual sleep duration for subjects receiving 30 mg compared with those receiving placebo ( p < 0.05). There were no significant differences on sleep duration or sleep schedule between the two stimulant medications. The trial is complete and closed to follow-up. Conclusions: Higher stimulant doses were associated with reduced sleep duration and later sleep start times, regardless of medication class. Trial registration: ClinicalTrials.gov: NCT00393042. [ABSTRACT FROM AUTHOR]

Aims: The objective of this study is to evaluate the effects of a paste-like bone substitute material with easy handling properties and improved mechanical stability on periodontal regeneration of intrabony defects in dogs. Materials and methods: Mandibular and maxillary first and third premolars were extracted, and three-wall intrabony defects were created on second and fourth premolars. After a healing period of 3 months, acute type defects were filled with a paste-like formulation of deproteinized bovine bone mineral (DBBM) (particle size, 0.125-0.25 mm) in a collagenous carrier matrix (T1), pulverized DBBM (particle size, 0.125-0.25 mm) without the carrier (T2), or Bio-Oss® granules (particle size, 0.25-1.00 mm) as control (C). All defects were covered with a Bio-Gide® membrane. The dogs were sacrificed after 12 weeks, and the specimens were analyzed histologically and histometrically. Results: Postoperative healing of all defects was uneventful, and no histological signs of inflammation were observed in the augmented and gingival regions. New cementum, new periodontal ligament, and new bone were observed in all three groups. The mean vertical bone gain was 3.26 mm (T1), 3.60 mm (T2), and 3.81 mm (C). That of new cementum was 2.25 mm (T1), 3.88 mm (T2), and 3.53 mm (C). The differences did not reach statistical significance. The DBBM particles were both incorporated in new bone and embedded in immature bone marrow. Conclusions: The results of this preclinical study showed that the 0.125-0.25-mm DBBM particles in a powder or paste formulation resulted in periodontal regeneration comparable to the commercially available DBBM. Osteoconductivity, in particular, was not affected by DBBM size or paste formulation. Clinical relevance: The improved handling properties of the paste-like bone substitute consisting of small DBBM particles embedded in a collagen-based carrier hold promise for clinical applications. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cell therapy is a strategy to enhance bone formation in regenerative dentistry. Osteogenic cells can be isolated and expanded from total bone marrow by the use of biodegradable microcarriers. It remains, however, unknown whether the cells on the surface of microcarriers can provide bone substitutes with an osteogenic potential. METHODS: We therefore isolated and expanded rat bone marrow cells on the surface of CultiSpher G microcarriers in a spinner-flask bioreactor. Isolated cells were viable as determined by MTT assay and stained positive for alkaline phosphatase activity. CultiSpher G microcarriers loaded with osteogenic cells were mixed with two bone substitutes, natural bone mineral, and hydroxyapatite/tricalcium, phosphate before subcutaneous implantation into immunodeficient mice. RESULTS: Isolated cells showed positive formazan formation indicating cell viability. Alkaline phosphatase activity being a marker gene for osteogenic differentiation was detectable. However, implants recovered after eight weeks from ectopic sites failed to show bone formation, even though blood vessels were present. CONCLUSIONS: These results suggest that the presence of osteogenic cells on the surface of microcarriers is not sufficient to provide bone substitutes with a bone forming capacity. The lack of bone formation at ectopic sites does not rule out the possibility that supplementation of bone substitutes with cell-loaded microcarrier support bone regeneration at orthotopic sites. Moreover, our data do not exclude the possibility that the current concept can be optimized to achieve ectopic bone formation. [ABSTRACT FROM AUTHOR]

Abstract   Objective The study aimed to assess adherence of prescribed medication in primary care to nationally recognised guideline criteria using case note review applying a previously developed medication assessment tool for coronary heart disease (MAT-CHD). Setting Primary care medical centre serving 17,991 patients. A sample of 208 from 463 patients with type 2 diabetes aged 20–75 years with or without a history of ischaemic heart disease (IHD). Method Patients’ records were accessed via medical and pharmacy databases. The criteria of the 23-item audit tool were applied to medical records from case notes in order to quantify adherence to individual guideline criteria. Main outcome measure Frequency of adherence to agreed definitions of medication use quality criteria. Results A total of 1,433 guideline criteria were applied and 1,107 (77.2%, CI: 75.0, 79.4) criteria standards were met with 326 (22.7%, CI: 20.6, 25.0) non-adherences. The overall adherence to guideline criteria was significantly lower for secondary prevention than for primary prevention (74.4 vs. 80.1%, P Conclusion The MAT-CHD highlighted areas for review and possible improvement. The tool can be used in primary care from case record examination and offers a means of co-operation between community pharmacists and general practitioners in clinical guideline implementation. [ABSTRACT FROM AUTHOR]

Effects of vasopressin via V1a- and V2-receptors are closely implicated in a variety of water-retaining diseases and cardiovascular diseases, including heart failure, hyponatraemia, hypertension, renal diseases, syndrome of inappropriate antidiuretic hormone secretion, cirrhosis and ocular hypertension. As vasopressin receptors are found in many different tissues, vasopressin antagonists may benefit the treatment of disorders such as cerebral ischaemia and stroke, Raynaud’s disease, dysmenorrhoea and tocolytic treatment. V1b selective vasopressin antagonists are discussed in terms of their usefulness in the treatment of emotional and psychiatric disorders. The vaptans are vasopressin receptor antagonists with V1a (relcovaptan) or V2 (tolvaptan, lixivaptan) selectivity or non-selective activity (conivaptan) which may be advantageous in some disorders. The V1a/V2 non-selective vasopressin antagonist conivaptan is the first vaptan which is approved by the FDA for the treatment of euvolaemic hyponatraemia. [ABSTRACT FROM AUTHOR]

The electromechanical and -physiological effects of beauvericin were studied in isolated smooth and heart muscle preparations of the guinea pig. Beauvericin concentration-dependently decreased the force of contraction in precontracted (60 mM KCl) terminal ilea with an IC50 of 0.86 μM, and in electrically stimulated (1 Hz) papillary muscles with an IC50 of 18 μM. This negative inotropic effect in papillary muscles was antagonised in a non-competitive way by increased extracellular calcium concentrations. Spontaneous activity in right atria was affected at concentrations >10 μM beauvericin. The negative chronotropic effect was less pronounced than the negative inotropic effect. In action potentials of electrically driven (1 Hz) papillary muscles, 10 μM beauvericin significantly decreased membrane resting potential until unexcitability of the preparation occurred. Despite depolarisation of the membrane the maximum rate of rise of the action potential was not changed. The action potential duration was shortened, but the decrease was only significant at times to 20% and 50% repolarisation. These data, derived from the electrophysiological experiments, not only imply an effect on the calcium current as suggested by the effects on contractility, but also an interaction with the sodium inward and potassium outward currents. [ABSTRACT FROM AUTHOR]

It is absolutely necessary to classify children's fractures for quality controls and clinical research. It is not possible that a classification of children's fractures will follow hierarchies, such as the prognosis of growth, the kind of treatment, the severity of the lesion, the patient's age, as well as medical expenditures and different techniques of therapy. The prognosis of growth is dependent on the patient's age and the localisation of the fracture in the bone and in the skeleton. The kind of treatment is dependent on the extent of displacement as well as on the localisation in the bone. Thus, a classification of children's fractures can only be characterized by the localisation of the fracture and the morphology. In addition, a parameter of “tolerable displacement” should be involved in the classification – as a sign for the possibility of spontaneous correction of displacements by further growth. From the morphological/functional point of view, the epiphyseal plate injuries should be differentiated into a metaphyseal part without proliferation but with mineralisation potential, and an epiphyseal part with proliferation but without mineralisation potential. From this aspect of functional morphology the epiphyseal separation – as a lesion in the metaphyseal part of the physis – belongs to the metaphyseal fractures (so to speak, it is the most peripheral shaft fracture), and the epiphyseal fracture – as a lesion in the epiphyseal part of the physis – belongs to the joint fractures. The localisation is differentiated into 4 main segments: upper arm, forearm, femur, and lower leg. In the segment itself, a subdivision is made into proximal, middle, and distal, with proximal and distal being further differentiated in metaphysis and epiphysis. In addition, it is possible to differentiate between radial and ulnar and tibial and fibular. The morphology is differentiated into typical fractures of the epiphysis, the metaphysis and the shaft fractures as well as avulsion fractures of ligaments, avulsion fractures of muscles and flake fractures. Exceptions in the consequent classification of morphology are only made at the distal end of the humerus and at the neck of the femur. the parameter of “tolerable displacement” showes up already known “ spontaneous corrections” of displacements in the joints, the metaphysis and the epiphysis. The proposed classification should be used in prospective clinical studies to evaluate the prognosis of growth and the results of different therapeutic approaches. [ABSTRACT FROM AUTHOR]

Abstract Immunological abnormalities in schizophrenic patients have been reported for many years. However, the question of whether these parameters are involved in the pathophysiology of the disorder or represent treatment effects is still not answered. We investigated a combination of humoral and soluble immune parameters in 30 unmedicated schizophrenic patients before and during antipsychotic treatment and in 31 healthy controls. The aim of our study was to unravel an underlying immune process, to elucidate the influence of neuroleptic treatment and to identify a subgroup of schizophrenics. Antibodies against human 60-kDa heat-shock protein (HSP60), serum levels of soluble ICAM-1 and IL-2R were determined and correlated with parameters of blood-brain barrier and of psychopathology. In 10% of the drug-free but in 20% of the medicated schizophrenics, especially in females, we observed immunoreactivity against HSP60, high levels of IgG in CSF and a blood-brain barrier impairment. The high HSP antibody titres correlated with high levels of sIL-2R and sICAM-1. Only one of the controls showed antibodies against HSP60. Our results suggest that the observed immunological alterations are more pronounced during neuroleptic treatment than in the drug-free state. Whether or not this differential response to treatment with altered antibody production represents a subgroup of patients has yet to be determined. [ABSTRACT FROM AUTHOR]

Unlike monoclonal antibodies, clinical application of bispecific antibodies has so far lagged behind because of difficult, low-yield production techniques as well as considerable toxicity attributed to bispecific antibody preparations containing immunoglobulin-Fc parts and anti-CD3 homodimers [10, 2]. These difficulties were overcome by recombinant generation of a bispecific single-chain antibody (bscAb) joining two single-chain Fv fragments via a five-amino-acid glycine-serine linker. The anti-CD3 specificity directed against human T cells was combined with another specificity against the epithelial 17-1A antigen. The following domain arrangement was critical in this individual case to obtain a fully functional bscAb: VL17-1A-VH17-1A-VHCD3-VLCD3. The bscAb was expressed in chinese hamster ovary cells with a yield of 15 mg/l culture supernatant whereas numerous attempts to obtain a functional protein expression in Escherichia coli failed. The low-molecular-mass bispecific construct (60 kDa) could easily be purified by its C-terminal histidine tail. The antigen-binding properties are indistinguishable from those of the corresponding univalent single-chain Fv fragments as shown by enzyme immunoassay and flow cytometry. We could show that the bscAb, which lacks Fc parts and anti-CD3 homodimers is highly cytotoxic for 17-1A positive tumor cells in nanomolar concentrations and in the presence of human T cells. Most remarkably, it does not stimulate T lymphocyte proliferation in the absence of tumor cells and, moreover, does not induce CD25 up-regulation and the secretion of potentially toxic lymphokines such as tumor necrosis factor α, interleukin-6 and interferon γ. Maximal cytotoxicity (51Cr release) was achieved without notable costimulation and was not further enhanced by adding costimulatory signals such as those delivered by anti-CD28 antibodies. CD8+ as well as CD4+ T cell subpopulations were recruited to exert cytotoxicity against tumor cells with different kinetics. CD8+ cells induced high 51Cr release within 4 h while CD4+ cells required a 20-h incubation. The systemic application of the 17-1A/CD3-bscAb could be a major improvement in therapy against disseminated micrometastatic tumor cells. A prospective, randomized clinical trial showing that an anti-17-1A monoclonal antibody could prolong survival of colorectal cancer patients after 5 and 7 years, warrants an assessment of the clinical efficacy of this bscAb exhibiting a 1000-fold higher specific cytotoxicity against tumor cells in virto. [ABSTRACT FROM AUTHOR]

Austrian isolates of Fusarium subglutinans and Fusarium proliferatum were studied for their ability to produce beauvericin, moniliformin and fumonisin B1 and B2 under laboratory conditions. Analytical methodology for beauvericin was specially adapted for this task. Our analyses showed that the strains produced beauvericin up to 687 mg /kg maize and moniliformin up to 70 mg/kg. The culture of F. proliferatum in addition produced fumonisin B1 and B2 at levels of 106 and 61 mg/kg, respectively. The preliminary toxicity experiments performed in this study clearly indicated a toxic effect of beauvericin on the contractility of mammalian smooth muscle and thus on mammalian cells. [ABSTRACT FROM AUTHOR]

Copyright of Der Orthopäde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zeitschrift für Angewandte Mathematik und Physik (ZAMP) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

GE 68 ((Rac.)-1-[3-(Phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol hydrochloride) is structurally related to propafenone, and exerts negative inotropic and negative chronotropic effects similar to the parent drug, but lacks any β-adrenoceptor blocking activity contrary to propafenone. Thus, the electrophysiological effects of GE 68 were studied in papillary muscles, left atria, Purkinje fibres, sinoatrial nodes and ventricular myocytes of the guinea-pig heart with the intracellular microelectrode technique and the patch-clamp technique in the cell-attached mode. The decrease of the maximum upstroke velocity (V˙max) by GE 68 (1 to 10 μM) was use- and frequency-dependent. V˙max recovered from the use-dependent block with a time constant of 4.1 ± 0.6 s. In papillary muscles and Purkinje fibres action potential duration was shortened, while it was prolonged in left atria and sinoatrial nodes. Half-maximal steady-state inactivation of the sodium channels was shifted to more negative membrane potentials (control: –91.5 ± 0.8 mV, 10 μM GE 68: –97.9 ± 2.5 mV). The peak of the current-voltage relationship and the reversal potential were not changed by GE 68. The amplitude of the unitary current remained unaltered, while open state probability was decreased. The most striking effect of GE 68 was an increase of the number of sweeps without single channel openings (1 μM: 2 fold, 10 μM: 6 fold). GE 68 also caused a decrease of the mean open times, and an increase of the mean closed times in unmodified and pronase-modified sodium channels. Besides the lack of β-adrenoceptor blocking activity, data present a faster recovery from the use-dependent block by GE 68 and a lower affinity to inactivated sodium channels compared to the reference drug propafenone, as well as differences in the effect on single channel kinetics. [ABSTRACT FROM AUTHOR]

In connection with recent assumptions, that weak vector-bosons might couple only to μ μ currents (and not to e e-ones) the question arises, how to check these bosons, since no colliding μ μ beams are available. We have shown in this paper that this check could be performed by means of the resonance appearing in a pair production process from μ-beams and that this process would work at μ-energies beyond 20 Bev. [ABSTRACT FROM AUTHOR]

This case report describes the delayed presentation of bilateral Morgagni herniae in a 4 1/2-year-old boy with Down's syndrome. The authors emphasize the difficulties in establishing the diagnosis, although ultrasonography appears to be valuable. A review of the literature suggests an association between Morgagni hernias and trisomy 21. [ABSTRACT FROM AUTHOR]