Pain assessment in surgical patients with impaired cognition

Pain is considered the 5th vital sign and its measurement/assessment and records are required and must be systematic. Ineffective pain management involves complications in clinical status of patients, longer hospitalization times and higher costs with health. In the surgical patient with impaired cognition, hetero measurements should be made, based on behavioural and physiological indicators. We used to determine the efficacy and efficiency of the Observer Scale, the Abbey Pain Scale and Pain Assessment in Advanced Dementia (PAINAD). Our study is an applied, non-experimental, quantitative, descriptive and analytical research. The data collection instrument consisted of patients’ sociodemographic and clinical data, the Observer Scale, the Abbey Pain Scale (Rodrigues, 2013) and PAINAD (Batalha et al., 2012). We assessed pain at an early phase and 45 minutes after an intervention for its relief. The sample is non-probabilistic for convenience, consisting of 76 surgical patients with impaired cognition, admitted to the surgery services of a central hospital, aged between 38 and 96 years. There was a positive correlation between the results of the three scales, most evident in the initial evaluation. Pain intensity in the same patient is higher when assessed with PAINAD (OM = 2.16) and lower when assessed with the Observer Scale (OM = 1.78). The most effective and efficient scale is PAINAD. Due to the small sample size, we suggest confirmatory studies so that the results can be generalized

Heme-Dependent and Independent Soluble Guanylate Cyclase Activators and Vasodilation

Since the discovery of nitric oxide (NO), which is released from endothelial cells as the main mediator of vasodilation, its target, the soluble guanylyl cyclase (sGC), has become a focus of interest for the treatment of diseases associated with endothelial dysfunction. NO donors were developed to suppress NO deficiency; however, tolerance to organic nitrates was reported. Non-NO-based drugs targeting sGC were developed to overcome the problem of tolerance. In this review, we briefly describe the process of sGC activation by its main physiological activator NO and the advances in the development of drugs capable of activating sGC in a NO-independent manner. sGC stimulators, as some of these drugs are called, require the integrity of the reduced heme moiety of the prosthetic group within the sGC and therefore are called heme-dependent stimulators. Other drugs are able to activate sGC independent of heme moiety and are hence called heme-independent activators. Because pathologic conditions modulate sGC and oxidize the heme moiety, the heme-independent sGC activators could potentially become drugs of choice because of their higher affinity to the oxidized enzyme. However, these drugs are still undergoing clinical trials and are not available for clinical use.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Heme-dependent And Independent Soluble Guanylate Cyclase Activators And Vasodilation.

Since the discovery of nitric oxide (NO), which is released from endothelial cells as the main mediator of vasodilation, its target, the soluble guanylyl cyclase (sGC), has become a focus of interest for the treatment of diseases associated with endothelial dysfunction. NO donors were developed to suppress NO deficiency; however, tolerance to organic nitrates was reported. Non-NO-based drugs targeting sGC were developed to overcome the problem of tolerance. In this review, we briefly describe the process of sGC activation by its main physiological activator NO and the advances in the development of drugs capable of activating sGC in a NO-independent manner. sGC stimulators, as some of these drugs are called, require the integrity of the reduced heme moiety of the prosthetic group within the sGC and therefore are called heme-dependent stimulators. Other drugs are able to activate sGC independent of heme moiety and are hence called heme-independent activators. Because pathologic conditions modulate sGC and oxidize the heme moiety, the heme-independent sGC activators could potentially become drugs of choice because of their higher affinity to the oxidized enzyme. However, these drugs are still undergoing clinical trials and are not available for clinical use.56229-3

Comparative Pharmacological Analysis Of Rho-kinase Inhibitors And Identification Of Molecular Components Of Ca2+ Sensitization In The Rat Lower Urinary Tract.

We aimed to compare the expression and function of molecular components of the RhoA/Rho-kinase signaling pathway in the contractile responses of detrusor, trigonal and urethral smooth muscle, using selective Rho-kinase inhibitors. Contractility studies and molecular approaches were employed to demonstrate the expression patterns and functional activity of the RhoA/Rho-kinase signaling pathway in the lower urinary tract. Frequency-response curves (1-32 Hz) and concentration-response curves (CRC) to carbachol (CCh, 0.01-30 microM), phenylephrine (PE, 0.01-300 microM) and endothelin-1 (ET-1, 0.01-100 nM) were significantly attenuated (p<0.01) following incubation with the Rho-kinase inhibitors H-1152 (0.1-1 microM), Y-27632 (1-10 microM) or HA-1077 (10 microM). Addition of Rho-kinase inhibitors also markedly reduced (p<0.01) the contractions evoked by either KCl (80 mM) or alpha,beta-methylene ATP (alpha,beta-mATP, 10 microM). Among the Rho-kinase inhibitors tested, H-1152 was approximately 9-16 times more potent than Y-27632 or HA-1077. In addition, basal tone of detrusor and trigonal strips was reduced following addition of Y-27632 (10 microM), H-1152 (1 microM) and HA-1077 (10 microM). The expression of RhoA, RhoGDI, leukemia-associated RhoGEF (LARG) and p115RhoGEF was similar among the detrusor, trigone and urethra, whereas Rho-kinase alpha, Rho-kinase beta and PDZ-RhoGEF protein levels were significantly lower in the urethra. Components of the RhoA/Rho-kinase signaling are expressed in detrusor, trigonal and urethral smooth muscle and dynamically regulate contraction and tone. Manipulation of RhoGEF expression may provide further understanding of mechanisms involving Ca(2+) sensitization in the lower urinary tract.74647-5

Oxidative Stress Impairs Vasorelaxation Induced by the Soluble Guanylyl Cyclase Activator BAY 41-2272 in Spontaneously Hypertensive Rats

BACKGROUNDBAY 41-2272 (5-cyclopropyl-2-(1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-pyrimidin-4-ylamine) relaxes mesenteric arteries (MA) in a synergistic fashion with nitric oxide (NO). We hypothesized that the relaxation to BAY 41-2272 is decreased in spontaneously hypertensive rats (SHR) because of the reduced NO bioavailability in this strain and that relaxation would be improved by inhibiting the oxidative stress. We aimed to evaluate the influence of oxidative stress in BAY 41-2272-induced vasorelaxation in isolated MA from SHR.METHODSMA function was evaluated by concentration-response curves to BAY 41-2272. We measured protein expression of endothelial NO synthase (eNOS), soluble guanylyl cyclase (sGC) and human-antigen R (HuR) (sGC mRNA-stabilizing protein), sGC activity and plasma levels of superoxide dismutase (SOD), and total antioxidant status (TAS).RESULTSCyclic guanosine monophosphate (cGMP)-dependent and -independent relaxation induced by BAY 41-2272 (0.0001 - 1 mu mol/l) was impaired in SHR compared with Wistar-Kyoto (WKY). We observed reduced expression of eNOS, sGC and HuR, and decreased sGC activity in SHR. Plasma levels of SOD and TAS were also diminished in SHR. Incubation with SOD or indomethacin increased relaxation to BAY 41-2272 in SHR. Furthermore, acetylcholine (ACh)-induced relaxation was increased in the presence of BAY 41-2272 or SOD, apocynin, or indomethacin.CONCLUSIONAugmented oxidative stress in SHR impaired cGMP-dependent and -independent relaxation induced by BAY 41-2272, by decreasing NO bioavailability and sGC expression and by increasing contractile activity. Inhibiton of oxidative stress improved the relaxation of BAY 41-2272 in SHR. BAY 41-2272 might be an alternative therapeutic tool for hypertension if administrated with antioxidant compounds.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Pharmacological Characterization Of The Presynaptic Activity Of Tityus Serrulatus Venom In The Rat Anococcygeus Muscle.

Scorpion venoms are known to cause peripheral nerve stimulation with enhanced autonomic responses. This study, therefore, examined the effects of Tityus serrulatus venom (TSV) on adrenergic, cholinergic and nitrergic nerve fibers using the rat anococcygeus muscle. The contractile effects of TSV (1 microg/ml) and electrical field stimulation were markedly reduced by phentolamine (5 microM), prazosin (0.1 microM), guanethidine (30 microM) and tetrodotoxin (TTX, 1 microM), whereas imipramine (3 microM) enhanced these responses. The responses to tyramine (10 microM) were partially reduced by guanethidine and completely blocked by phentolamine, prazosin and imipramine. Atropine (1 microM) fully prevented carbachol (CCh, 30 microM)-induced contractions without affecting those mediated by TSV. Neostigmine significantly potentiated TSV-and ACh-evoked contractions, whereas hexamethonium had no effect. The relaxant responses induced by EFS and TSV (3 microg/ml) were completely blocked by L-NAME (100 microM), ODQ (1 microM) or TTX (1 microM). Addition of L-arginine (1 mM) reversed the effect of L-NAME. Thus, the motor and inhibitory responses of TSV in the rat anococcygeus muscle are mediated by prejunctional mechanisms dependent on Na(+) channel activation, causing the stimulation of NA and NO release from adrenergic and nitrergic nerve fibers, respectively.42451-6

Effect Of The Phosphodiesterase 5 Inhibitors Sildenafil, Tadalafil And Vardenafil On Rat Anococcygeus Muscle: Functional And Biochemical Aspects.

1. The anococcygeus muscle is part of the erectile machinery in male rodents. Phosphodiesterase (PDE) 5 inhibitors enhance and prolong the effects of cGMP, which has a key role in penile erection. The aim of the present study was to provide a functional and biochemical comparison of the three PDE5 inhibitors, namely sildenafil, tadalafil and vardenafil, in the rat anococcygeus muscle. 2. Muscle strips were mounted in 4 mL organ baths and isometric force recorded. Levels of cGMP were measured using an enzyme immunoassay kit. Western blots were used to determine PDE5 protein expression. 3. The PDE5 inhibitors concentration-dependently relaxed carbachol-precontracted anococcygeus muscle; however, vardenafil was more potent (pEC(50) = 8.11 +/- 0.05) than sildenafil (7.72 +/- 0.06) or tadalafil (7.69 +/- 0.05). Addition of N(G)-nitro-l-arginine methyl ester (100 micromol/L) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 micromol/L) to the organ baths caused significant rightward shifts in concentration-response curves for all PDE5 inhibitors. 4. Sildenafil, tadalafil and vardenafil (all at 0.1 micromol/L) caused leftward shifts in the glyceryl trinitrate (GTN) concentration-response curves (by 4.0-, 3.7- and 5.5-fold, respectively). In addition, all three PDE5 inhibitors significantly potentiated relaxation responses to both GTN (0.01-10 micromol/L) and electrical field stimulation (EFS; 1-32 Hz), with vardenafil having more pronounced effects. 5. All three PDE5 inhibitors reduced EFS-evoked contractions in a concentration-dependent manner over the concentration range 0.001-1 micromol/L. There were no significant differences between the effects of the three PDE5 inhibitors. 6. Vardenafil (0.01-0.1 micromol/L) was more potent in preventing cGMP degradation in vitro than sildenafil (0.01-0.1 micromol/L) and tadalafil (0.01-0.1 micromol/L). 7. Under control conditions, the expression of PDE5 was higher in the anococcygeus muscle than in the corpus cavernosum. 8. In conclusion, PDE5 inhibitors enhance exogenous and endogenous nitric oxide-mediated relaxation in the rat anococcygeus muscle. The potency of vardenafil was greater than that of either sildenafil or tadalafil.36358-6

L-Carnitine supplementation impairs endothelium-dependent relaxation in mesenteric arteries from rats

L-Carnitine (L-Car) is taken as fat burner. The risks of L-Car supplementation for the cardiovascular system are unclear. We evaluated the relaxing responses of the mesenteric and aorta rings from rats after four weeks of L-Car supplementation and/or physical training. Concentration response curves to acetylcholine (ACh) and sodium nitroprusside (SNP), as well as cyclic GMP levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) were evaluated. Physical training decreased body weight gain that was potentiated by L-Car. In mesenteric rings, L-Car impaired endothelium-dependent relaxation whereas endothelium independent relaxation was increased. In aorta, exercise improved endothelium-dependent relaxation; however, it was partially inhibited by L-Car. SNP-induced relaxation was similar in aorta of all groups. Basal cGMP were increased in aorta of exercised rats. SOD activity and MDA levels were unaltered. In conclusion, L-Car and physical exercise promotes body weight loss; however, it impairs endothelium-dependent vaso-relaxation possibly involving alterations in muscarinic receptors/eNOS/NO signalling pathway in mesenteric artery.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP