Reutilização do dialisador e uso único: episódios de pirogenia e bacteremia / Reutilización del dializador y uso único: episodios de reacciones pirógenas y bacteriemias / Dialyzer reuse and single use: pyrogenesis and bacteremia episodes

Resumo Objetivos Comparar a reutilização do dialisador com o uso único deste material para marcadores bioquímicos, hematológicos, episódios de pirogenias e bacteremias. Métodos Estudo longitudinal com coleta de dados retrospectiva em prontuários de pacientes em hemodiálise, em hospital público universitário. A investigação foi conduzida seis meses com a reutilização do dialisador e seis meses com uso único. Os dados foram analisados no SPSS Versão 18.0. Para comparação das médias dos exames utilizou-se teste t pareado e Wilcoxon, episódios de pirogenia e bacteremia foram analisados pelo teste de Wilcoxon e Razão de Chances (RC) como medida de força de associação. Variáveis categóricas foram analisadas pelos testes de McNemar e Exato de Fisher. O estudo foi aprovado pelo Comitê de Ética e Pesquisa. Resultados Foram analisadas 5.508 sessões de hemodiálise de pacientes predominantemente masculinos 21(62%), média de idade 58(± 14) anos, hipertensos 14(41%), tempo médio de tratamento 6±3 anos. Durante uso único identificou-se redução da ureia pós diálise, creatinina, fósforo, ferritina, hematócrito e hemoglogina em relação ao reutilizado (p < 0,05) e 91% menos risco de pirogenia comparado a reutilização do dialisador (Razão de Chance= 0,091; IC 95%: 0,002-0,625). Não houve diferença significativa na ocorrência de bacteremias. Conclusão Os resultados sugerem maior remoção de biomarcadores bioquímicos e menos episódios de pirogenias quando o dialisador é uso único.ater removal of biochemical biomarkers and fewer pyrogenics episodes when the dialyzer is a single use.

Resumen Objetivos Comparar la reutilización del dializador con el uso único de este material en marcadores bioquímicos, hematológicos, episodios de reacciones pirógenas y bacteriemias. Métodos Estudio longitudinal con recolección de datos retrospectiva en historias clínicas de pacientes en hemodiálisis, en un hospital público universitario. La investigación fue conducida seis meses con la reutilización del dializador y seis meses con un único uso. Los datos fueron analizados en SPSS Versión 18.0. Para comparar los promedios de los análisis, se utilizó el Test-T pareado y prueba de Wilcoxon, los episodios de reacciones pirógenas y bacteriemia fueron analizados mediante la prueba de Wilcoxon y Razón de Momios (RM) como medida de fuerza de asociación. Las variables categóricas se analizaron con la prueba de McNemar y la prueba exacta de Fisher. El estudio fue aprobado por el Comité de Ética e Investigación. Resultados Se analizaron 5.508 sesiones de hemodiálisis de pacientes predominantemente masculinos 21 (62 %), promedio de edad 58 (±14) años, hipertensos 14 (41 %), tiempo promedio de tratamiento 6±3 años. Durante el uso único del dializador, se identificó una reducción de la urea posdiálisis, creatinina, fósforo, ferritina, hematocrito y hemoglobina respecto al dializador reutilizado (p < 0,05) y un 91 % menos de riesgo de reacción pirógena comparado con la reutilización del dializador (Razón de Momios = 0,091; IC 95 %: 0,002-0,625). No hubo diferencia significativa en episodios de bacteriemias. Conclusión Los resultados sugieren mayor eliminación de biomarcadores bioquímicos y menos episodios de reacciones pirógenas cuando el dializador se utiliza una única vez.

Abstract Objectives To compare dialyzer reuse with its single use for biochemical, hematological markers, pyrogenesis and bacteremia episodes. Methods A longitudinal study with retrospective data collection from medical records of patients on dialysis in a public university hospital. The investigation was conducted six months with dialyzer reuse and six months with single use. Data were analyzed using SPSS Version 18.0. To compare the tests means, paired t-test and Wilcoxon were used. Pyrogenesis and bacteremia episodes were analyzed using the Wilcoxon test and Odds Ratio (OR) as association strength measures. Categorical variables were analyzed using McNemar and Fisher's Exact tests. The study was approved by the hospital's Research Ethics Committee. Results Five thousand five hundred eight dialysis sessions of predominantly male patients were analyzed, 21 (62%), with mean age of 58 (± 14) years, hypertensive 14 (41%), with mean treatment time 6 ± 3 years. During single use, a reduction in urea after dialysis, creatinine, phosphorus, ferritin, hematocrit and hemoglogin was identified in relation to reuse (p<0.05) and 91% less risk of pyrogenesis compared to dialyzer reuse (Odds Ratio=0.091; 95% CI: 0.002-0.625). There was no significant difference in the occurrence of bacteremia. Conclusion The results suggest greater removal of biochemical biomarkers and fewer pyrogenics episodes when the dialyzer is a single use.

Monocyte Activation Test (MAT) as a possibility of replacement for the rabbit pyrogen test in hyperimmune sera

ABSTRACT The use of a commercial kit for the monocyte-activation test (MAT) was evaluated for assessing pyrogenic contamination of hyperimmune sera . Three batches of sera, two pyrogen free and one pyrogenic, were tested. Endotoxin spike recover indicated that sample dilutions from 1/2 to 1/10 are suitable. Kit transport and storage conditions were also evaluated, proving that an adequate cold chain must be assured to achieve good results. Furthermore, the commercial MAT kit seemed suitable to replace the rabbit pyrogen test (RPT) for pyrogen testing of hyperimmune sera, although further tests are needed to a full validation.

Toxicity studies in vivo and in vitro for sheep skin acellular dermal matrix / 中南大学学报(医学版)

To detect the toxic reaction degree for sheep acellular dermal matrix (ADM) in vivo or vitro by using hemolytic, pyrogen and cell-cytotoxic reaction experiments, respectively.
 Methods: Leach liquor of cross-linked and non-cross-linked sheep ADMs were set for cross-linked group and non-cross-linked group, respectively, with a positive control group (10 mL sterile water for injection in test tube) and a negative control group (10 mL 0.9% sodium chloride solution in test tube). The supernatants were obtained from each group and were measured for the absorbance. The hemolysis degree was calculated; 16 New-Zealand rabbits were selected and then divided into 4 groups, A, B, C and D group. The leach liquor of cross-linked and non-cross-linked sheep ADMs were injected into bodies of the 6 New-Zealand rabbits in the A and B groups, and then the body temperatures were measured in every half hour after injection, 6 times in total. The value of highest temperature among 6 measurements minus the normal temperature was the fever degree for the body temperature. Based on these fever degree, the criterion of biological pyrogen reaction for sheep ADM pyrogen experiment was evaluated; the mice fibroblasts were collected during logarithmic phase and were cultured in the nutrient medium containing sheep ADM leach liquor with different density. The absorbance was measured to evaluate relative growth rate for fibroblast.
 Results: The hemolysis degree for the group A and B are less than 5%. The summary of fever degree for New-Zealand rabbits were lower than 1.8 ℃. MTT experiment showed that the toxicity of 10%-90% or 100% leach liquor nutrient medium with sheep ADM for the mice fibroblast is at level 1 or level 2. There was no significant difference between leach liquor of cross-linked and non-cross-linked sheep ADMs (P>0.05). The effects on relative growth rate for mice fibroblasts were minor. 
 Conclusion: The hemolytic and pyrogen reactions for the sheep ADMs embedded in New-Zealand rabbit were within the evaluation criterion, and the effects on vitality and growth rate for the fibroblast were not significant.

Depyrogenation in key manufacturing processes of Reduning injection / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of removing bacterial endotoxin in the key processes of Reduning injection.</p><p><b>METHOD</b>The content of bacterial endotoxins was detected by kenitic-turbidimetry and the removal efficacy was studied before and after using 0.8% of activated carbon and ultrafiltration with molecular weight cut-off of 10 x 10(3).</p><p><b>RESULT</b>The adsorption rate of bacterial endotoxins was 78.7% by using activated carbon, while the removal efficacy of bacterial endotoxins was 99.6% with ultrafiltration membrane at cut-off molecular weight 10 x 10(3).</p><p><b>CONCLUSION</b>The key technology can effectively guarantee the safety of Reduning injection.</p>

Effect of affinity medium and solution conditions on endotoxin removal from protein solutions / 生物工程学报

Endotoxin removal is essential for the safety of biological products. To remove endotoxin efficiently, we used polymyxin B (PMB) affinity adsorbent to remove endotoxin from protein solutions by static adsorption. We studied the effects of spacer length and ligand density of the affinity adsorbent, pH, salt type and concentration, protein type and concentration, endotoxin concentration, and additive on endotoxin removal and protein recovery. Endotoxin content and protein concentration were determined by test and Lowry assay respectively. The results showed that PMB affinity adsorbent had high capacity, high adsorption speed, high removal efficiency and good reusability. In addition, ligand density, pH, salt concentration and the isoelectric point and hydrophobicity of protein all had remarkable influence on the endotoxin removal. Under the optimal conditions, the recoveries of hemoglobin, human serum albumin and lysozyme were 87.2%, 73.4% and 97.3%, respectively, and the corresponding endotoxin removal rates 99.8%, 97.9% and 99.7%, respectively. This study illustrated the effects of solution conditions on the efficiency of endotoxin removal and protein recovery, and would provide useful reference for the efficient removal of endotoxin from biological products.

Busca ativa de possíveis causas de pirogenia em pacientes submetidos a procedimentos coronários diagnósticos e terapêuticos / Active search of pyrogen reaction sources in patients undergoing diagnostic and therapeutic coronary procedures

Introdução: A reação pirogênica é desencadeada pela presença, na corrente sanguínea, de soluções contaminadas, infundidas no paciente, contendo endotoxinas ou produtos de degradação proteica. Apesar da baixa incidência, seu foco deve ser investigado e erradicado, pois essas ocorrências podem ser deletérias e refletem a qualidade do serviço prestado, já que a causa pode ser proveniente de fatores relacionados ao exame, às soluções utilizadas ou ao processo de esterilização. Método: Estudo prospectivo avaliando pacientes submetidos a procedimentos coronários percutâneos diagnósticos ou terapêuticos que desenvolveram reação pirogênica. Essa amostra foi comparada a um grupo controle de pacientes consecutivos que não apresentaram a referida intercorrência, sendo a possível causa pesquisada por meio do uso de um protocolo tipo check list...

Background: Pyrogen reactions are triggered by intravenous injection of fluids or medications contaminated by bacterial endotoxins. Despite its low incidence, it must be investigated and eliminated, as it may be harmful to the patient and reflects the quality of the catheterization laboratory. Methods: Prospective study to evaluate patients undergoing diagnostic or therapeutic percutaneous coronary procedures who develop pyrogen reactions. This group was compared with a historical cohort of patients undergoing invasive procedures with no pyrogen reactions. The possible causes of pyrogen reactions were established based on the use of a check-list protocol...

Effects of gypsum on the firing of pyrogen-treated thermosensitive neurons in PO/AH of cats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the possible central mechanism of antipyretic effects of Chinese medicine gypsum.</p><p><b>METHODS</b>Gypsum was injected after the fever model was established. The firing rate of thermosensitive neurons in preoptic-anterior hypothalamus(PO/AH) region was recorded by using extracellular microelectrode technique.</p><p><b>RESULTS</b>The injection of pyrogen evoked decrease in firing rate of the warm-sensitive neurons and increase in the cold-sensitive neurons in the region of PO/AH; the changes of the firing rate of pyrogen- treated warm-sensitive and cold-sensitive neurons could be reversed by the injection of gypsum.</p><p><b>CONCLUSION</b>The result may suggest that antipyretic action of gypsum is mediated by its influences on the thermosensitivity neurons in the region of PO/AH.</p>

Drug fever - A Hospital based study

To study the frequency, causative agents, symptomatology of drug fever in children. A hospital based descriptive study. The study was carried out from Jan 01,2005 to Dec 31,2005. All children examined by author were included, both in private and public sector hospitals at Hyderabad. Children 1 to 12 years of age with febrile illness of more than 10 days duration and prior use of drugs for at least 5-7 days were included in this study and were evaluated for having drug fever. 62 [0.72% of total 8560] febrile children, 32 of them males and 30 females, were diagnosed as having drug fever, with Cephalosporins being the common group responsible for causing fever in 33 [53.22%] followed by penicillins in 14 [22.60%], antituberculous in 12 [19.35%],Phenytoin in 2 [3.2%] and carbamezapine in 1 [1.61%].1] Drugs should be considered as a cause of fever of obscure origin. 2] Judicious use of drugs especially antibiotics can not be over emphasized

Comparative evaluation of pyrogens tests in pharmaceutical products

Realizou-se a comparação de metodologia para avaliação de pirogênios em produtos farmacêuticos. Otimizou-se o teste da hipertermia em coelhos elaborando a curva dose-resposta com o 2º Padrão Internacional de endotoxinas bacterianas, com base na qual determinou-se a concentração de 13,81 UE/mL por kg de peso corporal, necessária para produzir aumento de temperatura de 0,5ºC. Observou-se que o limite de 0,5ºC forneceu resultados comparáveis com as doses pirogênicas para o homem. Padronizou-se o teste do lisado de amebócitos do Limulus (LAL) com determinação do ponto final cromogênico e por geleificação, que foram utilizados para a avaliação de produtos farmacêuticos obtendo-se resultados concordantes. Avaliaram-se as respostas de reagentes LAL reativos e não-reativos a b-glicanos, observando diferenças que poderiam reprovar amostras com base em resultados falso-positivos. Executou-se o teste de interferências, validou-se o procedimento e estabeleceu-se a máxima diluição válida para produtos farmacêuticos sem especificações farmacopéicas. Os resultados enfatizam a importância e as limitações dos ensaios preconizados para avaliação da pureza e controle da qualidade de produtos farmacêuticos parenterais, contribuindo para aprimorar as metodologias existentes no contexto da redução e substituição dos modelos animais.

The hyperthermic effect of nitric oxide in central nervous system

The precise mechanism of set-point regulation in hypothalamus was not elucidated. Nitric oxide synthases (NOS) were detected in hypothalamus, however, the roles of NO in hypothalamus was not fully studied. So, we tested the effects of NO on body temperature because preoptic-anterior hypothalamus was known as the presumptive primary fever-producing site. NO donor sodium nitroprusside (SNP, 4 nmol, i.c.v.) elicited marked febrile response, and this febrile response was completely blocked by indomethacin (a cyclooxygenase inhibitor). But, ODQ (selective guanylate cyclase inhibitor, 50 microgram, i.c.v.) did not inhibit fever induced by SNP. The cyclic GMP analogue dibutyryl-cGMP (100 microgram, i.c.v.) induced significant pyreses, which is blocked by indomethacin. NG-nitro-L-arginine methyl ester (L-NAME, non selective NOS inhibitor) inhibited fever induced by interleukin-1 beta (IL-1 beta, 10 ng, i.c.v.), one of endogenous pyrogens. These results indicate that NO may have an important role, not related to stimulation of soluble guanylate cyclase, in the signal pathway of thermoregulation in hypothalamus.

Valoración de endotoxinas bacterianas en sueros antiofídicos de origen equino: optimización de métodos en el control de la calidad / Evaluation of bacterial endotoxins in equine antiophidic sera: quality control methods optimization

Se valoró la presencia de pirógenos en el antisuero contra venenos de serpientes de los genéros Bothrops, Crotalus y Lachesis elaborado por la planta de producción de sueros antiofídico del Instituto Nacional de Salud en Bogotá Colombia. Se evaluó materia prima, proceso y producto terminado utilizando las técnicas de pirógenos en conejos USP y limulus amebocito lisado (LAL). Los resultados por los dos métodos de análisis para los cinco lotes de materia prima fueron negativos a pirógenos y positivos para los ocho lotes analizados de producto terminado en los que se determinó por LAL niveles de endotoxina entre >13.87 UE/ml y > 24.7 UE/ml; superiores al permitido por la Farmacopea Americana USP XXIII, que fija un valor máximo de 1.67 UE/ml para este tipo de producto. Se estandarizó el uso de la técnica del LAL en el suero de origen equino utilizado como materia prima, el cual presenta inhibidores naturales para la técnica; mediante pretratamientos al plasma para la extracción de inhibidores aplicando diferente técnicas, con los siguientes resultados de mayor a menor capacidad de detección de endotoxina: técnica de sulfato de amonio hasta 0.125 UE/ml; técnica de dilución calor 0.21 UE/ml; técnica de cloroformo dilución 0.42 UE/ml y la técnica con ajuste de pH no detécto endotoxina en la muestra. Se valoró la potencialización de las muestras sometidas a extracción, con la adición de iones mono y divalentes. Se ensayaron los iones NaCl, MnCl, CaCl subíndice 2 y MgCl subíndice 2, en concentraciones de 0.02, 0.05, 0.08M. El mejor resultado se obtuvo con los iones MgCl subíndice 2 y CaCl subíndice 2 a 0.05M, asociado a la técnica de extracción de cloroformo y dilución, en la que aumentó la detección de endotoxina de 0.42 a 0.125 UE/ml con MgCl subíndice 2 y de 0.42 a 0.35 UE/ml con CaCl subíndice 2. Se concluyó que la técnica del LAL ajustada con la técnica sulfato de amonio y calor y la adición MgCL subíndice 2 a 0.05M, sirve como prueba de control para ser aplicada a la materia prima. En el estudio se demostró que durante el proceso de purificación de las inmunoglobulinas, el producto se contamina con endotoxinas bacterianas; fueron responsables de esta contaminación 11.44 por ciento de los materiales, 51.17 por ciento de los equipos y 2.35 por ciento de los reactivos utilizados. Se detecto endotoxinas en 64.96 por ciento de las mustras analizadas. La aplicación del método del LAL en la línea de proceso permitió...

Preclinical evaluation of prototype products

Preclinical evaluation of medical devices (prototype products) offers the opportunity to investigate and study the intended use of device materials. Preclinical evaluation programs are designed to determine the efficacy, safety, and biocompatibility of biomaterials, prostheses, and medical devices. The purpose of safety testing is to determine if a material presents potential harm to the human; it evaluates the interaction of the material with the in vivo environment and determines the effect of the host on the implant. Preclinical evaluation is the determination of the ability of the prototype product to perform with appropriate host response in a specific application, considered from the perspective of human clinical use. Therefore, preclinical data should include materials science and engineering, biology, biochemistry, medicine, host reactions and their evaluation, the testing of biomaterials, and the degradation of materials in a biological environment.

Peróxido de hidrogênio como agente despirogenizante de componentes para produtos médicos-hospitalares / Hydrogen peroxide as depyrogenation agent for medical devices componentes

A atual busca de solventes alternativos aos fluorados, frente ao problema de depleçäo de ozônio da estratosfera, obriga a desenvolvimentos de processos aplicáveis à fabricaçäo de produtos médico-hospitalares. Frente ao desafio, e considerando a água estar sendo opçäo de escolha de outros segmentos industriais, preocupa a rápida proliferaçäo microbiana na mesma, tornando-se fonte potencial de endotoxinas. Tal risco incompatibiliza-se por exemplo, com a produçäo de itens destinados ao emprego em procedimentos cirúrgicos da área cardiovascular. Desta forma foi realizada pesquisa com o objetivo de investigar possibilidade de emprego da água como agente de limpeza de componentes para tais produtos, desde que incorporada de peróxido de hidrogêncio. Trabalhou-se inoculando água e soluçöes de peróxido com níveis de 0,1, 0,25, 0,5 e 1,0 UE/ml; obteve-se a confirmaçäo de efetividade de açäo a concentraçäo de 5 por cento de peróxido de hidrogênio, através de determinaçäo analítica pelo método "in vitro". Investigou-se, em peças injetadas em policarbonato, destinadas a fabricaçäo de oxigenadores e reservatórios sanguíneos, inoculadas com endotoxina, a efetivade no uso do peróxido. Os resultados permitem concluir pela possibilidade de sucesso do processo proposto, seja pelo aspecto biológico ou pela remoçäo de sujidades

Plasma kallikrein clearance by the liver: a review

1. The liver is the main organ clearing both plasma and tissue kallikereins from the circulation. Hepatocytes are responsible for the internalization of rat plasma kallikrein (RPK) and liver cell is located on its heavy chain which is not exposed on prokallikrein. An S-type lectin accounts for the receptor-mediated endocytosis of TPK. 2. These properties of the liver are affected by pathological situations, particularly the acute-phase response to inflammation, in which the kallikrein-kinin system plays a major role. The hepatic clearance of the alfa2-macroglobulin-plasma kallikrein complex is less efficient than the clearance of the free enzyme