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Biomedical subjects

B Palumbo

Publications and source records attributed to B Palumbo.

At least 19 recordsLinked to original sources

Natriuretic peptides levels are related to HDL-cholesterol with no influence on endothelium dependent vasodilatation.

BACKGROUND: The natriuretic peptides, Brain Natriuretic Peptide (BNP), C-type Natriuretic Peptide (CNP), are mediators of cardiovascular homeostasis. The impairment of arterial ability to vasodilate, also known as endothelial dysfunction, represents the first stage of atherosclerotic damage and may be assessed as brachial flow mediated vasodilation (FMV) in human. Generally an altered brachial FMV is documented in association to several cardiovascular risk factors as hypercholesterolemia. Aim of the study was to evaluate the behaviour of BNP and CNP in hyperlipemia and the potential relationship to FMV. PATIENTS AND METHODS: Forty-four hyperlipemic patients (LDL-cholesterol > 130 mg/dl and/or triglycerides > 150, age 35-60 y) of both genders and 20 normolipemic patients, matched for age and sex were investigated. RESULTS: Patients had lower values of brachial FMV in comparison to controls (3.9 +/- 3.5 vs 7.5 +/- 0.5%, p < 0.005), no differences were observed in BNP (4.6 +/- 4.6 vs 5.9 +/- 3.4 ng/mL, p = n.s) and CNP (4.1 +/- 5.8 vs 5.7 +/- 3.3 ng/mL, p = n.s). Univariate analysis showed a positive correlation between BNP and HDL-cholesterol values (r = 0.36, p = 0.001). In the multivariate analysis, LDL-cholesterol (beta = -0.57), HDL-cholesterol (beta = 0.26) and brachial artery diameter (beta = -0.33) were predictors of brachial FMV. The only predictive variable for CNP was HDL-cholesterol (beta = 0.37). CONCLUSIONS: The present study suggested that natriuretic peptides, BNP and CNP, are not altered in patients affected by hypercholesterolemia. Nevertheless, the levels of HDL-cholesterol are strictly related to the values of CNP. This observation, in humans, adds another mechanism to the vascular control exerted by HDL.

Adult↗

Association of 99mTc-MIBI brain SPECT and proton magnetic resonance spectroscopy (1H-MRS) to assess glioma recurrence after radiotherapy.

AIM: The aim of this study was to compare 99mTc-MIBI brain SPECT and proton magnetic resonance spectroscopy (1H-MRS) findings and to evaluate their association. METHODS: Both exams were performed on 30 glioma patients, previously operated and treated with radiotherapy, having MRI doubtful between recurrence and radiotherapy effects. SPECT images were acquired 15 minutes after radiopharmaceutical administration with a dual-head gamma camera. T1/B1 uptake ratio was calculated between a tumor ROI (T1) and a normal mirror symmetric ROI (B1) and T2/B2 ratio was obtained between a ROI in the hottest neoplastic part (T2) and a normal mirror symmetric ROI (B2). 1H-MRS was performed using a 1.5 T system equipped with a spectroscopy package. SPECT and 1H-MRS data were compared with histology after new surgery or with follow-up. RESULTS: SPECT and 1H-MRS showed recurrence in 18 patients (confirmed by biopsy, coinciding only in 17 cases) and were negative in 10 (1 false negative). SPECT and 1H-MRS disagreed in 2 cases of recurrence (1 diagnosed by brain SPECT, 1 by 1H-MRS). T1/B1 ratio mean value (4.26+/-2.5) was significantly lower than T2/B2 (4.93+/-2.81; P<0.001). SPECT and 1H-MRS sensitivity in detecting recurrence was 90%, specificity 100%, accuracy 93%, negative predictive value (NPV) 83% and positive predictive value (PPV) 100%; the associated exams sensitivity was 95%, specificity 100%, accuracy 96.6%, NPV 90.9%, PPV 100%. CONCLUSIONS: Brain SPECT and 1H-MRS have equivalent values of diagnostic parameters in differentiating tumor recurrence and radiation effects, and their association might provide additional information.

Adult↗

Platelet function after single [153Sm]EDTMP therapy in prostate cancer.

AIM: Aim of the study was to assess whether [153Sm] EDTMP therapy at a low-dose is associated with platelet activation. METHODS: In 29 patients suffering from metastatic prostate cancer platelet count and various platelet function parameters have been monitored for 2 months after a single (the first) application of 1.1 GBq mCi [153Sm]EDTMP. RESULTS: After 3 days insignificant signs of platelet activation (increase in malondialdehyde, adenosine diphosphate-induced platelet aggregation, decreased platelet sensitivity) occur, normalizing rapidly. At the nadir of platelet count (3-4 weeks) platelet aggregation response in non-count adjusted samples is somewhat lower, while activity per cell (count adjusted samples) is unchanged. Platelet proteins do not change at all. Insignificant activation of platelet function at day 3 is interpreted as an indicator of mild oxidation injury, late aggregation response changes in non-adjusted samples seem only to reflect temporarily decreased number of circulating platelets. Samarium-153-EDTMP therapy at doses (1.1 GBq) used in the Vienna-protocol is not associated with a significantly altered functional behavior of platelets. CONCLUSIONS: We conclude that a single dose of 1.1 GBq 153Sm-EDTMP does not significantly affect in vivo and ex vivo platelet function.

Aged↗

Effect of giving up cigarette smoking and restarting in patients with clinically manifested atherosclerosis.

Cigarette smoking, a key risk factor for the development of vascular disease, is associated with an increased 8-epi-prostaglandin (PG) F(2alpha). Elevated 8-epi-PGF(2alpha) has been found in vascular tissue, blood and urine as well. We examined the influence of quitting cigarette smoking in 71 patients (38 males, 33 females; aged 32-67 a) with clinically manifested atherosclerosis and various risk factors. In addition, in eight patients with hypercholesterolemia without clinical manifestation of atherosclerosis quitting smoking was monitored as well. Twenty-six of the patients with manifested atherosclerosis and five with hypercholesterolemia restarted and the isoprostanes in plasma, serum and urine were monitored in these patients as well. Quitting cigarette smoking induces an immediate decline becoming significant after 1 or 2 weeks. Restarting smoking results in an increase in 8-epi-PGF(2alpha) reaching prevalues within almost 1 week. These findings indicate that the in vivo oxidation injury associated with cigarette smoking quickly decreases after quitting but increases soon after restarting immediately.

Adult↗

Postprandial lipemia and associated metabolic disturbances in healthy and hyperlipemic postmenopausal women.

The increased risk for coronary artery disease observed in postmenopausal women is partly explained by a more atherogenic fasting lipoprotein profile. Moreover, natural menopause has been associated with an altered postprandial lipid profile. To better characterize the interaction between fasting and postprandial lipid profile after menopause, we examined postprandial changes in several lipid parameters in three age-matched groups of postmenopausal women (16 affected by mixed hyperlipemia, 17 by common hypercholesterolemia, and 17 normolipemic), who underwent a standardized oral fat-loading test. The magnitude of postprandial lipemia, expressed as 8-hour triglyceride incremental area under the curve, was greater in women with mixed hyperlipemia (1,326 +/- 372 mg x dL(-1) x h(-1)) than in normal (484 +/- 384 mg x dL(-1) x h(-1)) and hypercholesterolemic (473 +/- 223 mg x dL(-1) x h(-1); both P <.0001) women, and the differences held after adjustment for body mass index and fasting insulin. Women with mixed hyperlipemia showed a significant postprandial decrease in high-density lipoprotein 2 (HDL(2)) cholesterol, lipoprotein (a), and low-density lipoprotein (LDL) particle size. Both hypercholesterolemic and normolipemic women showed a significant postprandial decrease in HDL cholesterol and lipoprotein (a) levels but not in LDL size. In a multiple linear regression analysis, fasting triglyceride levels, insulin level, and waist-hip ratio were all independent predictors of the magnitude of postprandial lipemia. In conclusion, postmenopausal women with mixed hyperlipemia show a greater postprandial triglyceride increase and a more pronounced reduction in HDL cholesterol level and LDL size than hypercholesterolemic and normolipemic subjects. The presence of the features of insulin resistance syndrome could contribute to the deterioration of postprandial lipemic response in these subjects.

Cholesterol, HDL↗

Increase of isoprostane 8-epi-PGF(2alpha)after restarting smoking.

Isoprostanes are known as reliable markers of in vivo oxidation injury. Cigarette smoking has been shown to be associated with a significant increase in 8-epi-PGF(2alpha), a major member of this family of compounds. Quitting smoking reduces 8-epi-PGF(2alpha) values to normal within a couple of weeks only. In this follow-up we checked the 8-epi-PGF(2alpha), values in plasma, serum and urine in 28 people who restarted smoking after a quitting attempt of various duration. 8-epi-PGF(2alpha)shows a certain increase after restarting smoking reaching a maximum after already 1 week. Continuation of smoking does not significantly further increase 8-epi-PGF(2alpha). These data indicate a fast response of restarting as on quitting smoking on in vivo oxidation injury. The oxidation injury reflected by 8-epi-PGF(2alpha)may be a key pathogenetic mechanism in smoking-induced vascular injury.

Adult↗

Statin induced myopathy does not show up in MIBI scintigraphy.

Statin induced myopathy is the most commonly seen side effect in users of this family of drugs. Their different forms present with either creatine phosphokinase (CK) elevation or not, signs of in vivo oxidation injury or not or a combination of both. The pathogenetic background, however, still remains obscure. As MIBI, beside myocardial and tumour scintigraphy, is useful in detecting muscle metabolic abnormalities, an increased uptake of MIBI in the diseased muscular segments could be expected. We investigated seven patients (five males, two females; aged 36-56 years) with statin induced myopathy with either elevated CK, isoprostanes or muscle pains at varying combinations. MIBI whole-body imaging was done immediately, the patients still being on the respective statin. Sixteen patients (six males, 10 females) suffering from lung or breast cancer and being on statins served as controls. No uptake abnormalities in any muscular segment either in the patients or the control group were seen. Thus, MIBI scintigraphy is not useful, apparently, in diagnosing and eventually localizing statin induced myopathy. These findings indicate that MIBI scintigraphy is of no help for diagnosis and gaining further insight into statin induced myopathy.

Adult↗

Quitting cigarette smoking results in a fast improvement of in vivo oxidation injury (determined via plasma, serum and urinary isoprostane).

Isoprostanes (IP) have been identified as reliable markers of in vivo oxidation injury. Recently, in vascular tissue and blood as well as urine of cigarette smokers, increased IP values have been discovered. We examined 47 adults (26 males, 21 females; aged 30-66 years), admitted to a cardiovascular unit on an outpatient basis, with various risk factors but without any sign of manifestation of atherosclerosis. Refraining from cigarette smoking for a few days resulted in a significant drop of plasma, serum, and urinary 8-epi-PGF(2alpha). Thereafter, a further continuous decrease was monitored, reaching a steady state after about 4 weeks after quitting cigarette smoking. Prevalues of 8-epi-PGF(2alpha) were higher, depending on the type and number of risk factors; the decrease after quitting, however, was comparable. These results indicate that exsmokers may rapidly recover from their enhanced in vivo oxidation.

Adult↗

Isoprostanes quickly normalize after quitting cigarette smoking in healthy adults.

BACKGROUND: Isoprostanes and in particular 8-epi-PGF2 alpha have been claimed as a useful measure for invivo oxidation injury. While smokers show elevated 8-epi-PGF2 alpha the behaviour during quitting smoking is unknown. METHODS AND RESULTS: We determined 8-epi-PGF2 alpha in 7 healthy adults ready to quit smoking in plasma, serum and urine by means of an enzyme immunoassay after extraction and purification before quitting smoking and during a follow-up period of 4 weeks. After quitting smoking, 8-epi-PGF2 alpha shows a rapid decline within a few days almost completely normalizing within 4 weeks. CONCLUSION: The cigarette-smoking associated invivo oxidation injury almost completely disappears within 4 weeks of quitting smoking.

Adult↗

Prostaglandin E1-therapy reduces circulating adhesion molecules (ICAM-1, E-selectin, VCAM-1) in peripheral vascular disease.

BACKGROUND: It has been postulated that adhesion molecules (AM) may be involved in development and progression of human atherosclerosis. We examined whether prostaglandin (PG) E1 affects circulating levels of the AM (ICAM-1, VCAM-1 and E-selectin) in peripheral vascular disease (PVD) patients. METHODS AND RESULTS: AM are significantly (p < 0.01) increased in PVD (n = 65) as compared to controls (n = 31). There was no influence of risk factors. 26 PVD-patients received 2 different schemes of PGE1-therapy (group A [n = 17]; 5 ng PGE1/kg/min x 6 h x 5 d x 4 wk; group B [n = 9]; 60 micrograms PGE1/2 h x 5 d x 2 wk). PGE1 decreases all the AM significantly (p < 0.01) using both therapeutic schemes. Stopping PGE1-therapy reverses values within about 4 weeks. Details on therapeutic regimens (dose, duration, route, etc.) and individual response still need to be assessed. CONCLUSION: Our results indicate that PGE1-treatment of PVD is associated with a significant benefit on circulating AM. These findings are in line with the described anti-inflammatory actions of PGE1 and may represent a further contributing factor to the great variety of beneficial actions of PGE1 on human atherosclerosis.

Aged↗

Angiotensin converting enzyme deletion allele in different kinds of dementia disorders.

In order to verify the association of Angiotensin converting enzyme (ACE) gene with different kinds of dementia, as well as its association with APO-E (genotype), we performed ACE genotyping in subjects with late-onset probable Alzheimer's disease (LOAD, n = 64), early-onset probable Alzheimer's disease (EOAD, n = 32), possible Alzheimer's disease (pAD, n = 44), vascular dementia (VD, n = 12), age-associated memory impairment (AAMI, n = 15) and 40 healthy age-matched controls, who were previously characterized for APO-E. After the principal component analysis ACE D and Apo-Eepsilon4 alleles disclosed the highest prevalence in the cognitively impaired groups of subjects, Apo-Eepsilon4 being more specific for LOAD and pAD. ACE D allele seems to be an unspecific susceptibility factor for mental decline.

Age Factors↗

Vascular 131I-low-density lipoprotein imaging in patients with hypertension and early atherosclerotic lesions in the carotid artery.

BACKGROUND: The reinjection of autologous 131I-labelled low-density lipoprotein (LDL) followed by vascular scintigraphy has been used to investigate lipid-containing plaques, but no information is available on the early stages of plaques in hypertensives. Vascular scintigraphy after re-injection of autologous 131I-labelled LDL was used to investigate early atherosclerotic lesions visualized by sonography in the carotid arteries of patients with hypertension. PATIENTS AND METHODS: 10 male patients (4 smokers; mean age 56 +/- 8 years;) with early carotid atherosclerosis (mono- or bilateral; intima-media-thickness ranging from 1.5 to 3.5 mm) as shown by sonography were studied. All these normolipemic patients suffered from primary hypertension and were treated with diuretics. As controls 6 healthy male subjects (3 smokers; mean age 54 +/- 9 years;), with normal blood pressure and lipid pattern were recruited. RESULTS: Hot spots appeared in the areas with early atherosclerosis in 7 patients, while none were seen in controls. Positive kinetic curves were observed in 4 patients. No significant differences emerged in the target/non-target ratios. CONCLUSIONS: Vascular lipoprotein uptake in hypertensive patients is apparently late and rather limited; the uptake pattern may depend on plaque composition.

Adult↗

Apolipoprotein-E genotype in normal aging, age-associated memory impairment, Alzheimer's disease and vascular dementia patients.

Apolipoprotein-E (Apo-E) genotype and allele frequencies were evaluated in patients with late-onset probable Alzheimer's disease (LOAD; n = 64), early-onset probable Alzheimer's disease (EOAD; n = 32), possible Alzheimer's disease (pAD; n = 44), vascular dementia (VD; n = 12), age-associated memory impairment (AAMI; n = 15) and 40 healthy age-matched controls. APO-E was performed by polymerase chain reaction products digested by the restriction enzyme HhaI. A statistically significant increase of epsilon4 frequency was found in LOAD as compared to the other groups, and in pAD with respect to controls, while VD and AAMI groups did not disclose any difference as regards to control subjects. Multivariate analysis showed a significant association of epsilon4 with female gender. Our results confirm the increased frequency of epsilon4 in both probable and possible LOAD, failing to show a similar trend in VD and AAMI.

Adult↗

Proton magnetic resonance spectroscopy can differentiate Alzheimer's disease from normal aging.

In order to evaluate the pattern of proton magnetic resonance spectroscopy (1H-MRS) in the gray and white matter of patients with Alzheimer's disease (AD) and healthy controls, a cross-sectional study was carried out on 13 consecutive AD patients and 7 healthy older subjects who were referred to the Day-Hospital for diagnostic assessment. All examinations were performed on a 1.5 Tesla whole-body scanner. Volumes of interest were selected in both the gray (temporal region) and the white (frontal region) matter. N-acetyl group, total creatine, total choline and myo-inositol were quantified referring the metabolite peak area to the unsuppressed water peak area acquired under the same conditions, and the ratio was expressed in arbitrary units. A significant decrease in N-acetyl-aspartate (NAA) in both gray and white matter and an increase in myo-inositol (mI) in gray matter of AD patients were observed. The gray matter NAA/mI ratio clearly separated the two groups. White matter mI was significantly associated with severity and duration of dementia. No association with age was documented. It can be concluded that in vivo 1H-MRS can contribute to the knowledge of pathophysiology of AD, giving neurochemical details of both gray and white matter. In particular, the gray matter NAA/ml ratio seems to be able to differentiate normal cerebral aging from Alzheimer's disease.

Aged↗

Pharmacokinetic profile and endocrine effects of posatirelin treatment in healthy elderly subjects.

The pharmacokinetics and endocrine effects of a therapeutic dose (10 mg/day) of posatirelin (L-pyro-2-aminoadipyl-L-leucyl-L-prolinamide) were investigated in healthy elderly subjects. Posatirelin was given once daily by intramuscular injection for 7 days. Pharmacokinetic parameters were estimated using a model-independent approach. The plasma concentrations of free triiodotyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) and the circadian rhythms of prolactin and cortisol were considered as indicator variables of endocrine response to posatirelin administration. Posatirelin was well tolerated and no significant adverse effects were observed during the study. Peak plasma concentration (Cmax), time of peak plasma concentration (tmax), area under the plasma concentration-time curve from time zero to infinity (AUC0-infinity), elimination half-life (t1/2), and total clearance (CI/F) were measured after single-dose intramuscular injection (day 1) and after multiple-dose administration (day 7). There were no significant changes in these parameters after multiple-dose administration (day 7). Posatirelin induced a progressive reduction in basal TSH levels and maximum response. There were no significant changes during treatment in the time at which basal levels of FT3 and FT4 occurred, and these levels remained within the normal range throughout the study. The circadian rhythms of cortisol and prolactin were not influenced by posatirelin treatment. The pharmacokinetics of posatirelin were not time dependent, and the drug did not accumulate after multiple-dose administration. Short-term treatment with posatirelin did not induce clinically relevant endocrine consequences in healthy elderly subjects.

Aged↗