3-Diazopyrroles. Part 5 (1). Antibacterial activity of 3-diazo-2-phenylpyrroles.

3-Diazo-2-phenylpyrroles 3a-g showed antimicrobial activity against Gram-positive bacteria, whereas against Gram-negative strains the inhibitory activity is limited to derivatives 3a and 3c. The substituents at 4 and 5 positions strongly influence the inhibitory activity, but the presence of the diazo group is crucial for appearance of activity.     

Effects of 'central hypervolemia' by Water immersion on renin-aldosterone system and ACTH-cortisol axis in hemodialyzed patients

Water immersion up to the neck (WI) results in a central hypervolemia; the increased atrial pressure, evoked by this maneuver, stimulates low pressure receptors (LPR) which exert tonic inhibition on sympathetic activity and suppresses both the renin (PRA)-aldosterone (PA) system and the ACTH-cortisol axis in normal man. In hemodialyzed patients (HP), in whom autonomic neuropathy has been frequently found, PRA and ACTH were not suppressed during WI while plasma cortisol and PA were reduced. Other modulators, like dopamine, are supposed to be involved in regulating cortisol and PA levels in HP.     

Patients with antinuclear antibody-positive juvenile idiopathic arthritis constitute a homogeneous subgroup irrespective of the course of joint disease

OBJECTIVE: We recently hypothesized that in the International League of Associations for Rheumatology (ILAR) classification of juvenile idiopathic arthritis (JIA), the presumably homogeneous patient group characterized by early onset of disease, a female predilection, the presence of antinuclear antibodies (ANA), asymmetric arthritis, and the risk for iridocyclitis is classified into different categories. We sought to investigate whether ANA-positive patients belonging to the ILAR categories of oligoarthritis and rheumatoid factor (RF)-negative polyarthritis share homogeneous features and to compare these features with those of ANA-negative patients with JIA in the same categories. METHODS: We identified patients who were followed up during a 15-year period. All patients had JIA according to the ILAR criteria, with oligoarticular or polyarticular onset. ANA positivity was defined as 2 or more positive results at a titer of >or=1:160. Demographic and clinical features, including the number of joints involved over time and measures of JIA severity at the last followup visit, were recorded retrospectively. RESULTS: A total of 256 patients were included: 190 were ANA positive (109 had persistent oligoarthritis, 48 had extended oligoarthritis, and 33 had RF-negative polyarthritis), and 66 were ANA negative (35 had RF-negative polyarthritis, and 31 had oligoarthritis). All patients who were positive for ANA were similar in terms of age at disease presentation, female-to-male ratio, and frequency of symmetric arthritis and iridocyclitis. Compared with ANA-positive patients with polyarticular disease, ANA-negative patients with polyarticular arthritis were older at disease presentation and had a lower frequency of iridocyclitis, a higher frequency of symmetric arthritis, a greater cumulative number of joints affected over time, and a different pattern of joint disease, with a greater frequency of shoulder and hip involvement. The strong relationship between the presence of ANA and younger age at disease presentation, asymmetric arthritis, and development of iridocyclitis was confirmed by multivariate regression analysis. CONCLUSION: Our results support the hypothesis that patients with similar characteristics are currently classified into different JIA categories. The value of ANA positivity as a possible modifier of the current classification system deserves consideration.     

Body weight, diet and water intake in preventing stone disease

Nutrition plays a major role in the pathogenesis of the most widespread forms of nephrolithiasis, i.e. calcium (calcium oxalate and phosphate) and uric acid stone disease. For this reason, dietary measures are the first level of intervention in primary prevention, as well as in secondary prevention of recurrences. An unbalanced diet or particular sensitivity to various foods in stone formers can lead to urinary alterations such as hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia and an excessively acid urinary pH. Over the course of time, these conditions contribute to the formation or recurrence of kidney stones, due to the effect they exert on the lithogenous salt profile. The fundamental aspects of the nutritional approach to the treatment of idiopathic nephrolithiasis are body weight, diet and water intake. This paper will present data resulting from our own investigations and the most significant evidence in literature.     

Role of blood pressure in the natriuretic response to acute calcium channel blockade in humans.

Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and renal excretion of sodium and lithium were measured before and after acute oral administration of 20 mg nifedipine in 19 essential hypertensive patients. In 10 of them, with a diastolic pressure less than 105 mm Hg, nifedipine resulted in a decrease in mean blood pressure toward normal (109 +/- 2 to 97 +/- 2, p less than 0.001), a 27% increase in ERPF (p less than 0.001), no change in GFR, and an increase in fractional sodium excretion (28%, p less than 0.001). In nine subjects with a diastolic pressure greater than or equal to 105 mm Hg, nifedipine produced a decrease in mean blood pressure (133 +/- 6 to 117 +/- 4, p less than 0.001), which however remained higher than in mild hypertensives (p less than 0.001). ERPF rose by 29% (p less than 0.001), GFR remained unchanged, and fractional sodium excretion definitely increased more than in mild hypertensives (126%, p less than 0.001), as did fractional lithium excretion, used as an estimate of proximal tubular sodium handling. Acute nifedipine produces renal vasodilation in hypertensives, but with a greater natriuretic response in those subjects whose blood pressure remains elevated. Thus, acute natriuresis following nifedipine administration is largely dependent on the interaction between changes in arterial pressure and renal hemodynamics.     

Dopamine blockade and natriuresis during water immersion in normal man

Natriuresis was studied during water immersion in eight normal subjects either in the absence or in the presence of dopamine blockade by domperidone. Creatinine clearance showed no significant changes; urine flow remained significantly above control values during water immersion, implying persistent suppression of antidiuretic hormone. The marked natriuresis seen during water immersion alone was significantly blunted (P less than 0.05) but not abolished during water immersion plus domperidone. Suppression of the renin-aldosterone system by water immersion alone was not significantly different from that obtained during water immersion plus dopamine blockade. On the contrary, plasma prolactin levels, previously suppressed during water immersion alone, were significantly stimulated during water immersion plus domperidone, thus indirectly suggesting a role of dopamine in mediating the blunted natriuresis seen during water immersion.     

The influence of ubiquinone (Co Q10) on the metabolic response to work

Ubiquinone (Co Q10) is a natural substance suitable for therapeutic use in cardiology and in the treatment of some muscular diseases. It might therefore be used during strenuous exercise (as in athletic competitions), especially in the presence of metabolic modifications which may justify its use. For this purpose, we have evaluated the effect of prolonged treatment with Co Q10 (100 mg/day per os for one month) on the biological changes induced by prolonged work on an ergometer bicycle (equal to about 50% of the single VO2max per 60 m'), immediately followed by exhaustive work (25 watts increase every 2 m'). From the venous blood of 12 healthy untrained subjects (students, volunteers, mean age 25.7 and body mass index 23.3) we examined some biological parameters [free fatty acids (FFA), free glycerol, lactate, glucose, insulin, CK] before, at the end of aerobic work, at the end of exhaustive work, and after 30 and 60 m' of the recovery phase. The same indexes, measured after identical times and work, were evaluated after one month of treatment with Co Q10. The only relevant modifications observed were those concerning FFA: at the end of aerobic work and after the administration of the drug, lower levels were reached (before, 1011 +/- 329 microEq/l; after 790 +/- 392; p less than 0.05); the same trend was observed at the end of the exhaustive work (1031 +/- 320 microEq/l vs 826 +/- 387; p less than 0.05). At the subsequent times, as well as for the other biological parameters examined, we did not observe any variation before or after the period of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of urine dilution on quantity, size and aggregation of calcium oxalate crystals induced in vitro by an oxalate load.

Increasing urinary volume is an important tool in the prevention of calcium renal stones. However, the mechanism of how it actually works is only partially understood. This study aimed at assessing how urine dilution affects urinary calcium oxalate crystallization. A total of 16 male idiopathic calcium oxalate (CaOx) stone-formers and 12 normal male subjects were studied and 4 h urine samples were taken twice, under low (undiluted urine) and high hydration conditions (diluted urine). An equal oxalate load (1.3 mmol/L) was added to both types of urine and the crystallization parameters were assessed. In both stone-formers and normal subjects, the crystallization processes were significantly (p<0.05 or less) more marked in the undiluted urine than in the diluted urine in terms of: a) total quantity of calcium oxalate dihydrate (COD) and calcium oxalate monohydrate (COM) crystals; b) total quantity of crystalline aggregates; and c) aggregation index (i.e., ratio between the area occupied by crystalline aggregates and the area occupied by all the crystals present). The comparison between stone-formers and normal subjects showed that the greatest difference was for the size of COD crystals, which were larger in the urine of the stone-formers. A further important finding was an inverse relationship between changes in urinary volume and in the aggregation index (r = -0.53, p = 0.004). In conclusion, urine dilution considerably reduces crystallization phenomena induced in vitro by an oxalate load in both calcium stone-formers and normal subjects.     

Calcium oxalate crystallization in untreated urine, centrifuged and filtered urine and ultrafiltered urine.

Centrifuged and filtered urine is often used to evaluate in vitro the crystallization processes of calcium oxalate (CaOx), but even such simple manipulations can alter the composition of the urine, as regards its protein and lipid concentrations. In urine samples taken from 17 normal male adults, we evaluated CaOx crystallization by simultaneously using three different types of urine: untreated (U), centrifuged at 2000 rpm (800 g) and filtered at 0.22 microm (CF), and centrifuged-filtered and ultrafiltered at 10 000 Da (CFU). The addition of 1.2 mmol/l of oxalate to each type of urine produced notably different results. The total amount of CaOx crystals (expressed as calcium oxalate dihydrate crystals (COD) + oxalate monohydrate crystals (COM) area/total area x 100) was on average 13.2% in U urine, 70.7% in CF urine and 11.1% in CFU urine (CF > U and CFU, U = CFU); the relative prevalence of COD and COM (expressed as COD area/COM area) was on average 71.4 in U urine, 0.0026 in CF urine and 5.5 in CFU urine (U > CF and CFU, CFU > CF); the diameter of COD (expressed in microns) was on average 15.2 in U urine, 3.7 in CF urine and 24.3 in CFU urine (CFU > U and CF, U > CF); the diameter of COM (expressed in microns) was on average 5.2 in U urine, 2.6 in CF urine and 8.9 in CFU urine (CFU > U and CF, U > CF); the total amount of CaOx aggregates (expressed as CaOxAgg area/total area x 100) was on average 8.5% in U urine, 22.1% in CF urine and 2.9% in CFU urine (CF > U and CFU, U > CF). We conclude that CaOx crystallization processes in manipulated urine are extremely different, probably due to changes in macromolecular compounds.