Biomedical subjects

R B Oliveira

Publications and source records attributed to R B Oliveira.

At least 19 recordsLinked to original sources

PubMed2006

A novel biomagnetic approach to study caecocolonic motility in humans.

Motility patterns play a major role in human colonic functions; however, its physiological significance is poorly understood. Several studies have been introducing the Alternating Current Biosusceptometry (ACB) as a valuable tool in gastroenterology and pharmaceutical research. Using gold standard techniques, great effort has been made to validate ACB as a method for measuring gastrointestinal motility in humans and animals. The aim of this study was to evaluate caecocolonic motility and its response to a meal in healthy volunteers. The results showed a dominant frequency of 3.17 +/- 0.13 cycles per minute (mean +/- SD) that remained unchanged even after a standardized meal (P > 0.01). The colonic response to a meal was recorded as a considerable increase in amplitude, reflected by motility index (P < 0.01) and was observed for all the volunteers. The caecocolonic motility could be assessed by the ACB providing new insights into physiological patterns of motility. Moreover, the method is non-invasive, radiation-free, cost-effective and independent of bowel preparation.

Adult↗

PubMed2005

Magnetic images of the disintegration process of tablets in the human stomach by ac biosusceptometry.

Oral administration of solid dosage forms is usually preferred in drug therapy. Conventional imaging methods are essential tools to investigate the in vivo performance of these formulations. The non-invasive technique of ac biosusceptometry has been introduced as an alternative in studies focusing on gastrointestinal motility and, more recently, to evaluate the behaviour of magnetic tablets in vivo. The aim of this work was to employ a multisensor ac biosusceptometer system to obtain magnetic images of disintegration of tablets in vitro and in the human stomach. The results showed that the transition between the magnetic marker and the magnetic tracer characterized the onset of disintegration (t(50)) and occurred in a short time interval (1.1 +/- 0.4 min). The multisensor ac biosusceptometer was reliable to monitor and analyse the in vivo performance of magnetic tablets showing accuracy to quantify disintegration through the magnetic images and to characterize the profile of this process.

Administration, Oral↗

PubMed2005

AC biosusceptometry in the study of drug delivery.

Conventionally, pharmaceutical substances are administered orally because the gastrointestinal tract possesses the appropriate features for drug absorption. Nevertheless, the gastrointestinal tract physiology is complex and influenced by many factors. These factors must be completely understood for the optimization of oral drug delivery systems. Although in vitro tests provide information about release and drug absorption profiles, in vivo studies are essential, due to the biological variability. Several techniques have been employed in an attempt to conveniently characterize the behavior of solid dosage forms in vivo. The noninvasive biomagnetic technique of alternate current biosusceptometry (ACB) has been used in studies focusing on gastrointestinal motility and, more recently, to evaluate the performance of magnetic dosage forms. This article will discuss the main characteristics of AC biosusceptometry and its applicability for determination of the relationship between the human gastrointestinal tract and orally administered pharmaceutical dosage forms.

Drug Delivery Systems↗

PubMed2005

Spatiotemporal evaluation of human colon motility using three-axis fluxgates and magnetic markers.

An alternative method to study the mechanical activity of the human colon in fasting and postprandial states is presented. The method is based on measurements of the magnetic fields produced by a magnetic marker, a small cylindrical NdBFe magnet, when it was ingested by the subjects. A portable magnetic probe, consisting of two digital three-axis fluxgate magnetometers, arranged in a first-order electronic gradiometer, was implemented for this research. Measurements were taken in 16 healthy male subjects. Contractile activity frequency measurements were taken along the colon length, including the ascending, transverse and descending sections, as well as the rectal sigmoidal section. Values for the contractile activity frequency of 2-5 cycles min(-1) were measured. The set-up is simple, low-cost and suitable for use in an unshielded environment.

Adult↗

PubMed2004

Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice.

BACKGROUND: Tumour necrosis factor alpha (TNF-alpha) is involved in non-steroidal anti-inflammatory drug induced gastropathy. Nitric oxide (NO) is a mediator of gastrointestinal mucosal defence but, paradoxically, it also contributes to mucosal damage. AIMS: We optimised the C57BL/6 mouse model of indomethacin induced gastropathy to evaluate the role of TNF-alpha and inducible nitric oxide synthase (iNOS) generated NO in gastric damage and granulocyte infiltration using tumour necrosis factor receptor 1 (TNF-R1-/-) or iNOS (iNOS-/-) deficient mice. METHODS: Different doses of indomethacin (2.5, 5, 10, 20 mg/kg) were administered and animals were assessed 6, 12, or 24 hours later. Gastric damage was measured by the sum of all erosions in the gastric mucosa, and gastric granulocyte infiltration was determined by myeloperoxidase (MPO) activity. Other groups of wild-type mice received thalidomide, dexamethasone, fucoidin, L-NAME, or 1400W, and then indomethacin was administered. Additionally, indomethacin was administered to TNF-R1-/- or iNOS-/-. Gastric damage and MPO activity were evaluated 12 hours later. RESULTS: Indomethacin induced dose and time dependent gastric damage and increase in MPO activity in wild-type mice, with the greatest effect at a dose of 10 mg/kg and after 12 hours. Treatment with thalidomide, dexamethasone, or fucoidin reduced gastric damage and MPO activity induced by indomethacin. After indomethacin administration, TNF-R1-/- had less gastric damage and MPO activity than controls. Genetic (knockout mice) or pharmacological (1400W and L-NAME) inhibition of iNOS activity reduced indomethacin induced gastric damage, despite no reduction in MPO activity. CONCLUSION: TNF-alpha, acting via TNF-R1, is involved in indomethacin induced gastric damage and granulocyte infiltration. Furthermore, iNOS generated NO is involved in gastric damage induced by indomethacin.

Amidines↗

PubMed2003

Decreased gastric tone and delayed gastric emptying precede neutrophil infiltration and mucosal lesion formation in indomethacin-induced gastric damage in rats.

Gastric antral dysmotility has been implicated in the pathogenesis of indomethacin-induced gastric damage, but the relationship between gastric motor abnormalities and mucosal lesions has not been extensively studied. We investigated whether changes in gastric tone and gastric retention correlate with mucosal lesions and neutrophil migration in indomethacin-induced gastric damage in rats. Indomethacin, either 5 or 20 mg/kg (INDO-5 and INDO-20), was instilled into the stomach, and then gastric damage, neutrophil migration, gastric tone and gastric retention were assessed 1 or 3 h later. Gastric damage was calculated as the sum of the lengths of all mucosal lesions, and neutrophil migration was measured by assaying myeloperoxidase activity. Gastric tone was determined by a plethysmometric method, and gastric retention of either saline or Sustacal was evaluated by a scintigraphic method. Gastric damage was detectable 3 h after either INDO-5 or INDO-20, but not after 1 h. Neutrophil migration was significantly higher 3 h after INDO-20 as compared with INDO-5 or control group, but not after 1 h. Values of gastric tone 1 and 3 h after either INDO-5 (1 h = 1.73+/-0.07 ml; 3 h = 1.87+/-0.03 ml) or INDO-20 (1 h = 1.70+/-0.02 ml; 3 h = 1.79+/-0.03 ml) were significantly lower than in controls (1 h = 1.48+/-0.05 ml; 3 h = 1.60+/-0.06 ml). Gastric retention of saline was higher 1 h after INDO-5 (58.9+/-3.3%) or INDO-20 (56.1+/-3.1%) compared to control (45.5+/-1.7%), but not after 3 h. There were no differences concerning gastric retention of Sustacal between the various groups. Indomethacin induced decreased gastric tone and delayed gastric emptying, which precede mucosal lesion and neutrophil infiltration. These results indicate that there is no relationship between these gastric motor abnormalities and mucosal lesion in indomethacin-induced gastropathy.

Animals↗

PubMed2003

Measurement of gastric contraction activity in dogs by means of AC biosusceptometry.

The mechanical nature of gastric contraction activity (GCA) plays an important role in gastrointestinal motility. The aim of this study was to detect GCA in anaesthetized dogs, using simultaneously the techniques of AC biosusceptometry (ACB) and manometry, analysing the characteristics of frequency and amplitude (motility index) of GCA, modified by drugs such as prostigmine and N-butyl-scopolamine. The ACB method is based on a differential transformer of magnetic flux and the magnetic tracer works as a changeable external nucleus. This magnetic tracer causes a modification in the magnetic flux, which is detected by the coils. The results obtained from the ACB showed a performance comparable to the manometry in measuring the modifications in the frequency and amplitude of the GCA. We concluded that this ACB technique, non-invasive and free of ionizing radiation, is an option for evaluating GCA and can be employed in future clinical studies.

Anesthesia↗

PubMed2001

Distribution of methylmercury and inorganic mercury in neonate hamsters dosed with methylmercury during fetal life.

The study of the effects of methylmercury (MeHg) contamination has intensified since the MeHg outbreaks in Japan and Iraq. However, most of these studies used high doses of MeHg to obtain its most severe effects. This work identified the MeHg targets in neonate hamsters after administration of two different single oral doses of radiolabeled methylmercury chloride (Me203HgCl) to two groups of pregnant hamsters. The low-dose group received 0.05 microg of 203Hg as Me203HgCl per gram of body weight and the radioactivity was 6.6x10(3) Bq. The high-dose group received 0.55 microg of 203Hg as Me203HgCl per gram of body weight with 2x104 Bq. In the first day of life, the brain was the organ with the highest Me203Hg concentration, followed by the liver, kidneys, and intestines. However, these values of Me203Hg decreased at different rates in all organs until 12 days of life, whereas total 203Hg in the body did not change during the same period. This suggests an age-dependent Me203Hg body distribution instead of an elimination of Me203Hg from the body.

Animals↗

PubMed2001

Pharyngeal clearance and pharyngeal transit time determined by a biomagnetic method in normal humans.

Clearance and transit time are parameters of great value in studies of digestive transit. Such parameters are nowadays obtained by means of scintigraphy and videofluoroscopy, with each technique having advantages and disadvantages. In this study we present a new, noninvasive method to study swallowing pharyngeal clearance (PC) and pharyngeal transit time (PTT). This new method is based on variations of magnetic flux produced by a magnetic bolus passing through the pharynx and detected by an AC biosusceptometer (ACB). These measurements may be performed in a simple way, cause no discomfort, and do not use radiation. We measured PC in 8 volunteers (7 males and 1 female, 23-33 years old) and PTT in 8 other volunteers (7 males and 1 female, 21-29 years old). PC was 0.82 +/- 0.10 s (mean +/- SD) and PTT was 0.75 +/- 0.03 s. The results were similar for PC but longer for PTT than those determined by means of other techniques. We conclude that the biomagnetic method can be used to evaluate PC and PTT.

Adult↗

PubMed2000

Pharmacological profile of nitrergic nerve-, nitric oxide-, nitrosoglutathione- and hydroxylamine-induced relaxations of the rat duodenum.

Activation of inhibitory nonadrenergic noncholinergic (NANC) nerves in the rat duodenum cause relaxations, which are reduced by nitric oxide synthase (NOS) inhibitors indicating that this response involves a nitrergic neurotransmission. The precise nature of the nitrergic neurotransmitter is still controversial since nitric oxide (NO) scavengers and superoxide generators, even in the presence of superoxide dismutase inhibitors, failed to inhibit nitrergic neurotransmission mediated relaxations. In order to understand the role of NOS in nitrergic neurotransmission and considering that N-OH-arginine (OH-L-Arg), L-citrulline, NO, S-nitrosoglutathione (GSNO) and hydroxylamine (NH2OH) can be formed in cells during the N(G)-oxidation of L-arginine catalyzed by NOS we explored whether any of these products could exhibit biological properties comparable to those of the nitrergic neurotransmitter. After establishing which of them was able to relax the rat duodenum, the pharmacological profile of such effect was determined employing oxyhemoglobin (OxyHb), pyrogallol (PYR), hydroquinone (HQ), hydroxocobalamin (HC) or carboxy-PTIO (C-PTIO) and compared with that of nerve mediated relaxations. NO, GSNO and NH2OH, but not OH-L-ARG and L-citrulline, caused concentration-dependent relaxations that were not affected by tetrodotoxin or L-NOARG. OxyHb almost abolished NO-induced relaxations but decreased only marginally the magnitude of nerve-, NH2OH- and SNG-induced relaxations. PYR, HQ and C-PTIO reduced significantly GSNO- and NO- induced relaxations but did not affect those induced by NH2OH or nerve activation. In contrast, HC abolished NO-induced relaxations while it did not affect those induced by GSNO, NH2OH and nerve activation. The catalase inhibitor 1,2,4 aminotriazole failed to affect nerve and NH2OH induced relaxations. These findings indicate that among the products that can be formed during NOS catalyzed L-arginine N(G)-oxidation, only NH2OH caused relaxations that exhibited a pharmacological profile similar to those induced by the nitrergic neurotransmitter. Furthermore, if NH2OH is the actual neurotransmitter it appears to be acting either directly or by a catalase independent release of NO.

Animals↗

PubMed2000

T cell-monocyte contact enhances tumor necrosis factor-alpha production in response to Mycobacterium leprae.

Tumor necrosis factor (TNF)-alpha has been implicated as a key factor in inflammatory processes occurring in erythema nodosum leprosum (ENL). In the present study, the roles of soluble factors and contact-mediated interaction in the induction of enhanced TNF-alpha secretion in leprosy have been investigated. In vitro studies have demonstrated that Mycobacterium leprae per se is a poor stimulus for TNF-alpha production by purified monocytes obtained from normal subjects, although this could be enhanced by either exogenous interferon-gamma or cell contact with fixed activated T lymphocytes. Further investigations demonstrated that monocyte-T cell contact enhanced M. leprae-induced TNF-alpha production by peripheral blood mononuclear cells of ENL patients and was modulated by blocking antibodies to CD40L, CD69, and CD18. These results suggest that physical contact with T cells isolated from patients in a particular disease state (ENL) modulates monocyte function and may contribute to the secretion of proinflammatory cytokines described in ENL.

Adult↗

PubMed2000

Abnormally rapid gastric emptying of an isosmotic liquid meal in patients with megaduodenum.

Duodenal resistance to gastric outflow is known to participate in the regulation of gastric emptying of liquids in animals, but the role of this mechanism in humans has not been extensively investigated. In this work we studied the gastric emptying of liquids in patients with megaduodenum, who putatively have increased duodenal receptivity to gastroduodenal transfer of liquids. Subjects included eight patients with megaduodenum and eight healthy volunteers. Since megaduodenum in all cases was associated with Chagas' disease, a further reference group consisting of 11 chagasic patients without megaduodenum was also studied. Fasted subjects ingested 200 ml of an isotonic dextrose solution labeled with 15 MBq of technetium-99m coupled to sulfur colloid, as an unabsorbable marker. Images of the anterior aspect of the stomach were taken immediately after test meal ingestion and thereafter up to 1 hr. Decay-corrected counts over the gastric region along time yield the calculation of early (5 min) and late (60 min) gastric retention as well as gastric emptying half-times (T1/2). Early gastric retention in patients with megaduodenum (median; range: 48%; 18-64%) was significantly lower (P < 0.05) than in both patients without megaduodenum (59%; 40-86%) and controls (82%; 68-99%). T1/2 values in patients with megaduodenum (5 min; 3-17 min) were also significantly lower (P < 0.01) than in patients without megaduodenum (23 min; 4 to >60 min) and controls (29 min; 13-60 min). There were no significant differences between the three groups concerning late gastric retention. We conclude that the early phase of gastric emptying of liquids is abnormally accelerated in patients with megaduodenum, which suggests that increased duodenal receptivity may have a significant effect on the gastroduodenal transfer of liquids in humans.

Adult↗

PubMed2000

Autonomic nervous function in alcohol-related chronic pancreatitis.

Patients with alcohol-related chronic pancreatitis (ARCP) often have peripheral neuropathy, but no data on the occurrence of autonomic neuropathy (AN) are available for this condition. To assess the autonomic function and the significance of its abnormalities for the prognosis of ARCP, 18 patients with ARCP and associated diabetes mellitus (P-DM group), 10 with ARCP without evidence of diabetes mellitus (P group), 17 patients with insulin-dependent diabetes mellitus (IDDM group), and 18 healthy controls answered a structured questionnaire and underwent three standardized cardiovascular (CV) tests that yielded six different parameters for autonomic nerve function. Patients with at least one symptom plus two abnormal results on CV tests were regarded as having AN. ARCP patients were followed up for 48 months and mortality rates were recorded. The proportions of patients with AN were 66.6% in the P-DM group, 30.0% in the P group, and 29.4% in IDDM patients. Seven of 15 ARCP patients with AN died during follow-up, compared with one of 13 of those without AN (p < 0.037). In conclusion, AN is commonly found in ARCP patients and carries an ominous prognosis.

Adolescent↗

PubMed1999

Neutrophils isolated from leprosy patients release TNF-alpha and exhibit accelerated apoptosis in vitro.

This study demonstrated that polymorphonuclear neutrophils (PMN) participate in the acute inflammatory response in leprosy as effector cells. Lepromatous patients present intense infiltrate of neutrophils in reactional (ENL) lesions. Circulating PMN of nonreactional patients, healthy donors, and reactional patients were purified and analyzed in vitro. The study confirmed the short lifespan of these cells in culture with progressive changes characteristic of apoptosis. Apoptosis was greatly accelerated in ENL patients as shown by cellular morphology, later confirmed by qualitative and quantitative analysis of fragmented DNA. It was observed that neutrophils stimulated with lipopolysaccharide, Mycobacterium leprae, and lipoarabinomannan secrete interleukin-8 and tumor necrosis factor alpha (TNF-alpha). Thalidomide, a drug known to inhibit TNF-alpha synthesis on monocytes, also exerted an inhibitory effect on TNF-alpha secretion in neutrophils. These data suggest that PMN can participate in the regulation of the immune response in leprosy and can contribute to the amplification of TNF-alpha production at the site of ENL lesion.

Apoptosis↗

PubMed1999

Prognostic factors in fetal hydronephrosis: a multivariate analysis.

With the increasing use of obstetric echography fetal hydronephrosis has been reported more frequently. The purpose of this study was to identify prognostic factors associated with adverse outcome, such as renal failure and death, in fetal hydronephrosis. One hundred and forty-eight children with fetal hydronephrosis were admitted, submitted to a systematic protocol, and prospectively followed. Prognostic factors associated with fetal echography and clinical and laboratory findings on admission were studied. The median follow-up was 39 months. The analysis was conducted in two steps. In a univariate analysis, variables associated with adverse outcome were identified by the Kaplan-Meier method. The variables that were significantly associated with adverse outcome were then included in a multivariate analysis. This analysis, using the multivariate Cox's model, was performed to identify variables that were independently associated with a worse prognosis. Only variables that remained independently associated with adverse outcome were included in the final model. After final adjustment by Cox's multivariate model, three variables were identified as independent predictors of adverse outcome: oligohydramnios, prematurity, and glomerular filtration rate lower than 20 ml/min. Thus, in the presence of oligohydramnios, prematurity, and abnormal renal function, the medical team must plan appropriate follow-up for infants at health centers prepared to investigate and treat uropathies in newborns.

Algorithms↗

PubMed1999

Effect of hydroquinone, hydroxocobalamin and carboxy-PTIO on non-adrenergic non-cholinergic nerve mediated relaxations of the rat duodenum.

Relaxation induced by NANC-nerve stimulation is reduced by nitric oxide synthase (NOS) inhibitors but not by superoxide generators or NO scavengers, casting doubts on the precise nature of the neurotransmitter being released by these nerves. The lack of effect of superoxide anion generators to inhibit nitrergic nerve-mediated relaxations has been attributed to the protective action of high tissue levels of superoxide dismutase (SOD). The effects of hydroquinone, hydroxocobalamin and carboxy-PTIO, three NO inactivators which do not depend on superoxide anion generation, upon nitrergic nerve-mediated relaxations of the rat proximal duodenum were determined in order to elucidate whether they are mediated by free NO. GABA and nicotine caused relaxations of isolated segments of the rat proximal duodenum in a concentration-dependent manner that were abolished by tetrodotoxin (TTX). Similarly, transmural electrical stimulation (TES) caused frequency-dependent relaxations that were also abolished by TTX. The NOS inhibitors L-NAME and L-NOARG reduced in a concentration-dependent manner nerve-mediated relaxations elicited by TES, nicotine and GABA. The effect of NOS inhibitors was prevented by L-arginine but not D-arginine. NO caused concentration-dependent relaxations that were not affected by TTX or L-NOARG but were abolished by hydroquinone, hydroxocobalamin and carboxy-PTIO. In contrast, these compounds failed to affect TES-, nicotine- and GABA-induced relaxations. The lack of effect of hydroquinone, hydroxocobalamin and carboxy-PTIO upon nerve-mediated relaxations was unaltered by pretreatment with the SOD irreversible inhibitor DETCA. The present findings show that nitrergic nerve-mediated relaxations of the rat duodenum are unaffected by NO inactivators that do not generate superoxide anion. It is suggested that either a NO-containing molecule that is unreactive with the inactivators tested is the inhibitory neurotransmitter released by nitrergic nerves or that NOS activity fulfills another role in nitrergic nerves which could be related to the release of an still unidentified transmitter.

Animals↗

PubMed1999

Study of stomach motility using the relaxation of magnetic tracers.

Magnetic tracers can be observed in the interior of the human body to give information about their quantity, position and state of order. With the aim of detecting and studying the degree of disorder of these tracers after they have been previously magnetized inside the stomach, a system composed of magnetization coils and magnetic detectors was developed. Helmholtz coils of diameter 84 cm were used to magnetize the sample and the remanent magnetization (RM) was detected with two first-order gradiometric fluxgate arrays each with a 15 cm base line, sensitivity of 0.5 nT and common mode rejection (CMR) of at least 10. The system allows simultaneous measurement in the anterior and posterior projections of the stomach. Measurements of the time evolution of the RM were performed in vitro and in normal subjects after the ingestion of a test meal labelled with magnetic particles. The data were fitted with an exponential curve and the relaxation time tau was obtained. Initial studies were performed to ascertain the action of a drug that is known to affect the gastric motility, showing that the decay of the remanent magnetization was indeed due to stomach contractions.

Butylscopolammonium Bromide↗

PubMed1998

Abnormal intragastric distribution of a liquid nutrient meal in patients with diabetes mellitus.

Disordered gastric motility and emptying are well known complications of diabetes mellitus (DM), but the pattern of intragastric distribution of food has not been extensively studied in diabetics. We examined the partition of a liquid nutrient meal between the proximal and distal stomach and the relationships between intragastric distribution of food and gastric emptying (GE) and the symptoms in DM patients with and without autonomic neuropathy (AN). Fourteen healthy volunteers and 20 DM patients (13 with AN; 9 with dyspepsia symptoms) ingested a liquid nutrient meal (250 ml; 437 kcal) labeled with [99mTc]phytate. Anterior and posterior serial images of the stomach were taken for 90 min with a gamma camera. Regions of interest for the proximal and the distal halves of the stomach and for the total gastric area were defined. Counts from each region along time allowed estimation of GE and the proportion of activity retained in the proximal stomach after meal ingestion (initial) and throughout GE (mean). GE half-times in controls (median; range: 66 min; 29-90 min) were not significantly different from diabetics (76 min; 5->150 min, P > 0.10), but abnormal GE was found in 11 DM patients (seven delayed and four rapid). In DM patients, initial retention in the proximal stomach (42%; 16-79%) was significantly lower (P < 0.02) than in controls (55%; 44-71%). Mean retention in the proximal stomach throughout emptying also was significantly lower (P < 0.05) in DM patients (43%; 18-58%) than in controls (51%; 32-69%). There were no differences between subgroups of patients with normal, delayed, or rapid gastric emptying regarding mean meal retention in the proximal stomach. Patients with evidence of AN or with dyspepsia symptoms had significantly decreased retention of food in the proximal stomach throughout gastric emptying. We concluded that patients with diabetes mellitus have abnormally decreased retention of gastric contents in the proximal stomach after a liquid meal, which seems to be related to the occurrence of autonomic neuropathy and dyspepsia symptoms, but not to disordered gastric emptying.

Adult↗