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1.
Diabetes Res Clin Pract ; 153: 14-22, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31078666

RESUMO

AIMS: To compare the effects of long-term treatment with the GLP-1RA exenatide twice-daily versus titrated insulin glargine (iGlar) on renal function and albuminuria in type 2 diabetes (T2DM) patients. METHODS: We post-hoc evaluated renal outcome-data of 54 overweight T2DM patients (mean  ±â€¯SD age 60 ±â€¯8 years, HbA1c 7.5 ±â€¯0.9%, eGFR 86 ±â€¯16 mL/min/1.73 m2, median [IQR] urinary albumin-to-creatinine-ratio (UACR) 0.75 [0.44-1.29] mg/mmol) randomised to exenatide 10 µg twice-daily or titrated iGlar on-top-of metformin for 52-weeks. Renal efficacy endpoints were change in creatinine clearance (CrCl) and albuminuria (urinary albumin-excretion [UAE] and UACR) based on 24-h urines, collected at baseline and Week-52. eGFR and exploratory endpoints were collected throughout the intervention-period, and after a 4-week wash-out. RESULTS: HbA1c-reductions were similar with exenatide (mean ±â€¯SEM -0.80 ±â€¯0.10%) and iGlar (-0.79 ±â€¯0.14%; treatment-difference 0.02%; 95% CI -0.31 to 0.42%). Change from baseline to Week-52 in CrCl, UAE or UACR did not statistically differ; only iGlar reduced albuminuria (P < 0.05; within-group). eGFR decreased from baseline to Week-4 with exenatide (-3.9 ±â€¯2.1 mL/min/1.73 m2; P = 0.069) and iGlar (-2.7 ±â€¯1.2 mL/min/1.73 m2; P = 0.034), without treatment-differences in ensuing trajectory. Exenatide versus iGlar reduced bodyweight (-5.4 kg; 2.9-7.9; P < 0.001), but did not affect blood pressure, lipids or plasma uric acid. CONCLUSIONS: Among T2DM patients without overt nephropathy, one-year treatment with exenatide twice-daily does not affect renal function-decline or onset/progression of albuminuria compared to titrated iGlar. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT00097500.


Assuntos
Albuminúria/urina , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Exenatida/uso terapêutico , Hipoglicemiantes/uso terapêutico , Insulina Glargina/uso terapêutico , Testes de Função Renal/métodos , Nefropatias Diabéticas/patologia , Exenatida/farmacologia , Feminino , Humanos , Hipoglicemiantes/farmacologia , Insulina Glargina/farmacologia , Masculino , Pessoa de Meia-Idade
2.
Diabetes Obes Metab ; 13(4): 374-7, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21205127

RESUMO

Preclinical studies suggest that incretin-based therapies may be beneficial for the bone; however, clinical data are largely lacking. We assessed whether the differential effects of these therapies on body weight differed with respect to their effect on bone mineral density (BMD) and markers of calcium homeostasis in patients with type 2 diabetes (T2D). Sixty-nine metformin-treated patients with T2D were randomized to exenatide twice daily (n = 36) or insulin glargine once daily (n = 33). Total body BMD, measured by dual-energy X-ray absorptiometry, and serum markers of calcium homeostasis were assessed before and after 44-week treatment. Exenatide or insulin glargine treatment decreased body weight by 6%. Endpoint BMD was similar in both groups after 44-week therapy (LSmean ± s.e.m. between-group difference -0.002 ± 0.007 g/cm(2) ; p = 0.782). Fasting serum alkaline phosphatase, calcium and phosphate remained unaffected. Forty-four-week treatment with exenatide or insulin glargine had no adverse effects on bone density in patients with T2D, despite differential effects on body weight.


Assuntos
Peso Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos/farmacologia , Peçonhas/farmacologia , Absorciometria de Fóton , Densidade Óssea/fisiologia , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/fisiopatologia , Exenatida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/administração & dosagem , Cintilografia , Ensaios Clínicos Controlados Aleatórios como Assunto , Peçonhas/administração & dosagem
3.
Int J Oral Maxillofac Surg ; 38(8): 846-9, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19423295

RESUMO

The use of elective tracheostomy in major head and neck surgery is well established, although practice varies between units. There is no published method that reliably predicts the need for tracheostomy. This paper describes the development of a surgical scoring system designed to achieve that aim. The system was devised using data obtained retrospectively from 148 consecutive major head and neck procedures. These procedures were grouped according to the airway management plan in place at the end of the procedure: elective extubation (group E, 52 procedures, 50 patients); elective overnight ventilation via an endotracheal tube (group ETT, 55 procedures, 52 patients); and elective overnight ventilation via a tracheostomy (group T, 41 procedures, 41 patients). 8 patients from group ETT required a late tracheostomy for either medical or surgical indications. Using statistical methods, a threshold score was defined above which the high risk of upper airway obstruction should prompt consideration of an elective tracheostomy.


Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Respiração , Traqueostomia/estatística & dados numéricos , Adulto , Idoso , Obstrução das Vias Respiratórias/etiologia , Carcinoma de Células Escamosas/cirurgia , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Feminino , Previsões , Humanos , Ventilação com Pressão Positiva Intermitente/estatística & dados numéricos , Intubação Intratraqueal/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Mandíbula/cirurgia , Pessoa de Meia-Idade , Neoplasias Bucais/cirurgia , Esvaziamento Cervical/estatística & dados numéricos , Neoplasias Orofaríngeas/cirurgia , Osteotomia/estatística & dados numéricos , Complicações Pós-Operatórias , Procedimentos de Cirurgia Plástica/estatística & dados numéricos , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
4.
Int J Obes (Lond) ; 31(10): 1617-25, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17452990

RESUMO

OBJECTIVE: To determine whether increased expression of macrophage markers and of inflammatory markers in subcutaneous adipose tissue is associated with liver fat in human obesity. We also determined whether expression of TNF (gene encoding TNF-alpha), HSD11B1 (gene encoding 11beta-HSD-1) and RETN (gene encoding resistin) in cultured monocyte-derived macrophages differs between obese/overweight and non-obese subjects. DESIGN: Cross-sectional comparison of obese/overweight and non-obese subjects with respect to adipose tissue gene expression, gene expression in monocyte-derived macrophages, liver fat content and in vivo insulin sensitivity. SUBJECTS: Adipose tissue gene expression, gene expression in monocyte-derived macrophages, liver fat content and in vivo insulin sensitivity: 10 healthy non-obese (24.2+/-1.0 kg/m(2)) and 10 healthy obese/overweight (33.1+/-1.7 kg/m(2)) women. Gene expression in monocyte-derived macrophages: seven healthy non-obese (22.1+/-0.7 kg/m(2)) and seven healthy obese/overweight (36.9+/-2.2 kg/m(2)) women. MEASUREMENTS: Adipose tissue biopsies and blood samples for isolation of peripheral mononuclear cells were taken after an overnight fast. Liver fat content was measured using magnetic resonance proton spectroscopy. Whole body insulin sensitivity was measured using the hyperinsulinemic euglycemic clamp technique. Expression levels of TNF, HSD11B1, RETN and the macrophage markers CD68 and ITGAM were determined by real-time PCR. RESULTS: In adipose tissue, expression of HSD11B1, ITGAM and CD68 was significantly increased in the obese/overweight as compared to the non-obese group. Expression of all these genes was closely positively correlated with liver fat content and inversely correlated with whole body insulin sensitivity. The associations between expression of CD68, ITGAM and HSD11B1 and liver fat were independent of obesity. There were no differences in TNF, HSD11B1, RETN or CD68 gene expression basally or after stimulation with lipopolysaccharide in monocyte-derived macrophages between obese/overweight and non-obese subjects. CONCLUSION: Accumulation of fat in the liver is associated with increased adipose tissue inflammation independent of obesity.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Fígado/anatomia & histologia , Obesidade/metabolismo , Gordura Subcutânea/metabolismo , Tecido Adiposo/anatomia & histologia , Adolescente , Adulto , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Biomarcadores/metabolismo , Antígeno CD11b/metabolismo , Células Cultivadas , Jejum , Feminino , Expressão Gênica , Humanos , Inflamação/metabolismo , Resistência à Insulina/fisiologia , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Pessoa de Meia-Idade
7.
Diabetologia ; 49(1): 132-40, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16362280

RESUMO

AIMS/HYPOTHESIS: We determined the response of selected genes to in vivo insulin in adipose tissue in 21 non-diabetic women. MATERIALS AND METHODS: The women were divided into insulin-sensitive and -resistant groups based on their median whole-body insulin sensitivity (8.7+/-0.4 vs 4.2+/-0.3 mg kg(-1) min(-1) for insulin-sensitive vs -resistant group). Subcutaneous adipose tissue biopsies were obtained before and after 3 and 6 h of i.v. maintained euglycaemic hyperinsulinaemia. Adipose tissue mRNA concentrations of facilitated glucose transporter, member 1 (SLC2A1, previously known as GLUT1), facilitated glucose transporter, member 4 (SLC2A4, previously known as GLUT4), peroxisome proliferator-activated receptor gamma ( PPARG), peroxisome proliferator-activated receptor gamma co-activator 1alpha (PPARGC1A), 11beta-hydroxysteroid dehydrogenase-1 (HSD11B1), TNF, adiponectin (ADIPOQ), IL6 and the macrophage marker CD68 were measured using real-time PCR. RESULTS: Basal expression of 'insulin-sensitivity genes' SLC2A4 and ADIPOQ was lower while that of 'insulin-resistance genes', HSD11B1 and IL6 was significantly higher in the insulin-resistant than in the insulin-sensitive group. Insulin significantly increased expression of 'insulin-sensitivity genes' SLC2A4, PPARG, PPARGC1A and ADIPOQ in the insulin-sensitive group, while only expression of PPARG and PPARGC1A was increased in the insulin-resistant group. The expression of 'insulin-resistance genes' HSD11B1 and IL6 was increased by insulin in the insulin-resistant group, but insulin failed to increase HSD11B1 expression in the insulin-sensitive group. At 6 h, expression of HSD11B1, TNF and IL6 was significantly higher in the insulin-resistant than in the insulin-sensitive group. IL6 expression increased significantly more in response to insulin in the insulin-resistant than in the insulin-sensitive group. CD68 was overexpressed in the insulin-resistant as compared with the insulin-sensitive group at both 0 and 6 h. CONCLUSIONS/INTERPRETATION: These data suggest that genes adversely affecting insulin sensitivity hyperrespond to insulin, while genes enhancing insulin sensitivity hyporespond to insulin in insulin-resistant human adipose tissue in vivo.


Assuntos
Tecido Adiposo/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Resistência à Insulina/fisiologia , Insulina/farmacologia , Tecido Adiposo/efeitos dos fármacos , Adolescente , Adulto , Índice de Massa Corporal , Peso Corporal , Feminino , Humanos , Pessoa de Meia-Idade , Valores de Referência
8.
Gastroenterol. hepatol. (Ed. impr.) ; 28(5): 292-297, may. 2005. ilus, tab
Artigo em Es | IBECS | ID: ibc-038865

RESUMO

El carcinoma hepatocelular es una neoplasia muy frecuente que se desarrolla en la mayoría de los casos en pacientes afectados de cirrosis hepática. En estos pacientes es la principal causa de muerte, por lo que es importante incluirlos en un programa de seguimiento intencionado con el fin de detectar este tumor en un estadio inicial, en el que podrá aplicarse un tratamiento con intención curativa (trasplante hepático, resección quirúrgica o ablación percutánea) y, por tanto, disminuir la mortalidad relacionada con este tumor. Este seguimiento se realiza mediante la determinación de alfafetoproteína y una ecografía de abdomen cada 6 meses. Es importante destacar que esta estrategia de seguimiento sólo debe realizarse en los pacientes que, en caso de ser diagnosticados de carcinoma hepatocelular, recibirán un tratamiento curativo. Con este seguimiento intencionado un 40-80% de los tumores son únicos en el momento del diagnóstico, aunque sólo la mitad de ellos podrán beneficiarse de un tratamiento curativo


Hepatocellular carcinoma is a frequent neoplasm that usually develops in patients with liver cirrhosis. Because it is the main cause of death in these patients, they should be included in a surveillance program in order to identify these tumors at an early stage and be able to indicate curative treatment (liver transplantation, surgical resection or percutaneous ablation therapy) and to reduce mortality. Surveillance should include determination of alpha-fetoprotein and abdominal ultrasound every 6 months. This strategy should only be applied to patients suitable to receive curative treatment if diagnosed of hepatocellular carcinoma. Using this approach, 40-80% of tumors identified are solitary at diagnosis, although only half of these patients can benefit from curative treatment


Assuntos
Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/prevenção & controle , Carcinoma Hepatocelular/terapia , Seguimentos , Fatores de Risco
9.
Diabetologia ; 47(8): 1360-9, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15309287

RESUMO

AIMS/HYPOTHESIS: Fat accumulation in the liver has been shown to be closely correlated with hepatic insulin resistance and features of insulin resistance, also independently of body weight. It remains to be established how fat in the liver correlates with that in other depots, and whether any association differs between men and women. METHODS: Liver fat (assessed using proton spectroscopy), intra-abdominal and subcutaneous fat (measured using magnetic resonance imaging) and markers of insulin resistance, including serum adiponectin, were determined in 132 non-diabetic subjects: 66 men (age 41+/-1 years) and 66 women (age 42+/-1 years). RESULTS: Although the women had almost twice as much subcutaneous fat as the men (5045+/-207 vs 2610+/-144 cm3, p<0.0001), amounts of intra-abdominal fat (1305+/-80 vs 1552+/-111 cm3, NS) and liver fat (6.7+/-0.8 vs 8.9+/-1.2%, NS) were similar. In this study, no sex differences were observed with respect to serum insulin, adiponectin, triglyceride and HDL cholesterol concentrations. Of all measures of body composition, liver fat was best correlated with serum insulin (r=0.58, p<0.001), with no difference observed between men and women. Serum adiponectin was inversely correlated with liver fat content (r=-0.21, p<0.05). Multiple linear regression analysis revealed that intra-abdominal fat was significantly associated with liver fat, independently of serum adiponectin and subcutaneous fat. Liver fat, but not intra-abdominal fat, significantly explained the variation in serum insulin concentrations. CONCLUSIONS/INTERPRETATION: Intra-abdominal fat is independently associated with liver fat, whereas subcutaneous fat is not. Liver fat, but not intra-abdominal fat, is independently associated with serum insulin. Men and women with similar amounts of intra-abdominal and liver fat do not exhibit sex differences in markers of insulin resistance (serum insulin, triglycerides, HDL cholesterol and adiponectin).


Assuntos
Tecido Adiposo/anatomia & histologia , Doenças Cardiovasculares/epidemiologia , Caracteres Sexuais , Abdome , Adiponectina , Adolescente , Adulto , Biomarcadores , Feminino , Humanos , Resistência à Insulina , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Pele , Suécia , População Branca
11.
Biochemistry ; 36(7): 1608-20, 1997 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-9048544

RESUMO

The crystal structure of the complex between the copper amine oxidase from Escherichia coli (ECAO) and a covalently bound inhibitor, 2-hydrazinopyridine, has been determined to a resolution of 2.0 A. The inhibitor covalently binds at the 5 position of the quinone ring of the cofactor, 2,4,5-trihydroxyphenylalaninequinone (TPQ). The inhibitor complex is analogous to the substrate Schiff base formed during the reaction with natural monoamine substrate. A proton is abstracted from a methylene group adjacent to the amine group by a catalytic base during the reaction. The inhibitor, however, has a nitrogen at this position, preventing proton abstraction and trapping the enzyme in a covalent complex. The electron density shows this nitrogen is hydrogen bonded to the side chain of Asp383, a totally conserved residue, identifying it as the probable catalytic base. The positioning of Asp383 is such that the pro-S proton of a substrate would be abstracted, consistent with the stereospecificity of the enzyme determined by 1H NMR spectroscopy. Site-directed mutagenesis and in vivo suppression have been used to substitute Asp383 for 12 other residues. The resulting proteins either lack or, in the case of glutamic acid, have very low enzyme activity consistent with an essential catalytic role for Asp383. The O4 position on the quinone ring is involved in a short hydrogen bond with the hydroxyl of conserved residue Tyr369. The distance between the oxygens is less than 2.5 A, consistent with a shared proton, and suggesting ionization at the O4 position of the quinone ring. The Tyr369 residue appears to play an important role in stabilizing the position of the quinone/inhibitor complex. The O2 position on the quinone ring is hydrogen bonded to the apical water ligand of the copper. The basal water ligand, which lies 2.0 A from the copper in the native structure, is at a distance of 3.0 A in the complex. In the native structure, the active site is completely buried, with no obvious route for entry of substrate. In the complex, the tip of the pyridine ring of the bound inhibitor is on the surface of the protein at the edge of the interface between domains 3 and 4, suggesting this as the entry point for the amine substrate.


Assuntos
Amina Oxidase (contendo Cobre)/química , Amina Oxidase (contendo Cobre)/metabolismo , Escherichia coli/enzimologia , Sítios de Ligação , Catálise , Cobre/química , Cristalografia por Raios X , Elétrons , Escherichia coli/química , Ligantes , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Oxirredução , Piridonas/química , Estereoisomerismo
12.
Structure ; 3(11): 1171-84, 1995 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-8591028

RESUMO

BACKGROUND: Copper amine oxidases are a ubiquitous and novel group of quinoenzymes that catalyze the oxidative deamination of primary amines to the corresponding aldehydes, with concomitant reduction of molecular oxygen to hydrogen peroxide. The enzymes are dimers of identical 70-90 kDa subunits, each of which contains a single copper ion and a covalently bound cofactor formed by the post-translational modification of a tyrosine side chain to 2,4,5-trihydroxyphenylalanine quinone (TPQ). RESULTS: The crystal structure of amine oxidase from Escherichia coli has been determined in both an active and an inactive form. The only structural differences are in the active site, where differences in copper coordination geometry and in the position and interactions of the redox cofactor, TPQ, are observed. Each subunit of the mushroom-shaped dimer comprises four domains: a 440 amino acid C-terminal beta sandwich domain, which contains the active site and provides the dimer interface, and three smaller peripheral alpha/beta domains (D1-D3), each of about 100 amino acids. D2 and D3 show remarkable structural and sequence similarity to each other and are conserved throughout the quinoenzyme family. In contrast, D1 is absent from some amine oxidases. The active sites are well buried from solvent and lie some 35 A apart, connected by a pair of beta hairpin arms. CONCLUSIONS: The crystal structure of E. coli copper amine oxidase reveals a number of unexpected features and provides a basis for investigating the intriguing similarities and differences in catalytic mechanism of members of this enzyme family. In addition to the three conserved histidines that bind the copper, our studies identify a number of other conserved residues close to the active site, including a candidate for the catalytic base and a fourth conserved histidine which is involved in an interesting intersubunit interaction.


Assuntos
Amina Oxidase (contendo Cobre)/química , Proteínas de Bactérias/química , Di-Hidroxifenilalanina/análogos & derivados , Escherichia coli/enzimologia , Modelos Moleculares , Conformação Proteica , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação , Catálise , Clonagem Molecular , Cristalografia por Raios X , Di-Hidroxifenilalanina/química , Histidina/química , Dados de Sequência Molecular , Alinhamento de Sequência
13.
J Nematol ; 25(4): 548-54, 1993 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19279808

RESUMO

Three genes in the major sperm protein (MSP) gene family from the potato cyst nematode Globodera rostochiensis were cloned and sequenced. In contrast to the absence of introns in Caenorhabditis elegans MSP genes, these genes in G. rostochiensis contained a 57 nucleotide intron, with normal exon-intron boundaries, in the same relative location as the intron in Onchocerca volvulus. The MSP genes of G. rostochiensis had putative CAAT, TATA, and polyadenylation signals. The predicted G. rostochiensis MSP gene product is 126 amino acids long, one residue shorter than the products in the other species. The comparison of MSP amino acid sequences from four diverse nematode species suggests that O. volvulus, Ascaris suum, and C. elegans may be more closely related to each other than they are to G. rostochiensis.

14.
J Clin Microbiol ; 29(8): 1659-64, 1991 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1761688

RESUMO

The protein antigens A and D were purified from culture filtrates and sonic extracts of laboratory strains of Mycobacterium paratuberculosis by salt precipitation and chromatography. The characterization of antigen A is shown here, and both antigens were evaluated along with lipoarabinomannan antigen in indirect enzyme-linked immunosorbent assays (ELISA) for the serodiagnosis of ovine paratuberculosis. After anion-exchange (DEAE-5PW) and hydrophobic (phenyl-5PW) chromatography using high-performance liquid chromatography, antigen A showed a prominant band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) at 31 kDa with small amounts of low-molecular-mass proteins but with no evidence of antigen D. A single precipitin arc was evident with purified antigen A in crossed immunoelectrophoresis. The determination of the N-terminal amino acid sequence showed a high degree of homology between the 31-kDa component of antigen A and antigens of the BCG85 complex of Mycobacterium bovis BCG, a total of 24 of 26 residues being identical to those of BCG85C. A prominant SDS-PAGE band at 400 kDa and a single crossed-immunoelectrophoresis arc was also evident for antigen D after gel filtration (Sephacryl S-200), anion-exchange (DEAE-Sephacel), and concanavalin A-Sepharose affinity chromatography. By ELISA, purified antigen A detected antibody in the sera of 18 of 22 paratuberculosis-infected sheep (82% sensitivity), whereas the purified antigen D detected antibody in all 22 infected animals (100% sensitivity). Combined ELISA results showed increased specificity with some loss in sensitivity.


Assuntos
Antígenos de Bactérias/isolamento & purificação , Proteínas de Bactérias/isolamento & purificação , Proteínas de Choque Térmico , Paratuberculose/diagnóstico , Sequência de Aminoácidos , Animais , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Precipitação Química , Cromatografia Líquida de Alta Pressão , Cromatografia por Troca Iônica , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Imunoeletroforese Bidimensional , Lipopolissacarídeos/biossíntese , Linfadenite/diagnóstico , Dados de Sequência Molecular , Paratuberculose/imunologia , Sensibilidade e Especificidade , Homologia de Sequência do Ácido Nucleico , Ovinos
15.
J Clin Dent ; 2(2): 34-8, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2090157

RESUMO

In vitro studies have demonstrated the antiplaque properties of C31G, a potent broad spectrum antimicrobial agent consisting of an equimolar mixture of alkyl dimethyl glycine and alkyl dimethyl amine oxide, buffered with citric acid. In this initial clinical study, C31G at concentrations of 0.05%, 0.1%, 0.2% and 0.5%. Listerine, and placebo were tested in a complete crossover design. Twelve subjects were evaluated, with a minimum of 2 days between treatments. Parameters monitored were salivary bacterial counts and saliva glycolysis. The 0.5% and 0.2% C31G mouthrinses significantly reduced total bacterial counts in saliva samples obtained up to and including three hours after rinsing, compared with counts obtained prerinsing or after placebo rinsing. Both 0.5%, and 0.2% C31G significantly inhibited glycolysis of salivary bacteria for up to 6 hours postrinsing, compared with pH values obtained prerinsing. 0.1% and 0.05% C31G exhibited little or no effect in either assay. Listerine showed a significant reduction in bacterial counts for up to 1 hour postrinsing, compared with prerinse counts, but the effect was less sustained. Listerine showed no significant inhibition of glycolysis at any time point. No tooth staining or altered taste sensation was noted with either product.


Assuntos
Antibacterianos/administração & dosagem , Betaína/análogos & derivados , Placa Dentária/prevenção & controle , Ácidos Graxos Insaturados/administração & dosagem , Antissépticos Bucais/administração & dosagem , Saliva/microbiologia , Streptococcus/efeitos dos fármacos , Adulto , Análise de Variância , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Betaína/administração & dosagem , Betaína/farmacologia , Combinação de Medicamentos , Ácidos Graxos Insaturados/farmacologia , Glicólise/efeitos dos fármacos , Humanos , Antissépticos Bucais/farmacologia , Salicilatos/administração & dosagem , Salicilatos/farmacologia , Terpenos/administração & dosagem , Terpenos/farmacologia
16.
Am J Vet Res ; 50(6): 850-4, 1989 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2504085

RESUMO

The use of lipoarabinomannan (LAM; obtained from Mycobacterium paratuberculosis) in and ELISA (LAM-ELISA) to test 75 sheep sera from a paratuberculosis-infected flock resulted in an approximate threefold increase in sensitivity (from 23.5% to 70.6%), compared with the use of Annau's polysaccharide in a complement fixation test (P-CFT). Even after manipulation of the LAM-ELISA cut-off value to produce a specificity of 100% to match that of the P-CFT, the sensitivity still was approximately twofold greater than that of the P-CFT. Anti-bovine monoclonal antiglobulin-enzyme conjugates matched commercially available anti-ovine polyclonal antiglobulin-enzyme conjugates with respect to sensitivity and specificity. False-positive results were found to be less frequent after combining 2 serodiagnostic tests, LAM-ELISA and D antigenagar gel immunodiffusion, resulting in an increase in specificity from 88.1% to 95.2%. The repeatability of true seropositive and seronegative results was found to be 89.5% and 91.1%, respectively, for sera obtained less than or equal to 1 month prior to slaughter and 91.7% and 95.5%, respectively, for reanalysis of sera obtained at the time of slaughter.


Assuntos
Anticorpos Antibacterianos/análise , Lipopolissacarídeos/imunologia , Paratuberculose/diagnóstico , Doenças dos Ovinos/diagnóstico , Animais , Antígenos de Bactérias/imunologia , Ensaio de Imunoadsorção Enzimática/veterinária , Imunodifusão , Mycobacterium , Paratuberculose/imunologia , Ovinos , Doenças dos Ovinos/imunologia
17.
Infect Immun ; 56(9): 2484-90, 1988 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-3410546

RESUMO

Human saliva contains a high-molecular-weight glycoprotein (agglutinin) which binds to specific streptococci in a calcium-dependent reaction leading to the formation of bacterial aggregates. We report the cloning of a gene encoding a surface antigen from Streptococcus sanguis M5 and show that the expressed protein inhibits agglutinin-mediated aggregation and specifically binds the salivary agglutinin in a calcium-dependent fashion. Clones isolated from the immunological screening of S. sanguis M5 genomic libraries with polyclonal antibodies against whole cells were assayed for the ability to compete with S. sanguis for agglutinin. One clone, pSSP-5, expressed antigens of 165 and 130 kilodaltons (kDa) possessing this activity. A 3-kilobase-pair (kbp) insert fragment from this clone was used to screen a genomic library in lambda EMBL3 which resulted in the isolation of clone SSP-5A. This clone contained an insert of 17 kb and expressed proteins of 170 to 205 kDa that reacted with the anti-S. sanguis antibodies. Subcloning of a 5.3-kbp EcoRI-BamHI fragment from SSP-5A produced pEB-5, which expressed streptococcal components that were indistinguishable from SSP-5A. The streptococcal antigen was purified by gel permeation and ion exchange chromatography and shown to potently compete with S. sanguis M5 cells for agglutinin. The antigen also bound purified salivary agglutinin in the presence of 1 mM CaCl2. This binding was inhibited by EDTA. Both the SSP-5 antigen and a 205-kDa protein in surface protein extracts from S. sanguis M5 cross-reacted with antibodies directed against antigen B from S. mutans and SpaA from S. sobrinus 6715. These results indicate that a 205-kDa surface protein that is antigenically related to SpaA and antigen B is involved in the binding of salivary agglutinin to S. sanguis M5.


Assuntos
Aglutininas/metabolismo , Antígenos de Bactérias/genética , Antígenos de Superfície/genética , Proteínas de Bactérias/metabolismo , Saliva/metabolismo , Streptococcus sanguis/genética , Aglutininas/imunologia , Reações Antígeno-Anticorpo , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/isolamento & purificação , Antígenos de Superfície/imunologia , Antígenos de Superfície/isolamento & purificação , Proteínas de Bactérias/imunologia , Clonagem Molecular , Glicoproteínas/imunologia , Glicoproteínas/metabolismo , Humanos , Peso Molecular , Saliva/imunologia , Streptococcus sanguis/imunologia
18.
Can J Vet Res ; 52(2): 199-204, 1988 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3130975

RESUMO

Sera from 74 sheep culled from one flock on the basis of performance and response to immunological tests for paratuberculosis or maedi visna were used to evaluate the serological response to a sonicated antigen of Mycobacterium paratuberculosis by crossed immunoelectrophoresis. A total of seven precipitating components was demonstrated. Four components (A,C,V,W) were detected in low frequency only with sera from animals with paratuberculosis while two components (X,Y) were detected in high frequency with sera from animals with or without paratuberculosis. One component (D) was observed in high frequency with sera from animals with paratuberculosis. The magnitude of the serological response to the D component as measured by crossed immunoelectrophoresis correlated well with bacterial load and generally agreed with the quantitative assessment by agar gel immunodiffusion. A development time for crossed immunoelectrophoresis of 24-72 hours after electrophoresis was required to achieve correlation with agar gel immunodiffusion.


Assuntos
Anticorpos Antibacterianos/análise , Mycobacterium/imunologia , Paratuberculose/imunologia , Precipitinas/análise , Doenças dos Ovinos/imunologia , Animais , Testes de Fixação de Complemento/veterinária , Estudos de Avaliação como Assunto , Imunodifusão/veterinária , Imunoeletroforese Bidimensional , Ovinos , Doenças dos Ovinos/microbiologia
19.
Lipids ; 23(3): 199-206, 1988 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3374273

RESUMO

Male, female and castrated rats, three wk of age, were fed a low-fat diet for 14 wk followed by high-fat diets (20% by weight) for one wk containing graded levels of erucic acid from 1 to 50%, to evaluate the effect of short-term feeding and interaction of male sex hormones on formation of heart lesions. Some rats within each group were returned to the low-fat diet for one wk after the test period. For comparison, one group of three-wk-old male rats was fed the high fat 50% erucic acid diet for 15 wk. Erucic acid depressed growth rate and food consumption and increased cardiac lipidosis and triglycerides proportional to the erucic acid content of the diet. There were no sex differences, and the effects disappeared once rats were returned to the low-fat diet for one week. There was a significance (P less than 0.05) in the incidence of myocardial necrosis among male rats fed increased levels of erucic acid for one week, but the response was not linear to the increase in dietary erucic acid. Furthermore, the response was much less than in males fed the 50% erucic acid diet continually for 15 weeks. These results suggest that the short-term model is not a suitable substitute for the long-term feeding trial to test the cardiopathogenicity of a vegetable oil. The significantly lower incidence in myocardial lesions in female and castrated male rats compared with male rats suggests involvement of sex hormones.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Gorduras na Dieta/efeitos adversos , Ácidos Erúcicos/efeitos adversos , Ácidos Graxos Monoinsaturados/efeitos adversos , Miocárdio/análise , Óleos de Plantas/efeitos adversos , Animais , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Castração , Feminino , Hormônios Esteroides Gonadais/fisiologia , Lipidoses/induzido quimicamente , Lipidoses/metabolismo , Lipidoses/patologia , Masculino , Miocárdio/patologia , Necrose , Fosfolipídeos/análise , Ratos , Ratos Endogâmicos , Esfingomielinas/análise , Fatores de Tempo
20.
Antimicrob Agents Chemother ; 32(3): 350-3, 1988 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3364952

RESUMO

C31G, an equimolar mixture of alkyl dimethyl glycine and alkyl dimethyl amine oxide, was evaluated for antimicrobial and antiadherence properties. The efficacy of C31G, its two components, and several commercial mouth rinses was determined in assays measuring inhibition of glycolysis, inhibition of bacterial adherence, and MICs. Inhibition of glycolysis was determined by using a saliva sediment model, with glycolytic activity expressed as the change in pH relative to that of a control. Adherence studies were undertaken with Streptococcus sobrinus 6715 to measure inhibition of adherence to nichrome wires. MICs were determined against selected microorganisms by standard methods. C31G demonstrated broad-spectrum antimicrobial properties, with activity against both gram-positive and gram-negative organisms and Candida albicans, a yeast. C31G inhibited both glycolysis by salivary bacteria and adherence of Streptococcus strains to wire mesh. C31G was more effective in the assays conducted than any commercial formulation tested and was as effective as chlorhexidine. A synergistic effect was demonstrated between the individual components of C31G, and no loss of activity was noted when it was formulated into a mouth rinse vehicle.


Assuntos
Antibacterianos/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Betaína/análogos & derivados , Ácidos Graxos Insaturados/farmacologia , Antibacterianos/administração & dosagem , Bactérias/efeitos dos fármacos , Betaína/administração & dosagem , Betaína/farmacologia , Ácidos Graxos Insaturados/administração & dosagem , Glicólise/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Antissépticos Bucais
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