Relationship between aging and susceptibility of erythrocytes to oxidative damage: in view of nutraceutical interventions.

Twelve (12) healthy elderly subjects were divided into two groups: (a) those given an antioxidant/NO-modulating fermented papaya preparation (FPP) 9 g/day for 4 weeks, and (b) a placebo group. No protein/lipid distribution in erythrocytes (RBC) membranes was noted among different ages and treatments. Higher RBC concentration of malondialdehyde and nitric oxide synthase were found in the elderly (p < 0.05 versus "young" controls), whereas superoxide dismutase was unaltered. Such abnormalities were prevented by FPP supplementation (p < 0.01). RBC and RBC ghosts showed an enhanced susceptibility to lipid peroxidation by using cumene hydroperoxide (p < 0.01 versus young) but FPP supplementation significantly protected intact RBC (p < 0.05). These preliminary data suggest that nutraceuticals with antioxidant/NO-regulating properties significantly protect from RBC oxidative damage, and are potential weapons for the aging process and chronic and degenerative diseases.

Molecular biology and the staging of prostate cancer.

Cancer of the prostate is still controlled or cured by surgery, radiotherapy, and hormone therapy. The present criteria of complication and prediction are criticized more and more for not being sufficiently reliable, due to the high heterogeneity of prostatic cells. The continuing discoveries of intra- and extracellular mechanisms of the molecular informational network, which allow the continuity or discontinuity of the cell's life, are also related to prostate cancer. The role of androgen receptors is now under close scrutiny, in the light of the knowledge of regulatory genes and their molecular expression. In the near future, a complete study of prostate cancer's DNA is certainly envisaged. Looking forward to the extraordinary applications of molecular biology in this field, this article is aimed at establishing a clear link between the conventional ways of interpreting the clinical expression of prostate cancer and the oncoming applications of genomics and proteomics.

Comparison of the effects of carvedilol and nifedipine in patients with essential hypertension and non-insulin-dependent diabetes mellitus.

The safety and tolerability of carvedilol, a new antihypertensive agent with the combined pharmacological activities of beta-blockade and vasodilation, and of nifedipine were investigated in patients with essential hypertension and non-insulin-dependent (type II) diabetes mellitus. Twenty patients were openly randomized to receive 25 mg carvedilol once daily (five men and five women; mean age, 63 years) or 10 mg nifedipine t.i.d. (three men and seven women; mean age, 64 years) for a period of 4 weeks. Baseline mean sitting blood pressures were 168/98 and 169/95 mm Hg in the carvedilol and nifedipine groups, respectively. Baseline mean areas under the curve (AUC) of the intravenous glucose tolerance test (IVGTT) for the carvedilol and nifedipine groups were 6,136 +/- 1,195 and 6,287 +/- 1,228 mg/dl/min, respectively. Demographic and efficacy variables were not statistically different between treatment groups. After 4 weeks of therapy, mean sitting blood pressure was significantly (p less than 0.02) reduced to 144/91 mm Hg in the carvedilol group and to 149/87 mm Hg in the nifedipine group. Week 4 IVGTT AUC values of 5,735 +/- 1,464 mg/dl/min in the carvedilol group and 5,988 +/- 993 mg/dl/min in the nifedipine group, representing mean reductions of 6.14% and 3.17%, respectively, were not statistically different from baseline. Both treatments were well tolerated. No patient experienced adverse events in the carvedilol treatment group, whereas two patients in the nifedipine group reported episodes of headache (one patient) and palpitations (one patient); each episode was mild in severity and considered to be related to study medication.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential effects of aging on the heart rate and blood pressure influences of arterial baroreceptors in awake rats.

The effect of aging on arterial baroreceptor control of heart rate and blood pressure was evaluated in unanesthetized normotensive rats aged 5-6 (young), 12-16 (adult) and 75-90 (old) weeks. Each rat was chronically implanted with arterial and venous femoral catheters and with bilateral balloon-in-cuff occluders around the common carotid arteries. Baroreceptor control of heart rate was assessed by the bradycardic and tachycardic response to intravenous boluses of phenylephrine and nitroprusside, respectively. Carotid baroreceptor control of blood pressure was assessed by a 12-s bilateral common carotid occlusion (CCO). All baroreflex responses were similar in young and adult rats. Compared with the young group, old rats showed a marked reduction of the bradycardic and tachycardic baroreflex response (-42% and -46%, respectively, P less than 0.05). The initial pressor responses to CCO were also impaired in the old animals (3 s: -63%, 6 s: -54%; both P less than 0.01), whereas the peak pressor response (9 and 12 s) was virtually identical in the young and old groups. The preservation of the peak pressor response to CCO in old rats was independent of chemoreceptor activation, aortic baroreceptors or cerebral ischemia. Thus, aging impairs baroreceptor control of heart rate but alters baroreceptor control of blood pressure, as assessed by the pressor response to CCO, only in its fast-developing component, leaving its longer-term component unaffected.

Intra-arterial pressure alterations during tail-cuff blood pressure measurements in normotensive and hypertensive rats.

The heating and restraint inherent to tail-cuff measurement of systolic blood pressure (SBP) in rats may alter SBP and introduce a 'biological' error in its estimation by this technique. This problem was examined in unanesthetized normotensive and hypertensive rats fitted with an arterial catheter. All SBP values recorded in unrestrained rats during a 2 h period were averaged by computer and compared with intra-arterial SBP measurements observed while the rat was being subjected to the tail-cuff procedure. With the latter procedure, SBP was 16 +/- 2 mmHg lower in normotensive rats (P less than 0.001) and 7 +/- 3 mmHg higher in hypertensive rats (P less than 0.05) than when the rats were unrestrained. The effects of heat and restraint, both separately and in combination, on SBP were evaluated during four additional 30-min monitoring periods. In both groups of rats, restraint failed to alter SBP and heat lowered it slightly. The two stimuli, combined, lowered SBP in normotensive rats, but raised it by 12 +/- 2 mmHg in hypertensive rats (P less than 0.01). Thus, tail-cuff SBP measurements represent under- and overestimates in normotensive and hypertensive rats, respectively, since the two groups respond to the procedure in opposite manners.

Inverse relationship between heart rate and blood pressure variabilities in rats.

The interplay of heart rate variability, baroreceptor control of heart rate, and blood pressure (BP) variability was examined in chronically instrumented, unanesthetized, freely moving rats in which the efferent neural influences on heart rate were pharmacologically altered. In each rat, BP was recorded continuously for 90 minutes in the control condition and in one or more of the following conditions: 1) beta-adrenergic receptor blockade by propranolol, 1 mg/kg; 2) cholinergic blockade by atropine, 0.75 mg/kg, and 3) combined blockade by propranolol plus atropine. Each BP recording was analyzed beat-to-beat by a computer that calculated heart rate and BP variabilities, both expressed as variation coefficients. In addition, under each condition the sensitivity of the arterial baroreceptor control of heart rate was assessed by measuring the reflex changes in pulse interval in response to BP changes induced by bolus i.v. injections of phenylephrine and nitroprusside. As compared with the control condition, 1) propranolol (n = 10) reduced heart rate variability by 23 +/- 4% (p less than 0.01), only slightly impaired baroreceptor reflex sensitivity, and did not significantly modify BP variability (+11 +/- 7%); 2) atropine (n = 11) reduced heart rate variability by 30 +/- 7% (p less than 0.01), drastically impaired baroreceptor reflex sensitivity, and increased BP variability (+40 +/- 8%, p less than 0.01); 3) combined blockade (n = 10) caused variability and baroreceptor reflex changes similar to those induced by atropine alone. Thus, heart rate variability depends on both vagal and sympathetic influences. However, only the former component affects BP variability, that is, it plays an antioscillatory role.(ABSTRACT TRUNCATED AT 250 WORDS)