RESUMO
BACKGROUND: Clinical risk factors for postoperative nausea and vomiting (PONV) are evaluated with the Apfel score, however patients with low Apfel scores still experience PONV suggesting a genetic predisposition. PONV risk associates with specific M3 muscarinic acetylcholine receptor (CHRM3) rs 2165870 polymorphism. We investigated whether the Apfel score and this genetic variation independently contribute to PONV risk and whether prophylaxis reduces PONV in patients with low Apfel score but at high genetic risk. METHODS: In a prospective, controlled study, 454 subjects undergoing elective surgery were genotyped for rs2165870 and its association with PONV was investigated with log-binomial regression analysis. Subjects were randomised to receive acustimulation/dexamethasone, acustimulation/vehicle, sham acustimulation/dexamethasone, or sham acustimulation/vehicle to investigate their effects on PONV risk. RESULTS: Early PONV occurred in 37% of subjects. The rs2165870 genotype distribution was GG in 191, GA in 207, and AA in 56 subjects. The CHRM3 polymorphism was associated with a relative risk (RR) of 1.5 for GA vs GG [95% confidence interval (CI): 1.1-1.9; P=0.003] and 1.6 for AA vs GG (95% CI: 1.1-2.2; P=0.009) genotypes to develop PONV, and this was independent from the Apfel score (RR per Apfel point: 1.3, 95% CI: 1.2-1.5; P<0.0001). While dexamethasone and acustimulation each reduced the PONV risk by 30% in AA genotype carriers with low Apfel score, combined therapy reduced the risk by 86% (P=0.015). CONCLUSIONS: The CHRM3 polymorphism and the Apfel score independently predict PONV susceptibility. Dexamethasone/acustimulation should be considered in patients with low Apfel score but at high genetic risk. CLINICAL TRIAL REGISTRATION: DRKS00005664.
Assuntos
Polimorfismo Genético/genética , Náusea e Vômito Pós-Operatórios/epidemiologia , Náusea e Vômito Pós-Operatórios/genética , Receptor Muscarínico M3/genética , Terapia por Acupuntura , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia Geral , Antieméticos , Terapia Combinada , Dexametasona , Procedimentos Cirúrgicos Eletivos , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Náusea e Vômito Pós-Operatórios/prevenção & controle , Valor Preditivo dos Testes , Estudos Prospectivos , Risco , Adulto JovemRESUMO
INTRODUCTION: The aim of this study was to obtain the diagnostic, therapeutic and prophylactic approach among Swiss veterinary practitioners in cows with parturient hypocalcemia. All members of the Association for Ruminant Health were contacted per e-mail. The survey was completed by 108 (28%) of 393 that were contacted. According to the questionnaire responses, the typical presentation of a parturient paresis cow is a pluriparous middle-yielding dairy cow one day post-partum in sternal recumbency with normal consciousness. The diagnosis is usually based upon the medical history. Therapy of parturient paresis consists of mixed infusions (with calcium, phosphorus, magnesium or glucose) as well as oral preparations with calcium. The veterinarians estimate that 25-50% of the cows treated for parturient paresis need more than one treatment and that one case of parturient paresis costs CHF 200-300. Prophylactic treatments are usually used for cows, which have suffered from parturient paresis in the previous lactation, elder cows (≥ 3 lactations) as well as cows with a high body condition score (> 3.25). Prophylactic measures used by the veterinarians are vitamin D3 injections and oral preparations with calcium. They recommended a special diet, for example a low calcium diet ante-partum.
INTRODUCTION: Le but de la présente enquête en ligne était de relever les méthodes de diagnostic, de traitement et de prophylaxie utilisées en pratique en matière de parésie puerpérale hypocalcémique. Tous les membres de l'Association suisse pour la santé des ruminants ont été contactés par courriel. Sur les 393 questionnaires envoyés, 108 (28%) ont été remplis complètement et exploités. L'anamnèse typique est un animal pluripare avec une production de parésie puerpérale, il est mentionné des animaux pluripares avec une production laitière moyenne, incapables de se lever un jour après le vêlage et présentant un état de conscience normal. Le diagnostic est fréquemment posé sur la base de l'anamnèse. Les vaches laitières concernées sont traitées avec des perfusions mixtes (produits à base de calcium et de phosphore, parfois avec du magnésium et du glucose) et des préparations de calcium orales. Les vétérinaires estiment que 25 à 50% des vaches nécessitent plusieurs traitements et que les coûts totaux par animal de l'ordre de CHF 200 à 300. Du point de vue prophylactique, ce sont principalement les animaux ayant déjà souffert d'une parésie lors de la lactation précédente ainsi que les vaches plus âgées (3ème lactation et plus) et celles présentant un indice de condition élevé (> 3.25) qui sont traitées. Les vétérinaires utilisent pour cette prophylaxie des injections de vitamine D3 ainsi que des préparations orales de calcium et/ou conseillent aux propriétaires une alimentation pauvre en calcium ante partum.
Assuntos
Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/terapia , Indústria de Laticínios/métodos , Paresia Puerperal/diagnóstico , Paresia Puerperal/terapia , Médicos Veterinários/estatística & dados numéricos , Animais , Cálcio/uso terapêutico , Bovinos , Doenças dos Bovinos/tratamento farmacológico , Doenças dos Bovinos/prevenção & controle , Colecalciferol/uso terapêutico , Estudos Transversais , Feminino , Humanos , Paresia Puerperal/tratamento farmacológico , Paresia Puerperal/prevenção & controle , Gravidez , Inquéritos e Questionários , SuíçaRESUMO
BACKGROUND: The minor allele of two caspase 8 polymorphisms, namely CASP8 -652 6N InsDel (rs3834129) and CASP8 Asp302His (rs1045485), were repeatedly associated with reduced breast cancer susceptibility. Contrarily, the presence of the -652 6N Del or the CASP8 302His variant was reported to be an unfavorable prognostic factor in colorectal cancer or neuroblastoma. However, prognostic relevance of these genetic variants for breast cancer is completely unknown and is therefore adressed by the current study. METHODS: Genotyping was performed by pyrosequencing. Caspase 8 mRNA expression was quantified by comparative RT-qPCR. RESULTS: We observed an allele-dose dependent association between CASP8 -652 6N InsDel and caspase 8 mRNA expression in breast cancer tissue, with homozygous deletion carriers showing lowest relative caspase 8 expression (p = 0.0131). Intriguingly, the presence of the -652 6N Del or the 302His variant was shown to be a negative prognostic factor for breast cancer in terms of an allele-dose dependent influence on overall survival (OS, p = 0.0018, p = 0.0150, respectively). Moreover, both polymorphisms were independent predictors of OS after adjusting for co-variats (p = 0.007, p = 0.037, respectively). Prognostic relevance of both polymorphisms were confirmed to be independent from each other and combined analysis of diplotypes revealed an additive influence upon OS (p = 0.0002). CONCLUSION: This is the first report, showing negative and independent prognostic impact of the CASP8 -652 6N Del and the 302His variant for breast cancer. Our data provide rationale to further validate clinical utility of these polymorphisms for breast cancer and to extend this investigation to a broad scope of other malignancies.
Assuntos
Neoplasias da Mama/genética , Caspase 8/genética , Predisposição Genética para Doença/genética , Adulto , Idoso , Neoplasias da Mama/mortalidade , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo RealRESUMO
The peptide hormone calcitonin (CT) is known to inhibit bone resorption and has previously been shown also to prevent particle-induced osteolysis, the leading cause of revision arthroplasty. In the present study, the influence of human CT on the initial inflammatory response to particulate wear debris or bacterial endotoxins, ultimately leading to osteoclast-mediated bone resorption, was analysed in human THP-1 macrophage-like cells. The cells were activated with either ultra-high molecular weight polyethylene (UHMWPE) particles or bacterial lipopolysaccharides (LPS) in order to simulate an osteolysis-associated inflammatory response. The cells were simultaneously treated with human CT (10(-9) M). Cytokine production of tumour necrosis factor (TNF)-α was quantified on both RNA and protein levels while interleukins (IL)-1ß and IL-6 were measured as secreted protein only. Stimulation of the cells with either particles or LPS led to a dose- and time-dependent increase of TNF-α mRNA production and protein secretion of TNF-α, IL-1ß, and IL-6. Application of CT mostly enhanced cytokine production as elicited by UHMWPE particles while a pronounced transient inhibitory effect on LPS-induced inflammation became evident at 24 h of incubation. Human CT displayed ambivalent effects on the wear- and LPS-induced production of pro-inflammatory cytokines. Thereby, the peptide primarily upregulated particle-induced inflammation while LPS-induced cytokine secretion was temporarily attenuated in a distinct manner. It needs to be evaluated whether the pro- or anti-inflammatory action of CT contributes to its known anti-resorptive effects. Thus, the therapeutic potential of the peptide in the treatment of either particle- or endotoxin-mediated bone resorption could be determined.
Assuntos
Reabsorção Óssea/tratamento farmacológico , Calcitonina/metabolismo , Citocinas/metabolismo , Endotoxinas/farmacologia , Inflamação/patologia , Macrófagos/metabolismo , Monócitos/metabolismo , Fragmentos de Peptídeos/farmacologia , Western Blotting , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Células Cultivadas , Citocinas/genética , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Monócitos/citologia , Monócitos/efeitos dos fármacos , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteólise , Fragmentos de Peptídeos/administração & dosagem , Polietilenos/química , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
INTRODUCTION: The safety of supplementing broiler feed with a standardised herbal extract, Solanum Glaucophyllum Standardised Leaves (SGSL) containing glycosylated 1a,25-dihydroxyvitamin D3 (1,25(OH)2D3) and standardised to contain 10 µg/g 1,25(OH)2D3 equivalent, was examined in two studies. In a first study, we examined the potential of SGSL to substitute vitamin D3 (VD3) and the tolerated dose range of SGSL when applied without concomitant VD3 by analyzing performance and blood chemical parameters after 14, 25 and 38 days on diets containing two doses of SGSL (1 and 10 g/kg feed) as source of 1,25(OH)2D3. In the second study, the no adverse effect level of SGSL was determined by analyzing the same parameters after 35 days on diets containing basic VD3 supply and in addition 0.2, 1.0, 2.0 and 4.0 g of SGSL/kg feed. We showed that SGSL was able to substitute VD3 in broilers as far as the performance parameters were concerned. Also, we found that the no adverse effect level is at least 4 g SGSL/kg feed when used with moderate doses of VD3. This is 20 times higher than the upper limit of the commercially recommended dose. We concluded that SGSL is a safe feed additive to use in broiler chicken.
INTRODUCTION: Dans la cadre de deux études, on a examiné la sécurité de l'extrait de plante standardisé Solanum Glaucophyllum Standardised Leaves (SGSL) comme complément alimentaire chez les poulets d'engraissement. Le SGSL contient de façon standardisée 10 µg/g de 1,25(OH)2D3 sous forme glycolysée. Dans la première étude, on a examiné le potentiel d'action en tant que remplaçant de la vitamine D3 (VD3) et le domaine de dose de SGSL toléré, ceci en ne donnant que du SGSL sans addition de VD3 . On a examiné la performance et les paramètres de chimie sanguine après 14, 25 et 38 jours d'affouragement de deux doses différentes (1 et 10 g/kg d'aliment) de SGSL comme source de 1,25(OH)2D3. Dans la seconde étude, on a recherché le No Adverse Effect Level sur la base des mêmes paramètres après 35 jours avec une alimentation contenant, outre une quantité modérée de VD3, 0.2, 1.0, 2.0 et 4.0 g de SGSL/kg. On a pu démontrer que le SGSL peut remplacer la vitamine D3 chez les poulets d'engraissement en ce qui concerne les performances étudiées. Le No Adverse Effect Level se situait aux environs d'au moins 4g de SGSL/kg d'aliment lorsqu'il était associé avec des quantités modérées de Vitamine D3. Cette dose est vingt fois supérieure à la dose maximale recommandée par le fabriquant. Nous en déduisons que le SGSL est un complément alimentaire sûr pour les poulets d'engraissement.
Assuntos
Ração Animal , Calcitriol/normas , Galinhas , Alimentos Fortificados/normas , Extratos Vegetais/normas , Solanum glaucophyllum/química , Animais , Calcitriol/administração & dosagem , Calcitriol/sangue , Galinhas/sangue , Extratos Vegetais/administração & dosagem , Extratos Vegetais/sangue , SegurançaRESUMO
AIMS: To construct and validate the recombinase-based in vivo expression technology (R-IVET) tool in Streptococcus thermophilus (ST). METHODS AND RESULTS: The R-IVET system we constructed in the LMD-9 strain includes the plasmid pULNcreB allowing transcriptional fusion with the gene of the site-specific recombinase Cre and the chromosomal cassette containing a spectinomycin resistance gene flanked by two loxP sites. When tested in M17 medium, promoters of the genes encoding the protease PrtS, the heat-shock protein Hsp16 and of the lactose operon triggered deletion of the cassette, indicating promoter activity in these conditions. The lactose operon promoter was also found to be activated during the transit in the murine gastrointestinal tract. CONCLUSIONS: The R-IVET system developed in ST is relatively stable, functional, very sensitive and can be used to assay activity of promoters, which are specifically active in in vivo conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: This first adaptation of R-IVET to ST provides a highly valuable tool allowing an exploration of the physiological state of ST in the GIT of mammals, fermentation processes or dairy products.
Assuntos
Integrases/genética , Óperon Lac , Regiões Promotoras Genéticas , Streptococcus thermophilus/genética , Animais , Técnicas Genéticas , Vetores Genéticos , Proteínas de Choque Térmico/genética , Camundongos , Camundongos Endogâmicos C57BL , PlasmídeosRESUMO
1. Chemical characterisation of an extract of Solanum glaucophyllum (SG) leaves affirmed the predominant presence of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) glycosides. The compound 1-(ß-D-glucopyranosyl)-1α,25-dihydroxycholecalciferol was isolated for the first time from a natural source. 2. Vitamin D activity of the extract was confirmed by the calcaemic properties shown in a quail eggshell bioassay. The results suggested a 1,25(OH)2D3 bioavailability of approximately 15%. 3. A broiler feeding experiment replicated in time was carried out with 6 treatments. A basic control diet containing 25 µg cholecalciferol/kg was supplemented with 2.5 and 5 µg free 1,25(OH)2D3/kg, with a product based on dried SG leaves (Panbonis) providing 10 µg of 1,25(OH)2D3-glycosides/kg, with two concentrations of an SG extract providing 8.8 and 37.8 µg of 1,25(OH)2D3-glycosides/kg. 4. Tibia breaking strength and stiffness were numerically greater in all treatment groups with free 1,25(OH)2D3 and with SG products compared to controls, though the overall treatment effects only had probabilities in the range of P = 0.07 to P = 0.1. Values for both characteristics increased progressively, with additions of synthetic 1,25(OH)2D3; values with the dried SG product were similar to those with 5 µg synthetic 1,25(OH)2D3/kg. 5. Plasma calcium was mildly elevated (P < 0.05) in treatment groups. The SG extract treatment containing 37.8 µg 1,25(OH)2D3/kg gave the highest plasma calcium concentration and lowest bodyweight, signs of marginal hypervitaminosis D. Plasma 1,25(OH)2D3 concentrations were in the normal range for all treatments. 6. Tibial dyschondroplasia occurred in only one replicate. The incidences were 31% in controls but considerably lower or zero with all other treatments. 7. Bioavailability of 1,25(OH)2D3 in the SG product seemed to be higher in broiler chickens than in Japanese quails. 8. It is concluded that the inclusion of the dried SG product as a source of vitamin D3 in broiler diets at a dietary concentration of 1 g/kg, providing 10 µg 1,25(OH)2D3/kg, is safe and efficacious.
Assuntos
Calcitriol/análogos & derivados , Galinhas/metabolismo , Coturnix/metabolismo , Extratos Vegetais/farmacologia , Solanum glaucophyllum/química , Tíbia/química , Fosfatase Alcalina/sangue , Animais , Calcitriol/administração & dosagem , Calcitriol/farmacologia , Cálcio/sangue , Casca de Ovo/efeitos dos fármacos , Feminino , Histocitoquímica/veterinária , Masculino , Fosfatos/sangue , Extratos Vegetais/administração & dosagem , Folhas de Planta/química , Distribuição AleatóriaRESUMO
There are high interindividual differences regarding the intensity of withdrawal symptoms. in opiate addicts. This study was carried out in order to test whether the intensity of withdrawal is influenced by the 393T>C polymorphism of the GNASI gene. Only patients addicted exclusively to opiates were included. Thirty-three out of 39 patients undergoing inpatient detoxification treatment achieved a drug-free state. During the most intense period of withdrawal (stop of methadone and following days) TT homozygotes (n=4) had a significantly higher pulse rate (primary outcome criterion) than C-allele carriers (n=29). This study and a previous study about GNB3 825C> T underline the possible role of G-protein polymorphisms in the interindividual variability of opiate withdrawal.
Assuntos
Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Dependência de Heroína/terapia , Polimorfismo de Nucleotídeo Único , Síndrome de Abstinência a Substâncias/genética , Síndrome de Abstinência a Substâncias/fisiopatologia , Adulto , Cromograninas , Feminino , Estudos de Associação Genética , Alemanha , Humanos , Masculino , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Expression of the antiapoptotic and antiproliferative protein B-cell lymphoma 2 (Bcl-2) has been repeatedly shown to be associated with better locoregional control and patients' survival in oropharyngeal squamous cell carcinoma (OSCC). A regulatory (-938C>A) single-nucleotide polymorphism (SNP) in the inhibitory P2 BCL2 gene promoter generates significantly different BCL2 promoter activities and has been associated with outcome in different malignancies. The aim of the present study was to analyze the possible influence of the (-938C>A) SNP on survival of patients suffering from OSCC. MATERIALS AND METHODS: One hundred and thirty-three patients with primary OSCC were retrospectively investigated. Bcl-2 expression of tumor cells was demonstrated by means of immunohistochemistry. Both the Bcl-2 expression and the (-938C>A) genotypes were correlated with the patients' survival. RESULTS: The (-938C>A) SNP was significantly related to Bcl-2 expression (P = 0.008). Kaplan-Meier curves revealed a significant association of the -938 SNP with relapse-free (P = 0.0283) and overall survival (P = 0.0247). Multiple Cox regression identified the BCL2 (-938CC) genotype as an independent prognostic factor for relapse [hazard ratio (HR) 1.898, P = 0.021] as well as for death in OSCC patients (HR 1.897, P = 0.013). CONCLUSIONS: The (-938C>A) SNP represents a potential novel prognostic marker in patients with OSCC that could help to identify a group of patients at high risk for relapse and death.
Assuntos
Carcinoma de Células Escamosas/genética , Genes bcl-2/genética , Recidiva Local de Neoplasia/genética , Neoplasias Orofaríngeas/genética , Idoso , Carcinoma de Células Escamosas/mortalidade , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/mortalidade , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-bcl-2/genética , Estudos Retrospectivos , Análise de SobrevidaRESUMO
The search for influencing factors and new pathways in aseptic loosening of arthroplasties is a major focus of recent studies. Analyses of polymorphisms of genes revealed a correlation between a specific allele variant and aseptic loosening. The BCL2 gene encoding Bcl-2 with its BCL2 -938C>A polymorphism is a crucial factor of cell cycle control and cell survival. The CALCA -1786T>C polymorphism belongs to the CALCA gene encoding alpha-Calcitonin Gene Related Peptide (CGRP) and Calcitonin. Both proteins are important in bone metabolism and capable to influence the process of aseptic loosening. To date, no studies are reported for aseptic loosening with these two single nucleotide polymorphisms (SNPs). In a retrospective study we determined the distribution of the BCL2-938C>A and the CALCA-1786T>C polymorphisms in 87 subjects with aseptic loosened hip arthroplasties using RFLP and pyrosequencing analysis. Genotype distribution with prognosis of the hip arthroplasty showed neither an association with clinical characteristics of the patients nor the implantation technique. We were unable to detect any influence of these polymorphisms on time to aseptic loosening. motion.
Assuntos
Artroplastia de Quadril , Calcitonina/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Falha de Prótese , Precursores de Proteínas/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Peptídeo Relacionado com Gene de Calcitonina , Feminino , Genótipo , Prótese de Quadril , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Complicações Pós-Operatórias , Estudos RetrospectivosRESUMO
Cheese making is a process in which enzymatic coagulation of milk is followed by protein separation, carbohydrate removal, and an extended bacterial fermentation. The number of variables in this complex process that influence cheese quality is so large that the developments of new manufacturing protocols are cumbersome. To reduce screening costs, several models have been developed to miniaturize the cheese manufacturing process. However, these models are not able to accommodate the throughputs required for systematic screening programs. Here, we describe a protocol that allows the parallel manufacturing of approximately 600 cheeses in individual cheese vats each with individual process specifications. Protocols for the production of miniaturized Gouda- and Cheddar-type cheeses have been developed. Starting with as little as 1.7 mL of milk, miniature cheeses of about 170 mg can be produced and they closely resemble conventionally produced cheese in terms of acidification profiles, moisture and salt contents, proteolysis, flavor profiles, and microstructure. Flavor profiling of miniature cheeses manufactured with and without mixed-strain adjunct starter cultures allowed the distinguishing of the different cheeses. Moreover, single-strain adjunct starter cultures engineered to overexpress important flavor-related enzymes revealed effects similar to those described in industrial cheese. Benchmarking against industrial cheese produced from the same raw materials established a good correlation between their proteolytic degradation products and their flavor profiles. These miniature cheeses, referred to as microcheeses, open new possibilities to study many aspects of cheese production, which will not only accelerate product development but also allow a more systematic approach to investigate the complex biochemistry and microbiology of cheese making.
Assuntos
Queijo/microbiologia , Queijo/normas , Manipulação de Alimentos/métodos , Bactérias/crescimento & desenvolvimento , Fenômenos Fisiológicos Bacterianos , Queijo/análise , Contagem de Colônia Microbiana , Concentração de Íons de Hidrogênio , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
Lifestyle diseases such as diabetes and arteriosclerosis are rising in the increasingly aging society, and the number of patients with daily intake of glucose-lowering medication has also increased. Interestingly, knowledge about oral antidiabetics with regard to wound healing is scarce. Therefore, the aim of this study was to identify possible (side) effects of the most frequently prescribed oral antidiabetics on skin cells and wound healing. Four oral antidiabetics of different substance classes (i.e., metformin, glibenclamide, sitagliptin, repaglinide) were investigated with regard to the promotion of cell metabolism and migration of human skin fibroblasts and keratinocytes by XTT and scratch assays. In addition, histological and immunohistochemical analyses were performed in a 3D wound model to address the impact of the antidiabetics on regeneration processes, such as cell migration, fibroblast activity, epidermal thickness, and cell apoptosis. In comparison to systemic application, metformin displayed the most adverse effects in vitro in nearly all analyses, interestingly at serum equivalent concentrations. In contrast, sitagliptin and glibenclamide had a slight but insignificant effect on fibroblasts compared with keratinocytes. Repaglinide tended to have a negative influence on keratinocyte metabolism. Interestingly, antidiabetics generally induced a significantly enhanced rate of apoptosis in fibroblasts, with the exception of repaglinide.Antidiabetics influenced key players in wound healing, namely, keratinocytes and fibroblasts. Particularly, metformin impaired human skin cells. These findings should be kept in mind in further studies because of their putative relevance in patients suffering from chronic wounds that do not respond to various wound therapies.
Assuntos
Fibroblastos/efeitos dos fármacos , Hipoglicemiantes/efeitos adversos , Queratinócitos/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Administração Oral , Apoptose/efeitos dos fármacos , Carbamatos/farmacologia , Caspases/metabolismo , Linhagem Celular , Endopeptidases , Fibroblastos/metabolismo , Gelatinases/metabolismo , Glibureto/farmacologia , Humanos , Proteínas de Membrana/metabolismo , Metformina/farmacologia , Piperidinas/farmacologia , Receptores CXCR4/metabolismo , Serina Endopeptidases/metabolismo , Fosfato de Sitagliptina/farmacologiaRESUMO
Based on the concept that the so-called resistance to anti-platelet drugs is meant to describe a phenomenon where the drug does not hit its direct pharmacodynamic target, assays, used to evaluated the effects of anti-platelet drugs, should as closely as possible measure the direct pharmacodynamic effect of a particular drug. Thus, for the detection of aspirin effects, thromboxane concentrations or arachidonic acid-induced responses (light aggregometry, whole-blood aggregometry) should be measured. For the detection of clopidogrel actions, VASP phosphorylation (flow cytometry) or ADP-induced responses (light aggregometry, whole blood aggregometry) should be analysed.
Assuntos
Aspirina/uso terapêutico , Resistência a Medicamentos , Inibidores da Agregação Plaquetária/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Ticlopidina/análogos & derivados , Clopidogrel , Humanos , Ticlopidina/uso terapêuticoRESUMO
Adequate supply of vitamin D(3) is not sufficient for the prevention of post-menopausal osteoporosis, because of a tightly regulated critical step in formation of the most active vitamin D metabolite 1,25-dihydroxyvitamin D(3). Direct application of 1,25(OH)(2)D(3), however, was effective in reducing fracture rate and increasing bone mineral density as has been shown in large clinical studies. Extracts from Solanum glaucophyllum and Trisetum flavescens plants containing 1,25(OH)(2)D(3)-glycosides were characterized by their vitamin D-activity in a quail eggshell bioassay and applied in an osteoporosis model in ovariectomized rats. An extract from the grass T. flavescens and a purified extract from S. glaucophyllum were characterized by the absence of alkaloids and the analytically determined content of 1,25(OH)(2)D(3). In the ovariectomized rat model after 6 months duration, the bone metabolism relevant markers serum calcium, 1,25(OH)(2)D(3), urinary crosslinks and calcium were measured. At termination tibial mineral content was determined and as imaging procedure micro-computerized tomography was applied. The bisphosphonate alendronate was used as a positive standard. While alendronate reduced bone resorption, as seen in a reduced urinary crosslink excretion, both vitamin D metabolite-containing extracts were able to improve bone mineral density by an enhanced calcium turnover.
Assuntos
Calcifediol/biossíntese , Calcifediol/uso terapêutico , Osteoporose/tratamento farmacológico , Animais , Densidade Óssea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Magnoliopsida/química , Modelos Animais , Osteoporose/patologia , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Ratos , Ratos WistarRESUMO
Urinary tract infections (UTI) are among the most common bacterial infections in infants and children. The early diagnosis of a pyelonephritis and its rapid, calculated antibacterial therapy are decisive for the prognosis. Urogenital anomalies, renal damage and bladder dysfunction may influence the risk of recurrences of UTI and pyelonephritic scarring. Diagnostic strategies therefore should focus on their early recognition. Pediatricians, urologists and infectiologists are cooperating in diagnostic, therapy and prophylaxis of UTI. The aim of the interdisciplinary consensus presented was to work out a concept which may help to manage childhood UTI in daily practice.
Assuntos
Antibacterianos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Administração Oral , Antibacterianos/uso terapêutico , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/etiologia , Criança , Pré-Escolar , Comportamento Cooperativo , Feminino , Humanos , Lactente , Recém-Nascido , Infusões Intravenosas , Assistência de Longa Duração , Masculino , Equipe de Assistência ao Paciente , Infecções Urinárias/diagnóstico , Infecções Urinárias/etiologiaRESUMO
OBJECTIVE: This study aimed to link expression patterns of AQP1, AQP5, Bcl-2 and p16 to clinicopathological characteristics of oro-hypopharyngeal squamous cell carcinomas. METHODS: Immunohistochemical expression of AQP1, AQP5, Bcl-2 and p16 was investigated in 107 consecutive oro-hypopharyngeal squamous cell carcinoma cases. Molecular interrelationship and correlations with clinicopathological parameters and survival were computed. RESULTS: AQP1 was expressed exclusively by a subgroup of basaloid-like squamous cell carcinomas. AQP5 was detected in 25.2 per cent of the samples, showing significant association with the absence of p16 and Bcl-2 (p = 0.018; p = 0.010). In multivariate analysis, overexpression of p16 was significantly correlated with favourable overall survival (p = 0.014). CONCLUSION: AQP5 defined a subset of patients with Bcl-2-negative and p16-negative tumours with a poor clinical outcome. AQP1 was found to be a marker of a subgroup of aggressive basaloid-like squamous cell carcinomas. These findings suggest that AQP1 and AQP5 are interesting candidates for further studies on risk group classification and personalised treatment of oro-hypopharyngeal squamous cell carcinomas.
Assuntos
Aquaporina 1/genética , Aquaporina 5/genética , Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hipofaríngeas/genética , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Aquaporina 1/biossíntese , Aquaporina 5/biossíntese , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Inibidor p16 de Quinase Dependente de Ciclina , DNA de Neoplasias/genética , Feminino , Genótipo , Humanos , Neoplasias Hipofaríngeas/metabolismo , Neoplasias Hipofaríngeas/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/biossínteseRESUMO
The widely used TBA assay for lipid peroxidation was modified to minimize artefactual oxidative degradation of lipids during the assay. Formation of the TBA-MDA condensation product was studied with and without exclusion of oxygen, and the concentration effect of BHT addition was examined. Oxygen was depleted from the reaction mixture by extensive argon gassing. Exclusion of oxygen resulted in decreased TBARS production in plasma but not in standard solutions. High BHT concentrations resulted in a similar effect. At concentrations higher than 3 mmol/l BHT exclusion of oxygen had no additional effect. By measuring n-butanol extracts in a multititer plate reader this modified method was made suitable as a preliminary screening assay of human body fluids for lipid peroxidation.
Assuntos
Diabetes Mellitus/sangue , Malondialdeído/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Artefatos , Biomarcadores , Hidroxitolueno Butilado , Humanos , Indicadores e Reagentes , Masculino , Pessoa de Meia-Idade , Oxigênio , Valores de Referência , Análise de Regressão , Sensibilidade e Especificidade , Espectrofotometria/métodos , Substâncias Reativas com Ácido TiobarbitúricoRESUMO
In an attempt to study and prevent the development of hypertension, there is a growing interest in measuring blood pressure in children. The aim of this is to detect and monitor those with a relatively high level of blood pressure. Until now, reference values on blood pressure in children are based on data from North-American youngsters. The present study provides percentile charts based on pooled data from studies on blood pressure conducted in six North-West European countries among 28,043 children. These blood pressure centiles are presented as age-, height- and gender-specific. Brief guidelines for blood pressure measurements in childhood and for detection of children with a relatively high blood pressure are included.
Assuntos
Pressão Sanguínea/fisiologia , Hipertensão/epidemiologia , Adolescente , Determinação da Pressão Arterial/normas , Criança , Pré-Escolar , Estudos Transversais , Dinamarca/epidemiologia , Feminino , França/epidemiologia , Alemanha Ocidental/epidemiologia , Humanos , Hipertensão/prevenção & controle , Masculino , Países Baixos/epidemiologia , Valores de ReferênciaRESUMO
We investigated a possible correlation between the serologic status concerning Cytomegalovirus (CMV), Chlamydia pneumoniae (CP) and Helicobacter pylori (HP) and the occurrence of restenosis in patients undergoing percutaneous transluminal coronary angioplasty for symptomatic coronary artery disease. Tests for anti-CMV IgG, anti-Chlamydia pneumoniae IgG and IgA and HP IgG and IgA were performed with an enzyme-linked immunosorbent assay (ELISA). Restenosis was defined as >/=50% stenosis at follow-up angiography in a vessel with less than 50% stenosis immediately after PTCA. Of 148 patients, 112 (75.7%) were seropositive for CMV, 75 (50.7%) were seropositive for CP and 78 (52.7%) were seropositive for HP. Restenosis occured in 31.8% of patients. CMV seropositivity was established in 74.5% of patients with restenosis versus 76.2% without restenosis (P=0.82), CP seropositivity was established in 44. 7% of patients with restenosis versus 53.5% without restenosis (P=0. 32), HP seropositivity was established in 53.2% of patients with restenosis versus 52.5% without restenosis (P=0.94). In contrast to some earlier studies CMV or HP seropositivity could not be found to be associated with the risk of restenosis after coronary intervention. An association between the serological status of CP and restenosis could also not be established.