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Biomedical subjects

M Vaz

Publications and source records attributed to M Vaz.

At least 37 records · Page 2Linked to original sources

Phenotypic evidence of faulty neuronal norepinephrine reuptake in essential hypertension.

Previous reports suggest that neuronal norepinephrine (NE) reuptake may be impaired in essential hypertension, perhaps because of dysfunction of the NE transporter, although the evidence is inconclusive. To further test this proposition, we applied phenotypically relevant radiotracer methodology, infusion of tritiated NE and quantification of NE metabolites, to 34 healthy lean subjects (body mass index <27.0 kg/m(2)), 19 overweight (body mass index >28.0 kg/m(2)) but otherwise healthy normotensive subjects, 13 untreated lean patients with essential hypertension, and 14 obesity-related hypertensives. Spillover of NE from the heart was increased in lean hypertensives only (mean+/-SD 33.4+/-20.6 versus 16.1+/-11.7 ng/min in lean normotensives, P<0.05), but this could have resulted from high cardiac sympathetic nerve firing rates, faulty NE reuptake, or both. The arterial plasma concentration of 3-methoxy-4-hydroxylphenylglycol, an extraneuronal metabolite of NE, was elevated in lean hypertensives only (3942+/-1068 versus 3055+/-888 pg/mL in healthy subjects, P:<0.05). The fractional extraction of plasma tritiated NE in passage through the heart, determined on the basis of neuronal NE uptake, was reduced in lean essential hypertensives (0.65+/-0.19 versus 0.81+/-0.11 in healthy subjects, P<0.05). Cardiac release of the tritiated NE metabolite [(3)H]dihydroxylphenylglycol, produced intraneuronally by monoamine oxidase after uptake of [(3)H]NE by the transporter, was reduced in lean hypertensives only (992+/-1435 versus 4588+/-3189 dpm/min in healthy subjects, P<0.01) These findings suggest that neuronal reuptake of NE is impaired in essential hypertension. Through amplification of the neural signal, such a defect could constitute a neurogenic variant of essential hypertension. In obesity-related hypertension, there was no phenotypic evidence of NE transporter dysfunction.

Adolescent↗

Skeletal muscle endurance is reduced in chronically energy deficient adults.

Fifty eight adult males (well nourished; WN = 25, underweight; UW = 13, chronically energy deficient; CED = 20), aged 18 to 30 yr underwent an assessment of skeletal muscle function using a load cell based handgrip dynamometer coupled to a polygraph. WN subjects had higher handgrip strengths than either the UW or CED subjects (P < 0.05), though not when corrected for forearm muscle area or forearm volume. CED subjects fatigued faster than WN subjects during sustained maximal isometric contraction (P < 0.05) as well as during prolonged isotonic exercise (P < 0.05). During the latter, the onset of fatigue in the CED subjects was also faster than that in their anthropometrically similar UW controls. These data are consonant with reports of decreased productivity in undernourished adults during real life tasks.

Adolescent↗

The development & characteristics of a physical activity questionnaire for epidemiological studies in urban middle class Indians.

A single page physical activity questionnaire was designed for use in epidemiological studies. The questionnaire estimates 24 h energy expenditure as well as components of occupation and discretionary leisure time activities. Estimates of physical activity were highly repeatable, when the questionnaire was re-administered within a 4 wk period (e.g., r = 0.86, P < 0.01 for 24 h energy expenditure). Relative validity was assessed by comparing energy intake (using repeated 24 h dietary recalls) and expenditure (using the physical activity questionnaire) over the same period. A correlate of r = 0.33, P < 0.05 between the two measures compared well with reports from literature. The discriminatory power of the questionnaire was assessed by comparing the physical activity patterns of young (18-30 yr) and older (> 60 yr), free living healthy subjects. The questionnaire provides a tool for the assessment of physical activity patterns of urban middle class Indians, which despite its importance has been inadequately studied so far.

Adolescent↗

Human obesity is associated with a chronic elevation in brain 5-hydroxytryptamine turnover.

The afferent signals that evoke changes in energy intake with regard to body weight regulation are presumed to arise partly from body stores, with the most likely candidate being adipose tissue depots. However, clinical investigation of the neuronal circuitry involved in the central nervous system's processing of such satiety signals remains largely unexplored. Using percutaneously placed catheters in either the right or left internal jugular veins, we were able to quantify the release of central nervous system monoamine and indoleamine neurotransmitters in 64 weight-stable male subjects with varying degrees of adiposity. Veno-arterial plasma concentration differences and internal jugular blood or plasma flow were used, according to the Fick Principle, to quantify the amount of neurotransmitter stemming from the brain. By combining this technique with a noradrenaline and adrenaline isotope dilution method for examining neuronal transmitter release, we were able to examine the association between central nervous system neurotransmitters and efferent sympathetic nervous outflow and adrenomedullary function in human obesity. We found that brain 5-hydroxytryptamine (serotonin) turnover is chronically elevated in proportion to adiposity and is increased postprandially to a similar degree in lean and obese individuals. There was no difference in the degree of sympathetic nervous activity or rate of adrenaline secretion in the subjects examined. It therefore seems that in human obesity, in the face of a chronic elevation in peripheral satiety signals, brain serotonergic processes are switched on accordingly, but the subsequent physiological response involving a reduction in food intake, increased thermogenesis and sympathetic activity is in some way impeded.

Adult↗

Neural mechanisms in human obesity-related hypertension.

OBJECTIVE: Two hypotheses concerning mechanisms of weight gain and of blood pressure elevation in obesity were tested. The first hypothesis is that in human obesity sympathetic nervous system underactivity is present, as a metabolic basis for the obesity. The second hypothesis, attributable to Landsberg, is that sympathetic nervous activation occurs with chronic overeating, elevating blood pressure. These are not mutually exclusive hypotheses, since obesity is a heterogeneous disorder. DESIGN AND METHODS: Whole body and regional sympathetic nervous system activity, in the kidneys and heart, was measured at rest using noradrenaline isotope dilution methodology in a total of 86 research voluteers in four different subject groups, in lean and in obese people who either did, or did not, have high blood pressure. RESULTS: In the lean hypertensive patients, noradrenaline spillover for the whole body, and from the heart and kidneys was substantially higher than in the healthy lean volunteers. In normotensive obesity, the whole body noradrenaline spillover rate was normal, mean renal noradrenaline spillover was elevated (twice normal), and cardiac noradrenaline spillover reduced by approximately 50%. In obesity-related hypertension, there was elevation of renal noradrenaline spillover, comparable to that present in normotensive obese individuals but not accompanied by suppression of cardiac noradrenaline spillover, which was more than double that of normotensive obese individuals (P<0.05), and 25% higher than in healthy volunteers. There was a parallel elevation of heart rate in hypertensive obese individuals. CONCLUSIONS: The sympathetic underactivity hypothesis of obesity causation now looks untenable, as based on measures of noradrenaline spillover, sympathetic nervous system activity was normal for the whole body and increased for the kidneys; the low sympathetic activity in the heart would have only a trifling impact on total energy balance. The increase in renal sympathetic activity in obesity may possibly be a necessary cause for the development of hypertension in obese individuals, although clearly not a sufficient cause, being present in both normotensive and hypertensive obese individuals. The discriminating feature of obesity-related hypertension was an absence of the suppression of the cardiac sympathetic outflow seen in normotensive obese individuals. Sympathetic nervous changes in obesity-related hypertension conformed rather closely to those expected from the Landsberg hypothesis.

Adolescent↗

Leptin is released from the human brain: influence of adiposity and gender.

Leptin, a 16-kDa circulating protein primarily derived from adipocytes, is an important factor in the regulation of appetite and energy expenditure. Using simultaneous arterio-venous blood sampling, several organs were assessed with regard to their individual roles in leptin metabolism in healthy male and female subjects constituting a range of body mass indices. Plasma leptin levels were unchanged after passage through the hepatosplanchnic and forearm circulations. In contrast, concentrations in the renal vein were consistently lower than those in the renal artery (-15%; P<0.005), indicating net extraction, whereas the brain was observed to be a net leptin releaser. Concentrations in the internal jugular vein were significantly higher than arterial levels in lean females (change, 3.0+/-1.2 ng/mL; P<0.02) and in obese males (body mass index, >28 kg/m2), but not lean (change, 2.3+/-2.3 vs. 0.1+/-0.1 ng/mL, respectively; P<0.05), indicating a probable influence of both gender and adiposity on brain leptin release. An attempt to grossly localize the site of brain release by using cerebral venous scans to distinguish between jugular venous drainage from cortical and subcortical brain areas revealed no region-specific secretion. These data raise the possibility that the brain is a nonadipose source of leptin. In addition, the higher level of brain release observed in females may contribute to the well documented gender differences in overall plasma leptin levels.

Adipose Tissue↗

Body fat topography in Indian and Tibetan males of low and normal body mass index.

Body fat topography was determined using anthropometric techniques in young, healthy, Indian and Tibetan adults. Indian subjects had significantly higher fat contents with greater abdominal obesity when compared with Tibetans matched for body mass index (BMI). This differential fat distribution may contribute, in part, to the greater cardiovascular risk of Indians. Using a cross sectional model, the data was also analysed to assess the probable changes in body fat topography with weight gain. This model suggests a preferential gain in abdominal subcutaneous fat as compared to other sites. This data may have implications while evaluating disease risks with weight gain.

Adipose Tissue↗

The development and validation of a digital peak respiratory pressure monitor and its characteristics in healthy human subjects.

A digital peak respiratory pressure (DPRP) monitor for determining maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) was developed using a pressure transducer and an analog to digital converter. It was calibrated using a mercury manometer. Human studies were conducted in healthy young adults in order to determine within-subject and inter-individual variability, as well as diurnal variations and gender differences in maximal respiratory pressures. The calibration studies for the instrument indicated that the instrument recorded accurate pressures, with little temporal drift. Within-subject variability was generally low while inter-individual variability was higher and significant. Gender differences were similar to those recorded in literature for other racial groups. The DPRP monitor described is inexpensive, accurate and portable, making it ideal for use at the patient's bedside.

Adult↗

Gender differences in muscle strength & endurance in young Indian adults.

Muscle strength was studied in 70 males and 53 females between the ages of 17-30 yr, using a handgrip dynamometer. In a subset group of 31 males and 20 females, muscle endurance during sustained isometric contraction was studied using a load cell based handgrip dynamometer coupled to a polygraph. The males had a significantly greater muscle mass and lower body fat as compared to the females. Males had close to twice the handgrip strength of females in absolute terms (P < 0.01) and this difference persisted after correction for forearm muscle area (P < 0.05). In contrast, the rate of decline of muscle strength during sustained isometric contraction was lower in females as compared to males (P < 0.05), suggestive of greater skeletal muscle endurance in females. Physical activity patterns were not a determinant of skeletal muscle function. These findings are consistent with gender specific muscle fibre characteristics reported in literature in other racial groups.

Adolescent↗

The characteristics and determinants of maximal expiratory pressure in young, healthy, Indian males.

Maximal expiratory pressure (MEP) can be used as an index of respiratory muscle strength and of the ability of an individual to cough effectively. The influence of anthropometry, nutritional status and ethnicity on MEP was studied in 113 young healthy Indian males and 53 Tibetans between 18 and 30 years of age. All subjects underwent an anthropometric assessment. Anthropometric variables (BMI, log BMI) explained only 12.5% of the variance in MEP. MEP was significantly lower in chronically undernourished subjects when compared with anthropometrically similar underweight subjects (P < 0.05). The Indian subjects had significantly lower MEP's than BMI matched Tibetan subjects (P < 0.01). This difference may have been due to the higher chest circumferences in the Tibetans (P < 0.01). While general muscle strength (maximal hand grip) and MEP were significantly correlated (r = 0.26, P < 0.01), the strength of the correlation was relatively low, suggesting that the determinants of the two measures were considerably different.

Adolescent↗

Internal jugular venous spillover of noradrenaline and metabolites and their association with sympathetic nervous activity.

It is recognized that the brain plays a pivotal role in the maintenance of blood pressure and the control of myocardial function. By combining direct sampling of internal jugular venous blood with a noradrenaline isotope dilution method, for examining neuronal transmitter release, and microneurographic nerve recording, we were able to quantify the release of central nervous system noradrenaline and its metabolites and investigate their association with efferent sympathetic nervous outflow in healthy subjects and patients with pure autonomic failure. To further investigate the relationship between brain noradrenaline, sympathetic nervous activity and blood pressure regulation we examined brain catecholamine turnover, based on the internal jugular venous overflow of noradrenaline and its principal central nervous system metabolites, in response to a variety of pharmacological challenges. A substantial increase was seen in brain noradrenaline turnover following trimethaphan, presumably resulting from a compensatory response in sympathoexcitatory forebrain noradrenergic neurones in the face of interruption of sympathetic neural traffic and reduction in arterial blood pressure. In contrast, reduction in central nervous system noradrenaline turnover accompanied the blood pressure fall produced by intravenous clonidine administration, thus representing the blood pressure lowering action of the drug. Following vasodilatation elicited by intravenous adrenaline infusion, brain noradrenaline turnover increased in parallel with elevation in muscle sympathetic nervous activity. While it is difficult to assess the source of the noradrenaline and metabolites determined in our studies, available evidence implicates noradrenergic cell groups of the posterolateral hypothalamus, amygdala, the A5 region and the locus coeruleus as being involved in the regulation of sympathetic outflow and autonomic cardiovascular control.

Adolescent↗

Epidemiological control of tuberculosis in pelotas, rio grande do sul, brazil: treatment compliance

This study assesses risk factors for treatment noncompliance by patients registered with the Tuberculosis Control Program who live in the urban area of Pelotas, Rio Grande do Sul State. The study lasted from June 1994 to December 1995. All new cases diagnosed as pulmonary tuberculosis in the 20-80-year age bracket were monitored by the Tuberculosis Unit, hub of the tuberculosis control program in Pelotas. All patients was monitored from time of diagnosis through end of treatment, six months later. Patients answered a standard questionnaire. From June 1994 to June 1995, 152 cases were recorded, with some 20% treatment noncompliance. We observed no significant association between noncompliance and employment status for head-of-family, age, gender, alcoholism, or presence of symptoms, while the only risk factor significantly associated with noncompliance was non-white skin color, probably due to the study's weak power as a function of sample size.

Journal Article↗

Integrating biostatistics and experimental physiology: students' perceptions and future scope.

The use of biostatistics in experimental physiology is recognised by researchers. However, there has been no concerted attempt to integrate biostatistics into the undergraduate experimental physiology programme. This paper describes one such initiative. The student's response to the exercise was largely positive; it enabled them to describe and interpret data more effectively and understand the experiments more completely. The attitudes of the students to the exercise and their performance at a statistics examination at the end of the exercise was determined by a number of parameters, including prior statistical knowledge, general academic performance and the extent to which they liked mathematics. However, even those students who disliked mathematics indicated that they appreciated the value of the exercise. The results indicate the need to integrate biostatistics into the undergraduate physiology course.

Biometry↗

The perceptions of first-year medical students on animal and human experiments in physiology.

This study was conducted to ascertain the attitudes of first year medical students to human and animal experimentation, while undergoing a course in Muscle and Nerve experimental Physiology. At the time of administration of the questionnaire, students had been exposed to both human as well as animal experiments. Approximately 81% of the students preferred human experiments (P < 0.05). This preference, however, was related more to the issue of enjoyability rather than the extent to which the experiment contributed to overall understanding and learning. 55% of students identified ethical issues related to laboratory experimentation. Gender and academic performance were not determinants of student's attitude to animal and human experimentation, although ethical insight was. The results suggest that while students recognize the importance and value of animal experiments, they would prefer the introduction of a larger number of human experiments.

Adult↗

Metabolic responses to repeated infusions of identical doses of norepinephrine in chronically energy deficient human subjects.

The physiological effects of three 30 min infusions of identical doses of norepinephrine (0.15 microgram/kg FFM/min) separated by 60 min intervals were assessed in well nourished (WN; n = 6) and chronically energy deficient (CED; n = 6) subjects. Each subject also underwent control, vehicle infusions with 0.9 per cent saline on a separate day. Oxygen consumption (VO2) was significantly higher during the third infusion of NE as compared to the first in both groups. This increment in VO2 occurred despite similar plasma peak NE levels in both infusions. Increments in plasma glucose and free fatty acids were also similar during the first and third infusions. The study demonstrates that thermogenic potentiation which we had earlier demonstrated in WN subjects, occurs in CED subjects as well. Thermogenic potentiation is not associated with altered plasma NE kinetics or mobilisation of substrates.

Adolescent↗