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Aim To evaluate the effects of photodynamic therapy (PDT) in the nonsurgical treatment of chronic periodontitis. Materials and methods A randomized, single-blind, controlled, parallel-group clinical trial was performed. Sixty patients were enrolled: 20 healthy controls and 40 patients with periodontitis. The 40 patients were randomized for scaling and root planing (SRP) or SRP+PDT. Periodontal (plaque index, probing depth, clinical recession, clinical attachment level, bleeding on probing, and gingival crevicular fluid volume, corresponding to 381 vs 428 critical sites), microbiological (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia and Campylobacter rectus presence, 18 vs 19 samples) and biochemical (interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α, receptor activator of nuclear factor-kappaB ligand (RANK-L) and osteoprotegerin (OPG) levels, 18 vs 19 samples) parameters were recorded. Results Within each group, significant improvements were found for clinical parameters, though without significant differences between groups. RANK-L was significantly decreased at week 13 in the SRP+PDT group compared with the SRP group. SRP+PDT, but not SRP alone, significantly reduced the abundance of A. actinomycetemcomitans. Conclusions Except for a significant decrease in the pathogenic burden of A. actinomycetemcomitans, coadjuvant PDT resulted in no additional improvement compared with SRP alone in patients diagnosed with moderate to advanced chronic periodontitis. This article is protected by copyright. All rights reserved.

OBJECTIVES Ranolazine improves vascular function in animal models. We evaluate the effects of ranolazine on vascular function and adrenergic response in human saphenous vein. METHODS Rings from 53 patients undergoing coronary artery bypass grafting were mounted in organ baths. Concentration–response curves to ranolazine were constructed in rings precontracted with phenylephrine, endothelin-1, vasopressin, KCl and the thromboxane A2 analogue U-46619. In rings precontracted with phenylephrine, relaxation to ranolazine was tested in the absence and presence of endothelial factors inhibitors, K+ channel blockers and verapamil. The effects of ranolazine on frequency–response and concentration–response curves to phenylephrine were performed in the absence and presence of endothelial factors inhibitors and K+ channel blockers. Endothelial nitric oxide synthase, α1 adrenergic receptor and large conductance Ca2+-activated K+ channel protein expressions were measured by Western blotting. RESULTS Ranolazine (10−9–10−4 M) produced a concentration-dependent relaxation only in rings precontracted with phenylephrine that was reduced by endothelial denudation, NG-nitro-l-arginine methyl ester (10−4 M), charybdotoxin (10−7 M) and verapamil (10−6 M). Ranolazine diminished adrenergic contractions induced by electrical field stimulation (2–4 Hz) and phenylephrine (10−9–10−5 M) that were prevented by tetraethylammonium (10−3 M) and charybdotoxin (10−7 M). Ranolazine significantly decreased α1 adrenergic receptor and increased large conductance Ca2+-activated K+ channel protein expression in the saphenous vein. CONCLUSIONS Ranolazine diminishes the adrenergic vasoconstriction, acting as α1 antagonist, and by increasing large conductance Ca2+-activated K+ channel involvement. The relaxant effects of ranolazine are partially mediated by endothelial nitric oxide, large conductance Ca2+-activated K+ channels and the blockade of voltage-dependent Ca2+ channels.

Objective To investigate the effect of antiangiogenic treatment on experimental endometriotic lesion nerve fibers. Design Heterologous mouse model of endometriosis. Setting University Institute IVI, University Hospital La Fe. Animal(s) Ovariectomized nude mice (n = 16) receiving human endometrial fragments from oocyte donors (n = 4). Intervention(s) Endometrium fragments stuck in the peritoneum of 5-week-old female nude mice treated with vehicle (n = 8) and antiangiogenic agent cabergoline (n = 8; Cb 2, 0.05 mg/kg/day) for 14 days. Main Outcome Measure(s) Immunofluorescence analysis of von-Willebrand factor (vWF) and vascular smooth muscle cells (αSMA) for evaluating the number of immature blood vessels (IBV) and microvascular density (MVD); immunochemical analysis of protein-gene product 9.5 (PGP 9.5) to assess nerve fibers density (NFD), and blue toluidine staining to confirm presence of mast cells and macrophages in endometriotic lesions. Result(s) All the results were quantified by morphometric techniques. The IBV, NFD, and number of macrophages and mast cells were statistically significantly decreased in the Cb2-treated group when compared with controls. Conclusion(s) Antiangiogenic treatment statistically significantly diminishes new blood vessel formation after macrophage, mast cell, and nerve fiber reduction, providing a rationale to test antiangiogenic agents as a novel therapeutic approach to severe pelvic pain associated with human peritoneal endometriosis.

Objectives: Plasma levels of endogenous guanidino-substituted analogues of L -arginine are increased in various pathologic conditions. In the present study we determined the effects of some of these compounds on basal and stimulated release of nitric oxide in human internal thoracic and radial arteries. Methods: Rings of human internal thoracic and radial arteries were obtained from 16 multiorgan donors. The rings were suspended in organ baths for isometric recording of tension. Results: N G -monomethyl L -arginine (10 –6 to 10 –3 mol/L) and N G ,N G -dimethyl L -arginine (10 –6 to 10 –3 mol/L) caused concentration- and endothelium-dependent contractions. Maximal force of contractions for N G -monomethyl L -arginine and N G ,N G -dimethyl L -arginine in the internal thoracic artery were 18.0% ± 4.3% and 17.8% ± 3.8%, respectively, of the contraction to 100 mmol/L KCl, and those found in the radial artery were 9.6% ± 2.5% and 9.1% ± 2.4%, respectively. Aminoguanidine (10 –5 to 3 × 10 –3 mol/L) and methylguanidine (10 –5 to 3 × 10 –3 mol/L) produced endothelium-independent contractions. L -Arginine (10 –3 mol/L) prevented the contractions by N G -monomethyl L -arginine and N G ,N G -dimethyl L -arginine but did not change contractions induced by aminoguanidine and methylguanidine. N G -monomethyl L -arginine and N G ,N G -dimethyl L -arginine inhibited, in a concentration-dependent manner, the endothelium-dependent relaxation to acetylcholine in the internal thoracic artery and had little attenuating effect in the radial artery; aminoguanidine and methylguanidine were without effect. Conclusions: The results suggest that the contractions induced by N G -monomethyl L -arginine and N G ,N G -dimethyl L -arginine are due to inhibition of both basal and stimulated nitric oxide production, whereas aminoguanidine and methylguanidine do not affect the synthesis of nitric oxide. An increase in the plasma concentration of N G -monomethyl L -arginine and N G ,N G -dimethyl L -arginine is likely to represent a risk factor for abnormal vasomotor tone in conduit arteries used as coronary grafts. (J Thorac Cardiovasc Surg 2000;120:729-36)

The present study was designed to characterize the response of human penile dorsal artery and deep dorsal vein to dilator drugs used in the diagnosis and treatment of erectile dysfunction with special emphasis on the effects on sympathetic neurotransmission. Ring segments of penile dorsal artery and deep dorsal vein were obtained from 20 multi-organ donors during procurement of organs for transplantation. The rings (3 ;mm long) were suspended in organ bath chambers for isometric recording of tension. We then studied the relaxant responses to prostaglandin E1 (PGE1), vasoactive intestinal peptide (VIP), papaverine (PV), sodium nitroprusside (SNP) and linsidomine chlorhydrate (SIN-1), and analysed the effects of these drugs on contractions induced by stimulation of perivascular sympathetic nerves. In artery and vein rings contracted by noradrenaline, all the drugs tested caused concentration-dependent relaxation. The order of potencies in terms of IC50 values (concentration of agonist causing 50% of the maximal relaxation) was PGE1 = VIP > SNP > SIN-1 = PV. Both arteries and veins contracted to electrical field stimulation (15 ;V, 0.5–2 ;Hz, 0.2 ;ms duration for 15 ;s) in a frequency-dependent manner. All relaxant drugs caused concentration-dependent inhibition of neurogenic contractions; the relative order of potencies was PGE1 > VIP > SNP > SIN-1 = PV. It is concluded that inhibition of sympathetic activity constitutes an effective relaxing mechanism in penile dorsal artery and vein. Modulation of sympathetic activity together with the direct effects on smooth muscle should be considered to evaluate adequately the efficacy of relaxant drugs to increase human penile blood supply.

Morbid obesity is a chronic multifunctional disease characterized by an accumulation of fat. Epidemiological studies have shown that obesity is associated with cardiovascular and metabolic disorders. Endothelial dysfunction, as defined by an imbalance between relaxing and contractile endothelial factors, plays a central role in the pathogenesis of these cardiometabolic diseases. Diminished bioavailability of nitric oxide (NO) contributes to endothelial dysfunction and impairs endothelium- dependent vasodilatation. But this is not the only mechanism that drives to endothelial dysfunction. Obesity has been associated with a chronic inflammatory process, atherosclerosis, and oxidative stress. Moreover levels of asymmetrical dimethyl-L-arginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (eNOS), are elevated in obesity. On the other hand, increasing prostanoid-dependent vasoconstriction and decreasing vasodilator prostanoids also lead to endothelial dysfunction in obesity. Other mechanisms related to endothelin-1 (ET-1) or endothelium derived hyperpolarizing factor (EDHF) have been proposed. Bariatric surgery (BS) is a safe and effective means to achieve significant weight loss, but its use is limited only to patients with severe obesity including morbid obesity. BS also proved efficient in endothelial dysfunction reduction improving cardiovascular and metabolic comorbidities associated with morbid obesity such as diabetes, coronary artery disease, nonalcoholic fatty liver disease and cancer. This review will provide a brief overview of the mechanisms that link obesity with endothelial dysfunction, and how weight loss is a cornerstone treatment for cardiovascular comorbidities obesity-related. A better understanding of the mechanisms of obesity-induced endothelial dysfunction may help develop new therapeutic strategies to reduce cardiovascular morbidity and mortality.

The aim of this study was to analyze whether tyrosine phosphorylation in tumoral arteries may modulate their vascular response. To do this, mesenteric arteries supplying blood flow to colorectal tumors or to normal intestine were obtained during surgery and prepared for isometric tension recording in an organ bath. Increasing tyrosine phosphorylation with the phosphatase inhibitor, sodium orthovanadate produced arterial contraction which was lower in tumoral than in control arteries, whereas it reduced the contraction to noradrenaline in tumoral but not in control arteries and reduced the relaxation to bradykinin in control but not in tumoral arteries. Protein expression of VEGF-A and of the VEGF receptor FLT1 was similar in control and tumoral arteries, but expression of the VEGF receptor KDR was increased in tumoral compared with control arteries. This suggests that tyrosine phosphorylation may produce inhibition of the contraction in tumoral mesenteric arteries, which may increase blood flow to the tumor when tyrosine phosphorylation is increased by stimulation of VEGF receptors, This work was financed by Fondo de Investigaciones Sanitarias (PS09/00394) and Fundaci´on Mutua Madrileña (AP57242009)

Twin reverse arterial perfusion (TRAP) sequence is a rare complication that occurs exclusively in monochorionic multiple gestations (Wong and Sepulveda 2005). It consists in a normal twin, who acts...

The effects of vasopressin were studied in isolated rings from branches (2-3 mm in external diameter) of human renal arteries obtained from 18 patients undergoing nephrectomy for non-obstructive neoplasia. In arterial rings under resting tension, vasopressin produced concentration-dependent and endothelium-independent contractions with an EC 50 of 9.1 x 10 -10 mol L -1 . The vasopressin V 1 receptor antagonist d(CH 2 ) 5 Tyr(Me)AVP (10 -6 mol L -1 ) displaced the control curve to vasopressin 564-fold to the right in a parallel manner. In precontracted arterial rings and previously treated with the V 1 antagonist (10 -6 mol L -1 ) vasopressin caused endothelium-independent relaxation. The relaxation to vasopressin was reduced significantly by indomethacin (10 -6 mol L -1 ) and unaffected by the V 1 /V 2 receptor antagonist desGly d(CH 2 ) 5 -D-Tyr(Et)ValAVP (10 -6 mol L -1 ) or by N G -nitro-L-arginine methyl ester (10 -4 mol L -1 ). These observations indicate that vasopressin is primarily a constrictor of human renal arteries by V 1 -receptor stimulation. Vasopressin causes prostaglandin-mediated dilatation of human renal arteries only if V 1 -receptor blockade is present. The effects of vasopressin on human renal arteries may be relevant in those clinical situations characterized by increased plasma vasopressin levels.

We studied the effects of vasopressin on isolated rings of human deferential artery and vas deferens (prostatic portion) obtained from patients undergoing radical cystectomy (n = 11) or prostatectomy (n = 10). Ring segments of artery or vas deferens were studied in organ bath experiments at optimal resting tension. In artery rings, vasopressin produced concentration-dependent, endothelium-independent contractions with an EC50 of 4.5 x 10(-10) M. The presence of NG-nitro-L-arginine methyl ester hydrochloride (10(-4) M), an inhibitor of nitric oxide synthase, did not change significantly (P > 0.05) the vasopressin-induced contraction. In ring preparations of the prostatic part of the vas deferens, vasopressin induced phasic contractions with an EC50 of 7.0 x 10(-9) M. The vasopressin V1 receptor antagonist, d(CH2)5Tyr(Me)AVP (10(-8) and 10(-6)), displaced to the right in parallel the control curve to vasopressin in artery and vas deferens rings. These results indicate that vasopressin exerts a powerful constrictor action on human deferential artery and vas deferens by direct stimulation of V1 receptors. It is concluded that the deferential artery may dampen the passage of blood to the vas deferens in circumstances characterized by increased plasma vasopressin levels.

Outpatient laparoscopic cholecystectomy (CL) has not been generalised due to the fear of complications by the surgeon and preference of patients for hospitalisation. This situation could be changed by setting up strict selection criteria and providing hospital home care. The aims of this study are to find out what percentage of our population fulfil these criteria, confirm their validity and find out if the surgical process should be improved before being introduced.A retrospective analysis was carried out on the first 200 elective CL cases dating from January 2006. The exclusion criteria were as follows: pre-operative criteria (social causes, age $ 70 years, unstable ASA III or ASA IV, an associated pathology or admission due to biliopancreatic patho-logy), intra-operative criteria (conversion, surgical time lasting longer than 90 minutes, non-identification or bleeding of the cystic artery, application of haemostatic material, haemorrhaging in the entrance ports, intra-abdominal bile spillage, drainage, difficulties in removing the gallbladder, anaesthetic and/or surgical complications) and post-operative (haemodynamic instability, excessive pain, nausea, and /or vomiting).Out of the 200 cases, 53 (26.5%) patients fulfilled the criteria. The outpatient system was preferred predominantly by females and by those younger in age. Post-operative incidents occurred in 9.4% of the cases and these were dealt with by the hospital home care team.Ambulatory CL procedure is safe. Patients of advanced age or with associated pathologies limit the inclusion. Hospital home care can solve any possible complications and contribute to the speedy discharge in those patients without criteria.

Previous studies have shown that asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and nitric oxide (NO) play a prominent role in liver dysfunction. The objective of this study was to determine whether plasma levels of ADMA, SDMA and NO are altered in patients with chronic hepatitis C.Plasma levels of ADMA, SDMA and NO (nitrite plus nitrate) were measured in 22 patients with chronic hepatitis C and 24 patients with sustained virologic response after treatment with peginterferon plus ribavirin. Seven healthy volunteers served as controls.Plasma levels of ADMA, SDMA and NO were not significantly different between groups: chronic hepatitis C, ADMA 0.55+/-0.06, SDMA 0.22+/-0.03, NO 36.3+/-5.9 micromol/l; treated patients, ADMA 0.60+/-0.15, SDMA 0.31+/-0.05, NO 36.1+/-5.5 micromol/l; controls, ADMA 0.65+/-0.08, SDMA 0.28+/-0.05, NO 40.7+/-8.9 micromol/l).Our results show that plasma NO, ADMA and SDMA concentrations are not changed in patients with chronic hepatitis C without superimposed signs of acute inflammatory activity. Furthermore, no significant differences in plasma values of NO and dimethylarginines were observed between the group of untreated patients and the group of patients treated with interferon plus ribavirin.

Vasopressin not only acts directly on blood vessels through V1-receptor stimulation but also may modulate adrenergic-mediated responses in animal experiments in vitro and in vivo. The aim of the present study was to investigate whether subpressor concentrations of vasopressin could modify the constrictor responses to norepinephrine and electrical stimulation of the perivascular nerves in human mesenteric arteries. Human mesenteric artery rings (3-3.5 mm long, 0.8-1.2 mm OD) were obtained from 38 patients undergoing abdominal operations. The arterial rings were suspended in organ bath chambers for isometric recording of tension. Vasopressin (3 x 10(-11) M) enhanced the contractions elicited by electrical stimulation at 2, 4, and 8 Hz (by 100, 100, and 72%, respectively) and produced a leftward shift of the concentration-response curves to norepinephrine (half-maximal effective concentration decreased from 2.2 x 10(-6) to 5.0 x 10(-7) M; P < 0.05) without any alteration in maximal contractions. Vasopressin also potentiated KCl- and calcium-induced contractions. The V1-receptor antagonist 1-[beta-mercapto-beta,beta-cyclopentamethylenepropionic acid-2-O-methyl-tyrosine, 8-arginine]vasopressin (10(-6) M) prevented the potentiation evoked by vasopressin in all cases. The calcium antagonist nifedipine (10(-6) M) did not affect the potentiation of electrical stimulation and norepinephrine induced by vasopressin but abolished KCl-induced contractions. The results suggest that vasopressin, in addition to its direct vasoconstrictor effect, strongly potentiates the responses to adrenergic stimulation and KCl depolarization. Both the direct and indirect effects of vasopressin appear to be mediated by V1-receptor stimulation. The amplifying effect of vasopressin on constrictor responses may be relevant in those clinical situations characterized by increased plasma vasopressin levels.

The present study was designed to investigate the contribution of the endothelium and that of the L-arginine pathway on the contractile responses of isolated human pulmonary arteries to electrical field stimulation (EFS) and noradrenaline. Isometric tension was measured in artery rings obtained from portions of human lung after thoracic surgery for removal of lung carcinoma (18 patients). Electrical field stimulation (EFS) induced frequency-dependent contractions of isolated human pulmonary arteries which were abolished by tetrodotoxin, guanethidine and prazosin (all at 10(-6) M). The increases in tension were of greater magnitude in arteries denuded of endothelium. NG-nitro-L-arginine methyl ester (L-NAME) (10(-4) M) potentiated the contractile response to EFS in artery rings with endothelium but not in endothelium-denuded arteries. The potentiation induced by L-NAME was completely reversed by L-arginine (10(-4) M) but not by D-arginine (10(-4) M). Indomethacin (3 x 10(-6) M) had no significant effect on the contractile response to EFS. Contractile responses to noradrenaline were similar in arteries with and without endothelium. Our results suggest that electrical field stimulation releases endothelium-derived nitric oxide, which inhibits the contractile responses of human pulmonary arteries. Although adrenergic nerves seem to be responsible for the contraction, the transmitter involved in the release of nitric oxide does not appear to be noradrenaline.

1. The effects of vasopressin and deamino-8-D-arginine vasopressin (DDAVP, desmopressin) were studied in artery rings (0.8-1 mm in external diameter) obtained from portions of human omentum during the course of abdominal operations (27 patients). 2. In arterial rings under resting tension, vasopressin produced concentration-dependent, endothelium-independent contractions with an EC50 of 0.59 +/- 0.12 nM. The V1 antagonist d(CH2)5Tyr(Me)AVP (1 microM) and the mixed V1-V2 antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (0.01 microM) displaced the control curve to vasopressin to the right in a parallel manner without differences in the maximal responses. In the presence of indomethacin (1 microM) the contractile response to vasopressin was significantly increased (P < 0.01). 3. In precontracted arterial rings, previously treated with the V1 antagonist, d(CH2)5Tyr(Me)AVP (1 microM), vasopressin produced endothelium-dependent relaxation. This relaxation was reduced significantly (P < 0.05) by indomethacin (1 microM) and unaffected by the V1-V2 receptor antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (1 microM) or by NG-nitro-L-arginine methyl ester (L-NAME, 0.1 mM). 4. The selective V2 receptor agonist, DDAVP, caused endothelium-independent, concentration-dependent relaxations in precontracted arterial rings that were inhibited by the mixed V1-V2 receptor antagonist, but not by the V1 receptor antagonist or by pretreatment with indomethacin or L-NAME. 5. Results from this study suggest that vasopressin is primarily a constrictor of human mesenteric arteries by V1 receptor stimulation; vasopressin causes dilatation only during V1 receptor blockade. The relaxation appears to be mediated by the release of vasodilator prostaglandins from the endothelial cell layer and is independent of V2 receptor stimulation or release of nitric oxide. In contrast, the relaxation induced by DDAVP is largely dependent on stimulation of V2 receptors.