Impaired counterregulatory hormonal and metabolic response to exhaustive exercise in obese subjects.

A reduction of postprandial thermogenesis has been described in obesity; insulin resistance and/or decreased sympathetic nervous system activity seem to play the major role in its pathogenesis. On the other hand, a normal energy expenditure during exercise has been reported. At present, the response and the role of catecholamines in energy metabolism during exercise in obesity have not been well clarified yet. The aim of this work was to study the metabolic and hormonal changes caused by intense exercise in obesity. Nine obese subjects and ten normal weight controls were submitted to exhaustive exercise on a cycloergometer. Blood glucose, free fatty acids (FFA), glycerol, lactate, beta-OH-butyrate, insulin, glucagon, plasma growth hormone (HGH), catecholamine plasma levels were assayed before and at the end of exercise, and after a recovery period. The energy cost of exercise was evaluated by indirect calorimetry. In our experiment muscular exercise did not provoke any change in blood glucose and FFA plasma levels in either of our groups. In the obese subjects the insulin plasma levels were higher than in the controls. Glucagon plasma levels did not change. The exercise responses of norepinephrine (NE) (4.28 +/- 0.74 vs 8.81 +/- 1.35 nmol/l; P < 0.01), epinephrine (E) (234.21 +/- 64.18 vs 560.51 +/- 83.38 pmol/l; P < 0.01) and plasma growth hormone (HGH) (134.84 +/- 58.97 vs 825.92 +/- 195.25 pmol/l; P < 0.01) were significantly lower in obese subjects. At the end of exercise, the thermic effect of exercise did not differ between obese and control subjects (0.335 +/- 0.038 vs 0.425 +/- 0.040 kJ/min x kg fat-free mass. Our findings indicate that an impaired counterregulatory hormone response to exercise exists in obese subjects. The thermic effect of exercise does not seem to be affected by either the reduced catecholamine response nor insulin resistance.

Twice-weekly dapsone for primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1 infection: efficacy, safety and pharmacokinetic data.

OBJECTIVES: In this study we evaluated the pharmacokinetics, efficacy and safety of dapsone given 100 mg twice weekly as primary prophylaxis against Pneumocystis carinii pneumonia (PCP) in patients with HIV-1 infection. METHODS: This was a prospective open trial, evaluating a total of 55 HIV-1-infected patients with CD4 cell counts below 200/mm3 and without previous episodes of PCP. Plasma concentrations of dapsone were determined with high-performance liquid chromatography (HPLC). After a mean follow-up of 471 days, the PCP rates per year of observation were 6.79%. Discontinuation of treatment as a result of severe side effects was required in four patients (7.5%). At steady state, mean plasma concentrations 24, 72, 96 and 144 h following the administration of dapsone were 1.46plus minus0.8, 0.28plus minus0.20, 0.30plus minus0.21 and 0.37plus minus0.27 mg/L, respectively. Dapsone plasma levels showed a high interpatient variability. The values for the pharmacokinetic parameters were comparable to those described for healthy volunteers. CONCLUSIONS: The administration of 100 mg twice weekly of dapsone seems appropriate to maintain effective plasma concentrations of the drug and to prevent PCP with good safety in patients with HIV-1-related immunodeficiency.

Left ventricular diastolic function during adrenergic stress in essential hypertension: acute and chronic effects of ACE inhibition.

We studied the changes in left ventricular (LV) diastolic function induced by angiotensin-converting enzyme (ACE) inhibition at rest and during adrenergic stimulation and their relation to blood pressure (BP) variations to determine whether reductions in the renin-angiotensin system may improve diastolic function irrespective of BP reduction. Echocardiographic indices of systolic and diastolic function, plasma catecholamines as estimated by high-pressure liquid chromatography, and BP variations (Dynamap) were determined at rest and during the cold pressor test (CPT) before and 6 hours and 20 days after ACE inhibition (lisinopril), 20 mg/day by mouth in 10 subjects with uncomplicated essential hypertension. Blood Pressure was significantly reduced after both 6 hours and 20 days of therapy. The cold pressor test induced similar increases in BP in both basal conditions and after acute and chronic treatment. Catecholamine levels were unchanged by the therapy. Systolic function, evaluated by fractional shortening, ejection fraction, and systolic dV/dt, was normal and unchanged during CPT and after treatment. Diastolic function, assessed by volume curve analysis, showed a reduced percentage contribution of rapid filling to total diastolic filling, an increase in the contribution of the atrial systole, and an increase in the isovolumetric relaxation time. During CPT these parameters deteriorated further in response to increased afterload. Lisinopril therapy induced significant increases in end-diastolic volume (p < 0.005) with a progressive increase in the rapid filling dV/dt (p < 0.005 at rest; p < 0.001 during CPT) and a reduction in isovolumetric relaxation (p < 0.0001 at rest and p < 0.01 during CPT). The correlation between systolic BP (afterload) and the rapid filling dV/dt, both at rest and during CPT, was modified by treatment with the ACE inhibitor, with significantly higher rapid filling dV/dt values, and with the pressure loads equal (reduction of the slope and rightward shift of the correlation line). The improvement in diastolic function achieved by ACE inhibition at rest and during CPT appears unrelated to plasma catecholamines and only partly ascribable to the reduced pressure load. The tissue angiotensin II reduction might by itself improve the myocardial response to the pressure load and adrenergic stimulation.

Biogenic amines in the taste organ.

The presence and content of biogenic amines in taste disk-bearing fungiform papillae of the frog, Rana esculenta, the only available model of an isolated taste organ, were verified by means of HPLC. Fungiform papillae were found to contain measurable amounts of serotonin, epinephrine and norepinephrine. The amounts of serotonin and epinephrine were significantly higher in fungiform papillae than in the general mucosa of the tongue. Moreover, the epinephrine content of fungiform papillae was found to differ across the tongue, in accordance with previous physiological studies showing an inhomogeneous response of different tongue regions to taste stimuli. Ultrastructural and histochemical investigations confirmed the presence of catecholamine and serotonin. The latter was found to be contained mainly in the basal cells of the frog taste disk. These results extend previous qualitative data on the presence of biogenic amines in taste chemoreceptors.

Influence of dietary taurine on vitamin D absorption.

To evaluate the influence of dietary taurine supplementation on vitamin D absorption, we studied three groups of infants: 21 (11 preterm) were fed a taurine-free formula, 21 (10 preterm) were fed a taurine-supplemented formula (50 mg/100 g of powder) and 20 (9 preterm) were fed human, not heat-treated milk. Taurine, total bile acids, glyco-(GBA) and tauro-(TBA) conjugated bile acids, 25-hydroxyvitamin D3 (25OHD3) and 1,25-dihydroxyvitamin D3 (1,25OH2D3) were determined in all infants at birth in blood cord and at one and three months of life. In preterm infants fed a taurine-free formula, we found lower plasma taurine levels than in infants of other groups at one and three months of life. In these infants, GBA predominated, with a G/T ratio of 1.1 and 1.4 at one and three months of life, whereas in all other infants TBA predominated with a G/T ratio always < 1. Also, 25OHD3 and 1,25OH2D3 levels were significantly lower in preterm infants fed a taurine-free formula than in infants fed a taurine-enriched formula or human milk. Term infants fed a taurine-free formula did not show differences in the parameters studied in comparison to infants of other groups. Low taurine dietary intake appears to compromise vitamin D absorption in preterm infants, and therefore taurine supplementation of preterm infant formulas should be encouraged.

Plasma acetate levels in a group of obese diabetic, obese normoglycemic, and control subjects and their relationships with other blood parameters.

Acetate is a short-chain fatty acid derived from colonic fermentation of carbohydrate and dietary fiber, and from endogenous glucose and fatty acid metabolism in the liver. An impaired acetate metabolism has been reported in diabetic subjects. The aim of the study was to evaluate plasma acetate levels in a group of obese diabetic subjects, compared with obese normoglycemic subjects and normal control subjects. Eleven noninsulin-dependent diabetic patients taking oral antidiabetic drugs, eight obese normoglycemic subjects, and seven control subjects were studied. Liver, kidney, and gut functions were normal in all subjects. Blood acetate, glucose, insulin, and C-peptide were evaluated in all subjects. Acetate levels were significantly higher in the diabetic subjects than in obese normoglycemic and normal subjects. Significant correlations between HbA1c, glucose, and acetate levels, but not between acetate and C-peptide or insulin, were also observed.

Preliminary report on histamine release, circulating immune complexes, and complement activation in children with atopic dermatitis after oral challenge with milk and egg antigens.

The effects of dietary restriction and food challenge were evaluated in five children with atopic dermatitis, as a possible predictive marker for the dietary management of this clinically perplexing disease. Two of the five showed significant elevation of plasma histamine; an additional two demonstrated the presence of immune complexes and in the fifth no change was described. The results of these study lend further support to the causal relationship between food allergy and atopic dermatitis, and suggest that the use of these immunologic parameters may be useful in the clinical assessment and management of these patients.

Simultaneous measurement of 1.25-dihydroxy-vitamin D, 24.25-dihydroxy-vitamin D and 25-hydroxy-vitamin D from a single two milliliters serum specimen. Preliminary clinical application.

A simple method for extraction, purification and separation of the principal vitamin D metabolites from a single serum sample is described. The method involved extraction of serum with acetonitrile followed by a first purification employing C-18 Sep-pak cartridges eluted with methanol/water and acetonitrile. Final separation before assay was carried out by high pressure liquid chromatography. 1.25-dihydroxy-vitamin D was measured with radioimmunoassay using an antiserum (S11) with high selectivity for 1 alpha-OH function of the hormone at a final dilution of 1:100,000. 24.25-dihydroxy-vitamin D and 25-hydroxy-vitamin D were measured employing a competitive binding assay with normal rat serum at a final dilution of 1:10,000 as source of binding protein. The mean (+/- SD) serum 1.25-dihydroxy-vitamin D, 24.25-dihydroxy-vitamin D and 25-hydroxy-vitamin D concentrations for a group of healthy subjects were 50.4 +/- 17.3 pg/ml, 2.3 +/- 2.6 ng/ml and 20.8 +/- 12.3 ng/ml, respectively. 1.25-dihydroxy-vitamin D concentrations were low or undetectable in patients on dialysis or with mild renal failure. High 1.25-dihydroxy-vitamin D levels were found in 2 out of 17 patients with primary hyperparathyroidism. In 4 normal subjects treated for two weeks with large doses of 25-hydroxy-vitamin D, serum 25-hydroxy-vitamin D rose from 12.5 ng/ml to 119 ng/ml and from 0.89 ng/ml to 15 ng/ml, respectively; no changes in the 1.25-dihydroxy-vitamin D assay were found.

Serum copper and ceruloplasmin levels in rheumatoid arthritis and degenerative joint disease and their pharmacological implications.

Serum copper concentration and ceruloplasmin activity were measured in patients with clinically established rheumatoid arthritis (R.A.) during the active phase, in patients with degenerative joint disease (D.J.D.) and in normal subjects. Copper and ceruloplasmin serum levels are significantly increased (P less than 0.01) in the arthritic group, but not in the degenerative joint disease group. Copper and ceruloplasmin levels are high significantly correlated in all the groups. This parallel enhancement of serum copper and ceruloplasmin in R.A. is commented in view of a possible protective role of endogenous copper and/or ceruloplasmin in inflammation.

A longitudinal study on plasma somatomedin activity in full-term, preterm and small-for-gestational age newborns.

Plasma somatomedin (SM) activity was measured longitudinally in the first days of life by Van den Brande bioassay in 10 term, 8 premature and 5 small-for-date newborns. Other term, premature and small-for-date newborns were assayed between the 4th and 8th days by a cross-sectional-type study. A very significant increase in SM activity was observed in term newborns on the 3rd day lasting for about a week, when values usually observed in young children were reached. In premature and small-for-date newborns such an increase was not present but rather a slight decrease on the 3rd day was observed. The presence of a circulating inhibitory substance in the plasma of premature and small-for-date newborns with undetectable SM activity was shown.

Copper IUD emission and its effects on human cervical mucus: spermatozoa interaction.

PIP: Total copper concentrations in the cervical mucus of 90 IUD-free women were measured at different times in their menstrual cycle using an atomic spectrophotometer and a 'Perkin Elmer 303' graphite furnace. The same procedure was done in another 109 subjects using various types of IUD (9 Dalkon Shields; 4 Progestaserts; 8 Copper Ts; 10 Copper Ts; 5 ml Cu 250s; 73 No-Gravid 1s, and; 4 No-Gravid 2s). Another groups of 123 IUD users was studied (16 Copper Ts; 16 Gravigards; 60 No. Gravid 1s; and 31 No-Gravid 2s), as were 17 IUD-free women and 30 No-Gravid IUD users. The cervical mucus samples were subjected to some spermetozoa tests (drop-to-drop admixture and penetration test and Kremer Test). The copper values in all subjects were lower in the follicular than in the luteal phase of the menstrual cycle. Women with copper IUDs also exhibited higher copper levels than those with non-copper IUDs. Copper levels were highest (up to 3 times) with the No-Gravid devices, even when measured after 30 months from insertions. Daily copper losses were also found to be greatest with the No-Gravid devices, with the greatest losses occurring within the 1st 6 months. Estimated time for 50% loss was 4 years. In comparing interaction of spermatozoa with the cervical mucus of women with No-Gravid devices and those without IUD, lower migration distances and penetration densities were observed in the No-Gravid cases.^ieng