Domenico Lapenna

Università degli Studi G. d'Annunzio Chieti e Pescara, Chieta, Abruzzo, Italy

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Publications (135)521.25 Total impact

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    ABSTRACT: The effects of ultramicronized palmitoylethanolamide (PEA-um) were evaluated on pain behaviours and markers of mast cell (MC) activity in a rat model of endometriosis plus ureteral calculosis (ENDO+STONE)-induced viscero-visceral hyperalgesia (VVH). Female Sprague-Dawley rats who underwent surgical induction of endometriosis were randomly assigned to receive active (PEA-um 10/mg/kg/day, orally) or placebo treatment for 25 days. At day 21 they underwent ureteral stone formation and were video-recorded till day 25 to evaluate ureteral and uterine pain behaviours. At autopsy (day 25), ureteral condition and number and diameter of endometrial cysts were evaluated. The following were then measured: number and percentage of degranulating MCs, number of vessels, chymase, Nerve Growth Factor (NGF), Vascular Endothelial Growth Factor (VEGF) and FLK-1 (VEGF receptor) in cysts and NGF in dorsal root ganglia (DRG). PEA-um-treated vs placebo-treated rats showed: significantly lower number, duration and complexity of ureteral crises, shorter duration of uterine pain and smaller cyst diameter (0.0001<p<0.004); a significantly higher percentage of expelled stones (p<0.0001); significantly lower MC number (p<0.01), vessel number (p<0.01), chymase (p<0.05), NGF (p<0.05), VEGF (p<0.01) and Flk1 (p<0.01) expression in cysts and NGF expression in DRG (p<0.01). In all animals, the global duration of ureteral crises correlated linearly and directly with cyst diameter, MC number and chymase in cysts, NGF in cysts and DRG (0.02<p<0.0002).PEA-um significantly reduces VVH from ENDO+STONE, probably by modulating MC expression/activity in cysts, thus reducing central sensitization due to noxious signals from endometriotic lesions. The results suggest that PEA-um could represent a valuable treatment for VVH in patients.
    Pain 05/2015; DOI:10.1097/j.pain.0000000000000220 · 5.84 Impact Factor
  • Francesca Santilli · Domenico Lapenna · Sara La Barba · Giovanni Davì
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    ABSTRACT: Type 2 diabetes mellitus (T2DM) is a major cardiovascular (CV) risk factor. Persistent platelet activation plays a key role in atherothrombosis in T2DM. However, current antiplatelet treatments appear less effective in T2DM patients vs. similar risk nondiabetics. A large body of evidence supports the contention that oxidative-stress, which characterizes DM, may be responsible at least in part, for less-than-expected response to aspirin, with multiple mechanisms acting at several levels. This review will discuss the pathophysiological mechanisms, related to oxidative stress, contributing to suboptimal aspirin action or responsiveness. These would include: 1) mechanisms counteracting the antiplatelet effect of aspirin, such as reduced platelet sensitivity to the antiaggregating effects of NO, due to high glucose-mediated oxidative stress; 2) mechanisms interfering with COX acetylation especially at platelet level, e.g. lipid hydroperoxide-dependent impaired acetylating effects of aspirin; 3) mechanisms favouring platelet priming (lipid hydroperoxides) or activation (F2-isoprostanes, acting as partial agonists of thromboxane receptor), or aldose-reductase pathway-mediated oxidative stress, leading to enhanced platelet thromboxane A2 generation or thromboxane receptor activation); 4) mechanisms favouring platelet recruitment, such as aspirin-induced platelet isoprostane formation); 5) modulation of megacaryocyte generation and thrombopoiesis by oxidative HO-1 inhibition; 6) aspirin-iron interaction, eventually resulting in impaired pharmacological activity of aspirin, lipoperoxide burden, and enhanced generation of hydroxyl radicals capable of promoting protein kinase C activation and platelet aggregation. Acknowledgment of oxidative stress as a major contributor, not only of vascular complications, but also of suboptimal response to antiplatelet agents in T2DM, may open the way to design and test novel antithrombotic strategies, specifically targeting oxidative-stress mediated mechanisms of less-than expected response to aspirin. Copyright © 2014. Published by Elsevier Inc.
    Free Radical Biology and Medicine 12/2014; 80. DOI:10.1016/j.freeradbiomed.2014.12.010 · 5.71 Impact Factor
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    ABSTRACT: Objective: To investigate enzymatic reactive aldehyde-scavenging enzyme capacity together with lipid peroxidation as expression of oxidative stress in atherosclerotic plaques of cigarette smokers and nonsmokers. Methods: We have assessed specific enzymatic activities of class 1, 2, and 3 aldehyde dehydrogenase (ALDH1, ALDH2, and ALDH3, respectively), glutathione S-transferase (isozyme A4-4, GSTA4-4), and aldose reductase (AR), namely the major reactive aldehyde-scavenging enzymes, together with lipid peroxidation, i.e., fluorescent damage products of lipid peroxidation (FDPL), in carotid atherosclerotic plaques surgically removed from 17 cigarette smokers and 17 nonsmokers. Results: The enzymatic activities of ALDH1 plus ALDH2, ALDH3, GSTA4-4, and AR were significantly lower in the atherosclerotic plaques of smokers than in those of nonsmokers, while plaque FDPL levels were significantly higher in the smokers than in the nonsmokers. The amount of cigarette smoking was correlated inversely with the aforementioned plaque enzymatic activities and directly with plaque FDPL content. Plaque FDPL levels were inversely correlated with plaque enzymatic activities in smokers and nonsmokers. The degree of carotid atherosclerotic stenosis, as expression of atherosclerosis severity, was correlated inversely with plaque enzymatic activities and directly with plaque FDPL levels in smokers and nonsmokers; moreover, the degree of carotid stenosis was directly correlated with the amount of cigarette smoking. Conclusion: atherosclerotic lesions of cigarette smokers are endowed with a depressed enzymatic reactive aldehyde-scavenging capacity eventually favoring oxidative stress and the severity of atherosclerosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Atherosclerosis 12/2014; 238(2):190-194. DOI:10.1016/j.atherosclerosis.2014.11.028 · 3.97 Impact Factor
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    ABSTRACT: Short-term fat feeding could exert adverse cardiac effects by altering myocardial glutathione-related antioxidant defenses. We have here assessed total glutathione (TG), the activities of glutathione reductase (GSSG-Red), γ-glutamylcysteine synthetase (γ-GCS), γ-glutamyl transpeptidase (γ-GT) and glutathione peroxidase (GSH-Px), fluorescent damage products of lipid peroxidation (FDPL), thiobarbituric acid-reactive substances (TBARS), H2O2, and ATP in the aerobically perfused hearts of control rabbits and of rabbits fed a fat-enriched diet for 18 days. Such biochemical parameters, myocardial hemodynamics and infarct size were assessed in the perfused hearts of other control and fat-fed rabbits subjected to 60 min global ischemia plus 30 min reperfusion. Compared to controls, a reduced activity of GSSG-Red and γ-GT associated with decreased TG content was detected in the aerobically perfused hearts of fat-fed rabbits, which also showed insignificant γ-GCS activation, GSH-Px depressed activity, FDPL, TBARS and H2O2 burden, and unaltered ATP content. Ischemia-reperfusion decreased the myocardial levels of TG, ATP, and γ-GCS activity and augmented those of FDPL, TBARS, and H2O2 especially in the fat-fed rabbits, without significant changes in myocardial GSSG-Red, γ-GT, and GSH-Px activities. Ischemia-reperfusion induced greater hemodynamic dysfunction and infarct size in the hearts of fat-fed rabbits than in those of controls. Thus, short-term fat feeding and hyperlipidemia alter glutathione metabolic status of the rabbit myocardium, inducing a GSSG-Red- and γ-GT-related decrement of myocardial glutathione content, which, together with GSH-Px dysfunction, may favor tissue oxidative stress and render the myocardium more susceptible to ischemia-reperfusion injury.
    Molecular and Cellular Biochemistry 02/2014; 390(1-2). DOI:10.1007/s11010-014-1975-9 · 2.39 Impact Factor
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    ABSTRACT: To evaluate whether a diclofenac epolamine + heparin topical (plaster) is more effective than diclofenac plaster alone in reducing deep somatic hyperalgesia in subjects without spontaneous pain and whether the effect is linked to or independent of the anti-edematous action of heparin. Prospective, double-blind, randomized and controlled, four-arm parallel design trial. One hundred and four patients (84 women, 20 men, mean age 42.2 ± 13.3 years), with deep somatic hyperalgesia in one thigh, randomly assigned to one of 4 groups of 26 each. Each group underwent one of the following plaster treatments on one thigh: diclofenac+heparin; diclofenac; heparin; placebo, for 7 days, renewing the plaster every 24 hours. Before treatment (day 1), at day 4 and day 8, assessment of (a) pressure and electrical pain thresholds of vastus lateralis and overlying subcutis and skin; and (b) structure/thickness of subcutis and muscle with ultrasounds at the same level. During treatment, in placebo and heparin, no significant threshold changes, except subcutis thresholds which increased slightly (P < 0.02); in diclofenac and diclofenac+heparin, significant increase in all thresholds (0.0001 < P < 0.04). Electrical muscle pain thresholds increased significantly more in diclofenac+heparin than in diclofenac, heparin, and placebo (0.0001 < P < 0.04). In all groups: no edema and thickness changes at ultrasounds in muscle and subcutis. Topical diclofenac+heparin is significantly more effective than diclofenac alone in reducing muscle hyperalgesia in subjects without spontaneous pain, independently of the anti-edematous action of heparin. The results provide a rationale for the use of diclofenac+heparin also in algogenic conditions without evident signs of injury/edema/hematoma.
    Pain Practice 01/2014; 15(1). DOI:10.1111/papr.12161 · 2.18 Impact Factor
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    ABSTRACT: The effects of tramadol versus placebo administration on behavioral indicators of ureteral pain, pelvic pain and referred lumbar muscle hyperalgesia were investigated in a rat model of viscero-visceral hyperalgesia from endometriosis plus ureteral calculosis (endo + stone). Fifty female Sprague-Dawley rats underwent surgical induction of endometriosis and, 2 weeks later, were randomly assigned to five groups (10 each), to be treated i.p., twice a day, with tramadol (0.625, 1.25, 2.5, or 5 mg/kg) or saline for 5 days (14-18th day postendometriosis; prestone treatment). On the 21st day, they underwent laparotomy for stone formation in the upper left ureter (dental cement injection). All were video-taped 24 h nonstop for 7 days before and 4 days after stone formation (14-25th day postendometriosis) to record ureteral and pelvic pain behaviors. Lumbar sensitivity (L1) was tested bilaterally, daily over the same period, by verifying presence/absence of vocalization upon muscle pinching at a predefined pressure (calibrated forceps). Additional fifty endo + stone rats underwent the same protocol, except that treatment was performed on 21st-25th day (poststone treatment). Tramadol vs. saline significantly reduced number and duration of ureteral crises, duration of pelvic behavior, and incidence of muscle hyperalgesia (P < 0.0001), with a dose-dependent effect. Prestone treatment was significantly more effective than poststone treatment for the 1.25 dose for all parameters and 2.5 dose for pelvic and muscle parameters (0.003 > P < 0.02). Tramadol, even at low doses, is thus highly protective against pain from 'viscero-visceral hyperalgesia' in endometriosis plus ureteral calculosis; it can represent a valid therapeutic approach in women with these comorbidities.
    Fundamental and Clinical Pharmacology 05/2013; 28(3). DOI:10.1111/fcp.12038 · 2.08 Impact Factor
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    ABSTRACT: Background & aims We investigated the effects of twice daily oral supplementation with different ascorbic acid (AA) dosages and formulations on oxidative stress status and platelet biochemical function in type 2 diabetic patients (T2DP). Methods Ten T2DP were supplemented with 250 mg/day liquid AA (liq-AA), 10 T2DP with 1,000 mg/day liq-AA and 10 T2DP with placebo for 4 weeks; after suspension of liq-AA supplementation, the 250 mg/day liq-AA and placebo groups were switched to, respectively, supplementation with placebo and 1,000 mg/day chewable AA for further 4 weeks. Plasma AA (P-AA), LDL and erythrocyte lipoperoxides, erythrocyte glutathione peroxidase (E-GSH-Px1) activity and platelet lipoperoxides generated during thrombin-stimulated aggregation were assessed before and after the supplementation periods. Results Supplementation with 1,000 mg/day liq-AA was significantly more effective than supplementation with 1,000 mg/day chewable AA in increasing P-AA concentration, i.e. by about 93% compared to about 62%, as well as in reducing LDL, erythrocyte and platelet lipoperoxide levels and in augmenting E-GSH-Px1 activity; supplementation with 250 mg/day liq-AA increased only by about 28% plasma AA concentration and was ineffective. Conclusions Supplementation with 1,000 mg/day liq-AA is most effective in reducing oxidative stress status and platelet biochemical function in T2DP.
    e-SPEN Journal 12/2012; 7(6):e245–e248. DOI:10.1016/j.clnme.2012.09.006
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    ABSTRACT: We have here investigated possible occurrence of bicarbonate-dependent, carbonate radical anion (CO3•−)-driven tocopherol-mediated human LDL peroxidation (TMP) in vitro and in vivo. CO3•−, generated in vitro by the SOD1/H2O2/bicarbonate system, readily promoted TMP, which was dependent on α-tocopherol and bicarbonate concentrations, and was inhibited by the CO3•− scavenger ethanol; moreover, TMP induced in vitro by the SOD1/H2O2/bicarbonate system occurred in the presence of α-tocopherol that typically underwent slow oxidative consumption. In the in vivo clinical setting, we showed that, compared to controls, hypertensive patients with diuretic-induced metabolic alkalosis and heightened blood bicarbonate concentration had lipid hydroperoxide burden and decreased α-tocopherol content in the LDL fraction, with direct significant correlation between the LDL levels of α-tocopherol and those of lipid hydroperoxides; remarkably, after resolution of metabolic alkalosis, together with normalization of blood bicarbonate concentration, the LDL content of lipid hydroperoxides was decreased and that of α-tocopherol augmented significantly. These findings suggest bicarbonate-dependent, CO3•−-driven LDL TMP in vivo. In conclusion, the present study highlights the occurrence of bicarbonate-dependent, CO3•−-driven human LDL TMP, the role of which in pathological conditions such as atherosclerosis warrants, however, further investigation.
    Free Radical Research 10/2012; 46(11). DOI:10.3109/10715762.2012.719613 · 2.99 Impact Factor
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    ABSTRACT: Hypertension and other risk factors (RFs) predispose to carotid plaques (CPs). An association between left ventricular hypertrophy (LVH) or epicardial adipose tissue (EAT) and CPs has also been reported. The aim of the study was to evaluate whether the assessment of LVH and EAT thickness, beyond RFs, would be of additive value in predicting CPs in hypertensive subjects. We studied 548 hypertensive patients aged ≥50 years without carotid bruit. LVH and CPs were evaluated and defined according to standard criteria. EAT was measured by echocardiography above the free wall of the right ventricle at end diastole. The presence of LVH and EAT thickness above the median value (3.9 mm) together significantly increased prevalence of CPs in subjects with 0-1 risk factor, but not in those with ≥2 RFs who showed high prevalence of CPs independently of LVH and/or EAT. Receiver operating characteristic curve analysis showed that the addition of LVH and higher EAT thickness together significantly improved prediction of CPs in patients with 0-1 risk factor. Indeed, the area under the curve improved from 0.63 (0.56-0.69) to 0.73 (0.67-0.79), which was significantly higher (p < 0.05). In patients with ≥2 RFs, the addition of LVH and EAT did not significantly improve prediction of CPs. This study shows that the presence of LVH and higher EAT thickness together improves prediction of CPs in hypertensive patients with 0-1 risk factor and that those with ≥2 RFs show high prevalence of CPs independently of LVH and/or EAT.
    Heart and Vessels 03/2012; 28(3). DOI:10.1007/s00380-012-0240-y · 2.11 Impact Factor
  • Domenico Lapenna · Sergio Gioia · Giuliano Ciofani · Franco Cuccurullo
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    ABSTRACT: Captopril has been reported to possess reducing and iron-binding properties, which could favour iron delocalization from ferritin and oxidative stress. In the present paper, we have found that the drug was effectively capable of inducing a significant mobilization of ferritin iron, which was apparently superoxide anion-independent. Once released from ferritin as a result of captopril action, iron became free in the reduced form and could induce oxidant damage, as evaluated by deoxyribose-oxidative degradation. This phenomenon was not antagonized by the reported oxygen radical-scavenging properties of the drug. These data indicate that captopril is not always an antioxidant drug, and suggest that it may act as a pro-oxidant in the presence of ferritin in-vivo.
    04/2011; 47(1):59 - 61. DOI:10.1111/j.2042-7158.1995.tb05734.x
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    ABSTRACT: It is debated whether subjects with concentric remodeling (CR, normal left ventricular mass index (LVMI) and increased relative wall thickness (RWT)) are at higher cardiovascular risk than those with normal geometry (NG, normal LVMI and RWT). The aim of this study was to perform a meta-analysis of studies evaluating cardiovascular events in subjects with CR and NG according to baseline classification. We searched for articles evaluating cardiovascular outcome in subjects with CR compared with those with NG, and reporting adjusted hazard ratio (HR) and 95% confidence interval (CI). Six studies were included in the meta-analysis. The pooled population consisted of 7465 subjects with CR and NG. During the follow-up, they experienced 852 events. When compared with NG, the overall adjusted HR was 1.36 (95% CI 1.03-1.78) for CR, P<0.03. There was some heterogeneity between studies. Subgroup meta-analysis showed that increased cardiovascular risk in subjects with CR was more relevant in studies evaluating hypertensive and Caucasian subjects and reporting both fatal and non-fatal events. Cardiovascular risk is significantly higher in subjects with CR than in those with NG. This aspect is more evident in studies including hypertensive patients and Caucasian populations and reporting global cardiovascular risk.
    Journal of human hypertension 03/2011; 25(10):585-91. DOI:10.1038/jhh.2011.24 · 2.69 Impact Factor
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    ABSTRACT: Iron deficiency anemia (IDA) is a frequently encountered condition in clinical practice. After conventional endoscopy, the cause of anemia remains unknown in up to 40% of patients. To evaluate prospectively the diagnostic efficacy of a systematic endoscopic approach to IDA and to compare the diagnostic yield of videocapsule endoscopy (VCE) and CT-enteroclysis in endoscopy-negative patients. Consecutive patients with IDA were enrolled prospectively. Open-access endoscopy within an academic hospital. This study involved 189 patients with IDA, including 98 women and 91 men; mean (±standard deviation) age 68 years±16.6 years. Patients with IDA underwent gastroscopy and colonoscopy plus ileoscopy. Endoscopy-negative patients were further blindly evaluated by both CT-enteroclysis and VCE. Diagnostic yield of conventional endoscopy; diagnostic yield of VCE versus CT-enteroclysis. Endoscopy results were positive in 144 of 189 patients (76.2%). CT-enteroclysis and VCE allowed a diagnosis in 37 of 45 endoscopy-negative patients (82.2%). Overall, VCE was superior to CT-enteroclysis (77.8% vs 22.2%; P<.001), in particular when flat lesions were found. Single-center study. A systematic approach to IDA, which includes standard endoscopy, VCE, and CT-enteroclysis allows an overall diagnostic rate of 95.7%; however, CT-enteroclysis should be limited to cases of nondiagnostic VCE.
    Gastrointestinal endoscopy 03/2011; 73(5):1002-8. DOI:10.1016/j.gie.2011.01.006 · 4.90 Impact Factor
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    ABSTRACT: To investigate the association of serum albumin (SA) with oxidative damage of human atherosclerotic plaques and the severity of atherosclerosis. Correlation of the levels of SA with those of lipid and protein oxidation of endarterectomy-removed carotid atherosclerotic plaques; SA and plaque oxidative biomarkers comparison between 2 groups of patients with different severity of atherosclerotic carotid stenosis, i.e. <90% (group I) or ≥90% (group II). SA was strongly inversely correlated with plaque oxidative damage; SA was lower and plaque oxidative damage higher in group II than group I. Lowered SA is associated with oxidative damage of atherosclerotic plaques and the severity of atherosclerosis.
    Clinical biochemistry 12/2010; 43(18):1458-60. DOI:10.1016/j.clinbiochem.2010.08.025 · 2.28 Impact Factor
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    ABSTRACT: Co-existing algogenic conditions in two internal organs in the same patient may mutually enhance pain symptoms (viscero-visceral hyperalgesia). The present study assessed this phenomenon in different models of visceral interaction. In a prospective evaluation, patients with: (a) coronary artery disease (CAD)+gallstone (Gs) (common sensory projection: T5); (b) irritable bowel syndrome (IBS)+dysmenorrhea (Dys) (T10-L1); (c) dysmenorrhea/endometriosis+urinary calculosis (Cal)(T10-L1); and (d) gallstone+left urinary calculosis (Gs+LCal) (unknown common projection) were compared with patients with CAD, Gs, IBS, Dys or Cal only, for spontaneous symptoms (number/intensity of pain episodes) over comparable time periods and for referred symptoms (muscle hyperalgesia; pressure/electrical pain thresholds) from each visceral location. In patients' subgroups, symptoms were also re-assessed after treatment of each condition or after no treatment. (a) CAD+Gs presented more numerous/intense angina/biliary episodes and more referred muscle chest/abdominal hyperalgesia than CAD or Gs; cardiac revascularization or cholecystectomy also reduced biliary or cardiac symptoms, respectively (0.001<p<0.05). (b) IBS+Dys had more intestinal/menstrual pain and abdomino/pelvic muscle hyperalgesia than IBS or Dys; hormonal dysmenorrhea treatment also reduced IBS symptoms; IBS dietary treatment also improved dysmenorrhea (0.001<p<0.05) while no treatment of either conditions resulted in no improvement in time of symptoms from both. (c) Cal+Dys had more urinary/menstrual pain and referred lumbar/abdominal hyperalgesia than Cal or Dys; hormonal dysmenorrhea treatment/laser treatment for endometriosis also improved urinary symptoms; lithotripsy for urinary stone also reduced menstrual symptoms (0.001<p<0.05). (d) In Gs+LCal, cholecystectomy or urinary lithotripsy did not improve urinary or biliary symptoms, respectively. Mechanisms of viscero-visceral hyperalgesia between organs with documented partially common sensory projection probably involve sensitization of viscero-viscero-somatic convergent neurons.
    Pain 11/2010; 151(2):307-22. DOI:10.1016/j.pain.2010.06.023 · 5.84 Impact Factor
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    ABSTRACT: Fibromyalgia syndrome (FS) frequently co-occurs with regional pain disorders. This study evaluated how these disorders contribute to FS, by assessing effects of local active vs placebo treatment of muscle/joint pain sources on FS symptoms. Female patients with (1) FS+myofascial pain syndromes from trigger points (n=68), or (2) FS+joint pain (n=56) underwent evaluation of myofascial/joint symptoms [number/intensity of pain episodes, pressure pain thresholds at trigger/joint site, paracetamol consumption] and FS symptoms [pain intensity, pressure pain thresholds at tender points, pressure and electrical pain thresholds in skin, subcutis and muscle in a non-painful site]. Patients of both protocols were randomly assigned to two groups [34 each for (1); 28 each for (2)] to receive active or placebo local TrP or joint treatment [injection/hydroelectrophoresis] on days 1 and 4. Evaluations were repeated on days 4 and 8. After therapy, in active--but not placebo-treated-- groups: number and intensity of myofascial/joint episodes and paracetamol consumption decreased and pressure thresholds at trigger/joint increased (p<0.001); FS pain intensity decreased and all thresholds increased progressively in tender points and the non-painful site (p<0.0001). At day 8, all placebo-treated patients requested active local therapy (days 8 and 11) vs only three patients under active treatment. At a 3-week follow-up, FS pain was still lower than basis in patients not undergoing further therapy and had decreased in those undergoing active therapy from day 8 (p<0.0001). Localized muscle/joint pains impact significantly on FS, probably through increased central sensitization by the peripheral input; their systematic identification and treatment are recommended in fibromyalgia.
    European journal of pain (London, England) 10/2010; 15(1):61-9. DOI:10.1016/j.ejpain.2010.09.002 · 3.22 Impact Factor
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    ABSTRACT: The independent prognostic significance of different indices of blood pressure (BP) variability is not clear. We investigated the prognostic value of BP variability estimated as s.d. or average real variability (ARV) of daytime and night time BP, in hypertensive patients. The occurrence of fatal and nonfatal cardiovascular events was evaluated in 1,280 sequential hypertensive patients (550 initially untreated and 730 initially treated) aged > or =40 years. Subjects with s.d. or ARV of daytime or night time systolic or diastolic BP below or above the median were classified as having low or high BP variability. During the follow-up (4.75 +/- 1.8 years), 104 cardiovascular events occurred. The event rate per 100 patient-years was 1.71 in the global population. After adjustment for other covariates, Cox regression analysis showed that cardiovascular risk was higher in subjects with high ARV of daytime systolic BP in initially untreated, initially treated, and all the subjects (high vs. low ARV, hazard ratio (HR) 2.29 (1.06-4.94), HR 1.90 (1.06-3.39), and HR 2.07 (1.31-3.28), respectively). ARV of daytime diastolic BP and night time BP, and s.d. of daytime and night time BP were not significantly associated with risk or were not independent predictors of outcome. In this study, high ARV of daytime systolic BP resulted in an independent predictor of cardiovascular risk in hypertensive patients, while high s.d. did not. Our data suggest that, in comparison to s.d., ARV could be a more appropriate index of BP variability and a more useful predictor of outcomes.
    American Journal of Hypertension 06/2009; 22(8):842-7. DOI:10.1038/ajh.2009.103 · 3.40 Impact Factor
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    ABSTRACT: Myofascial pain syndrome (MPS), a regional pain condition caused by trigger points in muscle or muscle fascia, produces muscle pain, tenderness, and disability. The gold standard of treatment for MPS-infiltration of trigger points with anesthetic-may provoke discomfort to the patients and require medical intervention. This study was designed to compare the effects of a topical lidocaine patch, a placebo patch, and injection of anesthetic (infiltration) for the symptoms of MPS in terms of pain, disability, and local tissue hypersensitivity, and to determine the acceptability of the lidocaine patch to the patients. Patients were randomly allocated to receive 1 of 3 treatments: a lidocaine patch applied to the trigger point for 4 days (replacement every 12 hours; total daily dose, 350 mg), a placebo patch applied to the trigger point for 4 days (replacement every 12 hours), or infiltration of the trigger point with two 1-mL injections of 0.5% bupivacaine hydrochloride given 2 days apart. Treatment with the patches was double-blinded, whereas treatment with infiltration was single-blinded. The number of pain attacks, pain intensity at rest and on movement, and pain-related interference with daily activity, work activity, mood, and quality of life were recorded before, during, and after treatment using a visual analog scale (VAS). Pressure and electrical pain thresholds of the skin, subcutis, and muscle in the trigger point, target area, and a pain-free area were evaluated before starting therapy (day 1) and on days 5 and 9. A VAS was used to measure discomfort from therapy, and a diary was given to each patient to record requests for additional treatment (if needed) and adverse effects. Sixty white patients (46 women and 14 men) 19 to 76 years of age were studied. Mean (SD) age was 46.88 (15.37) years, and mean (SD) weight was 69.58 (13.94) kg. Twenty patients were assigned to each treatment group. Subjective symptoms did not change with placebo, but decreased significantly with the lidocaine patch and infiltration (both, P < 0.001) relative to baseline. Pain thresholds did not vary with the placebo patch, but increased significantly with the lidocaine patch and infiltration (all, P < 0.001); effects at muscle trigger points and target areas were greater with infiltration. Discomfort from therapy was greater with infiltration than with the lidocaine patch. Only patients in the placebo group requested additional treatment (P < 0.001). No adverse events occurred in any group. Lidocaine patches were effective in, and highly acceptable to, these patients with MPS and high tissue hypersensitivity.
    Clinical Therapeutics 05/2009; 31(4):705-20. DOI:10.1016/j.clinthera.2009.04.006 · 2.59 Impact Factor
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    ABSTRACT: BackgroundSince iron is essential for lipoxygenase activity and salicylic acid (SA) can interact with the metal, possible lipoxygenase inhibition by SA was investigated.MethodsKinetic spectrophotometric evaluation of enzymatic lipid peroxidation catalyzed by soybean lipoxygenase (SLO), rabbit reticulocyte 15-lipoxygenase (RR15-LOX), porcine leukocyte 12-lipoxygenase (PL12-LOX) and human recombinant 5-lipoxygenase (HR5-LOX) with and without SA.ResultsSA inhibited linoleic, arachidonic and docosahexaenoic acid or human lipoprotein peroxidation catalyzed by SLO with IC50 of, respectively, 107, 153, 47 and 108 μM. Using the same substrates, SA inhibited RR15-LOX with IC50 of, respectively, 49, 63, 27 and 51 μM. Further, arachidonic acid peroxidation catalyzed by PL12-LOX and HR5-LOX was inhibited by SA with IC50 of 101 and 168 μM, respectively. Enzymatic inhibition was complete, reversible and non-competitive. Conceivably due to its lower hydrophobicity, aspirin was less effective, indicating acetylation-independent enzyme inhibition. SA and aspirin were ineffective peroxyl radical scavengers but readily reduced Fe3+, i.e. FeCl3, to Fe2+, suggesting their capacity to reduce Fe3+ at the enzyme active site. Indeed, similar to the catecholic redox inhibitor nordihydroguaiaretic acid, SA inhibited with the same efficiency both ferric and the native ferrous SLO form, indicating that these compounds reduce the active ferric enzyme leading to its inactivation.General significanceSA can inhibit lipoxygenase-catalyzed lipid peroxidation at therapeutic concentrations, suggesting its possible inhibitory activity against enzymatic lipid peroxidation in the clinical setting.
    Biochimica et Biophysica Acta 01/2009; 1790(1-1790):25-30. DOI:10.1016/j.bbagen.2008.09.007 · 4.66 Impact Factor
  • Sante D Pierdomenico · Domenico Lapenna · Franco Cuccurullo
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    ABSTRACT: The risk of atrial fibrillation (AF) in sustained hypertensive patients with different circadian blood pressure (BP) patterns is unknown. We investigated the risk of new onset AF in dipper and nondipper sustained hypertensive patients. The occurrence of AF was evaluated in 1141 patients aged > or = 40 years with sustained hypertension (clinic BP > or = 140 and/or 90 mmHg and daytime BP > or = 135 and/or 85 mmHg). Among these patients, 783 had night-time systolic BP fall > or = 10% (dippers) and 358 had night-time BP decline <10% (nondippers). During the follow-up (6.1+/-3.2, range 0.5-12.9 years), AF occurred in 43 patients. The AF rate per 100 patient-years in dippers and nondippers was 0.38 and 1.13, respectively. AF free survival was significantly different between the groups (P=0.0002). After adjustment for other covariates, including left atrial enlargement or left ventricular hypertrophy (these variables were analyzed in separate models because of a strong association between them) and 24-h BP, Cox regression analysis showed that the risk of AF was significantly higher in nondippers than in dippers [nondippers vs. dippers, relative risk (RR) 2.02, 95% confidence interval (CI) 1.08-3.79, P=0.028 in the model including left atrial enlargement, and RR 1.97, 95% CI: 1.05-3.69, P=0.035 in the model including left ventricular hypertrophy]. This study shows that nondipper sustained hypertensive patients have a two-fold greater risk of developing AF than dipper ones. This aspect could partly contribute to explain the higher cardiovascular risk previously observed in nondipper hypertensive patients.
    Blood Pressure Monitoring 08/2008; 13(4):193-7. DOI:10.1097/MBP.0b013e3282feea70 · 1.18 Impact Factor
  • High Blood Pressure & Cardiovascular Prevention 07/2008; 15(3):270. DOI:10.1007/BF03263682