Relaxant and antiadrenergic effects of ranolazine in human saphenous vein.

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.

Effects of photodynamic therapy in periodontal treatment: A randomized, controlled clinical trial.

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 versus 428 critical sites), microbiological (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia and Campylobacter rectus presence, 18 versus 19 samples) and biochemical (interleukin (IL)-1ß, IL-6 and tumour necrosis factor (TNF)-α, receptor activator of nuclear factor-kappaB ligand (RANK-L) and osteoprotegerin (OPG) levels, 18 versus 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.

[DESCRIPTION OF A RETROPERITONEAL ACCESS ROUTE TO THE VESSELS OF THE SPLEEN FOR SPLENORENAL ARTERIAL AND VENOUS ANASTOMOSIS]. / DESCRIPCIÓN DE UNA VÍA DE ACCESO RETROPERITONEAL A LOS VASOS DEL BAZO PARA LAS ANASTOMOSIS ESPLENORRENALES ARTERIALES Y VENOSAS.

To perform arterial or venous spleno-renal anastomoses, surgeons have so far systematically used the transperitoneal way whic is burdened by a high mortality an morbility percentage. On the basis of anatomo-surgical considerations, a retroperitoneal approach has been found reaching the hilus of the spleen via the lumbar region; the first arterial spleno-renal anastomosis by this way was performed in 1972 and the first venous spleno-renal anastomosis due to portal hipertension also by this way was performed in 1974, the alter proving to be the least aggresive by avoiding damaging the páncreas, the most surgical and direct for reaching the splenic vessels thereby enabling a better exposure and an easier performing of the anastomoses. By being retroperitoneal, the loss or infección of the ascitic liquid in the cirrhotic patient is prevented.

[OPERATION TO SUBSTITUTE THE LUMBAR URETER. LOWERING OF THE RENAL VEINS]. / OPERACIÓN PARA LA SUSTITUCIÓN DE URÉTER LUMBAR. DESCENSO DE LOS VASOS RENALES.

A new operation to lower the aortic anastomosis of the renal artery is de- scribed. This procedure allows the left Kidney to be lowered enough to enable repair after resections of the upper urinary tract. Renal hemodynamics were not altered and good results were obtained with no complications.

Tyrosine phosphorylation modulates the vascular responses of mesenteric arteries from human colorectal tumors.

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.

Endothelial dysfunction in morbid obesity.

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.

[New surgical intervention for correction of vesico-ureteral reflux. Current status]. / Nueva operación para la corrección del reflujo vesico-ureteral. Estado actual del procedimiento.

Vesicoureteral reflux (VUR) with urinary infection is a major risk factor which leads to End-stage renal disease and high blood pressure in between 3 and 25% of children and between 10 and 15% of adults. Classical techniques for the correction of VUR are very aggressive given the delicate structure of terminal ureter and they have the disinsertion of the ureteovesical junction, the extensive dissection and mobilization of the ureter, the creation of a new hiatus, the formation of a submucosal tunnel and the reimplantation of the ureter in common. They are very aggressive techniques and create the risk of complications such as obstruction due to ischemia and contralateral reflux. The new technique that we described in 1984 is based on preserving the anatomical and functional integrity of the terminal ureter. The ureters remain intact; they are only slid and moved to the midline of the trigone with a simple maneuver where they are fixed with one stitch, bloodlessly recovering a greater submucosal trajectory ad good muscular support. More than 25 years of experience worldwide have made the appraisal unanimous in considering it as the simplest, fastest, most effective and less invasive technique whili highlighting the absence of complications. This supports its use as one of the primary options in the treatment of VUR, giving rise to new applications of the procedure such as in secondary VUR in neurogenic bladders and in reflux in ureteral duplication.

[New surgery for complicated renal anomalies]. / Nueva cirugía de las anomalías renales complicadas.

The indications for "ex vivo" surgery and autotransplantation have been broadened o complicated renal anomalies; particularly in the cases of the horseshoe kikney and kidney malrotation. This position is justified as conventional techniques do not correct the multiple causes that are responsible for these complications. These complications requiere a surgical strategy that simultaneously deals with the pathology of the renal anomaly itself and that of its excretory tract. The aforementioned means that the abnormal kidney orientation and position must be retified to permit a large resectioning of the dysplasic or dystrophic excretory conduct in order to achieve normal urinary drainage while conserving all the renal parenchyma. It has been achieved in thirteen out of the 14 cases operated on that correspond to distinct types of complicated anomalies. The excellent results demonstrate that this new and innovative surgery has resolved the complex and difficult issue of kidney malformations. The surgical method and long-therm results in the adult and child, the first in the literature, are presented here.