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Biomedical subjects

K Becker

Publications and source records attributed to K Becker.

At least 19 recordsLinked to original sources

Influence of dietary non-essential amino acid profile on growth performance and amino acid metabolism of Nile tilapia, Oreochromis niloticus (L.).

The quality of dietary protein is an important factor influencing the growth performance of fish. To evaluate the quality of protein, the variables commonly studied are the composition of the essential amino acids, the digestibility and the protein use efficiency. The goal of the present experiment was to test the effect of the dietary non-essential amino acid composition on the growth of Nile tilapia (Oreochromis niloticus). The fish were fed three purified diets differing only in their non-essential amino acid composition. The influence of the experimental diets on the growth performance, on the activity of enzymes involved in the amino acid metabolism, aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT), and on whole body delta(15)N values was investigated. Body mass, lipid, protein and energy gain differed significantly between the feeding groups. The activity of ASAT in the whole liver was significantly higher in fish with a positive protein balance compared to fish which lost protein. Whole body delta(15)N values of fish were negatively correlated with their body mass gain. Despite the poor utilisation of synthetic amino acids, the experiment indicates the importance of the dietary non-essential amino acid composition for the growth performance of fish. The study reveals the possibility to trace the utilisation of synthetic amino acids by determining the isotopic composition of dietary amino acids and tissues or whole bodies of animals.

Alanine Transaminase↗

Is the serotonin transporter polymorphism (5-HTTLPR) associated with harm avoidance and internalising problems in childhood and adolescence?

The S allele of the 5-HTTLPR has been associated with anxiety-related behavioural traits and harm avoidance. The 5-HTTLPR polymorphism is suggested to modulate the serotonergic response to stress, meaning that individuals carrying the SS genotype who have significant stress histories may tend to develop depressive symptoms. In the Mannheim Study of Risk Children, which followed a cohort of n = 384 from birth to adolescence, the association of 5-HTTLPR with harm avoidance and internalising problems was examined, including gender and early life stress as possible moderators. Child and adolescent characteristics were assessed using the Junior Temperament and Character Inventory, the Child Behaviour Checklist and the Youth Self Report. Early life stress was determined by a risk index measuring the presence of 11 adversity factors. Results did not reveal an association with 5-HTTLPR genotype. There were no moderating effects of early life stress or gender. An explanation for the negative findings is that the S allele may be a necessary but not sufficient component cause in a composite risk factor.

Adolescent↗

Deposition of fluoride on enamel surfaces released from varnishes is limited to vicinity of fluoridation site.

The aim of the in-situ study was to determine fluoride uptake in non-fluoridated, demineralized enamel after application of fluoride varnishes on enamel samples located at various distances from the non-fluoridated samples. All enamel samples used were demineralized with acidic hydroxyethylcellulose before the experiment. Intra-oral appliances were worn by ten volunteers in three series: (1, Mirafluorid, 0.15% F; 2, Duraphat, 2.3% F and 3, unfluoridated controls) of 6 days each. Each two enamel samples were prepared from 30 bovine incisors. One sample was used for the determination of baseline fluoride content (BFC); the other was treated according to the respective series and fixed in the intra-oral appliance for 6 days. Additionally, from 120 incisors, each four enamel samples were prepared (one for BFC). Three samples (a-c) were placed into each appliance at different sites: (a) directly neighboured to the fluoridated specimen (=next), (b) at 1-cm distance (=1 cm) and (c) in the opposite buccal aspect of the appliance (=opposite). At these sites, new unfluoridated samples were placed at days 1, 3 and 5, which were left in place for 1 day. The volunteers brushed their teeth and the samples with fluoridated toothpaste twice per day. Both the KOH-soluble and structurally bound fluoride were determined in all samples to determine fluoride uptake and were statistically analyzed. One day, after fluoridation with Duraphat, KOH-soluble fluoride uptake in specimen a (=next) was significantly higher compared to the corresponding samples of both the control and Mirafluorid series, which in turn were not significantly different from each other. At all other sites and time points, fluoride uptake in the enamel samples were not different from controls for both fluoride varnishes. Within the first day after application, intra-oral-fluoride release from the tested fluoride varnish Duraphat leads to KOH-soluble fluoride uptake only in enamel samples located in close vicinity to the fluoridation site.

Adult↗

Interaction between the dopamine D4 receptor and the serotonin transporter promoter polymorphisms in alcohol and tobacco use among 15-year-olds.

Early onset of alcohol and tobacco use during adolescence increases the risk for establishing a substance use disorder in adulthood. Both alcohol and nicotine stimulate the dopamine (DA) and the serotonin (5-HT) systems. The DA system has been implicated in the mediation of the rewarding effects of self-administered drugs of abuse. A possible role of an interaction between these neurotransmitter systems in substance use behavior has been suggested but is as yet unknown. The present study was designed to examine the influence of the DA D4 receptor (DRD4) and the serotonin transporter (5-HTT) genotype and their interaction on adolescent alcohol and tobacco experimentation. Participants were from a longitudinal study of a birth cohort consisting initially of 384 children from a high-risk community sample. At the age of 15 years, adolescents completed a self-report questionnaire measuring tobacco and alcohol consumption. DNA was taken from 305 participants (146 boys, 159 girls) and genotyped for the DRD4 exon III and the 5-HTTLPR polymorphisms. The DRD4 7-repeat allele was associated with greater smoking and drinking involvement in boys. In girls, a significant DRD4 x 5-HTT interaction was detected. Girls without the DRD4 7-repeat allele and who were homozygous for the long allele of 5-HTTLPR displayed the highest smoking and drinking activity. The genetic and potential molecular background underlying adolescent vulnerability to substance abuse is discussed.

Adolescent↗

Association of DRD4 exon III polymorphism with auditory P300 amplitude in 8-year-old children.

OBJECTIVES: The present study was designed to investigate the association between the DRD4 genotype and auditory P300 amplitudes in a high-risk community sample. METHODS: ERPs were elicited in 197 eight-year-olds (98 boys, 99 girls) using a passive and an active oddball task. Auditory stimuli of 60 dB HL were presented binaurally at 1000 (standard stimulus) and 2000 Hz (target stimulus), at a relative frequency ratio of 80:20. Two trial blocks of 250 stimuli each were collected. P300 amplitudes were analyzed from Fz, Cz and Pz. DNA was genotyped for the DRD4 exon III polymorphism. RESULTS: A pattern of significant interactions of the DRD4 genotype with gender and experimental conditions was obtained. In both the active and the passive task, boys with at least one copy of the DRD4 7-repeat allele displayed significantly lower P300 amplitudes during the second trial block than boys carrying other alleles. CONCLUSIONS: This finding provides further evidence supporting a role of P300 amplitude reduction as an endophenotype for disinhibited psychopathology.

Alleles↗

Early neonatal and postweaning social emotional deprivation interferes with the maturation of serotonergic and tyrosine hydroxylase-immunoreactive afferent fiber systems in the rodent nucleus accumbens, hippocampus and amygdala.

The impact of early emotional experience on the development of serotonergic and dopaminergic fiber innervation of the nucleus accumbens, hippocampal formation and the amygdala was quantitatively investigated in the precocious rodent Octodon degus. Two animal groups were compared: 1) degus which were repeatedly separated from their parents during the first three postnatal weeks, after weaning they were individually reared in chronic social isolation and 2) controls which were reared undisturbed with their families. In the deprived animals 5-hydroxytryptamine-immunoreactive fiber densities were increased in the core region of the nucleus accumbens (up to 126%), in the central nucleus of the amygdala (up to 112%) and in the outer subregion of the dentate gyrus stratum moleculare (up to 149%), whereas decreased fiber densities were detected in the dentate subgranular layer (down to 86%) and in the stratum lacunosum of the hippocampal cornu ammonis region 1 (down to 86%). Tyrosine hydroxylase-immunoreactive fiber densities were increased in the core (up to 115%) and shell region (up to 113%) of the nucleus accumbens of deprived animals, whereas decreased fiber densities (down to 84%) were observed in the hilus of the dentate gyrus. In the stratum granulosum and subgranular layer the fiber densities increased up to 168% and 127% respectively. In summary, these results indicate that the postnatal establishment of the monoaminergic innervation of limbic areas is modulated in response to early emotional experience, and that this environmental morphological adaptation is highly region specific.

Adaptation, Physiological↗

Interleukin-1 alpha mediates the growth proliferative effects of transforming growth factor-beta in p21 null MCF-10A human mammary epithelial cells.

Transforming growth factor-beta type 1 (TGF-beta) has been implicated as both a tumor suppressor and a tumor promoter in many solid epithelial cancers. We have previously demonstrated that the cyclin dependent kinase (CDK) inhibitor p21 acts as a molecular switch in determining a growth inhibitory versus growth proliferative response to TGF-beta in the spontaneously immortalized human mammary epithelial cell line MCF-10A. We now demonstrate that this proliferative effect of TGF-beta is mediated through the proinflammatory cytokine, interleukin-1alpha (IL-1alpha). Using gene expression array analysis, we identified IL-1alpha as a cytokine specifically upregulated only in cells lacking p21 and only upon TGF-beta stimulation. Cell proliferation assays verified that recombinant IL-1alpha was capable of inducing a growth proliferative response in p21 null MCF-10A cells, while neutralizing antibodies against IL-1alpha prevented the growth proliferative effects of TGF-beta. Mechanistically, both the CDK and proliferating cell nuclear antigen (PCNA) inhibitory functions of p21 were responsible for preventing TGF-beta induced cell proliferation, but only PCNA inhibition by p21 regulated IL-1alpha gene expression. These studies demonstrate a novel role for IL-1alpha in mediating a proliferative response to TGF-beta signaling, and suggest that therapies directed against IL-1alpha could abate the growth proliferative effects of TGF-beta without compromising its tumor suppressive function.

Cell Line, Tumor↗

Specific inhibitors of Plasmodium falciparum thioredoxin reductase as potential antimalarial agents.

Plasmodium falciparum thioredoxin reductase (PfTrxR: NADPH+Trx(S)2+H+<-->NADP++Trx(SH)2) is a high Mr flavin-dependent TrxR that reduces thioredoxin (Trx) via a CysXXXXCys pair located penultimately to the C-terminal Gly. In this respect, PfTrxR differs significantly from its human counterpart which bears a Cys-Sec redox pair at the same position. PfTrxR is essentially involved in antioxidant defense and redox regulation of the parasite and has been previously validated by knock-out studies as a potential drug target for malaria chemotherapy. Moreover, human TrxR is present in most cancer cells at levels tenfold higher than in normal cells. Here we report the discovery of a series of potent inhibitors of PfTrxR. The three most promising inhibitors, 3(IC50(PfTrxR)=2 microM and IC50(hTrxR)=50 microM), 7(IC50(PfTrxR)=2 microM and IC50(hTrxR)=140 microM), and 11(IC50(PfTrxR)=0.5 microM and IC50(hTrxR)=4 microM) were selective for the parasite enzyme. Detailed mechanistic characterization of the effects of these compounds on the PfTrxR-catalyzed reaction showed clear uncompetitive inhibition with respect to both substrate and cofactor. For the most specific PfTrxR inhibitor 7, an alkylation mechanism study based on a thiol conjugation model was performed. Furthermore, all three compounds were active in the lower micromolar range on the chloroquine-resistant P. falciparum strain K1 in vitro.

Animals↗

A rare case of primary rectal rhabdomyosarcoma in an adult.

We report an extremely rare case (1:200 000) of primary rectal rhabdomyosarcoma (RMS) in an adult. In the literature, this case report is the first one dealing with an adult patient. The diagnosis was assessed by computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), endoscopy and histological examination. Neoadjuvant systemic chemotherapy with adriamycin and isofosfamide followed by anterior rectum resection was performed. This article should implicate RMS as a rare differential diagnosis of atypical rectal tumours in adults.

Adult↗

[Interdisciplinary recommendations concerning the therapy for hormone-refractory prostatic carcinoma].

Therapy with Docetaxel for hormone-refractory prostatic carcinoma has for the first time led to an increase in the survival time. Docetaxel has become established as a standard therapy for his indication. Since hormone-refractory prostatic carcinoma is not uniformly defined and is thus for prognosis not a homogeneous entity, the prospects at the start of chemotherapy are uncertain. In the summer of 2005 these questions were addressed in an interdisciplinary consensus conference. It was agreed that the 3-week scheme with 75 mg/m (2) as standard and the indication for symptomatic patients were above question. Opinions differed with regard to the use of chemotherapy in asymptomatic patients. In addition, recommendations for the performance and monitoring of the therapy were formulated.

Antineoplastic Agents, Hormonal↗

Induction of CXC chemokines in A549 airway epithelial cells by trypsin and staphylococcal proteases - a possible route for neutrophilic inflammation in chronic rhinosinusitis.

While various microorganisms have been recovered from patients with chronic rhinosinusitis, the inflammatory impact of virulence factors, in particular proteases from Staphylococcus aureus and coagulase negative staphylococci on the nasal epithelium, has not yet been investigated. Expression of CXC chemokines was determined in the epithelium of patients with chronic rhinosinusitis by immunohistochemistry. In a cell culture system of A549 respiratory epithelial cells, chemokine levels were quantified by enzyme-linked immunosorbent assay (ELISA) after stimulation with supernatants originating from three different staphylococcal strains or with trypsin, representing a serine protease. Inhibition experiments were performed with prednisolone, with the serine protease inhibitor 4-(2-aminoethyl)-benzenesulphonylfluoride (AEBSF) and with the nuclear transcription factor (NF)-kappaBeta inhibitor (2E)-3-[[4-(1,1-dimethylethyl)phenyl]sulphonyl]-2-propenenitrite (BAY) 11-7085. Electromobility shift assays (EMSA) were used to demonstrate NF-kappaB-dependent protein synthesis. CXC chemokines interleukin (IL)-8, growth-related oncogene alpha (GRO-alpha) and granulocyte chemotactic protein-2 (GCP-2) were expressed in the patients' epithelium whereas epithelial cell-derived neutrophil attractant 78 (ENA-78) was rarely detected. In A549 cells, chemokines IL-8, ENA-78 and GRO-alpha but not GCP-2 were induced by trypsin and almost equal levels were induced by staphylococcal supernatants. IL-8, GRO-alpha and ENA-78 synthesis was suppressed almost completely by AEBSF and BAY 11-7085, whereas prednisolone reduced chemokine levels differentially dependent on the supernatant added. CXC chemokines were detectable in the epithelium of patients with chronic rhinosinusitis. Staphylococcal serine proteases induced CXC chemokines in A549 cells, probably by the activation of proteases activated receptors, and thus might potentially be involved in neutrophilic inflammation in chronic sinusitis.

Adult↗

The dynamics of major fibrolytic microbes and enzyme activity in the rumen in response to short- and long-term feeding of Sapindus rarak saponins.

AIMS: To investigate the short- and long-term effects of an extract of Sapindus rarak saponins (SE) on the rumen fibrolytic enzyme activity and the major fibrolytic micro-organisms. METHODS AND RESULTS: Two feeding trials were conducted. In the short-term trial, four fistulated goats were fed a basal diet containing sugar cane tops and wheat pollard (65:35, w/w) and were supplemented for 7 days with SE at a level of 0.6 g kg(-1) body weight. Rumen liquor was taken before, during and after SE feeding. In the long-term trial, 28 sheep were fed the same basal diet as the goats and were supplemented for 105 days with 0.24, 0.48 and 0.72 g kg(-1) body mass of the extract. Rumen liquor was taken on days 98 and 100. Protozoal numbers were counted under the microscope. Cell wall degradation was determined by enzyme assays and the major fibrolytic micro-organisms were quantified by dot blot hybridization. Sapindus extract significantly depressed rumen xylanase activity in both trials and carboxymethylcellulase activity in the long-term trial (P < 0.01). Fibrobacter sp. were not affected by the SE in both trials, while ruminococci and the anaerobic fungi showed a short-term response to the application of saponins. Protozoal counts were decreased only in the long-term trial with sheep. CONCLUSION: These data suggest that there is an adaptation of Ruminococcus albus, Ruminococcus flavefaciens and Chytridiomycetes (fungi) to saponin when fed over a long period. The fact that no correlation between the cell wall degrading enzyme activities and the cell wall degrading micro-organisms was observed suggests that the organisms tracked in this experiment are not the only key players in ruminal cell wall degradation. SIGNIFICANCE AND IMPACT OF THE STUDY: Sapindus rarak saponins partially defaunate the rumen flora. Their negative effect on cell wall degradation, however, is not related to rumen organisms currently recognized as the major cell wall degrading species. The adaptation of microbes in the long-term feeding experiment suggests that the results from short-term trial on the ruminal microbial community have to be interpreted carefully.

Animal Feed↗

Recovery of peroxides in saliva during home bleaching--influence of smoking.

UNLABELLED: The study aimed at determining hydrogen peroxide recovery in saliva during use of different home bleaching products by smokers and non-smokers. Peroxide recovery was evaluated with respect to the safe level reported in the literature. Determination of peroxide levels in saliva was performed with peroxidase, phenol and 4-aminoantipyrin in a photometric method. Four different bleaching regimens were used by 10 smokers and 10 non-smokers: Whitestrips, Vivastyle (tray-based) and two paint-on products (Crest Night Effects, Colgate Simply White). Whole saliva was collected and total amount of peroxide (mg) released during the 60 min bleaching period was determined: Colgate Simply White: 2.67 +/-0.88 (non-smokers); 2.66 +/- 1.17 (smokers); Crest Night Effects: 0.23 +/- 0.13 (non-smokers); 0.25 +/-0.16 (smokers); Vivastyle: 2.47 +/- 0.82 (non-smokers), 2.44 +/- 1.31 (smokers); Whitestrips: 1.39 +/- 0.62 (non-smokers), 2.02 +/- 1.86 (smokers). In terms of amount of peroxide kg(-1) body weight the bleaching systems led to a single exposure of 0.004-0.046 mg kg(-1), which is distinctly less than safe daily dose of 0.26 mg kg(-1) day(-1), if calculated for a small person (58 kg). The criterion smoker versus non-smokers had no influence on peroxide levels in the oral cavity. CONCLUSION: Smoking did not appear to impact the anti-oxidant defence capacity of the oral cavity with respect to degrading peroxides released from bleaching products. Significantly lower amounts of peroxides were detected in saliva during application of the paint-on product Crest Nights Effects compared with the other bleaching systems.

Carbonates↗

Prevention of erosion and abrasion by a high fluoride concentration gel applied at high frequencies.

The aim of this study was to determine maximum attainable protection of enamel from erosion and erosion abrasion using a highly fluoridated gel with and without additional fluoride from toothpaste. Thirty-six bovine enamel specimens were subjected to six erosive attacks per day (1% citric acid with pH 2.3 for 30 s), while the rest of the day the specimens were in artificial saliva. There were four treatment groups (9 specimens in each group): fluoride-free toothpaste/saliva slurry twice daily (group T0), fluoride-containing toothpaste/saliva slurry twice daily using 1,250 ppm F toothpaste (group TF), fluoride-containing toothpaste/saliva slurry twice per day plus application of a highly fluoridated gel (12,500 ppm F) twice a day for 120 s (group 2F) and a group with gel application 8 times a day (group 8F). Additionally, half of each specimen in all groups was subjected to brushing abrasion during application of the toothpaste/saliva slurry. Brushing abrasion alone led to no observable enamel loss measured with profilometry. After 14 days of cycling of erosion without toothbrushing abrasion, high-fluoride gel application 2 or 8 times daily showed significantly less enamel loss (median 24/19 microm) than with toothpaste with or without fluoride (41/45 microm). After 14 days of cycling of erosion and toothbrushing abrasion, gel application 2 or 8 times daily (33/29 microm) showed significantly less enamel loss than toothpaste with or without fluoride (57/62 microm). We conclude that a highly fluoridated acidic gel is able to protect enamel from erosion and toothbrushing abrasion while fluoridated tooth paste provides little protection.

Amines↗

Effect of a casein/calcium phosphate-containing tooth cream and fluoride on enamel erosion in vitro.

The aim of this study was to determine whether a tooth cream containing casein/calcium phosphate (CasCP) protects enamel against erosion. Sixty bovine enamel specimens were prepared for profilometry and distributed into five groups. Specimens were rinsed with artificial saliva interrupted by 1% citric acid (pH 2.3) for 30 s 6 times daily for 14 days. Group 1 (n=12) was not treated (control); in group 2 (n=12) CasCP was applied for 120 s twice daily; in group 3 (n=12) 250 ppm fluoride as NaF was applied for 120 s twice daily; in group 4 (n=12) CasCP was applied for 120 s, then 250 ppm fluoride for 120 s twice daily, and in group 5 (n=12) amine fluoride (AmF) gel (12,500 ppm fluoride) was applied for 120 s twice daily. Differences between groups with respect to erosive enamel loss (profilometrically determined depth after 7 and 14 days) were tested by the Mann-Whitney test (alpha=0.05). After 7/14 days' erosive cycling, specimens treated with AmF gel showed significantly less enamel loss (18.5/35.5 microm; medians) than those treated with CasCP (25.5/46.9 microm), 250 ppm fluoride (25.0/ 40.9 microm), CasCP and 250 ppm fluoride (23.9/47.4 microm) or with no treatment (26.3/49.8 microm). It is concluded that highly fluoridated acidic AmF gel can protect enamel against erosion while CasCP, 250 ppm fluoride or a combination of CasCP and 250 ppm fluoride provide little protection.

Amines↗

Emerging Staphylococcus species as new pathogens in implant infections.

The vast use of prosthetic materials in medicine over the last decades has been accompanied by the appearance of new opportunistic pathogens previously considered incapable of causing infections with significant morbidity and/or mortality. In this regard, the genus Staphylococcus enlisting numerous species usually characterized by a saprophytic habit covers a special role. Apart from Staphylococcus aureus and Staphylococcus epidermidis, well known for their large prevalence in implant-related infections, a number of further staphylococcal species are progressively being indicated for their pathogenic potential. The increasing attention on these opportunistic bacteria is due to an ever growing number of clinical reports, which is also deriving from a more accurate identification of these species with currently available techniques. This synopsis intends to offer an overview on recently emerging coagulase-negative staphylococci (CoNS) as well as coagulase-positive/-variable staphylococci exhibiting distinct traits of virulence, pathogenicity, and epidemiologic impact depending among others on the medical field, the type of prosthetic device and its anatomic location.

Communicable Diseases, Emerging↗

Interference with redox-active enzymes as a basis for the design of antimalarial drugs.

Antimalarial drugs are urgently and continuously required. Parasite enzymes involved in antioxidant defence represent interesting target molecules for rational drug development. Here we summarize the currently available data on structural, biochemical, and functional properties of these proteins in an attempt to evaluate and compare their potential as drug targets.

Amino Acid Sequence↗