In der vorliegenden Untersuchung wurde der Einfluss des AT1-R -Antagonisten Valsartan auf die Nierenfunktion bei nierentransplantierten Ratten mit der Fragestellung analysiert, ob eine Langzeittherapie mit diesem Wirkstoff einen positiven Effekt auf die Nierenfunktion entfaltet und sich somit sein Einsatz gegen die Entwicklung einer chronischen Transplantatnephropathie empfiehlt. Die über den gesamten Versuchszeitraum gegenüber der allogenen Kontrollgruppe signifikant erhöhten Urinvolumina stellen allein kein Indiz für eine bessere Nierenfunktion unter Therapie mit Valsartan dar. Dieses Ergebnis ist am ehesten durch Veränderungen der glomerulären Hämodynamik post transplantationem zu erklären. Wie nunmehr in mehreren tierexperimentellen Untersuchungen und klinischen Patientenstudien nachgewiesen worden ist, zeigt sich auch in der Synopsis der eigenen Befunde ein signifikant günstigerer Verlauf des Serumkreatinins, des Serum-BUN, der Kreatinin-Clearance sowie der Proteinurie unter Blutdrucksenkung mit dem AT1-R-Antagonisten Valsartan. An einigen Zeitpunkten der Studie waren die Ergebnisse allerdings statistisch nicht signifikant. Eine positive Wirkung auf die Transplantatfunktion und auf das Langzeitüberleben der Versuchstiere ist anzunehmen, ist aber in dieser Studie nicht weiter verfolgt worden. Eine Untersuchung mit einer größeren Anzahl von Versuchstieren und über einem längeren Versuchzeitraum hin scheint sinnvoll, um signifikante Unterschiede zwischen den Kontrollgruppen und der Versuchgruppe unter Valsartan zu belegen. Die im Vergleich zu den Kontrollgruppen geringere Entwicklung des Körpergewichts hatte bei der o.g. Fragestellung keine Relevanz. Wie in zahlreichen klinischen Studien für die Progredienz des chronischen Nierenversagens seit längerem eindrucksvoll belegt ist, scheint eine pharmakologische Blockade des RAAS auch einen protektiven Effekt auf die Entstehung einer chronischen Transplantatnephropathie zu entfalten. Die eigene Untersuchung liefert hinreichend Belege für diese Vermutung. Auch wenn in einzelnen Studien über negative Auswirkungen einer Blockade des RAAS auf die Transplantatfunktion berichtet worden ist, gibt es genügend Anhaltspunkte für einen günstigeren Verlauf nach Transplantation sowohl in Tierversuchen als auch für den transplantierten Patienten. Das allmähliche Fortschreiten der chronischen Transplantatnephropathie kann damit allerdings nicht ganz aufgehalten werden. Somit bleibt trotz dieser erfolgversprechenden experimentellen Ergebnisse nach Organtransplantation durch diese neuen Therapieansätze (Immunsuppressiva, RAAS-Blockade, Plasmapherese u.a.) die chronische Transplantat-Abstoßung immer noch ein therapeutisch fortbestehendes Problem. Weitere Untersuchungen über die Zusammenhänge immunologischer sowie nicht-immunologischer Ursachen einer chronischen Transplantatnephropathie und eine Optimierung der Immunsuppression sind deshalb auch weiterhin dringend erforderlich. / In spite of the new immunosuppressive drug therapies used in renal transplants, chronic rejection continues to be a major cause of graft dysfunction after the first posttransplant year. This so called chronic allograft nephropathy is characterized by a slow but variable decrease in renal function appearing months or years after transplantation, is often accompanied or proceded by proteinuria ans hypertension and does not respond to immunosuppressive therapy. In our study we could show that posttransplant therapy with the angiotensin-II-receptor antagonist Valsartan improves chronic renal allograft nephropathy in Lewis rats. A similar effect on long-term survival of human kidney transplants can be supposed. Nevertheless further investigations have to be done in oder to understand all immunologigal and non immunological mechanisms of renal chronic rejection and to improve therapies.

Todas as células eucarióticas apresentam mecanismos para controlar e operar o cálcio (Ca2+). Apesar desse íon não ser importante para regulação osmótica e manutenção da concentração iônica da hemolinfa em crustáceos, ele é finamente regulado, pois desempenha papel fundamental no enrijecimento do exoesqueleto desses organismos. Dessa forma o crescimento e fisiologia desses organismos estão ligados ao massivo transporte de Ca2+ que ocorre através das células epiteliais durante o ciclo da muda. Para avaliar os mecanismos transportadores de Ca2+ presentes na membrana plasmática, foram utilizadas células isoladas a partir de hepatopâncreas de D. pagei, um crustáceo dulcícola. Quando essas células foram submetidas a um pulso de 1mM de ATP externo, ocorreu uma queda rápida (50 s) na concentração de cálcio intracelular ([Ca2+]i), que foi totalmente inibida por 10mM de vanadato e parcialmente por 2mM de amiloride, sugerindo que o efluxo ocorreu através de uma Ca-ATPase (PMCA) e de um trocador Na+/Ca2+ (NCX ou NHE), respectivamente. Essa queda foi seguida de uma recuperação dos valores iniciais, que pode ter ocorrido via influxo de Ca2+ do meio externo, sensível ao verapamil (1mM), ou através da liberação de Ca2+ de estoque intracelulares. Células incubadas em meio livre de Ca2+ apresentam uma redução no [Ca2+]i e quando são submetidas a um pulso de Ca2+ externo ocorre um influxo imediato do íon, que é sensível tanto a 1mM de verapamil quanto a 2mM de amiloride, sugerindo que a entrada ocorra via canais para cálcio e via trocador Na+/Ca2+, respectivamente. Juntos esses resultados sugerem que o transporte de cálcio em células isoladas de hepatopâncreas de D. pagei parece ocorrer de maneira semelhante ao modelo proposto em outros crustáceos: efluxo via Ca-ATPase (PMCA) sensível ao vanadato e via trocador Na+/Ca2+ (NCX ) sensível ao amiloride; influxo via canais para Ca2+ sensíveis ao verapamil e modo de influxo de Ca2+ do trocador Na+/Ca2+ ou trocador Na+/H+ (NHE) operando como Ca2+ /(n) Na+, sensíveis ao amiloride. Esses dados contribuem para um maior entendimento do transporte de cálcio em D. pagei (e outros crustáceos) e sua importância para a homeostase e o ciclo da muda. / All eukaryotic cells display several mechanisms to control and operate calcium (Ca2+). Although there is no apparent importance for hemolymph osmo-ionic regulation, it plays an essential role on exoskeleton calcification (hardening). Crustaceans growth and physiology are linked to massive calcium transport during molting cycle. The aim of this work was to evaluate calcium transport mechanisms in hepatopancreatic cells of the freshwater crab D. pagei. When these cells were exposed to external ATP pulse (1mM), it was observed a decrease in intracellular calcium concentration ([Ca2+]i), inhibited by 10mM vanadate and partially by 2mM amiloride, suggesting the involvement of a Ca-ATPase (PMCA) and Na+/Ca2+ exchanger (NCX ou NHE), respectively. Recovery of [Ca2+]i was inhibited by 1mM verapamil, a calcium channel blocker. The same was observed in calcium free environment and so, calcium must have been provided by intracellular stocks (endoplasmatic reticulum and/or mitochondria). When cells incubated in calcium free environment were exposed to calcium pulse (1mM or 10mM), a rapid rise in [Ca2+]i was observed, suggesting calcium influx. This could be partially inhibited by 1mM verapamil or 2mM amiloride, suggesting the participation of calcium channels and Na+/Ca2+ exchanger (Ca2+ influx mode), respectively. Calcium transport in these cell appears to be the same as described for other crustaceans: efflux occurs via a vanadate sensitive Ca-ATPase (PMCA) and by an amiloride sensitive Na+/Ca2+ (NCX exchanger); influx is mediated by a verapamil sensitive calcium channel and by an amiloride sensitive Na+/Ca2+ or Na+/H+ (NHE) operating as Ca2+ /(n) Na+ exchanger. Taken together, these data contributes to a better understanding of D. pagei calcium homeostasis and the moult cycle.

A apnéia central do sono (ACS) está associada à insuficiência cardíaca (IC). Objetivos: analisar o comportamento do sono em pacientes com IC e ACS com IAH>15 por hora e a influência dos betabloqueadores sobre o sono. Métodos: os pacientes realizaram duas polissonografias, com nitroglicerina e placebo, ambos transdérmicos. Resultados: em média, houve aumento da saturação de oxigênio e redução dos despertares e da frequência cardíaca, quando os pacientes fizeram uso de nitroglicerina. A prevalência de ACS no grupo betabloqueador foi menor do que relata a literatura. Conclusão: a nitroglicerina teve impacto positivo sobre variáveis polissonográficas. O betabloqueador reduziu a prevalência de apnéia. / The central sleep apnea (CSA) is associated to heart failure (HF). Objectives: Analyze sleeping behavior in patients with HF and CSA with AHI > 15 per hour, and the influence of beta-blocker on the sleep. Methods: patients were submitted to two sleep studies, with transdermic nitroglycerine and placebo. Results: On the average, we observed improvement in oxygen saturation and reduction in awakening episodes and in heart rate when patients slept with nitroglycerin compared to placebo. The prevalence of CSA in patients taking beta-blocker was inferior to that described in medical literature. Conclusion: Nitroglycerin had positive impact on sleep variables. Beta-blocker reduced CSA prevalence.

BEZERRA DE LIMA, BJS. Efeito da nifedipina por via sistêmica na analgesia pós-operatória induzida pelo sufentanil intratecal em pacientes submetidas à lipoabdominoplastia em caráter ambulatorial. 2011. 72 f. Tese (Doutorado) Faculdade de Medicina de Ribeirão Preto Universidade de São Paulo Canais de cálcio dependentes da voltagem têm um importante papel na transmissão de impulsos nociceptivos e alterações das concentrações extracelulares de íons cálcio podem modificar a analgesia opioide. No entanto, a utilização de bloqueadores de canais de cálcio produziu resultados conflitantes no tocante à potencialização ou prolongamento da analgesia opioide. O sufentanil, pela alta lipossolubilidade e consequente baixo potencial para depressão respiratória tardia, pode ser utilizado pela via subaracnoidea em pacientes ambulatoriais. Para ser considerado o opioide ideal para uso subaracnoideo falta-lhe a capacidade de produzir analgesia prolongada. O objetivo deste trabalho foi testar se a nifedipina oral pode aumentar a sua duração e potência. Trinte e seis pacientes do sexo feminino, ASA I ou II e idade entre 20 e 60 anos, submetidas à lipoabdominoplastia sob regime ambulatorial foram casualisada em 3 grupos, de acordo com a quantidade de nifedipina recebida no pré-operatório. Foram confeccionadas 13 cápsulas semelhantes que continham amido ou 10 mg de nifedipina e entregues para cada uma das pacientes durante a avaliação pré-anestésica que aconteceu com a antecedência mínima de cinco dias do procedimento cirúrgico. As pacientes foram orientadas a ingerir 3 (três) cápsulas por dia, com intervalo de 8 horas entre cada ingestão, durante 4 (quatro) dias, totalizando 12 cápsulas. A 13ª cápsula foi ingerida 60 minutos antes do procedimento anestésico. As pacientes do Grupo A ingeriram 13 cápsulas de amido, as do Grupo B ingeriram 12 cápsulas contendo amido e a 13ª contendo 10 mg de nifedipina e as do Grupo C ingeriram 13 cápsulas contendo 10 mg de nifedipina. A PA e a FC foram aferidas em seis momentos: imediatamente antes do procedimento anestésico (M1), 5 (cinco) minutos após a realização da punção subaracnoidea (M2), 60 (sessenta) minutos após a realização da punção subaracnóidea (M3), ao término do procedimento cirúrgico (M4), no momento da primeira queixa dolorosa (M5) e no momento da alta hospitalar (M6).A técnica anestésica foi semelhante em todos os grupos e constou de raquianestesia e administração de solução contendo 20 mg de bupivacaína pesada e 5 microgramas de sufentanil. Após a punção e administração das medicações, o nível do bloqueio pretendido (T4) foi controlado pelo posicionamento da mesa cirúrgica. As pacientes foram orientadas a informar o momento em que sentissem dor pela primeira vez. Considerou-se como tempo de analgesia, o tempo (minutos) decorrido entre a punção subaracnoidea e esta primeira queixa. Neste momento, foi realizada a mensuração da intensidade da dor por meio da escala analógica visual. A intensidade da dor foi novamente avaliada no momento da alta hospitalar, da mesma forma que no momento da primeira queixa. Não houve diferença no comportamento hemodinâmico entre os grupos. O grupo C apresentou maior tempo de analgesia e menor escore de dor no momento da primeira queixa. Não houve diferença entre os grupos quanto ao escore de dor no momento da alta hospitalar. A nifedipina administrada durante 4 dias no pré-operatório prolongou, de forma tênue, o tempo e a intensidade da analgesia induzida pelo fentanil. / BEZERRA DE LIMA, BJS. Effect of nifedipine in a systemic way in postoperative analgesia induced by intrathecal sufentanil in patients undergoing ambulatory lipoabdominoplasty. 2011. 72 f. Tese (Doutorado) Faculdade de Medicina de Ribeirão Preto Universidade de São Paulo Calcium channel voltage-gated play an important role in transmitting nociceptive impulses and changes in extracellular concentrations of calcium ions may reverse opioid analgesia. However, the use of calcium channel blockers produced conflicting results regarding the extension or enhancement of opioid analgesia. Sufentanil, high lipid solubility and consequent low potential for late respiratory depression, can be used by subarachnoid in outpatients. To be considered the ideal opioid for use subarachnoid lacks the ability to produce prolonged analgesia. The aim of this study was to test whether oral nifedipine may increase the duration and potency of sufentanil. Thirty-six female patients, ASA I or II and aged between 20 and 60 years undergoing ambulatory lipoabdominoplasty were randomized into three groups according to the amount received nifedipine preoperatively. 13 capsules were prepared containing similar starch or 10 mg of nifedipine and delivered to each of the patients during the preanesthetic evaluation that took place with at least five days after surgery. The patients were instructed to ingest three (3) capsules per day with 8 hours interval between each ingestion, during 4 (four) days, totaling 12 capsules. The 13th capsule was ingested 60 minutes before anesthesia. The Group A patients ingested 13 capsules of starch, the Group B ingested 12 capsules containing starch and 13th with 10 mg of nifedipine and those in Group C ingested 13 capsules containing 10 mg of nifedipine. BP and HR were measured on six occasions: just before anesthesia (M1), 5 (five) minutes after subarachnoid puncture (M2), 60 (sixty) minutes after spinal puncture (M3), the after surgery (T4), when the first complaint of pain (M5) and at discharge (M6). Anesthetic technique was similar in all groups and consisted of spinal anesthesia and administration of a solution containing 20 mg of heavy bupivacaine and 5 micrograms of sufentanil. After puncture and administration of medications, the desired level of the block (T4) was controlled by positioning the operating table. The patients were instructed to inform when they felt pain the first time. It was considered as a time of analgesia, time (minutes) elapsed between the subarachnoid puncture and this first complaint. At this point, we performed the measurement of pain intensity by visual analog scale. Pain intensity was evaluated again at discharge from hospital, the same way as when the first complaint. There was no difference in hemodynamic performance between the groups. The C group showed longer duration of analgesia and lower pain scores at the first complaint. There was no difference between the groups in pain scores at discharge from hospital. Nifedipine administered for 4 days preoperatively prolonged, weakly, the time and intensity of analgesia induced by fentanyl.

Recently short word-length (normally 1 bit or bits) processing has become a promising technique. However, there are unresolved issues in sigma-delta modulation, which is the basis for 1b/2b systems. These issues hindered the full adoption of single-bit techniues in industry. Among these problems is the stability of high-order modulators and the limit cycle behaviour. More importantly, there is no adaptive LMS structure of any kind in 1b/2b domain. The challenge in this problem is the harsh quantization that prevents straightforward LMS application. In this thesis, the focus has been made on three axes: designing new single-bit DSP applications, proposing novel approaches for stability analysis, and tacking the unresolved problems of 1b/2b adaptive filtering. Two structures for 1b digital comb filtering are proposed. A ternary DC blocker structure is also presented and performance is tested. We also proposed a single-bit multiplierless DC-blocking structure. The s tability of a single-bit high-order signma-delta modulator is studied under dc inputs. A new approach for stability analysis is proposed based on analogy with PLL analysis. Finally we succeeded in designing 1b/2b Wiener-like filtering and introduced (for the first time) three 1b/2b adaptive schemes.

Research Objectives Heart failure (HF) is a common condition in persons older than 65 years. Existing literature indicated that hospital readmission rates after discharge for heart failure patients are immensely high. However, previous studies showed that almost half of the early hospital readmissions could be prevented. Moreover, Angiotensin-converting enzyme (ACE) inhibitor and Angiotensin receptor blocker (ARB) are the commonly used medications for heart failure patients to control blood pressure. Nevertheless, studies indicated that these two medications could also cause the risk of hospital readmission. Little studies examined the associations of medication use and hospital readmission of heart failure patients in Taiwan. This study aims to investigate the influence factors of hospital readmissions among heart failure patients in Taiwan. Study Design We collected the data from National Health Insurance (NHI) database during the period from year 2000 to 2006. Based on the rule of Bureau of National Health Insurance in Taiwan, the 14-day readmission is considered as a poor quality indicator. We categorized readmissions into 4 groups (14-day, 30-day, 180-day and over 180-day) and evaluated each group¡¦s demographic, hospital characteristics, medical resource utilization, Charlson Comorbidity Index and medication utilizations of ACE inhibitor and ARB. We conducted descriptive analyses by using chi-square and t tests and applied multivariate logistic regression analyses to estimate the probabilities of hospital readmissions of heart failure patients. Population Studied Patients aged 50 or older with heart failure were identified based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Principle Findings Among 1920 heart failure patients, 19.9% of them were readmitted within 14 days, 7.6% were readmitted within 30 days and 26% were readmitted within 180 days. The medical resource utilizations such as average inpatients cost per patient, average outpatients cost per patient, total medical cost, average of inpatients times per patient and average of outpatients times per patient were significantly higher in patients with readmissions than those without readmission. Age, Charlson Comorbidity Index, patients who had been treated with ACE inhibitors and patients who had been treated with ARB were significantly affected the probabilities of readmissions. Conclusion The heart failure patients with readmissions had significantly higher medical resource utilizations than those without readmission. The medication uses of ACE inhibitors or ARB were significantly affected the probabilities of hospital readmissions. By understanding more about the influence factors of readmissions among heart failure patients, we may provide continue improvements of quality of care and reduce unnecessary medical costs. This study results provide useful reference for policy-makers to establish effective disease management program and appropriate health care financing arrangement in the future.

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.

Cerebral perfusion is optimized during hemodilution by both β1- and β2-adrenergic mechanisms. Antagonism of the β2-adrenoreceptor can impair cerebral vasodilation. We hypothesized that treatment with a highly β1-specific antagonist (nebivolol) would minimize the degree of cerebral hypoxia during hemodilution. Anesthetized rats were randomized to receive vehicle or nebivolol (1.25 or 2.5 mg/kg intravenously) prior to hemodilution. In vehicle-treated rats, hemodilution increased cardiac output (CO) and regional cerebral blood flow (rCBF) while microvascular brain PO2 (PBrO2) decreased. Both nebivolol doses reduced heart rate and attenuated the CO response to hemodilution. Only the higher dose of nebivolol attenuated the rCBF response to hemodilution and caused a further reduction in PBrO2. Brain hypoxic protein levels were only increased in the high dose nebivolol group. High dose nebivolol treatment resulted in drug levels near its affinity for the β2-adrenoreceptor supporting the hypothesis that cerebral perfusion is maintained by β2-dependent mechanisms during hemodilution.

Cerebral perfusion is optimized during hemodilution by both β1- and β2-adrenergic mechanisms. Antagonism of the β2-adrenoreceptor can impair cerebral vasodilation. We hypothesized that treatment with a highly β1-specific antagonist (nebivolol) would minimize the degree of cerebral hypoxia during hemodilution. Anesthetized rats were randomized to receive vehicle or nebivolol (1.25 or 2.5 mg/kg intravenously) prior to hemodilution. In vehicle-treated rats, hemodilution increased cardiac output (CO) and regional cerebral blood flow (rCBF) while microvascular brain PO2 (PBrO2) decreased. Both nebivolol doses reduced heart rate and attenuated the CO response to hemodilution. Only the higher dose of nebivolol attenuated the rCBF response to hemodilution and caused a further reduction in PBrO2. Brain hypoxic protein levels were only increased in the high dose nebivolol group. High dose nebivolol treatment resulted in drug levels near its affinity for the β2-adrenoreceptor supporting the hypothesis that cerebral perfusion is maintained by β2-dependent mechanisms during hemodilution.

Das EKG ist ein etabliertes und einfach durchzuführendes diagnostisches Routineverfahren. Belastungsuntersuchungen in denen das EKG beispielsweise Aufschluss über myokardiale Ischämien und Rhythmusstörungen geben kann, belegen den hohen diagnostischen Stellenwert des EKGs. Die Veränderungen der Parameter des EKGs sind charakteristisch und unterliegen dabei den unterschiedlichen physiologischen Bedingungen. Die vorliegende prospektive klinische Untersuchung beschäftigt sich mit der Fragestellung, welche physiologischen Bedingungen für diese Veränderungen ursächlich verantwortlich sind. Dazu wurden 10 männliche Probanden in 2 doppelten Stufen- und 2 Dauertests mit und ohne ß-Blockade untersucht. Es konnte festgestellt werden, dass in Ruhe und bei intensiver Belastung die ß-Blockade eine Wirkung hatte, was auf einen relevanten Einfluss des Sympathikus schließen lässt. Bei leichter und mittlerer Belastung und in der unmittelbaren Nachbelastungsphase waren hingegen keine Unterschiede in den Tests ohne und mit ß-Blockade festzustellen. Deshalb ist die Annahme plausibel, dass die Regulation der Herzfunktionen durch den Parasympathikus stattfindet, während der Sympathikus hier lediglich eine ergänzende Modulationsfunktion hat. Grundsätzlich unterstützt dies insgesamt die Theorie der zentralen Mitinnervation, die nach den vorliegenden Ergebnissen allerdings vorrangig in der Bedeutung des Parasympathikus und nachrangig in der des Sympathikus liegt.