RESUMO
STUDY DESIGN: Randomized, controlled clinical trial. OBJECTIVES: Bladder and bowel management may cause serious autonomic dysreflexia (AD) in subjects with high spinal cord injury (SCI). We aimed at investigating autonomic responses to digital rectal evacuation (DE), transanal irrigation (TAI) with 500 ml and filling cystometry (FC) in SCI. SETTING: Aarhus University Hospital, Denmark. METHODS: Eight subjects with SCI (AIS A) at or above T6 (high SCI) and a previous history of AD were compared with three subjects with SCI (AIS A) between T10 and L2 (low SCI). In randomized order, DE, TAI and FC were performed. AD was defined as an acute rise in systolic blood pressure (sBP) of ⩾30 mm Hg above baseline. Blood levels of norepinephrine and epinephrine were determined before and shortly after the procedures. RESULTS: During all three procedures, AD occurred in all patients with high SCI but not in those with low SCI. In high SCI subjects, DE increased median sBP from 127 (range: 86-154) to 188 (range: 140-206) mm Hg (P<0.02), TAI from 126 (range: 91-146) to 163 (range: 130-188) mm Hg (P<0.02) and FC from 125 (range: 106-149) to 200 (range: 179-220) mm Hg (P<0.01). The sBP increase was lower during TAI than during DE (P<0.05) or FC (P<0.02). In high SCI subjects, the blood levels of norepinephrine, but not those of epinephrine, increased significantly during all three stimuli (all P<0.05). CONCLUSION: Bowel and bladder management caused AD in high SCI. The response is less severe during TAI than during FC or DE.
Assuntos
Disreflexia Autonômica/fisiopatologia , Reto/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/reabilitação , Adulto , Idoso , Disreflexia Autonômica/etiologia , Pressão Sanguínea/fisiologia , Enema , Epinefrina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intestino Neurogênico/fisiopatologia , Norepinefrina/sangue , Bexiga Urinária/fisiopatologia , Bexiga Urinaria Neurogênica/fisiopatologia , Cateterismo UrinárioRESUMO
Chilli peppers have been shown to enhance diet-induced thermogenesis (DIT) and reduce energy intake (EI) in some studies, but there are few data on other pungent spices. The primary aim of the present study was to test the acute effects of black pepper (pepper), ginger, horseradish and mustard in a meal on 4 h postprandial DIT. The secondary aim was to examine the effects on subjective appetite measures, ad libitum EI and energy balance. In a five-way placebo-controlled, single-blind, cross-over trial, twenty-two young (age 24·9 (SD 4·6) years), normal-weight (BMI 21·8 (SD 2·1) kg/m²) males were randomly assigned to receive a brunch meal with either pepper (1·3 g), ginger (20 g), horseradish (8·3 g), mustard (21 g) or no spices (placebo). The amounts of spices were chosen from pre-testing to make the meal spicy but palatable. No significant treatment effects were observed on DIT, but mustard produced DIT, which tended to be larger than that of placebo (14 %, 59 (SE 3) v. 52 (SE 2) kJ/h, respectively, P=0·08). No other spice induced thermogenic effects approaching statistical significance. Subjective measures of appetite (P>0·85), ad libitum EI (P=0·63) and energy balance (P=0·67) also did not differ between the treatments. Finally, horseradish decreased heart rate (P=0·048) and increased diastolic blood pressure (P= 0·049) compared with placebo. In conclusion, no reliable treatment effects on appetite, EI or energy balance were observed, although mustard tended to be thermogenic at this dose. Further studies should explore the possible strength and mechanisms of the potential thermogenic effect of mustard actives, and potential enhancement by, for example, combinations with other food components.
Assuntos
Regulação do Apetite , Dieta , Ingestão de Energia , Metabolismo Energético , Hiperfagia/prevenção & controle , Especiarias , Adolescente , Armoracia/química , Estudos Cross-Over , Dinamarca , Dieta/efeitos adversos , Zingiber officinale/química , Humanos , Almoço , Masculino , Mostardeira/química , Piper nigrum/efeitos adversos , Período Pós-Prandial , Método Simples-Cego , Especiarias/efeitos adversos , Termogênese , Adulto JovemRESUMO
AIMS: Adding aldosterone receptor blockade to standard renoprotective treatment may provide additional renoprotection in patients with overt nephropathy. We expected an impact of spironolactone in early diabetic nephropathy, and for this hypothesis we studied the effect on markers of glomerular and tubular damage in patients with Type 1 diabetes and persistent microalbuminuria. METHODS: A double-blind, randomized, placebo-controlled crossover study in 21 patients with Type 1 diabetes and microalbuminuria using spironolactone 25 mg or placebo once daily, for 60 days added to standard antihypertensive treatment. After each treatment period, the primary endpoint were evaluated: urinary(u)-albumin excretion/24 hour(h) and secondary endpoints; 24 h blood pressure, glomerular filtration rate (GFR) and markers of tubular damage: urinary liver-type fatty-acid binding protein (LFABP), neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule 1 (KIM1). RESULTS: All patients completed the study. During spironolactone treatment, urinary albumin excretion rate was reduced by 60% (range 21-80%), from 90 mg/24 h to 35 mg/24 h (P=0.01). Blood pressure (24 h) did not change during spironolactone treatment (P>0.2 for all comparisons). The GFR (SD) decreased from 78 (6) mL/min/1.73 m(2) to 72 (6) mL/min/1.73 m(2) (P=0.003). Urinary liver-type fatty-acid binding protein, neutrophil gelatinase-associated lipocalin and kidney injury molecule 1 did not change during treatment (P>0.3 for all comparisons). Treatment was well-tolerated, but two patients had severe hyperkalaemia (plasma potassium = 5.7 mmol/l), which was sufficiently treated with diuretics and dietary intervention. CONCLUSIONS: Spironolactone treatment in addition to standard renoprotective treatment lowers urinary albumin excretion in microalbuminuric patients with Type 1 diabetes, and thus may offer additional renoprotection independent of blood pressure.
Assuntos
Albuminúria/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Diuréticos/uso terapêutico , Espironolactona/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminúria/urina , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Estudos Cross-Over , Diabetes Mellitus Tipo 1/urina , Nefropatias Diabéticas/urina , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
AIM: The optimal antiproteinuric dose of aliskiren is unknown. This study compared the effect of placebo and increasing doses of aliskiren on urinary albumin excretion rate (UAER). METHODS: The trial was a double-blind crossover design. Twenty-six patients with type 2 diabetes mellitus, hypertension and albuminuria were randomised to 2-month treatments with placebo or aliskiren 150 mg, 300 mg or 600 mg once daily, in random order. Primary endpoint was change in UAER; secondary endpoints included changes in 24-h BP, GFR, biomarkers and components of the renin-angiotensin-aldosterone system. RESULTS: Placebo geometric mean UAER was 350 mg/day, mean 24-h BP was 137/81 (SD 12/9) mmHg, GFR was 85 (SD 26) ml min(-1) 1.73 m(-2). Aliskiren 150, 300 and 600 mg daily reduced UAER significantly by 36% (95% CI 17-51), 48% (33-60) and 52% (38-63) respectively (p < 0.001) compared with placebo. UAER reduction during the 600 mg dose was not significantly different from the 300 mg dose. Twenty-four-hour systolic BP was reduced by 4.5, 8.0 and 9.2 mmHg versus placebo, significant for 300 and 600 mg (p < or = 0.001). Twenty-four-hour diastolic BP was reduced by 3.0, 4.1 and 4.4 mmHg, significant versus placebo (p = 0.019, p = 0.001 and p < 0.001). GFR was reduced by 3.0, 5.1 and 6.5 ml min(-1) 1.73 m(-2). hsPRA was reduced by 63%, 70%, and 82% (p < 0.001 for all). Adverse events, most frequently dizziness and fatigue, occurred during all doses. CONCLUSIONS: In patients with type 2 diabetes mellitus, hypertension and albuminuria there is no improved antiproteinuric effect when using 600 mg aliskiren daily compared with the maximal recommended antihypertensive dose of 300 mg. TRIAL REGISTRATION: Clinicaltrials.gov NCT00464776 FUNDING: Novartis Pharma AG.
Assuntos
Albuminúria/tratamento farmacológico , Amidas/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fumaratos/administração & dosagem , Hipertensão/tratamento farmacológico , Adulto , Albuminúria/complicações , Amidas/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Estudos Cross-Over , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Esquema de Medicação , Fumaratos/uso terapêutico , Humanos , Hipertensão/complicações , Renina/antagonistas & inibidoresRESUMO
AIMS/HYPOTHESIS: The purpose of this study was to evaluate the optimal renoprotective effect of ultrahigh doses of lisinopril, as reflected by short-term changes in urinary albumin excretion rate (UAER), in type 1 diabetic patients with diabetic nephropathy. METHODS: At the Steno Diabetes Center, 49 type 1 diabetic patients with diabetic nephropathy completed this double-masked randomised crossover trial consisting of an initial washout period followed by three treatment periods each lasting 2 months, where all patients received lisinopril 20, 40 and 60 mg once daily in randomised order in addition to slow-release furosemide. Allocation was concealed by sequentially numbered opaque sealed envelopes. UAER, 24 h ambulatory blood pressure (ABP) and estimated GFR were determined at baseline and after each treatment period. RESULTS: All 49 patients completed all three treatment periods. Baseline values were: UAER (geometric mean [95% CI]) 362 (240-545) mg/24 h, 24 h ABP (mean [SD]) 142 (14)/74 (8) mmHg and estimated GFR 75 (29) ml min(-1) 1.73 m(-2). Reductions in UAER from baseline were 63%, 71% and 70%, respectively, with the increasing doses of lisinopril (p < 0.001). Compared with lisinopril 20 mg there was a further reduction in UAER of 23% with lisinopril 40 mg and 19% with 60 mg, p < 0.05. ABP was reduced from baseline by 10/5, 13/7 and 12/7 mmHg (p < 0.001 vs baseline, p < 0.05 for diastolic ABP 20 vs 40 mg, otherwise NS between doses). The difference in UAER between 20 and 40 mg lisinopril was significant after adjustment for changes in ABP (p < 0.01). Two patients were excluded from the study because of an increase in plasma creatinine and one because of high BP; otherwise the study medication was well tolerated with few, mild, dose-independent adverse effects. CONCLUSIONS/INTERPRETATION: Lisinopril 40 mg once daily is generally safe and offers additional reductions in BP and UAER in comparison with the currently recommended dose of 20 mg. Lisinopril 60 mg offers no further beneficial effect. TRIAL REGISTRATION: ClinicalTrials.gov NCT00118976.
Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Lisinopril/uso terapêutico , Adulto , Albuminúria/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Estudos Cross-Over , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/fisiopatologia , Angiopatias Diabéticas/tratamento farmacológico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Substâncias Protetoras/uso terapêuticoRESUMO
Inhibition of renin with an active site inhibitor, aliskiren, lowers blood pressure (BP) in diabetic patients. Here, we studied the time course of the antihypertensive and antiproteinuric effect of renin inhibition in 15 patients with type 2 diabetes and elevated urinary albumin/creatinine ratios (UACRs) to check whether aliskiren can decrease proteinuria. After a 4-week washout of previous medications, patients received aliskiren and furosemide daily for 28 days followed by a 4-week withdrawal period. Twenty-four-hour BPs were measured at baseline throughout treatment and withdrawal periods. The UACR was significantly reduced after 2-4 days of treatment with another significant reduction after 28 days. Systolic blood pressure (SBP) was significantly lower after 7 days with no further reduction after 28 days. The BP returned toward baseline 3 days after withdrawal, whereas the UACR was still significantly reduced compared with baseline 12 days after withdrawal. Our study shows that aliskiren reduced 24 h SBP, and this was associated with a reduction in albuminuria in type 2 diabetic patients.
Assuntos
Albuminúria/tratamento farmacológico , Amidas/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Fumaratos/uso terapêutico , Hipertensão/tratamento farmacológico , Renina/antagonistas & inibidores , Idoso , Albuminúria/etiologia , Albuminúria/urina , Amidas/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Creatinina/urina , Feminino , Fumaratos/farmacologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Hipertensão/etiologia , Hipertensão/urina , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
UNLABELLED: Dental Unit Water Systems (DUWS) are used in dental practices to provide water for cooling of dental equipment and irrigation of the oral cavity. However, they have been demonstrated to be contaminated with micro-organisms. There are currently no European Union (EU) Commission guidelines for the microbial quality of water discharged by DUWS. This study was part of an EU research programme to investigate the microbial contamination of DUWS in general dental practice (GDP) in the UK, Denmark, Germany, The Netherlands, Ireland, Greece and Spain. OBJECTIVE: To undertake a questionnaire survey on the type of DUWS in use and determine the attitude of GDPs to the risk of microbial infection from DUWS. MATERIALS AND METHODS: The questionnaire was written and translated into the language of each country before being posted to each participating dentist. Dentists were asked to complete the questionnaire survey and return it by post. RESULTS AND CONCLUSIONS: The major findings were that the majority of dentists did not clean, disinfect or determine the microbial load of their DUWS, and that dentists would welcome regular monitoring and advice on maintaining their DUWS; the introduction of guidelines; and recommendations on controlling the microbial load of DUWS.
Assuntos
Atitude do Pessoal de Saúde , Equipamentos Odontológicos/microbiologia , Controle de Infecções Dentárias/métodos , Abastecimento de Água , Europa (Continente) , Humanos , Inquéritos e Questionários , Microbiologia da Água/normas , Abastecimento de Água/normasRESUMO
The association process of glucagon receptor binding in purified rat liver plasma membranes and prolonged incubation of the hormone-receptor complex at 30 degrees C did not result in degradation of bound labelled glucagon. In contrast, up to 95% of the non-membrane-bound labelled glucagon was degraded. The rate of spontaneous dissociation of the glucagon-receptor complex was slow, and amounted to about 0.1% per min of that bound. GTP greatly enhanced the rate of dissociation. Half the maximal dissociation of the complex was effected by 10(-5) mol/l of GTP under equilibrium binding conditions. At maximally effective concentrations of GTP, 80% of the glucagon-receptor complex was dissociated within 2 min. A microperifusion system for the perifusion of isolated plasma membranes was devised and used for the separation of labelled glucagon from the plasma membranes subsequent to a GTP-induced dissociation of the hormone-receptor complex. Rebinding of the dissociated peptide to fresh membranes showed that maximum binding ability was retained. The glucagon molecule was protected against degradation while bound to the receptor, indicating that the glucagon effector system is completely separate from the inactivating system(s) in isolated plasma membranes. Thus, the hormonal effect of glucagon could be exerted through the sequential interaction of each glucagon molecule with several receptors.
Assuntos
Membrana Celular/metabolismo , Glucagon/metabolismo , Fígado/metabolismo , Receptores dos Hormônios Gastrointestinais/metabolismo , Animais , Guanosina Trifosfato/farmacologia , Cinética , Peptídeo Hidrolases/metabolismo , Ligação Proteica , Ratos , Ratos Endogâmicos , Receptores dos Hormônios Gastrointestinais/efeitos dos fármacos , Receptores de GlucagonRESUMO
A new, simple insulin-receptor-binding assay has been devised. The assay is based on the separation of free and receptor-bound 125I-labeled insulin in 80% ethanol. It was found that the insulin-receptor complex was fully stable at this ethanol concentration, regardless of the source of the receptor employed. The assay has been evaluated with solubilized insulin receptors and membrane-bound receptors from human placenta and porcine liver as well as intact cells with the IM-9 cell line. The assay is simple, rapid, and has large capacity. Comparisons of the ethanol-based assay to the conventionally employed assays with polyethylene glycol or microfuge centrifugation for the separation of free and bound 125I-insulin revealed large discrepancies between the assays. The ethanol-based assay always appeared to provide a better separation. Microfuge centrifugation of placental membranes precipitated approximately 3% of the ethanol-precipitable insulin-receptor complex, while polyethylene glycol precipitation of solubilized insulin receptors varied between 40 and 80% of the ethanol precipitability, depending on the receptor concentration employed.
Assuntos
Receptor de Insulina/análise , Membrana Celular/metabolismo , Centrifugação , Precipitação Química , Etanol , Humanos , Insulina/metabolismo , Fígado/análise , Linfócitos/análise , Placenta/análise , PolietilenoglicóisRESUMO
Angiotensin II facilitates epinephrine release during insulin-induced hypoglycemia, and this effect appears to be independent of type 1 angiotensin II (AT1) receptors in man. In the present study, we hypothesized that the action of angiotensin II on adrenomedullary epinephrine release is mediated by an AT2 receptor-dependent mechanism. In conscious chronically instrumented rats, we measured plasma concentrations of catecholamines during acute insulin-induced hypoglycemia in groups of rats pretreated with the AT1 receptor antagonist losartan (10 mg/kg i.v.), the AT2 receptor antagonist PD123319 (30 mg/kg i.v.), combined losartan + PD123319, the converting enzyme inhibitor enalapril (1 mg/kg i.v.), or vehicle. In vehicle-treated rats, the area under the curve for changes in plasma epinephrine concentration [AUC(plasma epinephrine)] during insulin-induced hypoglycemia was 111+/-8 nmolXh/L (+/-SEM). Pretreatment with losartan alone did not affect AUC(plasma epinephrine) (113+/-17 nmol x h/L), while pretreatment with PD123319 tended to reduce the response (87+/-10 nmol x h/L; P=.08 versus vehicle). However, AUC(plasma epinephrine) was significantly reduced in rats that were pretreated with combined losartan + PD123319 (68+/-5 nmol x h/L; P<.001 versus vehicle) or enalapril: 86+/-10 nmol x h/L (P<.05 versus vehicle). Thus, combined treatment with losartan + PD 123319 proved more effective in attenuating the reflex increase in plasma epinephrine concentration during hypoglycemia than either of the two AT receptor antagonists given alone. We speculate that angiotensin II through binding to both receptor subtypes facilitates the sympathoadrenal reflex response by actions at several anatomical levels of the neural pathways involved in the sympathoadrenal reflex response elicited during insulin-induced hypoglycemia.
Assuntos
Antagonistas de Receptores de Angiotensina , Epinefrina/sangue , Hipoglicemia/fisiopatologia , Imidazóis/farmacologia , Insulina/farmacologia , Losartan/farmacologia , Piridinas/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Enalapril/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipoglicemia/sangue , Hipoglicemia/induzido quimicamente , Cinética , Masculino , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina , Receptor Tipo 2 de AngiotensinaRESUMO
BACKGROUND: Insulin is secreted in regular pulses at intervals of 12-14 min in normal fasting subjects. An abnormal pattern has been found in subjects with non-insulin-dependent diabetes mellitus (NIDDM) and in young individuals predisposed to NIDDM. It has been suggested that there might be a causal relationship between insulin-secretion abnormalities and insulin resistance. OBJECTIVE: To examine whether insulin-secretion abnormalities are also present in offspring of patients with essential hypertension. METHODS: Eleven young (aged 18-35 years) normotensive individuals each of whom had two parents with essential hypertension were compared with 10 age- and sex-matched controls each of whom had two normotensive parents. We verified that diabetes and morbid obesity were absent among the subjects and their parents. We studied basal insulin-secretion patterns during a 60 min period, glucose tolerance by administering an oral glucose-tolerance test, insulin resistance by using an isoglycaemic hyperinsulinaemic clamp and basal plasma catecholamine levels. RESULTS: Autocorrelation analysis of insulin concentrations showed that the hypertension-prone subjects had a significantly reduced or irregular oscillatory pattern compared with the regular insulin-level oscillations with a period of 12-14 min in control subjects. The hypertension-prone subjects had significantly higher systolic blood pressures and tended to be insulin-resistant. CONCLUSION: This is the first evidence of early insulin-secretion abnormalities in young normotensive individuals with a genetic predisposition to essential hypertension, but with a normal glucose tolerance and without a genetic predisposition to NIDDM. Early insulin-secretion abnormalities may be the very first step towards the development of insulin resistance and an important factor initiating the hypertension in hypertension-prone individuals.
Assuntos
Pressão Sanguínea/fisiologia , Hipertensão/sangue , Hipertensão/genética , Insulina/sangue , Adolescente , Adulto , Índice de Massa Corporal , Catecolaminas/sangue , Feminino , Técnica Clamp de Glucose , Teste de Tolerância a Glucose , Humanos , Hipertensão/fisiopatologia , Resistência à Insulina , MasculinoRESUMO
Cyclic adenosine 3',5'-monophosphage (cyclic AMP) levels in guinea-pig tracheal rings increased on incubation with the vasoactive intestinal peptide (VIP). The effect was potentiated by the addition of theophylline. The results suggest that the tracheo-bronchial relaxant action of VIP may be mediated by stimulation of tracheal adenylyl cyclase.
Assuntos
AMP Cíclico/metabolismo , Hormônios Gastrointestinais/farmacologia , Traqueia/metabolismo , Peptídeo Intestinal Vasoativo/farmacologia , Animais , Interações Medicamentosas , Cobaias , Técnicas In Vitro , Isoproterenol/farmacologia , Estimulação Química , Teofilina/farmacologia , Traqueia/efeitos dos fármacosRESUMO
OBJECTIVE: Short-term growth hormone (GH) treatment normalises body fluid distribution in adult GH deficient patients, but the impact of long-term treatment on body fluid homeostasis has hitherto not been thoroughly examined in placebo controlled trials. To investigate if the water retaining effect of GH persists for a longer time we examined the impact of 4 months GH treatment on extracellular volume (ECV) and plasma volume (PV) in GH deficient adults. DESIGN: Twenty-four (18 male, 6 female) adult GH deficient patients aged 25-64 years were included and received either GH (n=11) or placebo (n=13) in a double blind parallel design. METHODS: Before and at the end of each 4 month period ECV and PV were assessed directly using 82Br- and 125I-albumin respectively, and blood samples were obtained. RESULTS: During GH treatment ECV increased significantly (before: 20.48+/-0.99 l, 4 months: 23.77+/-1.38 l (P<0.01)), but remained unchanged during placebo administration (before: 16.92+/-1.01 l, 4 months: 17.60+/-1.24 l (P=0.37)). The difference between the groups was significant (P<0.05). GH treatment also increased PV (before: 3.39+/-0.27 l. 4 months: 3.71+/-0.261 (P=0.01)), although an insignificant increase in the placebo treated patients (before: 2.81+/-0.18 l, 4 months: 2.89+/-0.20 l (P=0.37)) resulted in an insignificant treatment effect (P=0.07). Serum insulin-like growth factor-I increased significantly during GH treatment and was not affected by placebo treatment. Plasma renin (mIU/l) increased during GH administration (before: 14.73+/-2.16, 4 months: 26.00+/-6.22 (P=0.03)) and remained unchanged following placebo (before: 20.77+/-5.13, 4 months: 20.69+/-6.67 (P=0.99)) leaving no significant treatment effect (P=0.08). CONCLUSION: The long-term impact of GH treatment on body fluid distribution in adult GH deficient patients involves expansion of ECV and probably also PV. These data substantiate the role of GH as a regulator of fluid homeostasis in adult GH deficiency.
Assuntos
Líquidos Corporais/metabolismo , Hormônio do Crescimento/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Adulto , Pressão Sanguínea , Composição Corporal , Método Duplo-Cego , Espaço Extracelular/química , Feminino , Homeostase , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Volume Plasmático , Renina/sangueRESUMO
IgA1 protease activity, which allows bacteria to cleave human IgA1 in the hinge region, represents a striking example of convergent evolution of a specific property in bacteria. Although it has been known since 1979 that IgA1 protease is produced by the three leading causes of bacterial meningitis in addition to important urogenital pathogens and some members of the oropharyngeal flora, the exact role of this enzyme in bacterial pathogenesis is still incompletely understood owing to lack of a satisfactory animal model. Cleavage of IgA1 by these post-proline endopeptidases efficiently separates the monomeric antigen-binding fragments from the secondary effector functions of the IgA1 antibody molecule. Several in vivo and in vitro observations indicate that the enzymes are important for the ability of bacteria to colonize mucosal membranes in the presence of S-IgA antibodies. Furthermore, the extensive cleavage of IgA sometimes observed in vivo, suggests that IgA1 protease activity results in a local functional IgA deficiency that may facilitate colonization of other microorganisms and the penetration of potential allergens. It has been hypothesized that IgA1 protease activity of Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae, under special immunological circumstances, allows these bacteria to take advantage of specific IgA1 antibodies in a strategy to evade other immune factors of the human body. The decisive factor is the balance between IgA antibodies against surface antigens of the respective bacteria and their IgA1 protease. Recent studies have shown that serine-type IgA1 proteases of H. influenzae, meningococci, and gonococci belong to a family of proteins used by a diverse group of Gram-negative bacteria for colonization and invasion.
Assuntos
Bactérias/enzimologia , Bactérias/patogenicidade , Infecções Bacterianas/enzimologia , Infecções Bacterianas/microbiologia , Imunoglobulina A/fisiologia , Serina Endopeptidases/fisiologia , Sequência de Aminoácidos , Animais , Bactérias/imunologia , Infecções Bacterianas/imunologia , Humanos , Dados de Sequência Molecular , VirulênciaRESUMO
It is suggested that the antigenic site of glucagon for the specific sera is located within the 24-29 section of the molecule and within the 2-23 section for the fully cross-reacting sera. Biologically inactivated glucagon may retain immunoreactivity in spite of the loss of receptor-binding activity.
Assuntos
Glucagon/imunologia , Animais , Reações Antígeno-Anticorpo , Reações Cruzadas , Glucagon/análogos & derivados , Soros Imunes , Intestinos , Ilhotas Pancreáticas , Fragmentos de Peptídeos/imunologia , Especificidade da Espécie , Relação Estrutura-AtividadeRESUMO
Rat intestinal mucosal cells contain receptors for pancreatic spasmolytic polypeptide (PSP). The binding of 125I-PSP was rapid, saturable, reversible and specific. PSP competed with 125I-PSP for binding to the receptors and 10(-7) M of PSP half-maximally inhibited 125I-PSP binding. The normalized PSP dose-response graphs in intact cells and crude membranes were superimposable. Scatchard plots of PSP binding to membranes were curvilinear, indicating multiple classes of binding sites, negative cooperative interaction between sites or a combination of both. PSP increased the rate of dissociation of the 125I-PSP-receptor complex compared to the rate observed by dilution only, thus giving evidence that negative cooperative interaction may occur between PSP binding sites. The half-life of the fast dissociating complex was about 1.5 min and that of the slow dissociating complex 38 min. These values were independent of the receptor occupancy. The increased rate of dissociation at high receptor occupancy stemmed from a shift in the ratio of the pool sizes of fast and slow dissociating receptor complexes.
Assuntos
Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Mucinas , Proteínas Musculares , Neuropeptídeos , Peptídeos/metabolismo , Receptores de Superfície Celular/metabolismo , Animais , Ligação Competitiva , Membrana Celular/metabolismo , Feminino , Técnicas In Vitro , Peptídeos e Proteínas de Sinalização Intercelular , Cinética , Masculino , Ratos , Ratos Endogâmicos , Fator Trefoil-2 , Fator Trefoil-3RESUMO
The recently isolated pancreatic spasmolytic polypeptide, PSP, interacted with specific binding sites in the gastrointestinal tract and inhibited the adenylate cyclase activity in rat intestinal mucosal cell membranes. The binding sites appeared to be heterogeneous and Scatchard analysis of the binding data indicated the presence of at least two classes of sites. The high-affinity low-capacity binding sites and the low-affinity high-capacity binding sites had apparent dissociation constants of 1.3 X 10(-7) mol/l and 4.2 X 10(-6) mol/l, respectively. The PSP induced inhibition of the adenylate cyclase activity was independent of the stimulatory state of the enzyme. The basal activity as well as that stimulated by VIP and secretin was half maximally inhibited at approximately 3 X 10(-5) mol/l of PSP. The inhibitory effect of PSP was independent of the agonist concentration employed. PSP did not affect the receptor binding of VIP nor did VIP affect the receptor binding of PSP.
Assuntos
Inibidores de Adenilil Ciclases , Mucosa Intestinal/metabolismo , Mucinas , Proteínas Musculares , Neuropeptídeos , Peptídeos/farmacologia , Animais , Sítios de Ligação , Membrana Celular/metabolismo , Relação Dose-Resposta a Droga , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Peptídeos/metabolismo , Ratos , Ratos Endogâmicos , Fator Trefoil-2 , Fator Trefoil-3 , Peptídeo Intestinal Vasoativo/farmacologiaRESUMO
The effect of periodontal healing after guided tissue regeneration (GTR) in association with local application of metronidazole gel was evaluated in this study. Twelve patients with one pair of vertical periodontal bone defects of comparable size and configuration participated in the study. In a matched paired design, the test defects were treated by GTR using expanded polytetrafluoroethylene (ePTFE) membranes in combination with local application of metronidazole gel. The controls were treated in the same way except for application of metronidazole. During the first month of membrane implantation, no statistically significant differences between test and control surfaces were noted with respect to inflammation of the marginal gingiva. Six weeks following insertion, the membranes were removed. Six months after removal of the membrane, the median gain in probing attachment level as a percentage of the initial defect depth was 92% for test defects and 50% for control defects (P = .001). No statistically significant differences were found between test and control sites regarding plaque, bleeding on probing, reduction in pocket depth, gain in bone height, or recession of the gingival margin. In conclusion, the results of the present study indicate that local application of metronidazole gel has a beneficial effect on healing of periodontal vertical defects treated by guided tissue regeneration.
Assuntos
Regeneração Tecidual Guiada Periodontal , Metronidazol/uso terapêutico , Doenças Periodontais/cirurgia , Periodonto/efeitos dos fármacos , Administração Tópica , Adulto , Perda do Osso Alveolar/patologia , Perda do Osso Alveolar/cirurgia , Placa Dentária/patologia , Feminino , Géis , Hemorragia Gengival/patologia , Retração Gengival/patologia , Gengivite/patologia , Humanos , Masculino , Membranas Artificiais , Metronidazol/administração & dosagem , Pessoa de Meia-Idade , Doenças Periodontais/patologia , Bolsa Periodontal/patologia , Bolsa Periodontal/cirurgia , Periodonto/fisiopatologia , Politetrafluoretileno , Cicatrização/efeitos dos fármacosRESUMO
The bacteriological colonization of healing periodontal defects was investigated after treatment with guided tissue regeneration using expanded polytetrafluoroethylene membranes together with local metronidazole gel (25%, 250 mg/g). Twelve patients, each with one pair of comparable defects, had the test defect treated with the membrane plus metronidazole gel and the control defect treated with the membrane alone. Thirty weeks after removal of the membrane, the median gain in probing attachment level as a percentage of the initial defect depth was 92% for the test defects and 50% for the control defects (P = 0.001). The median number of cultivable bacteria decreased from 1.2 x 10(6) at the presurgical examination to 3.0 x 10(5) at the one week examination in the test group (P = 0.02), whereas an increase was observed in the control group. Similarly, a lower median proportion of black-pigmented Gram-negative anaerobic rods was observed one week postsurgically in the test group (0.004%) compared to the control group (3.5%) (P = 0.02). Two weeks after membrane insertion, and at all following examinations, no microbiological differences between test and control group were observed. Consequently, the influence of the metronidazole gel on the treatment result appears to have been confined to the initial regeneration phase. Despite the good clinical results in the test group, all membranes from both test and control pockets were heavily colonized with bacteria at the time of removal. To ensure maximal periodontal regeneration with formation of bone, future research in this area should concentrate on reducing the microbial colonization of the wound area.
Assuntos
Bactérias Anaeróbias Gram-Negativas/efeitos dos fármacos , Regeneração Tecidual Guiada Periodontal , Metronidazol/uso terapêutico , Doenças Periodontais/microbiologia , Doenças Periodontais/cirurgia , Periodonto/efeitos dos fármacos , Periodonto/microbiologia , Administração Tópica , Adulto , Aggregatibacter actinomycetemcomitans/efeitos dos fármacos , Aggregatibacter actinomycetemcomitans/isolamento & purificação , Perda do Osso Alveolar/microbiologia , Perda do Osso Alveolar/patologia , Perda do Osso Alveolar/cirurgia , Contagem de Colônia Microbiana , Contaminação de Equipamentos , Géis , Bactérias Anaeróbias Gram-Negativas/isolamento & purificação , Humanos , Membranas Artificiais , Metronidazol/administração & dosagem , Pessoa de Meia-Idade , Doenças Periodontais/patologia , Bolsa Periodontal/microbiologia , Bolsa Periodontal/patologia , Bolsa Periodontal/cirurgia , Politetrafluoretileno , Porphyromonas gingivalis/efeitos dos fármacos , Porphyromonas gingivalis/isolamento & purificação , Prevotella intermedia/efeitos dos fármacos , Prevotella intermedia/isolamento & purificação , Cicatrização/efeitos dos fármacosRESUMO
OBJECTIVES: The aim was to compare a CCD-based sensor and a storage phosphor plate with respect to patient discomfort and the efficacy of a simple cross-infection control procedure in connection with a posterior bitewing examination. METHODS: 130 patients accepted to have one posterior bitewing of the left and right side taken with two digital radiography systems, the Digora phosphor plate and the Trophy RVG XL, CCD-based sensor system. The patients assessed their feeling of discomfort after the examination on a 100-mm. Visual Analogue Scale (VAS). Microbiological samples were taken from the RVG sensor and cord and from the Digora envelope, plate and scanner during examination of 14 patients. The samples were plated and incubated anaerobically, and the colony-forming units counted. RESULTS: Median VAS score for discomfort was 20 min for Digora and 32 min for the RVG sensor (P < 0.001). Median total counts of cultivable bacteria were low (< 20), the majority being catalase-positive, Gram-positive cocci and Gram-positive rods, presumably skin bacteria. Only the samples taken from the enveloped Digora plate and the rubber tube coated RVG sensor immediately after exposure yielded large numbers of oral bacteria. CONCLUSION: The phosphor plate was less unpleasant than the CCD sensor. Cross-contamination posed a minor problem for both systems when a simple, standard hygiene procedure was followed.