Biomedical subjects

Domenico Lapenna

Publications and source records attributed to Domenico Lapenna.

At least 19 recordsLinked to original sources

PubMed2006

Sensory and biomechanical characterization of two painful syndromes in the heel.

UNLABELLED: This study evaluated sensory and biomechanical assets in 2 heel pain conditions with similar symptoms, entrapment syndrome of the nerve to abductor digiti quinti and myofascial syndrome of abductor hallucis. Thirty-three patients with unilateral heel pain and 20 asymptomatic subjects underwent pressure pain threshold measurement in the painful area in site A (medial process of calcaneal tuberosity, trigger point site of abductor hallucis) and site B (1 cm posteriorly to site A, where the nerve to abductor digiti quinti becomes most superficial) and contralaterally; electroneurography of posterior tibial nerve; evaluation of ground-foot reaction on a dynamic platform. Eighteen patients had electric shock-type pain (entrapment syndrome, Group 1), 15 had cramp-like pain (myofascial syndrome, Group 2). Pain thresholds on the affected side versus contralaterally were significantly lower in site B in Group 1 and in site A in Group 2 (P < .001). Nerve conduction velocity was slightly reduced in Group 1 (P = .05). Ground-foot reaction was significantly altered on the affected side in all patients versus asymptomatic subjects; a significant difference between the 2 sides was found for peak of force (F1) in Group 1 and for all parameters except temporal phase of peak of force (TF3) (P = .05) for Group 2 (P < .0001). The different sensory and biomechanical patterns of the 2 examined syndromes help the differential diagnosis and consequent therapeutic approach. PERSPECTIVE: This study shows different sensory and biomechanical patterns in 2 algogenic conditions of the heel with similar pain location. These distinct patterns reflect different pathophysiologic mechanisms in the 2 cases, which has a potential significant impact on treatment.

Adult↗

PubMed2006

Blood pressure variability and cardiovascular risk in treated hypertensive patients.

BACKGROUND: The independent prognostic value of blood pressure (BP) variability in treated hypertension is not yet clear. We investigated the relationship between BP variability, evaluated by noninvasive monitoring, and cardiovascular outcome in treated hypertensive patients. METHODS: The occurrence of fatal and nonfatal cardiovascular events was evaluated in 1472 treated patients. Subjects with the standard deviation of daytime or night-time systolic BP below or above the median of the population were classified as having low or high BP variability. Specifically, 738 and 734 patients had low and high daytime BP variability, respectively, and 739 and 733 subjects had low and high night-time BP variability, respectively. RESULTS: During follow-up (4.88 +/- 2.9 years, range 0.2-11.6 years) there were 119 events. The event rates per 100 patient-years in subjects with low and high BP variability according to daytime BP were 1.18 and 2.01, respectively, and in those with low and high BP variability according to night-time BP were 1.2 and 2.05, respectively. Event-free survival was significantly different between the low and high BP variability groups (P = .006 for both daytime and night-time BP). However, after adjustment for other covariates in a Cox multivariate analysis, the adverse prognostic relevance of high BP variability was no longer detectable, whereas age, smoking habit, LDL cholesterol, diabetes, previous events, LV hypertrophy, and daytime or night-time systolic BP resulted independent predictors of risk. CONCLUSIONS: Increased BP variability is associated with higher incidence of cardiovascular events, but also with other relevant prognostic factors. Indeed, in multivariate analysis the possible adverse prognostic impact of BP variability is no longer evident. Thus, in treated hypertension, BP variability evaluated by noninvasive monitoring is not an independent predictor of outcome.

Aged↗

PubMed2006

Cardiovascular risk in patients receiving double therapy with false and true nonresponder hypertension.

OBJECTIVE: The aim of this study was to evaluate cardiovascular risk in hypertensive patients receiving double therapy with false and true nonresponder hypertension. METHODS: The occurrence of fatal and nonfatal cardiovascular events was evaluated in 730 patients receiving double therapy with uncontrolled clinic blood pressure. Two hundred and seventy had false nonresponder hypertension (clinic blood pressure > or =140 or 90 mmHg and daytime blood pressure <135/85 mmHg) and 460 had true nonresponder hypertension (clinic blood pressure > or =140 or 90 mmHg and daytime blood pressure > or =135 or 85 mmHg). RESULTS: During the follow-up (4.77+/-2.9 years, range 0.2-11.7 years), 55 cardiovascular events occurred. The event rates per 100 patient-years in patients with false and true nonresponder hypertension were 1.03 and 1.9, respectively. Event-free survival was significantly different between the groups (P<0.05). After adjustment for several covariates, including clinic blood pressure (forced into the model), Cox regression analysis showed that cardiovascular risk was significantly higher in true than in false nonresponder hypertension (relative risk 2.33, 95% confidence interval 1.14-4.77, P=0.02). CONCLUSIONS: This study shows that, among treated hypertensive patients receiving double therapy with uncontrolled clinic blood pressure those with true nonresponder hypertension are at higher cardiovascular risk. Ambulatory blood pressure monitoring should be performed in this population to achieve a better prognostic stratification.

Aged↗

PubMed2005

Relationship between pain symptoms and referred sensory and trophic changes in patients with gallbladder pathology.

The relationship was investigated between algogenic potential of gallbladder pathology and occurrence/extent of sensory and trophic changes in the referred area. Five groups of subjects were studied, with: symptomatic gallbladder calculosis (3-20 colics); asymptomatic calculosis; symptomatic gallbladder shape abnormality (8-18 colics); asymptomatic shape abnormality; normal gallbladder/no symptoms. At the cystic point (CP) and contralaterally, all underwent measurement of: pain thresholds to electrical stimulation of skin, subcutis and muscle; thickness of subcutis and muscle via ultrasounds. Contralaterally to CP, all thresholds were not significantly different in the five groups. At CP, subcutis and muscle thresholds were significantly lower in symptomatic vs asymptomatic patients and/or normals (0.0001<P< 0.05). In symptomatic cases, at CP compared to contralaterally, subcutis and muscle thresholds were significantly lower (0.0001<P<0.02), subcutis thickness was significantly higher and muscle thickness significantly lower (0.006<P<0.02). Subcutis and muscle thresholds at CP in symptomatic patients were significantly and inversely correlated linearly to the number of colics (P<0.0004; P<0.0001). Patients with symptomatic calculosis were re-evaluated after 6 months; those not presenting further colics showed a significant increase in subcutis and muscle thresholds at CP, while those who continued presenting colics showed a further significant threshold decrease (0.01<P<0.05); tissue thickness did not vary. Referred hyperalgesia and altered trophism from the gallbladder only occur in painful pathology, their extent being modulated by the amount of perceived pain. The results suggest different mechanisms by which visceral nociceptive inputs trigger sensory vs trophic changes in the referred area.

Abdominal Pain↗

PubMed2005

Copper, zinc superoxide dismutase plus hydrogen peroxide: a catalytic system for human lipoprotein oxidation.

We report for the first time that bovine or human CuZnSOD plus H2O2 can catalyze human lipoprotein oxidation, inducing like free copper ions a typical oxidative kinetics with lag and propagation phases. Free copper released from CuZnSOD by H2O2, but not enzyme peroxidase activity and carbonate radical anion, is responsible for lipoprotein oxidation, which is indeed totally inhibited by copper chelators and BHT but unaffected by bicarbonate. Moreover, lipoprotein oxidation is significantly counteracted by the OH* scavengers formate and azide, which can enter the active site of CuZnSOD and decrease copper release through scavenging of copper-bound OH*; benzoate and ethanol, which cannot enter, are instead ineffective, indicating no oxidative involvement of free OH* escaped from the enzyme active site. The possibility of CuZnSOD/H2O2-catalyzed lipoprotein oxidation in vivo is discussed.

Animals↗

PubMed2005

Blood pressure variability and prognosis in uncomplicated mild hypertension.

BACKGROUND: The independent prognostic value of blood pressure (BP) variability in essential hypertension and particularly in uncomplicated mild hypertension is not yet completely clear. We investigated the relationship between BP variability, evaluated by noninvasive monitoring, and cardiovascular outcome in uncomplicated mild hypertension patients. METHODS: The occurrence of fatal and nonfatal cardiovascular events was evaluated in 1088 uncomplicated mild hypertension patients, 626 with low BP variability (SD of daytime systolic BP below the mean of the study population) and 462 with high BP variability (SD of daytime systolic BP above the mean of the study population). RESULTS: During the follow-up (4.74 +/- 2.4 years, range 0.5-9.7 years), the event rates per 100 patient-years in subjects with low and high BP variability were 0.72 and 1.5, respectively. Event-free survival was significantly different between the groups (P = .01). However, after adjustment for other covariates in a Cox multivariate analysis, the adverse prognostic relevance of high BP variability was no longer detectable, whereas age, daytime systolic BP, low-density lipoprotein cholesterol, and smoking habit resulted as independent predictors of cardiovascular events. CONCLUSIONS: In uncomplicated mild hypertension population, BP variability evaluated by noninvasive monitoring is not an independent predictor of outcome.

Blood Pressure↗

PubMed2005

Cardiovascular outcome in treated hypertensive patients with responder, masked, false resistant, and true resistant hypertension.

BACKGROUND: The aim of this study was to evaluate the cardiovascular outcome in apparently responder hypertensive patients with responder and masked hypertension, and in apparently resistant hypertensive patients with false and true resistant hypertension. METHODS: The occurrence of fatal and nonfatal cardiovascular events was evaluated in 340 patients with responder hypertension (clinic blood pressure [BP] <140/90 mm Hg and daytime BP <135/85 mm Hg), 126 with masked hypertension (clinic BP <140/90 mm Hg and daytime BP >135 or 85 mm Hg), 146 with false resistant hypertension (clinic BP >or=140 or 90 mm Hg and daytime BP <135/85 mm Hg), and 130 with true resistant hypertension (clinic BP >or=140 or 90 mm Hg and daytime BP >135 or 85 mm Hg). RESULTS: During follow-up period (4.98 +/- 2.9 years), the event-rate per 100 patient-years was 0.87, 2.42, 1.2, and 4.1 in patients with responder, masked, false resistant, and true resistant hypertension, respectively. After adjustment for several covariates, including clinic BP (forced into the model), Cox regression analysis showed that cardiovascular risk was significantly higher in masked hypertension (masked versus responder hypertension, relative risk [RR] 2.28, 95% confidence interval [CI] 1.1-4.7, P < .05) and in true resistant hypertension (true resistant versus responder hypertension, RR 2.94, 95% CI 1.02-8.41, P < .05), whereas there was no significant difference between false resistant and responder hypertension. CONCLUSIONS: This study shows that patients with masked hypertension are at higher risk than those with responder hypertension, and that those with false resistant hypertension are at lower risk than those with true resistant hypertension. Ambulatory BP monitoring should be performed in treated hypertensive patients to obtain a better prognostic stratification.

Aged↗

PubMed2005

Visceral sensitivity and symptoms in patients with constipation- or diarrhea-predominant irritable bowel syndrome (IBS): effect of a low-fat intraduodenal infusion.

BACKGROUND: Visceral hypersensitivity is common in Irritable Bowel Syndrome (IBS) patients, and symptoms exacerbate postprandially. Yet the effects of nutrients on visceral sensitivity and symptoms in these patients have not been fully explored. AIMS: To evaluate the differences of visceral sensitivity and symptoms in healthy subjects and IBS patients during fasting and intraduodenal lipids infusion. METHODS: Graded rectal distensions at fixed tension levels were performed in 16 IBS patients (8 IBS-C and 8 IBS-D) and 6 healthy subjects before and during intraduodenal lipids infusion at 0.5 kcal/min. Tension levels were increased in 4 gr increments up to 64 gr or discomfort during both conditions. At each step, perception and symptoms were measured by means of a validated questionnaire. RESULTS: In basal conditions, perception thresholds in IBS patients and health were, respectively, 8 +/- 2 gr versus 32 +/- 9 gr (p < 0.001) with no changes during lipids. Intraduodenal lipids infusion significantly lowered threshold of discomfort in IBS patients in comparison to fasting (24 +/- 6 gr vs 34 +/- 4 gr; p < 0.05), while health tolerated all distension without discomfort. No differences of compliance, perception, or discomfort were observed between the two subgroups of patients at each tension step. The predominant symptom elicited in patients with IBS-C was abdominal pain (54%), while patients with IBS-D exhibited urgency (63%, p < 0.005); this pattern was maintained during lipids. CONCLUSIONS: Intraduodenal lipids increase visceral sensitivity in both IBS-C and IBS-D; symptoms specificity in response to rectal distension is maintained in the postprandial period. Lipids may be responsible for the postprandial symptoms exacerbation in IBS.

Adult↗

PubMed2004

Cardiovascular and renal events in uncomplicated mild hypertensive patients with sustained and white coat hypertension.

BACKGROUND: The prognostic value of white coat hypertension (WCH) in uncomplicated patients with mild hypertension is not yet completely clear. We investigated cardiovascular outcomes in patients with mild hypertension and without left ventricular hypertrophy, diabetes mellitus, and associated cardiovascular and renal disease, with sustained hypertension (SH) and WCH. METHODS: The occurrence of fatal and nonfatal cardiovascular events was evaluated in 1038 patients with mild hypertension and 241 normotensive subjects. The presence of WCH was defined as clinic hypertension and daytime blood pressure <135/85 mm Hg. RESULTS: During follow-up (4.5 +/- 2.3 years, range 0.5 to 9.2 years) the event rates per 100 patient-years in subjects with normotension, WCH, and SH were 0.27, 0.38, and 1.39, respectively. After adjustment for other covariates, Cox regression analysis showed that SH was an independent predictor of cardiovascular events (SH versus WCH, RR 5.17, 95% CI 2.04 to 13.1, P = 0 .001), whereas there was no significant difference between normotension and WCH (normotension versus WCH, RR 0.93, 95% CI 0.22 to 3.98, P = .92). At the end of follow-up, drug therapy was less frequent and intensive in WCH than in SH. CONCLUSIONS: In this study of individuals with mild hypertension and without left ventricular hypertrophy, diabetes mellitus, and associated cardiovascular and renal disease, subjects with WCH, despite less frequent and intensive drug therapy, had a significantly better prognosis than those with sustained hypertension.

Adult↗

PubMed2004

Prognostic value of left ventricular concentric remodeling in uncomplicated mild hypertension.

BACKGROUND: The prognostic value of left ventricular (LV) concentric remodeling in essential hypertension, and particularly in uncomplicated mild hypertension, is not yet completely clear. We investigated cardiovascular outcome in uncomplicated mild hypertensive patients with normal LV geometry and LV concentric remodeling. METHODS: The occurrence of fatal and nonfatal cardiovascular events was evaluated in 1088 uncomplicated mild hypertensive patients, 751 with normal LV geometry (LV mass index <125 g/m(2) in men and <110 g/m(2) in women and relative wall thickness <0.45) and 337 with LV concentric remodeling (LV mass index <125 g/m(2) in men and <110 g/m(2) in women and relative wall thickness >/=0.45). RESULTS: During follow-up (4.74 +/- 2.4 years, range 0.5 to 9.7 years) the event rates per 100 patient-years in subjects with normal LV geometry and LV concentric remodeling were 0.69 and 1.87, respectively. After adjustment for other covariates, Cox regression analysis showed that LV concentric remodeling (LV concentric remodeling versus normal LV geometry, RR 1.78, 95% CI 1.02 to 3.1, P < .05) was an independent predictor of cardiovascular events. CONCLUSION: In a population with uncomplicated mild hypertension, patients with LV concentric remodeling have a worse prognosis than those with normal LV geometry.

Adult↗

PubMed2004

Aortic glutathione metabolic status: time-dependent alterations in fat-fed rabbits.

Little is known about the vascular metabolic status of glutathione (GSH), which is crucial in cell antioxidant protection, in experimental conditions like high-fat diet-induced atherosclerosis. This issue was, therefore, investigated in two groups of seven rabbits fed a 0.5% cholesterol-, 5% lard- and 5% peanut oil-enriched diet for 18 and 80 days, which, respectively, raised the plasma values of total cholesterol by factors of about 12 and 37, and those of triglycerides by factors of 3 and 13; rabbits fed a standard diet for the same periods served as controls. Total GSH and the activities of the GSH level-maintaining enzymes glutathione reductase (GSSG-Red), gamma-glutamylcysteine synthetase (gamma-GCS) and gamma-glutamyl transpeptidase (gamma-GT) were specifically assessed in the aortic tissue, which was also assayed for fluorescent damage products of lipid peroxidation (FDPL). Sudan red staining of the aortic intima surface was also performed in two other groups of six controls and six fat-fed rabbits. After 18 days of fat feeding, a significant decrement of aortic GSSG-Red activity, associated with gamma-GCS activation, increased GSH levels and normal gamma-GT activity, was observed; FDPL were only moderately enhanced, and atherosclerotic lesions did not occur. After 80 days of atherogenic diet, aortic GSH content was significantly decreased in concomitance with a marked depression of gamma-GT activity, while GSSG-Red and gamma-GCS activities were not significantly changed with respect to 18 days of fat feeding; FDPL underwent further considerable augmentation, and extensive Sudan red-stained atherosclerotic lesions were evident. Thus, short-term fat feeding induces gamma-GCS-dependent GSH biosynthesis of the rabbit aorta; prolonged high-fat intake and hyperlipidemic burden result instead in vascular gamma-GT dysfunction with GSH depletion, eventually favoring oxidative atherogenic effects.

Analysis of Variance↗

PubMed2004

Transmural distribution of iron in the hypoxic and reoxygenated rabbit left ventricular myocardium.

Transmural distribution of low molecular weight iron (LMWI), total iron, and protein carbonyls (PC) was investigated in the perfused rabbit heart under aerobic conditions, and after 60 min hypoxia followed or not by 3 min reoxygenation. In the aerobic perfused hearts, LMWI, total iron and PC did not show significant transmural differences. Hypoxia increased LMWI and PC levels, which were significantly higher in the subendocardium than in the subepicardium; further significant changes were not observed after reoxygenation. Total iron showed no transmural difference and was not significantly affected by both hypoxia and reoxygenation. Free iron was undetectable in the myocardial effluent of all experimental groups. Thus, hypoxia favors myocardial iron decompartmentalisation and oxidative stress, which are significantly greater in the inner than in the outer ventricular layers. Such findings may add further insight into the problem of the vulnerability of the mammalian subendocardium to injury induced by oxygen deprivation.

Animals↗

PubMed2003

Dihydrolipoic acid inhibits 15-lipoxygenase-dependent lipid peroxidation.

The potential antioxidant effects of the hydrophobic therapeutic agent lipoic acid (LA) and of its reduced form dihydrolipoic acid (DHLA) on the peroxidation of either linoleic acid or human non-HDL fraction catalyzed by soybean 15-lipoxygenase (SLO) and rabbit reticulocyte 15-lipoxygenase (RR15-LOX) were investigated. DHLA, but not LA, did inhibit SLO-dependent lipid peroxidation, showing an IC(50) of 15 microM with linoleic acid and 5 microM with the non-HDL fraction. In specific experiments performed with linoleic acid, inhibition of SLO activity by DHLA was irreversible and of a complete, noncompetitive type. In comparison with DHLA, the well-known lipoxygenase inhibitor nordihydroguaiaretic acid and the nonspecific iron reductant sodium dithionite inhibited SLO-dependent linoleic acid peroxidation with an IC(50) of 4 and 100 microM, respectively, while the hydrophilic thiol N-acetylcysteine, albeit possessing iron-reducing and radical-scavenging properties, was ineffective. Remarkably, DHLA, but not LA, was also able to inhibit the peroxidation of linoleic acid and of the non-HDL fraction catalyzed by RR15-LOX with an IC(50) of, respectively, 10 and 5 microM. Finally, DHLA, but once again not LA, could readily reduce simple ferric ions and scavenge efficiently the stable free radical 1,1-diphenyl-2-pycrylhydrazyl in ethanol; DHLA was considerably less effective against 2,2'-azobis(2-amidinopropane) dihydrochloride-mediated, peroxyl radical-induced non-HDL peroxidation, showing an IC(50) of 850 microM. Thus, DHLA, at therapeutically relevant concentrations, can counteract 15-lipoxygenase-dependent lipid peroxidation; this antioxidant effect may stem primarily from reduction of the active ferric 15-lipoxygenase form to the inactive ferrous state after DHLA-enzyme hydrophobic interaction and, possibly, from scavenging of fatty acid peroxyl radicals formed during lipoperoxidative processes. Inhibition of 15-lipoxygenase oxidative activity by DHLA could occur in the clinical setting, eventually resulting in specific antioxidant and antiatherogenic effects.

Acetylcysteine↗

PubMed2003

Evaluation of indices of skeletal muscle contraction in areas of referred hyperalgesia from an artificial ureteric stone in rats.

This study examined indices of skeletal muscle contraction in a rat model of referred muscle hyperalgesia from artificial ureteric calculosis [left oblique muscle (OE) for ipsilateral stone]. In specimens from the left versus right OE of stone-implanted female rats, a significant increase was found in membrane fluidity (P<0.01) and Ca(2+)-ATPase activity (P<0.0001) and a significant decrease in 3H-ryanodine binding (P<0.0001) and in I band length/sarcomere length ratio (contraction index) (P<0.01). The increase in Ca(2+)-ATPase activity was directly and significantly related to the number of rats' ureteral 'crises' (P<0.02). The results indicate a state of contraction in the hyperalgesic muscle, whose extent correlates to the algogenic activity of the ureteral stone.

Animals↗

PubMed2002

Antioxidant properties of ursodeoxycholic acid.

We have investigated potential antioxidant properties of the clinically relevant bile acid UDCA, which reaches therapeutic concentrations up to 0.09 and 29 mM, respectively, in human plasma and bile. UDCA was an excellent scavenger of OHz.rad; generated by FeCl(3)-EDTA, H(2)O(2) and ascorbate in the deoxyribose oxidation test, showing IC(min) and IC(50) values of 0.02 and 0.2 mM, respectively, and a second-order rate constant for reaction with OHz.rad; of 2+/-0.1 x 10(10)M(-1)s(-1). Notably, the drug could enhance at 1.5 mM concentration the antioxidant capacity of human bile against OHz.rad;-induced deoxyribose oxidation. UDCA also showed antioxidant effects in the deoxyribose test performed with nonchelated iron ions, such as Fe(2+) plus H(2)O(2) (IC(min): 7 mM, IC(50): 20 mM) or Fe(3+) plus H(2)O(2) and ascorbate (IC(min): 0.3 mM, IC(50): 5 mM), and inhibited ferrozine-Fe(2+) and desferrioxamine-Fe(3+) complexes formation with IC(50) values of, respectively, 12 and 0.3 mM, indicating that the drug interacts more with iron(III) than with iron(II). Moreover, UDCA significantly inhibited phospholipid liposome peroxidation induced by the OHz.rad;-generating system FeCl(3)-EDTA, H(2)O(2) and ascorbate (IC(min): 0.75 mM, IC(50): 3 mM), and by peroxyl radicals generated in the aqueous phase by AAPH (IC(min): 8 mM, IC(50): 14 mM). UDCA, even at 25 mM concentration, was ineffective on the lipoperoxidation mediated by Fe(2+) alone, but at the same concentration counteracted significantly that by Fe(3+) plus ascorbate, further pointing to its preferential antioxidant interaction with iron(III). In conclusion, UDCA has direct antioxidant properties, which are especially relevant against Fe(3+)- and OHz.rad;-dependent biomolecular oxidative damage; such properties are evident at therapeutically relevant drug concentrations, suggesting that UDCA could act as an antioxidant in vivo.

Antioxidants↗

PubMed2002

Vanadyl as a catalyst of human lipoprotein oxidation.

Lipoprotein oxidation, which is relevant to atherogenesis, can be induced by redox-active transition metals, such as copper. Vanadium is a metal usually used as vanadyl to improve metabolic control in diabetic patients; given its redox-active properties, we have investigated possible oxidative effects of the metal on lipoproteins from healthy and diabetic subjects. Beginning from 10 microM, vanadyl, but not vanadate, induced oxidation of the non-HDL fraction, which was inhibited by EDTA, butylated hydroxytoluene and Vitamins E and C, but not by mannitol, SOD and catalase. Differently from copper, vanadyl could oxidize directly lipoprotein lipids, although it showed a lower oxidant activity against critical tryptophan residues of the lipoprotein protein moiety. Moreover, the non-HDL fraction of diabetic patients was more susceptible to vanadyl-dependent oxidation than that of controls. Thus, vanadium, in its reduced form which may be used in humans, can oxidize the non-HDL fraction through oxidative effects exerted especially on lipoprotein lipids; the specific pro-oxidant activity of vanadyl is more evident with lipoproteins of diabetic patients. Given also the tissue accumulating capacity of vanadium conceivably in a reduced form, its prolonged administration to humans, especially to diabetic patients without adequate antioxidant supplementation, needs caution.

Apolipoproteins B↗

PubMed2002

Influence of endometriosis on pain behaviors and muscle hyperalgesia induced by a ureteral calculosis in female rats.

Endometriosis and urinary calculosis can co-occur. Clinical studies have shown that both painful and non-painful endometriosis in women are associated with enhanced pain and referred muscle hyperalgesia from urinary calculosis, but the mechanisms underlying this phenomenon are still poorly understood. The aim of this study was to develop an animal model adequate to explore this viscero-visceral interaction in standardized conditions. Using a model of endometriosis previously developed to study reduced fertility and vaginal hyperalgesia, endometriosis (endo) or sham-endometriosis (sham-endo) was induced in rats by autotransplantation of small pieces of uterus (or, for sham-endo, fat) on cascade mesenteric arteries, ovary, and abdominal wall. After the endometrial, but not the fat autografts had produced fluid-filled cysts (3 weeks), urinary calculosis was induced by implanting an artificial stone into one ureter. Pain behaviors were monitored by continuous 24-h videotape recordings before and after stone implantation. Referred muscle hyperalgesia was assessed by measuring vocalization thresholds to electrical stimulation of the oblique musculature (L1 dermatome). The data were compared with previously reported data from rats that had received only the stone. Neither endo nor sham-endo alone induced pain behaviors. Following stone implantation, in endo rats compared to sham-endo and stone-only rats, pain behaviors specifically associated with urinary calculosis were significantly increased and new pain behaviors specifically associated with uterine pathology became evident. Muscle hyperalgesia was also significantly increased. To explore the relationship between the amount of endometriosis and that of ureteral pain behavior, two separate groups of endo rats were treated with either a standard non-steroidal anti-inflammatory drugs (ketoprofen) or placebo from the 12th to the 18th day after endometriosis induction. The stone was implanted on the 21st day. Ketoprofen treatment compared to placebo significantly reduced the size of the cysts and both ureteral and uterine pain behaviors post-stone implantation. The size of the cysts showed a significant linear correlation with the post-stone ureteral pain behaviors. In conclusion, endo increased pain crises and muscle hyperalgesia typically induced by a ureteral calculosis, and the ureteral calculosis revealed additional pain behaviors typically induced by uterine pathophysiology; and this enhancement was a function of the degree of endometriosis. This result closely reproduces the condition observed in humans and could be due to a phenomenon of 'viscero-visceral' hyperalgesia, in which increased input from the cyst implantation sites to common spinal cord segments (T10-L1) facilitates the central effect of input from the urinary tract.

Abdominal Muscles↗

PubMed2002

Endothelial function in sustained and white coat hypertension.

BACKGROUND: Endothelial dysfunction is a frequent finding in essential hypertension. The aim of this study was to assess endothelial function, by evaluating circulating nitric oxide metabolites, nitrate plus nitrite (NOx), and endothelium-dependent vasodilation (EDD), in white coat hypertension in comparison with sustained hypertension and normotension. METHODS: We selected 22 sustained hypertensive, 22 white coat hypertensive, and 22 normotensive subjects matched for age, gender, body mass index, and occupation. Women were also matched for menopausal status. Subjects with smoking habit, dyslipidemia, and diabetes mellitus were excluded from the study. White coat hypertension was defined as clinical hypertension and daytime ambulatory blood pressure (BP) <135/85 mm Hg. Groups received for 2 days a low-nitrate diet before obtaining blood samples for laboratory measurements. The NOx levels were measured by using the Griess reagent after enzymatic conversion of all nitrate to nitrite. Subjects also underwent brachial artery study by ultrasonography to evaluate EDD and endothelium-independent vasodilation. RESULTS: White coat hypertensive subjects had significantly higher levels of NOx than sustained hypertensive patients (30.8 +/- 12 v 22 +/- 8.5 micromol/L, P <.05) and significantly higher EDD (7.8% +/- 3.1% v 4.6% +/- 3.0%, P <.05). No significant difference was observed between white coat hypertensive and normotensive subjects regarding these parameters. Endothelium-independent vasodilation was not significantly different among sustained hypertensives, white coat hypertensives, and normotensives (18% +/- 4.2% v 18.3% +/- 3.9% v 18.6% +/- 4.8%, respectively, P = not significant). CONCLUSIONS: Our data suggest that middle-aged white coat hypertensive subjects without other cardiovascular risk factors do not show endothelial dysfunction in contrast with sustained hypertensive patients.

Adult↗