Research Objective Patients with chronic kidney disease (CKD) are at increased risk for atherosclerosis and peripheral artery disease (PAD). PAD has received far less attention than coronary artery disease (CAD) in CKD patients. Few studies have examined risk factors for PAD in CKD. We studied the possible related risk factors and benefit of hypertension treatment in CKD patients with PAD. Data Sources We included 129 patients of both sexes with stages 3 to 5 of CKD, as described by the Kidney Outcome Quality Initiatives (K/DOQI ) classification, without receiving dialysis therapy, not previously diagnosed with PAD. Study Design The following information were collected within six month period, including demographic characteristics, history of hypertension, anti-hypertension drug, diabetes, smoking, and pre-existing cardiovascular disease, body mass index (BMI), fasting blood glucose, HbA1c, total cholesterol, triglyceride(TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol(LDL), calcium (Ca), phosphate(P), Albumin, uric acid, urine protein. Ankle-brachial index (ABI) is a noninvasive diagnostic test that is efficient in detecting asymptomatic PAD with ABI <0.9. Findings There were 22 (17.7 %) participants with PAD. Higher systolic blood pressure (SBP), higher diastolic blood pressure (DBP), higher pulse pressure showed strong association with PAD in CKD patients. On further analysis, significant fewer patients treated with calcium channel blocker (CCB) in hypertensive CKD patients with PAD (£q2 =7.055, p =0.008). The multivariate logistic regression analysis in hypertensive patients demonstrated the risk factors for PAD was pulse pressure, and Calcium channel blocker treatment may correlate with decreasing PAD formation (odds ratio= 0.232, 95% CI=0.07-0.73, p =0.013) in CKD patients. Conclusion There is a high prevalence rate of PAD in population of CKD, especially those with hypertension. ABI should be routinely examined in these patients who can benefit earlier from therapeutic measures.

Ziel: Das Ziel dieser Studie war es den Zusammenhang zwischen Zahnextraktionen und Patientenfaktoren in 3 Deutschen Zahnarztpraxen zu untersuchen. Material & Methoden: In einer retrospektiven Auswertung aller Patientenkarten von 3 deutschen Zahnarztpraxen wurden Extraktionsfälle ab Januar 2007 (Praxis 1), Mai 2010 ( Praxis 2) und Januar 2010 ( Praxis 3 ) auf Extraktionen hin durchsucht, bis in jeder Praxis jeweils 100 Extraktionspatienten gefunden wurden, die die Einschlusskriterien erfüllten. Alle Patienten ohne Extraktionen die innerhalb dieses Zeitraumes behandelt wurden und die die Einschlusskriterien erfüllten, dienten als Kontrollgruppe. Es wurden nur Patienten eingeschlossen (Fall und Kontrollgruppe), von denen die spezifischen Patientendaten zur Verfügung standen. Alle Patientendaten wurden in einem „Case-Report-Form\"-Formular (CRF) erfasst. Die individuellen Parameter der Patienten der Fallgruppe und der Kontrollgruppe wurden verglichen. Mittels schrittweiser logistischer Regressionsanalyse konnten die Faktoren für ein Extraktionsrisiko bestimmt werden. Ergebnisse: Insgesamt wurden 2174 Patientenakten untersucht (Fallgruppe 300; Kontrollgruppe 1874). Die Gesamtsumme der Zähne vor der Extraktionstherapie betrug 54316. In der Fallgruppe wurden insgesamt 459 Zähne extrahiert. Die Patienten der Fallgruppe waren im Schnitt mehr als 6,7 Jahre älter als die Patienten der Kontrollgruppe(52,4/45,7 Jahre (P< 0,001)), sie waren zu einem größeren Anteil männlich. (58/ 52%) ,es gab eine höhere Zahl an Rauchern, es gab vermehrt Patienten mit einer Kalziumkanalblocker Medikation [15/8 % (p<0,001)] und der parodontale Befund festgestellt mittels PSI der Fallgruppe war schlechter als der der Kontrollgruppe [PSI 2,5/1,8 , (p<0,001)]. Das Risiko einer Zahnextraktion im Allgemeinen und in Folge von Parodontalerkrankungen waren assoziiert mit Kalziumkanalblockermedikation, (OR 1,49/1,65) aktivem Rauchen (OR 1,35/1,71), Alter (10Jahre) OR 1,13/1,37 , Praxis Nr.1 (1,48/1,99) und der Anzahl der Sextanten mit dem PSI Code 4 (1,33/1,76) (p<0,001). Schlussfolgerung: Kalziumkanalblockermedikation, aktives Rauchen, Alter, Zahnarzt und die Anzahl der Sextanten mit einem PSI Wert 4 sind Risikoindikatoren für Zahnextraktionen. Nutzen : Kalziumkanalblockermedikation kann das Extraktionsrisiko erhöhen. Zahnverlust zieht in den meisten Fällen Zahnersatz nach sich, welcher in aller Regel aufwändig ist, den Patienten zusätzliche Belastungen abverlangt und die Kosten einer Therapie erhöht. Die Information über die Einnahme von Kalziumkanalblockern ist ein leicht zu erfassender Parameter und könnte als Indikator genutzt werden, um Betreuungsintervalle zu verkürzen. Es muss jedoch noch geprüft werden, ob eine intensivere Betreuung dieser Patienten deren Zahnextraktionsrate tatsächlich verringern kann.

Background: Gingival enlargement (GE) is a frequent finding in cyclosporin users. The mechanisms of this association are not totally known and point out to a multifactorial model, with dose and associations with calcium channel blockers. Novel immunosuppression protocols are adjusting for drugs and dosages. Aim: This study aimed at investigating the prevalence and severity of gingival enlargement in renal transplanted individuals under cyclosporin and possible associations with clinical and pharmacological findings. Methods: With a cross- sectional design, 63 renal transplanted patients under cyclosporin therapy from the University Hospital of the Santa Maria Federal University were examined. Demographic, pharmacological and periodontal variables were assessed. Data analysis, independent sample t test and chi square were used to compare means values of different variables, comparing groups with or without gingival enlargement. Results: A response rate of 86,30% was achieved. In total, 40% of the patients presented some degree of GE. Eleven presented scores >10% and only 5 presented scores of 30%. Mean value for GE was low (6,79±15,83). Patients under nifedipine presented higher prevalence of GE, without reaching statistical significance. Mean values for serum levels of CsA were 3,20±0,94 mg/kg/day and 156,12±162,75 ng/ml, respectively. No statistically significant differences among individuals with or without GE was obtained relating to the use of nifedipine and/or none/verapamil. Conclusion: A lower prevalence and severity of GE was found in relation to previous studies, independent to the drug association. / Justificativa: Aumento gengival (AG) é um achado freqüente em pacientes que utilizam Ciclosporina (CsA). Os mecanismos dessa associação não são totalmente conhecidos e apontam para um modelo multifatorial, com doses e associações com outras drogas, como bloqueadores de canais de cálcio (BCC). Novos protocolos de imunossupressão vêm ajustando fármacos e doses visando obter melhores resultados na terapia, diminuindo também os efeitos adversos. Objetivo: Este estudo tem por objetivo investigar a prevalência e a gravidade de aumento gengival em transplantados renais medicados com CsA, e possíveis associações com fatores farmacológicos e clínicos. Metodologia: Utilizando um delineamento transversal, foram examinados 63 transplantados renais em terapia com CsA no Hospital Universitário de Santa Maria (HUSM). Dados demográficos, farmacológicos e periodontais foram coletados. Para a análise dos dados, foram utilizados o teste t não-pareado e qui-quadrado a fim de comparar as médias das variáveis para os grupos com e sem aumento gengival. Resultados: Uma taxa de resposta de 86,3% foi obtida. Ao todo 40% dos pacientes apresentaram algum grau de AG. Onze apresentaram escores acima de 10% e apenas 5 com 30%. A média de AG foi baixa (6,79). Pacientes que utilizam nifedipina apresentaram maior prevalência de AG, sem significância estatística. As médias de dosagem e níveis séricos de CsA foram 3,20 mg/kg/dia e 156,12 ng/ml, respectivamente. Não houve diferença estatística dessas variáveis entre os indivíduos com e sem aumento gengival e entre os gruposnifedipina e sem BCC ou verapamil. Conclusão: No presente estudo, o AG associado à CsA apresentou valores de prevalência e gravidade reduzidos , independentemente das interações medicamentosas.

Background: In the United States, one-third of adults have hypertension (HTN). Among African American (AA) adults, 43% of men and 45.7% of women have HTN. HTN in the AA adult population is more severe and occurs earlier in life compared to Caucasian adults, putting them at increased risk for cardiovascular events and renal disease. The Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8) Guideline Recommendations 7 and 8 were developed to aid in appropriate treatment and management of hypertensive AA adults. Purpose: The purpose of this Doctor of Nursing Practice (DNP) project was to improve the care, management, and outcomes of hypertensive AA adults by identifying current JNC 8 guideline prescribing patterns among a sample of hospitalized patients. The first project aim was to determine provider-prescribing rates of thiazide diuretics (TDs) and calcium channel blockers (CCBs) in newly diagnosed AA adults with HTN. The second project aim was to determine if AA adults previously diagnosed with HTN were currently prescribed TD and/or CCB medications. Methods: A retrospective medical record review of AA adult patients with a new HTN diagnosis or previously diagnosed with HTN was selected for this project. Participants were discharged from Medical City Dallas between 01/01/2017 and 03/31/2017. Results: In newly diagnosed participants with HTN, none were prescribed a TD (0%) and two were prescribed a CCB (40%). In previously diagnosed participants with HTN, 30 participants (16.3%) were prescribed a TD and/or CCB upon admission and 29 participants (15.76%) were prescribed a TD and/or CCB upon discharge. Among prescribing providers, beta blockers and other class hypertensive medications (i.e., furosemide, hydralazine, clonidine, and spironolactone) were most widely ordered for participants. Conclusions: The results of this DNP project display low provider compliance rates to guideline-recommended pharmacological therapy AA adults. This outcome highlights several potential reasons for the low adherence rates, including lack of provider documentation, lack of provider rationale for treatment selections, provider knowledge of HTN CPGs, and data analysis of prescribed medications. These factors present the opportunity for further research to identify the root cause of low compliance.

Made available in DSpace on 2015-05-14T12:59:25Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1262940 bytes, checksum: 3eb5eef404a585e59e9d6b96edc0609c (MD5) Previous issue date: 2011-02-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The pharmacological effects induced by CH2Cl2/MeOH extract (EDP) and Hexane/EtOAc phase (FDP) from the Brazilian alga Dictyota pulchella were studied on the cardiovascular system of Wistar rats using a combined in vivo and in vitro approach. All protocols in this study were approved by the CEPA/LTF (protocol nº 0208/10). In normotensive conscious male rats, EDP injections (5; 10; 20 and 40 mg/kg, i.v., randomly) produced hypotension (-4.1 ± 1.34; -7.0 ± 2.4; -46.9 ± 1.3 and - 54.8 ± 4.3%; respectively) and bradycardia (-2.1 ± 1.6; -4.0 ± 2.3; -66.8 ± 5.2 and - 74.7 ± 4.5%; respectively) (n=5). Isolated superior mesenteric artery rings (1-2 mm) were suspended by cotton threads for isometric tension recordings in a Tyrode s solution at 37 ºC, gassed with a 95% O2 and 5% CO2, under a resting tension of 0.75g. In phenylephrine (Phe, 1&#956;M)-pre-contracted rings, EDP (0.01 500 &#956;g/mL) induced a concentration-dependent relaxation (Maximum Response = 101.4 ± 4.5%; EC50 = 22.35 ± 5.09 &#956;g/mL) and this effect was not modified by removal of the vascular endothelium (MR = 103.3 ± 8.3%; EC50 = 21.43 ± 8.98 &#956;g/mL, n=7). Similar results were found in the presence of FDP (0.01 500 &#956;g/mL). FDP induced a concentration-dependent vasodilatation in both endothelium-intact (MR = 80.6 ± 5.8%; EC50 = 24.1 ± 8.95 &#956;g/mL, n=6) or endothelium-denuded mesenteric artery rings (MR = 95.6 ± 7.5%; EC50 = 23.7 ± 5.65 &#956;g/mL, n=6). Based on the preliminary results, the subsequent experiments were performed in rings without endothelium. To appreciate the involvement of potassium channels, the preparations were preincubated with Tyrode s modified solution, KCl (20 mM) or with non-selective K+ channel blocker, tetraethylammonium (TEA, 3 mM). In both preparations the vasorelaxant activity was not changed. In the presence of a tromboxane A2 agonist U-46619 (100 nM), EDP induced concentration-dependent vasodilatation (MR = 90.3 ± 7.8%; EC50 = 24.63 ± 4.04 &#956;g/mL, n=6) was similar to the response found under Phe-induced. After exposure to high concentrations of extracellular K+ (KCl, 60 mM), the EDP induced concentration-dependent vasodilatation (MR = 97.7 ± 4.0%; EC50 = 34.57 ± 5.11 mg/mL; n=6). In the same experimental condition, FDP induced concentration-dependent vasodilatation (MR = 113.5 ± 6.1%; EC50 = 10.92 ± 2.81 &#956;g/mL; n=6). This result indicates that both EDP and FDP act on voltage-operated calcium channel (Cav). Furthermore, EDP and FDP (0.03; 0.3; 10; 30 e 100 &#956;g/mL) antagonized CaCl2-induced contractions. The extract also induced vasodilatation in the contraction evoked by L-type Ca2+ channel agonist (Bay K 8644, 200 nM) (MR = 113.3 ± 6.7%; EC50 = 19.45 ± 6.66 &#956;g/mL, n=7). These results suggest that EDP induces hypotension and bradycardia. Both EDP and FDP induce endotheliumindependent vasodilatation that involves the inhibition of the Ca2+ influx through blockade of Cav. / Os efeitos farmacológicos do extrato CH2Cl2:MeOH (EDP) e fase Hexano:AcOEt (FDP) da alga marinha brasileira Dictyota pulchella foram estudados sobre o sistema cardiovascular de ratos, utilizando uma abordagem in vivo e in vitro. Em ratos normotensos não anestesiados, EDP (5; 10; 20 e 40 mg/kg, i.v., randomicamente) promoveu hipotensão (-4,1 ± 1,34; -7,0 ± 2,4; -46,9 ± 1,3 e -54,8 ± 4,3%, respectivamente) acompanhada de bradicardia (-2,1 ± 1,6; -4,0 ± 2,3; -66,8 ± 5,2 e - 74,7 ± 4,5%, respectivamente) (n=5). Em anéis de artéria mesentérica superior isolada de rato pré-contraídos com Fenilefrina (FEN) 1 &#956;M, EDP (0,01 500 &#956;g/mL) promoveu um efeito vasorrelaxante dependente de concentração na presença do endotélio vascular (Emáx = 101,4 ± 4,5%; CE50 = 22,35 ± 5,09 &#956;g/mL), e este efeito não foi alterado após a remoção do endotélio (Emáx = 103,3 ± 8,3%; CE50 = 21,43 ± 8,98 &#956;g/mL) (n=7). Resultados semelhantes foram obtidos na presença de FDP (0,01 500 &#956;g/mL), observando-se um vasorrelaxamento tanto na presença (Emáx = 80,6 ± 5,8%; CE50 = 24,1 ± 8,9 &#956;g/mL), quanto na ausência do endotélio funcional (Emáx = 95,6 ± 7,5%; CE50 = 23,70 ± 5,65 mg/mL). Para avaliar se o efeito de EDP era dependente do tônus vascular, este extrato foi testado no tônus basal, na presença ou ausência do endotélio, demonstrando que a resposta não foi alterada em nenhuma das duas situações. Baseado nos resultados preliminares, os experimentos subseqüentes foram realizados com endotélio desnudo. Para avaliar a participação dos canais para potássio (K+), utilizou-se uma solução com 20 mM de KCl ou tetraetilâmonio (TEA) 3 mM. Em ambas as preparações (Emáx = 102,3 ± 4,8%; CE50 = 25,40 ± 6,05 &#956;g/mL) ou (Emáx = 111,2 ± 5,3%; CE50 = 16,70 ± 3,61 &#956;g/mL) (n=7), respectivamente, a atividade vasorrelaxante de EDP não foi alterada. Na presença de outro agente contracturante, U46619 (100 nM), EDP promoveu um efeito vasorrelaxante (Emáx = 90,3 ± 7,8%; CE50 = 24,63 ± 4,04 &#956;g/mL) de maneira similar aos anéis pré-contraídos com FEN. Em experimentos contendo uma solução despolarizante de 60 mM de KCl, EDP causou vasorrelaxamento dependente de concentração (Emáx = 97,7 ± 4,0%; CE50 = 34,57 ± 5,11 mg/mL; n=6). Na mesma condição experimental, FDP também promoveu um efeito vasorrelaxante (Emáx = 113,5 ± 6,1%; CE50 = 10,92 ± 2,81 &#956;g/mL; n=6), não havendo diferença significante, para os dois compostos, quando comparados aos anéis pré-contraídos com FEN. Sugere-se que tanto EDP quanto FDP atuem sobre os canais para cálcio sensíveis a voltagem (Cav). Além disso, EDP e FDP (0,03; 0,3; 10; 30 e 100 &#956;g/mL) antagonizaram as contrações induzidas por CaCl2. O extrato ainda produziu vasorrelaxamento na presença de um agonista de canais para Ca2+ tipo-L (Bay K 8644; 200 nM) (Emáx = 113,3 ± 6,7% e CE50 = 19,45 ± 6,66 &#956;g/mL, n=7). Esses resultados sugerem que EDP produz hipotensão e bradicardia transientes, e tanto EDP quanto FDP promovem vasorrelaxamento independente do endotélio vascular por inibição do influxo de Ca2+, por meio do bloqueio dos Cav.

Made available in DSpace on 2015-05-14T12:59:27Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2410324 bytes, checksum: 683a4ac95271e3c06063aa05abced89b (MD5) Previous issue date: 2011-03-25 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The genus Lippia (Verbenaceae) has yielded a great number of medicinal and economically important species that are frequently used in folk medicine for treatment of several diseases, such as: coughs, bronchitis, liver disorders and hypertension. L. microphylla Cham. is a plant of the genus Lippia found in the Northeast of Brazil, and there is no information in the literature concerning its cardiovascular effects. Therefore, this study aimed to evaluate the cardiovascular effects of the essential oil of L. microphylla Cham. (EOLM) and of its main constituent, thymol. In normotensive non-anaesthetized rats, EOLM injections produced hypotension (ED50=5.5 (4.1-7.3) mg/Kg, n=5) and bradycardia (ED50=5.2 (4.3-6.2) mg/Kg, n=5). Isometric tension recordings revealed that EOLM (1 300 μg/mL) caused concentration-dependent relaxation in isolated mesenteric rings, with functional endothelium, pre-contracted with phenylephrine (10 μM) (EC50=28.2 (25.3-31.4) μg/mL, n=5) and this effect was not attenuated by removal of the vascular endothelia layer. In preparations without endothelium, pre-incubated with KCl 20 mM, the relaxantion was not changed. Furthermore, EOLM caused relaxation in mesenteric rings pre-contracted with KCl 60 mM and inhibited Ca2+ -induced vasoconstriction in a concentration-dependent manner. In addition, EOLM relaxed the contractions elicited by the L-type Ca2+ channel activator, S(-)-Bay K 8644, indicating that the vasodilatation is related to the inhibition of Ca2+ influx through L-type Ca2+ channels. To confirm this hypothesis, whole-cell L-type Ca2+ currents were recorded in freshly dispersed rat mesenteric artery myocytes. EOLM (1-100 μg/mL) significantly inhibited Ba2+ currents in a concentration-dependent manner (EC50=11.9 (9.4-15.0) μg/mL, n=4).These results suggest that OELM induce vasorelaxant effect in rat mesenteric artery due to the inhibition of the Ca2+ influx via voltage-dependent L-type Ca2+ channels. Interestingly, the relaxantion induced by thymol (EC50=9.3 (8.3-10.4) μg/mL, n=5, p<0.01) was more potent than that observed to EOLM (EC50=23.9 (22.0-26.0) μg/mL, n=5), indicating that the vascular actions of EOLM could be attributed to its main constituent, thymol. The cardiovascular responses evoked by thymol were investigated in SHR and WKY rats. In SHR and WKY non-anaesthetized rats, intravenous administration of thymol (0.1; 0.3; 1; 3; 6; 12 and 15 mg/Kg, i.v.) produced hypotension and bradycardia in a dose-dependent manner. Isometric tension recordings, the pharmacological profile of arterial relaxant effects of thymol was compared in rings of mesenteric arteries and aorta from SHR and WKY. In preparations without endothelium, thymol (1 μM 1 mM) produced relaxation in mesenteric arteries from SHR (pD2=4.40.04, n=5) and WKY (pD2=4.30.02, n=5) and aorta from SHR (pD2 = 4.40.03, n=5) and WKY (pD2=4.30.03, n=5) and this effect was not altered in preparations with functional endothelium. Furthermore, thymol relaxed the vasoconstriction induced by high K+ solution, U46619 and S(-)-Bay K 8644 in mesenteric arteries and aorta from SHR and WKY. The addition of thymol also inhibited Ca2+ -induced vasoconstriction in a concentration-dependent manner in mesenteric and aorta segments from SHR and WKY. In electrophysiological recordings, L-type Ca2+ current (ICa,L) was decreased by thymol in a concentration-dependent manner in cardiomyocytes isolated from SHR (pD2=3.40.06, n=4, p<0.05) and WKY (pD2=4.70.05, n=4). In addition, thymol lowed-down both the fast and slow time constants for L-type Ca2+ current inactivation. In conclusion, these results suggest that the vascular effects induced by EOLM and thymol are probably due to the inhibition of the Ca2+ influx via voltage-dependent L-type Ca2+ channels. / O gênero Lippia (Verbenaceae) contém um grande número de espécies medicinais e economicamente importantes, que são frequentemente utilizadas na medicina popular para o tratamento de várias doenças, tais como: tosse, bronquite, disordens hepáticas e hipertensão. L. microphylla Cham. é uma espécie do gênero Lippia encontrada no Nordeste brasileiro e não há informações na literatura a respeito de suas ações cardiovasculares. Portanto, o presente trabalho tem como objetivo avaliar os efeitos cardiovasculares do óleo essencial de L. microphylla Cham (OELM) e seu constituinte principal, o timol. Em ratos normotensos não-anestesiados, OELM produziu hipotensão (DE50=5,5 (4,1-7,3) mg/Kg, n=5) e bradicardia (DE50=5,2 (4,3-6,2) mg/Kg, n=5). Experimentos de tensão isométrica revelaram que o OELM (1 300 μg/mL) promove relaxamento dependente de concentração em anéis mesentéricos, com endotélio funcional, pré-contraídos com fenilefrina (10 μM) (EC50=28,2 (25,3-31,4) μg/mL, n=5), e este efeito não foi atenuado pela remoção do endotélio vascular. Em preparações pré-incubadas com KCl 20 mM, o relaxamento do OELM não foi alterada. Além disso, o OELM promoveu relaxamento em anéis mesentéricos pré-contraídos com KCl 60 mM e inibiu a vasoconstrição indizuda pelo Ca2+ de maneira dependente de concentração. O OELM relaxou as contrações induzidas pelo ativador de canais para Ca2+ tipo-L, o S(-)-Bay K 8644, indicando que a vasodilatação induzida pelo OELM está relacionada com a inibição do influxo de Ca2+ via canais para Ca2+ tipo-L. Para confirmar esta hipótese, correntes macroscópicas de Ca2+ foram registradas em miócitos de artéria mesentérica recém dispersas. O OELM (1 100 μg/mL) inibiu significantemente as correntes de Ba2+ de maneira dependente de concentração (CE50=11,9 (9,4-15,0) μg/mL, n=4). Estes resultados surgerem que o OELM induz efeito relaxante em artéria mesentérica de rato devido à inibição do influxo de Ca2+ via canais para Ca2+ dependente de voltage tipo-L. Interessantemente, o efeito relaxante induzido pelo timol (CE50=9,3 (8,3-10,4) μg/mL, n=5, p<0,01) foi mais potente do que o induzido pelo OELM (CE50=23,9 (22,0-26,0) μg/mL, n=5), indicando que os efeitos vasculares do OELM são provavelmente atribuídos ao seu principal constituinte, o timol. A partir dessas premissas, os efeitos cardiovasculares induzidos pelo timol foram investigados em ratos SHR e WKY. Em ratos SHR e WKY não-anestesiados, a administração intravenosa de timol (0,1; 0,3; 1; 3; 6; 12 e 15 mg/kg, i.v.) produziu hipotensão e bradicardia de maneira depedente de dose. Em experimentos de tensão isométrica, o perfil do efeito relaxante induzido pelo timol foi comparado entre artéria mesentérica e aorta isoladas de ratos SHR e WKY. Em preparações sem endotélio vascular, o timol (1 μM 1 mM) induziu relaxamento de maneira concentração dependente em artéria mesentérica isolada de SHR (pD2=4,40,04, n=5) e WKY (pD2=4,30,02, n=5) e aorta de SHR (pD2=4,40,04, n=5) e WKY (pD2=4,30,03, n=5) e este efeito não foi alterado em preparações com o endotélio. Além disso, o timol relaxou as contrações induzidas por KCl, U46619 e S(-)-Bay K 8644 em artéria mesentérica e aorta de ratos SHR e WKY. A adição do timol inibiu a vasoconstrição induzida por Ca2+ em anéis de artéria mesentérica e aorta de ratos SHR e WKY. O timol diminuiu as correntes de Ca2+ tipo-L de maneira concentração dependente em cardiomiócitos de SHR (pD2=3,40,06, n=4, p<0,05) e WKY (pD2=4,70,05, n=4). Além disso, o timol diminuiu a constante de tempo rápida e lenta para inativação das correntes de Ca2+. Em conclusão, estes resultados surgerem que os efeitos cardiovasculares induzidos pelo o OELM e timol são provavelmete devido a inibição do influxo de Ca2+ via canais para Ca2+ dependentes de voltage tipo-L.

Fundação de Amparo a Pesquisa no Estado do Rio Grande do Sul / Opioids are the most common drugs prescribed worldwide for alleviating moderate to severe pain. However, the use of opioids is associated with the development of tolerance to the analgesic effect and potential adverse effects, such as paradoxical hyperalgesia, withdrawal syndrome and constipation. An important target for morphine-induced analgesia is the blockade of voltage-gated calcium channels (VGCCs). However, the participation of VGCCs in the tolerance and adverse effects caused by morphine is poorly understood. Thus, the present study was conducted in order to evaluate the possible actions of Phα1β, a peptide inhibitor of VGCCs purified from the venom of the Phoneutria nigriventer spider on the antinociceptive and adverse effects produced by single or repeated administration of morphine. It was evaluated the effect of intrathecal injection Phα1β (0.01-30 pmol/site) on mechanical and heat hyperalgesia, tolerance, withdrawal syndrome and constipation induced throught single (10 mg/kg) or repeated (increasing doses, 3 times a day, for 3 consecutive days) subcutaneous treatment of morphine in C57BL/6 mice. We observed that a single administration of morphine was able to reduce heat but not mechanical nociception as well as decrease gastrointestinal transit. The antinociception, but not the constipation, caused by a single injection of morphine was slightly increased by an intrathecal injection of Phα1β. Repeated treatment with morphine caused not only tolerance to its antinociceptive effect but also induced paradoxical heat and mechanical hyperalgesia, withdrawal syndrome and constipation. Phα1β was able to reverse the tolerance, withdrawal syndrome, mechanical and heat hyperalgesia and constipation induced by repeated morphine treatment. Finally, the effects produced by the native form of Phα1β were fully mimicked by a recombinant version of this peptide in naïve mice. Our results suggest that Phα1β is effective in potentiating the analgesia as well as in reducing tolerance and the adverse effects induced by morphine, indicating its potential use as an adjuvant drug in combination with opioids. / Os opióides são os medicamentos mais comuns prescritos em todo o mundo para aliviar as dores moderadas a intensas. No entanto, a utilização de opióides está associada com o desenvolvimento de tolerância ao efeito analgésico e de efeitos adversos, tais como hiperalgesia paradoxal, síndrome de abstinência e constipação. Um alvo importante para a analgesia induzida pela morfina é o bloqueio dos canais de cálcio regulados por voltagem (CCRV). Porém pouco se sabe sobre o papel desses canais na tolerância e nos efeitos adversos produzidos pela morfina. Assim, o presente estudo foi realizado com o intuito de avaliar as possíveis ações da Phα1β, um inibidor peptídico dos CCRVs purificado do veneno da aranha Phoneutria nigriventer, sobre os efeitos antinociceptivos e adversos produzidos pela administração única ou repetida de morfina. Foi avaliado o efeito da administração intratecal da Phα1β (0.01-30 pmol/site) sobre a hiperalgesia térmica e mecânica, tolerância, síndrome de abstinência e constipação induzidos pelo tratamento único (10 mg/kg) ou repetido (doses crescentes, 3 vezes ao dia, durante três dias) de morfina por via subcutânea em camundongos C57BL/6. Observamos que uma única administração de morfina foi capaz de reduzir a nocicepção térmica mas não a mecânica em camundongos, bem como reduzir o trânsito gastrointestinal. A antinocicepção, mas não a constipação, causada por uma única dose de morfina foi levemente aumentada pela administração intratecal da Phα1β. O tratamento repetido com morfina não causou somente tolerância analgésica como também induziu hiperalgesia, síndrome de abstinência e constipação. A Phα1β foi capaz de reverter a tolerância, a síndrome de abstinência, a hiperalgesia mecânica e térmica e a constipação induzidas pelo tratamento repetido de morfina. Finalmente, os efeitos produzidos pela forma nativa Phα1β foram totalmente mimetizados por uma versão recombinante do presente peptídeo. Em conclusão, nossos resultados sugerem que a Phα1β é efetiva em potencializar a analgesia, bem como, reduzir a tolerância e os efeitos adversos induzidos pela morfina. Desta maneira, a Phα1β apresenta um uso potencial como uma droga adjuvante na terapia opióide.

Ziel: Das Ziel dieser Studie war es den Zusammenhang zwischen Zahnextraktionen und Patientenfaktoren in 3 Deutschen Zahnarztpraxen zu untersuchen. Material & Methoden: In einer retrospektiven Auswertung aller Patientenkarten von 3 deutschen Zahnarztpraxen wurden Extraktionsfälle ab Januar 2007 (Praxis 1), Mai 2010 ( Praxis 2) und Januar 2010 ( Praxis 3 ) auf Extraktionen hin durchsucht, bis in jeder Praxis jeweils 100 Extraktionspatienten gefunden wurden, die die Einschlusskriterien erfüllten. Alle Patienten ohne Extraktionen die innerhalb dieses Zeitraumes behandelt wurden und die die Einschlusskriterien erfüllten, dienten als Kontrollgruppe. Es wurden nur Patienten eingeschlossen (Fall und Kontrollgruppe), von denen die spezifischen Patientendaten zur Verfügung standen. Alle Patientendaten wurden in einem „Case-Report-Form\"-Formular (CRF) erfasst. Die individuellen Parameter der Patienten der Fallgruppe und der Kontrollgruppe wurden verglichen. Mittels schrittweiser logistischer Regressionsanalyse konnten die Faktoren für ein Extraktionsrisiko bestimmt werden. Ergebnisse: Insgesamt wurden 2174 Patientenakten untersucht (Fallgruppe 300; Kontrollgruppe 1874). Die Gesamtsumme der Zähne vor der Extraktionstherapie betrug 54316. In der Fallgruppe wurden insgesamt 459 Zähne extrahiert. Die Patienten der Fallgruppe waren im Schnitt mehr als 6,7 Jahre älter als die Patienten der Kontrollgruppe(52,4/45,7 Jahre (P< 0,001)), sie waren zu einem größeren Anteil männlich. (58/ 52%) ,es gab eine höhere Zahl an Rauchern, es gab vermehrt Patienten mit einer Kalziumkanalblocker Medikation [15/8 % (p<0,001)] und der parodontale Befund festgestellt mittels PSI der Fallgruppe war schlechter als der der Kontrollgruppe [PSI 2,5/1,8 , (p<0,001)]. Das Risiko einer Zahnextraktion im Allgemeinen und in Folge von Parodontalerkrankungen waren assoziiert mit Kalziumkanalblockermedikation, (OR 1,49/1,65) aktivem Rauchen (OR 1,35/1,71), Alter (10Jahre) OR 1,13/1,37 , Praxis Nr.1 (1,48/1,99) und der Anzahl der Sextanten mit dem PSI Code 4 (1,33/1,76) (p<0,001). Schlussfolgerung: Kalziumkanalblockermedikation, aktives Rauchen, Alter, Zahnarzt und die Anzahl der Sextanten mit einem PSI Wert 4 sind Risikoindikatoren für Zahnextraktionen. Nutzen : Kalziumkanalblockermedikation kann das Extraktionsrisiko erhöhen. Zahnverlust zieht in den meisten Fällen Zahnersatz nach sich, welcher in aller Regel aufwändig ist, den Patienten zusätzliche Belastungen abverlangt und die Kosten einer Therapie erhöht. Die Information über die Einnahme von Kalziumkanalblockern ist ein leicht zu erfassender Parameter und könnte als Indikator genutzt werden, um Betreuungsintervalle zu verkürzen. Es muss jedoch noch geprüft werden, ob eine intensivere Betreuung dieser Patienten deren Zahnextraktionsrate tatsächlich verringern kann.

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