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Realistically improving upper-limb prostheses is only possible if we listen to users' actual technological needs.
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Membros Artificiais , Robótica , Extremidade SuperiorRESUMO
Pelvic floor rehabilitation is frequently recommended for defecation disorders, in both constipation and fecal incontinence. However, the lack of patient selection, together with the variety of rehabilitation methods and protocols, often jeopardize the results of this approach, causing difficulty in evaluating outcomes and addressing proper management, and above all, in obtaining scientific evidence for the efficacy of these methods for specific indications. The authors represent different gastroenterological and surgical scientific societies in Italy, and their aim was to identify the indications and agree on treatment protocols for pelvic floor rehabilitation of patients with defecation disorders. This was achieved by means of a modified Delphi method, utilizing a working team (10 members) which developed the statements and a consensus group (15 members, different from the previous ones) which voted twice also suggesting modifications of the statements.
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Constipação Intestinal/reabilitação , Incontinência Fecal/reabilitação , Gastroenterologia/normas , Guias de Prática Clínica como Assunto/normas , Sociedades Médicas/normas , Defecação , Técnica Delphi , Humanos , Itália , Diafragma da PelveRESUMO
BACKGROUND: There is a certain number of subjects that consider themselves to be constipated (self diagnosed constipation; SDC). The Rome Criteria separate FC from IBS-C, but some SDC patients do not meet the Rome criteria (no Rome Constipation; NRC). Our aims were to evaluate the percentage of SDC subjects with a diagnosis of FC and IBS-C and to compare demographic and clinical features, symptoms, and quality of life in the different SDC groups (FC, IBS-C, NRC). METHODS: During a 2-month period, 934 patients and 980 accompanying persons (AP) were asked to complete a survey. The presence of FC or IBS-C was assessed. SDC subjects were invited to record the stool consistency (Bristol scale) and to fill in the Constipation Severity Index (CSI), obstructed defecation syndrome (ODS) and patient assessment of constipation-quality of life (PAC-QoL). The use of laxatives and enemas was evaluated. KEY RESULTS: The probability of the ROME III criteria being present was higher in SDC compared with no-SDC (OR 20.5). NRC was present in 13.5% of the SDC. In the patients' group the agreement between a diagnosis of Rome III and SDC was good (K 0.62), whereas in the AP it was moderate (K 0.56). NRC showed lower mean values of ODS, CSI and PAC-QoL, higher Bristol scale and a lower use of laxatives and enemas compared to IBS-C and FC. No differences were found between IBS-C and FC. CONCLUSIONS AND INFERENCES: The Rome III criteria identify subjects with a greater clinical impact, but separation of FC and IBS-C does not seem justified.
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The aim of the present study was to evaluate the immunological effects on human macrophages of four endocrine disruptor compounds (EDCs) using the differentiated human THP-1 cell line as a model. We studied first the effects of these EDCs, including Bisphenol A (BPA), di-ethylhexyl-phthalate (DEHP), dibutyl phthalate (DBP) and 4-tert-octylphenol (4-OP), either alone or in combination, on cytokine secretion, and phagocytosis. We then determined whether or not these effects were mediated by estrogen receptors via MAPK pathways. It was found that all four EDCs studied reduced strongly the phagocytosis of the differentiated THP-1 cells and that several of these EDCs disturbed also TNF-α, IL-1 ß and IL-8 cytokine secretions. Furthermore, relative to control treatment, decreased ERK 1/2 phosphorylation was always associated with EDCs treatments-either alone or in certain combinations (at 0.1 µM for each condition). Lastly, as treatments by an estrogen receptor antagonist suppressed the negative effects on ERK 1/2 phosphorylation observed in cells treated either alone with BPA, DEHP, 4-OP or with the combined treatment of BPA and DEHP, we suggested that estrogen receptor-dependent pathway is involved in mediating the effects of EDCs on human immune system. Altogether, these results advocate that EDCs can disturb human immune response at very low concentrations.
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Compostos Benzidrílicos/farmacologia , Dibutilftalato/farmacologia , Dietilexilftalato/farmacologia , Disruptores Endócrinos/farmacologia , Macrófagos/efeitos dos fármacos , Fenóis/farmacologia , Linhagem Celular , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica , Humanos , Interleucina-1beta/agonistas , Interleucina-1beta/metabolismo , Interleucina-8/agonistas , Interleucina-8/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fagocitose/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/agonistas , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Aspergilli are commonly found in soil and on decaying plant material. D-xylose and L-arabinose are highly abundant components of plant biomass. They are released from polysaccharides by fungi using a set of extracellular enzymes and subsequently converted intracellularly through the pentose catabolic pathway (PCP).In this study, the L-arabinose responsive transcriptional activator (AraR) is identified in Aspergillus niger and was shown to control the L-arabinose catabolic pathway as well as expression of genes encoding extracellular L-arabinose releasing enzymes. AraR interacts with the D-xylose-responsive transcriptional activator XlnR in the regulation of the pentose catabolic pathway, but not with respect to release of L-arabinose and D-xylose.AraR was only identified in the Eurotiales, more specifically in the family Trichocomaceae and appears to have originated from a gene duplication event (from XlnR) after this order or family split from the other filamentous ascomycetes. XlnR is present in all filamentous ascomycetes with the exception of members of the Onygenales. Since the Onygenales and Eurotiales are both part of the subclass Eurotiomycetidae, this indicates that strong adaptation of the regulation of pentose utilisation has occurred at this evolutionary node. In Eurotiales a unique two-component regulatory system for pentose release and metabolism has evolved, while the regulatory system was lost in the Onygenales. The observed evolutionary changes (in Eurotiomycetidae) mainly affect the regulatory system as in contrast, homologues for most genes of the L-arabinose/D-xylose catabolic pathway are present in all the filamentous fungi, irrespective of the presence of XlnR and/or AraR.
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BACKGROUND: Bloating is a fastidious symptom reported by many patients who also have other gastrointestinal functional disorders. Bloating is more common in women, and it is often associated with meals and improves or disappears overnight. No specific treatments are to date available for this disturbing symptom. AIMS: to evaluate the effects of an oral enterovaccine (Colifagina) on bloating and other abdominal symptoms in patients with prevalent complaints of functional bloating. PATIENTS AND METHODS: One hundred and forty-eight patients with functional bloating according to Rome III criteria were recruited. Questionnaires and a VAS scale on their symptoms were administered at baseline and after four weeks of therapy with Colifagina. RESULTS: After treatment, a significant amelioration of bloating (p < 0.0001), abdominal pain (p < 0.0001) and flatus (p < 0.0001) was observed; nausea and vomiting scores were not significantly different at the end of the treatment. Subjective wellbeing was also generally improved (p < 0.001) in treated patients. CONCLUSION: Treatment with an enterovaccine may help improve symptoms in patients with functional bloating.
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Adjuvantes Imunológicos/uso terapêutico , Bactérias/imunologia , Vacinas Bacterianas/uso terapêutico , Flatulência/terapia , Probióticos/uso terapêutico , Adolescente , Adulto , Animais , Modelos Animais de Doenças , Feminino , Flatulência/etiologia , Humanos , Entrevistas como Assunto , Masculino , Camundongos , Pessoa de Meia-Idade , Náusea/terapia , Medição da Dor , Estatísticas não Paramétricas , Inquéritos e Questionários , Resultado do Tratamento , Vômito/terapiaAssuntos
Toxinas Botulínicas/administração & dosagem , Doença de Chagas/diagnóstico , Doença de Chagas/tratamento farmacológico , Viagem , Trypanosoma cruzi/isolamento & purificação , Adulto , Alopurinol/uso terapêutico , Animais , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Esofagoscopia/métodos , Feminino , Seguimentos , Gastroscopia/métodos , Humanos , Manometria , Medição de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Patients with gastro-oesophageal reflux disease may complain of epigastric pain, bloating, early satiety, epigastric fullness, epigastric burning, nausea and vomiting. AIMS: To evaluate the symptoms in response to gastric distension and its relationship to a therapeutic course in patients with gastro-oesophageal reflux disease using the water load test, compared to healthy controls. METHODS: Thirty gastro-oesophageal reflux disease patients with grade A oesophagitis (studied before and after 4 weeks of therapy with esomeprazole, 40 mg per day) and 15 patients with reflux-related symptoms demonstrated at wireless pH monitoring (non-erosive reflux disease) were compared to 30 healthy volunteers. RESULTS: Patients with grade A oesophagitis and with reflux-related symptoms ingested significantly lower water volumes than did controls, before onset of fullness, without statistically significant difference between erosive or non-erosive gastro-oesophageal reflux disease; this variable improved in patients after treatment. Nausea scores were higher basally in patients, pre- and post-therapy, and improved after therapy. Thirty-minute fullness and bloating scores improved after therapy in all gastro-oesophageal reflux disease patients compared to controls and pre-therapy. In all pre-treatment patients, a significant correlation was found only with epigastric fullness; after treatment, there was no significant relationship between the water load and the symptom scores. CONCLUSIONS: In patients with reflux-related symptoms, with or without grade A oesophagitis, the water load test is frequently abnormal, suggesting an altered gastric function. This could explain the incomplete resolution of symptoms after treatment in some patients, and should lead to additional studies aimed at exploring gastric function in gastro-oesophageal reflux disease patients.
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Dispepsia/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Esomeprazol/uso terapêutico , Esofagite Péptica/tratamento farmacológico , Refluxo Gastroesofágico/tratamento farmacológico , Água , Adulto , Ingestão de Líquidos/fisiologia , Dispepsia/etiologia , Esofagite Péptica/complicações , Esofagite Péptica/diagnóstico , Feminino , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Treatment of oesophageal achalasia with intrasphincteric injections of botulinum toxin has proved to be a successful alternative treatment modality. However, little is known about its long-term effects in very old patients. AIM: To evaluate the effects of such treatment in octo-nonagerians during a 2-year follow-up period. PATIENTS AND METHODS: Thirty-three patients with idiopathic oesophageal achalasia (range 81-94 years) entered the study. After basal evaluation and screening procedures, 100 U of botulinum toxin was injected at the lower oesophageal sphincter, and the procedure was repeated 1 month later. Data were collected at baseline and were compared after 1 and 2 years following the procedure. RESULTS: Seventy-eight per cent of patients were considered responders at 1 year and 54% were considered responders at 2 years. The weight gain at the end of the follow-up period was 2 (0-3) kg. No significant relationship was found between baseline lower oesophageal sphincter pressure and symptoms score after 1 and 2 years of follow-up; moreover, no major complications of botulinum toxin therapy were reported. CONCLUSION: Treatment of very old achalasic patients with botulinum toxin is safe, effective and yields good quality of life in a substantial proportion of these subjects.
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Toxinas Botulínicas/uso terapêutico , Acalasia Esofágica/tratamento farmacológico , Fatores Etários , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Injeções , Masculino , Resultado do TratamentoRESUMO
OBJECTIVE: To report a case of Legionella pneumonia with unusual neurologic involvement. INTERVENTION: Chest X-ray, lumbar puncture, magnetic imaging of the brain, electroencephalography, audiometry, brainstem acoustic evoked potentials and institution of oral antibiotics and steroids. MAIN RESULT: Gradual clinical improvement of neurologic and pulmonary illness within 4 weeks. CONCLUSION: Legionellosis should be considered in the differential diagnosis of neurologic involvement in the setting of pneumonia.
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Encefalopatias/microbiologia , Tronco Encefálico/microbiologia , Legionella pneumophila/isolamento & purificação , Doença dos Legionários/complicações , Adulto , Humanos , Doença dos Legionários/microbiologia , MasculinoRESUMO
BACKGROUND: Colonic diverticular disease (diverticulosis) is a common disorder in Western countries. Although its pathogenesis is probably multifactorial, motor abnormalities of the large bowel are thought to play an important role. However, little is known about the basic mechanism that may underlie abnormal colon motility in diverticulosis. AIMS: To investigate the interstitial cells of Cajal (the gut pacemaker cells), together with myenteric and submucosal ganglion and glial cells, in patients with diverticulosis. PATIENTS: Full thickness colonic samples were obtained from 39 patients undergoing surgery for diverticulosis. Specimens from tumour free areas of the colon in 10 age matched subjects undergoing surgery for colorectal cancer served as controls. METHODS: Interstitial cells of Cajal were assessed using anti-Kit antibodies; submucosal and myenteric plexus neurones and glial cells were assessed by means of anti-PGP 9.5 and anti-S-100 monoclonal antibodies, respectively. RESULTS: Patients with diverticulosis had normal numbers of myenteric and submucosal plexus neurones compared with controls (p = 0.103 and p = 0.516, respectively). All subtypes of interstitial cells of Cajal were significantly (p = 0.0003) reduced compared with controls, as were glial cells (p = 0.0041). CONCLUSIONS: Interstitial cells of Cajal and glial cells are decreased in colonic diverticular disease, whereas enteric neurones appear to be normally represented. This finding might explain some of the large bowel motor abnormalities reported to occur in this condition.
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Relógios Biológicos , Diverticulose Cólica/patologia , Sistema Nervoso Entérico/patologia , Neuroglia/patologia , Idoso , Diverticulose Cólica/metabolismo , Diverticulose Cólica/fisiopatologia , Feminino , Trânsito Gastrointestinal , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Plexo Mientérico/patologia , Proteínas S100/metabolismo , Ubiquitina Tiolesterase/metabolismoRESUMO
BACKGROUND: Radiofrequency (RF) energy treatment is increasingly offered before invasive surgical procedures for selected patients with gastroesophageal reflux disease (GERD). METHODS: Thirty-two patients undergoing the Stretta procedure were prospectively evaluated with upper endoscopy, manometry, 24-hour pH testing, SF-36 surveys, and GERD-specific questionnaires (GERD HRQL). RESULTS: Significant clinical improvement was observed in 91% of patients (29/32). Mean heartburn and GERD HRQL scores decreased (p = 0.001 and p = 0.003, respectively), and physical SF-36 increased (p = 0.05). At a minimum follow-up of 12 months, median esophageal acid exposure decreased (p = 0.79) and was normalized in eight patients. Median lower esophageal sphincter (LES) pressure was unchanged. Esophagitis healed in six of eight patients, but two patients with nonerosive disease developed asymptomatic grade A esophagitis during follow-up. At 12 months, 56% of patients were off proton pump inhibits. Morbidity was minimal. CONCLUSIONS: RF delivery to LES is safe and significantly improves symptoms and quality of life in selected GERD patients.
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Terapia por Estimulação Elétrica , Refluxo Gastroesofágico/terapia , Terapia por Estimulação Elétrica/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
A number of recent findings seem to indicate that fat and bone metabolism are strictly connected. We investigated the relationship between lipid profile and bone mineral density (BMD) in 236 either pre- or postmenopausal women, aged 35-81 years, attending our osteoporosis center ("clinic group"). In order to verify the consistency of the results, 265 men and 481 women aged 68-75, participating in a population-based epidemiological investigation ("community cohort"), were also studied. Lumbar spine, femoral neck, total hip and total body BMD, total body fat, % fat mass and lean mass were measured using dual energy X-ray absorptiometry (DXA). In the clinic group, lumbar spine and hip BMD Z score values were both strongly related to all measured serum lipids: the relationship was negative for HDL cholesterol ( P < 0.05) and Apo A lipoprotein ( P < 0.000) and positive for LDL cholesterol ( P < 0.05), Apo B lipoprotein ( P < 0.001) and triglycerides ( P < 0.05). When BMD values were adjusted for body weight and BMI, most relationships remained statistically significant. In the community cohort, total body and hip BMD values were strongly related in both men and women to age, body weight, height, BMI, fat mass, lean mass, % fat mass. Total body and hip BMD were significantly related to serum lipids in both women and men. The relationship was negative for HDL cholesterol and positive for total cholesterol, triglycerides and LDL cholesterol. Most of these relationships (triglycerides, HDL cholesterol, LDL/HDL cholesterol ratio in women, and all measured lipids in men) remained statistically significant ( P values ranging from 0.000 to 0.03) when the BMD values were adjusted also for anthropometric measures (body weight, height, fat mass). This study demonstrates for the first time that the lipid profile is strictly related to bone mass in both men and women. The interpretation of this association remains hypothetical but it might open new perspectives for understanding the mechanisms controlling bone metabolism.
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Densidade Óssea/fisiologia , Osso e Ossos/metabolismo , Lipídeos/sangue , Absorciometria de Fóton , Tecido Adiposo/anatomia & histologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Osso e Ossos/diagnóstico por imagem , Climatério , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
AIM: The main cause of acute diverticulitis is the abnormal accumulation of fecal bacteria within the diverticular lumen, leading to a balancing between normal probiotic microflora and pathogenic species; Gram negative Entero-bacteriaceae, mainly Escherichia coli and Proteus spp, are the genders that usually cause the disease-related symptoms, due to their ability to adhere to intestinal mucosa. The intestine is well known as the largest human lymphoepithelial organ and daily produces more antibodies, mainly secretory IgAs, than do all other lymphoid tissues. IgAs have different immune and anti-inflammatory properties. The aim of this study was to verify the efficacy of an oral immunostimulant highly-purified, polymicrobial lysate in the prevention of recurrent attacks of diverticulitis and in the improvement of symptoms. METHODS: The study was carried out on 83 consecutive patients suffering from recurrent symptomatic acute diverticulitis and with at least 2 attacks in the previous year; patients were randomly assigned to receive (group A) an oral polybacterial lysate suspension or to a no-treatment clinical follow-up as controls (group B). RESULTS: A total of 76 patients (41 in group A and 35 in group B) terminated the study period. the sums of the scores for symptoms, reported on day schedules, were calculated and examined by means of ANOVA statistical analysis. Statistical differences between group A vs group B were recorded after 1 month (p<0.05) and 3 months (p<0.01) of treatment with the oral polybacterial lysate suspension. CONCLUSIONS: Our data suggest that the administration of an oral enterovaccine for the prophylaxis of recurrent diverticulitis is effective and well tolerated, probably due to a direct stimulation of IgA-mediated mucosal defences.
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Adjuvantes Imunológicos/administração & dosagem , Vacinas Bacterianas/administração & dosagem , Extratos Celulares/administração & dosagem , Diverticulite/prevenção & controle , Doença Aguda , Administração Oral , Idoso , Análise de Variância , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/uso terapêutico , Bactérias , Distribuição de Qui-Quadrado , Ciprofloxacina/administração & dosagem , Ciprofloxacina/uso terapêutico , Colonoscopia , Diverticulite/diagnóstico , Diverticulite/tratamento farmacológico , Diverticulite/imunologia , Diverticulite/microbiologia , Diverticulite/terapia , Doença Diverticular do Colo/diagnóstico , Doença Diverticular do Colo/tratamento farmacológico , Doença Diverticular do Colo/imunologia , Doença Diverticular do Colo/microbiologia , Doença Diverticular do Colo/prevenção & controle , Doença Diverticular do Colo/terapia , Feminino , Seguimentos , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/uso terapêutico , Humanos , Injeções Intravenosas , Mucosa Intestinal/imunologia , Masculino , Pessoa de Meia-Idade , Recidiva , Rifamicinas/administração & dosagem , Rifamicinas/uso terapêutico , Rifaximina , Fatores de TempoRESUMO
BACKGROUND: Pathogenesis of slow transit constipation still remains elusive. Some studies have shown several colonic motor abnormalities; however, it is not easy to understand the relative importance of the single ones. AIMS: Since it has been hypothesized that an excess of periodic distal motor activity may be of pathophysiological importance in patients with slow transit constipation, we evaluated regular colonic contractile frequencies in a homogeneous cohort of these patients. PATIENTS: A total of 26 female patients (age range 34 to 67 years) fulfilling the Rome II criteria for constipation entered the study. No patient had evidence of secondary forms of constipation and distal obstruction. METHODS: Twenty-four hour colonic manometric studies were obtained for each patient. Regular contractile patterns (with frequencies ranging from 2 to 8 cycles/min) were calculated for the entire recording period and in single colonic segments. RESULTS: Overall, regular patterns accounted for about 3% of the total colonic motor activity (average 30 min/day per subject), with the 3 cycles/min being the predominant contractile rhythm. Most of this activity was present in the sigmoid colon, accounting for >50% of the total amount of motility, and it was more prevalent than in the descending and transverse colon; no differences were revealed in the descending with respect to the transverse colon. No daily fluctuations of regular contractile activity, nor a cyclic pattern, nor migration between recording points were observed. CONCLUSIONS: Regular colonic frequency patterns are probably of minor pathophysiological importance in slow transit constipation, even in the light of the scant amount of such phenomena previously documented in healthy subjects.
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Colo/fisiopatologia , Constipação Intestinal/fisiopatologia , Trânsito Gastrointestinal/fisiologia , Manometria , Contração Muscular/fisiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Monitorização Fisiológica/instrumentação , Músculo Liso/fisiopatologia , Período Pós-Prandial/fisiologiaRESUMO
Bisphosphonates have been used with success in the treatment of osteoporosis, but oral therapy often lacks compliance. Here we report the results of clinical trial with aminobisphosphonate neridronate administered intravenously (i.v.). The study included 78 postmenopausal women with spine bone mineral density (BMD) at least -2.5 SD below peak. Patients were randomized to receive for 2 years either 50 mg i.v. neridronate bimonthly and 500 mg calcium plus 400 U vitamin D supplements daily (n=39) or calcium-vitamin D supplements alone (control group, n=39). Treatment was continued over 2 years with an additional 1 year follow-up of calcium-vitamin D supplements alone. Neridronate was well tolerated with the appearance of typical clinical signs of an acute phase reaction in only 3 of the patients after the first infusion. In the control group no significant changes in BMD or bone markers were observed. In the neridronate group BMD rose progressively at the spine rose up to 7.4% +/- 6.1% (SD) and at the femoral neck up to 5.8% +/- 8.2% (SD) at the end of the second year. In the succeeding follow-up these gains were maintained at both skeletal sites. Serum bone alkaline phosphatase (bone ALP) and serum type I collagen C-telopeptide (s-CTX) significantly decreased within 2 months. The bone ALP values reached a -35% plateau after 6 months, while s-CTX attained the lowest mean value (-47%) only by the end of the treatment with neridronate. Both bone markers returned almost to baseline values 1 year after treatment discontinuation. Treatment of postmenopausal osteoporosis with 50 mg i.v. neridronate bimonthly results in clinically relevant increases in BMD, among the largest so far observed with any other bisphosphonate.
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Densidade Óssea/efeitos dos fármacos , Difosfonatos/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Idoso , Feminino , Colo do Fêmur , Humanos , Injeções Intravenosas , Vértebras Lombares , Pessoa de Meia-Idade , Projetos PilotoRESUMO
INTRODUCTION: Diverticular disease of the colon is one of the most common pathologic entities in western countries. Although altered motility of the large bowel is commonly believed to be one of the major pathophysiologic mechanisms, no convincing evidence has been reported yet. In fact, only a few conflicting studies concerning distal colonic motility (with no information on forceful propulsive activity) are available in the literature. PURPOSE: The purpose of the present study was to investigate basal and stimulated (postprandial) colonic motility from the transverse (not affected), descending, and sigmoid colon in patients with diverticular disease, together with detection of high-amplitude propagated contractions (mass movements). Motility data from patients were compared with those obtained in healthy control subjects. METHODS: Ten patients and 16 control subjects of both sexes were recruited for the study. In all subjects, colonic motility was recorded for a 24-hour period by a colonoscopically positioned manometric catheter. Two 1000-kcal mixed meals were served during the study. RESULTS: Compared with control subjects, patients with diverticular disease displayed significantly increased amounts of motility in the affected segments; the response to a physiologic stimulus (meal) was also abnormal in the patients' group. Diverticular disease patients also had a significant increase of forceful propulsive activity compared with control subjects (average = 10.3 +/- 2.7/subject/day high-amplitude propagated contractions for patients and 5.5 +/- 0.8/subject/day for control subjects; P = 0.051); interestingly, about 20 percent of such activity was abnormal, being propagated in a retrograde fashion. CONCLUSIONS: We concluded that patients with diverticular disease of the colon have abnormal motor and propulsive activities of the large bowel, which are confined to the affected segments.
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Divertículo do Colo/fisiopatologia , Motilidade Gastrointestinal , Adulto , Idoso , Estudos de Casos e Controles , Ritmo Circadiano/fisiologia , Feminino , Humanos , Masculino , Manometria/instrumentação , Pessoa de Meia-Idade , Estatísticas não ParamétricasRESUMO
Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenol present in wine, which has been reported to have anti-inflammatory, anti-platelet, and anti-carcinogenic effects. The glucuronidation of this compound and that of the cis-isomer also naturally present, has been investigated in human liver microsomes. Both isomers were actively glucuronidated. The reaction led to the formation of two glucuronides (3-O- and 4'-O-glucuronides), whose structure was characterized by LC-MS and proton NMR. Glucuronidation was regio- and stereoselective. It occurred at a faster rate with the cis-isomer and preferred the 3-position on both isomers. In addition, the glucuronidation of resveratrol was tested using several recombinant UDP-glucuronosyltransferase (UGT) isoforms. The reaction was catalyzed by UGT of the family 1A (UGT1A1, 1A6, 1A7, 1A9, 1A10). The bilirubin conjugating UGT1A1 was mainly involved in the 3-O-glucuronidation of trans-resveratrol, whereas the phenol conjugating UGT1A6 activity was restricted to cis-resveratrol. The UGT1A9 and 1A10 were active toward both isomers. The activity supported by UGT2B7 and UGT2B15 was very low and restricted to cis-resveratrol. UGT1A3, 1A4, 2B4, and 2B11 were unable to form resveratrol glucuronides.
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Anti-Inflamatórios não Esteroides/metabolismo , Ácido Glucurônico/metabolismo , Microssomos Hepáticos/metabolismo , Estilbenos/metabolismo , Glucuronosiltransferase/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Microssomos Hepáticos/enzimologia , Conformação Molecular , Proteínas Recombinantes/metabolismo , Resveratrol , UDP-Glucuronosiltransferase 1ARESUMO
A wide array of drugs, xenobiotics, and endogenous compounds undergo detoxification by conjugation with glucuronic acid in the liver via the action of UDP-glucuronosyltransferases. The mechanism whereby glucuronides, generated by this enzyme system in the lumen of the endoplasmic reticulum (ER), are exported to the cytosol prior to excretion is unknown. We examined this process in purified rat liver microsomes using a rapid filtration technique and [(3)H]estradiol-17beta-d-glucuronide ([(3)H]E(2)17betaG) as model substrate. Time-dependent uptake of intact [(3)H]E(2)17betaG was observed and shrinkage of ER vesicles by raffinose lowered the steady-state level of [(3)H]E(2)17betaG accumulation. In addition, rapid efflux of [(3)H]E(2)17betaG from rat liver microsomal vesicles suggested that the transport process is bidirectional. Microsomal uptake was saturable with an apparent K(m) and V(max) of 3.29 +/- 0.58 microm and 0.19 +/- 0.02 nmol.min(-1).mg protein(-1), respectively. Transport of [(3)H]E(2)17betaG was inhibited by the anion transport inhibitors 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid and probenecid. Specificity of the transport process was investigated by studying the cis-inhibitory effect of anionic metabolites, as well as substrates of the plasma membrane multidrug resistance-associated proteins on the uptake of [(3)H]E(2)17betaG. Collectively, these data are indicative of a novel multifunctional and bidirectional protein carrier for E(2)17betaG and other anionic compounds in the hepatic ER. This intracellular membrane transporter may contribute to the phenomenon of multidrug resistance.