Реферат
Radiolabeling cidofovir with technetium-99m (99mTc-CDV) is an innovative procedure that enables real-time monitoring of the drug. Essays were performed in vitro, showing high radiolabel stability within 24 h. Blood clearance, biodistribution studies, and scintigraphic images were performed in healthy mice in order to evaluate the profile of the drug in vivo. 99mTc-CDV showed biphasic blood circulation time and significant kidney uptake, indicating that 99mTc-CDV is preferentially eliminated by the renal route. Bones also showed important uptake throughout the experiment. In summary, cidofovir was successfully labeled with technetium-99m and might be used in further studies to track the drug.
Тема - темы
Animals , Male , Female , Mice , In Vitro Techniques , Technetium/pharmacology , Cidofovir/pharmacology , Track and Field/classification , Blood Circulation Time/adverse effects , Pharmaceutical Preparations/analysis , Kidney , MethodsРеферат
ABSTRACT Objective: to evaluate the morphology and function of autogenous splenic tissue implanted in the greater omentum, 24 hours after storage in Ringer-lactate solution. Methods: we divided 35 male rats into seven groups (n=5): Group 1: no splenectomy; Group 2: total splenectomy without implant; Group 3: total splenectomy and immediate autogenous implant; Group 4: total splenectomy, preservation of the spleen in Ringer-lactate at room temperature, then sliced and implanted; Group 5: total splenectomy, spleen sliced and preserved in Ringer-lactate at room temperature before implantation; Group 6: total splenectomy with preservation of the spleen in Ringer-lactate at 4°C and then sliced and implanted; Group 7: total splenectomy and the spleen sliced for preservation in Ringer-lactate at 4°C before implantation. After 90 days, we performed scintigraphic studies with Tc99m-colloidal tin (liver, lung, spleen or implant and clot), haematological exams (erythrogram, leucometry, platelets), biochemical dosages (protein electrophoresis) and anatomopathological studies. Results: regeneration of autogenous splenic implants occurred in the animals of the groups with preservation of the spleen at 4ºC. The uptake of colloidal tin was higher in groups 1, 3, 6 and 7 compared with the others. There was no difference in hematimetric values in the seven groups. Protein electrophoresis showed a decrease in the gamma fraction in the group of splenectomized animals in relation to the operated groups. Conclusion: the splenic tissue preserved in Ringer-lactate solution at 4ºC maintains its morphological structure and allows functional recovery after being implanted on the greater omentum.
RESUMO Objetivo: avaliar morfologia e função de tecido esplênico autógeno, implantado no omento maior, 24 horas após conservação em solução de Ringer-lactato. Métodos: foram estudados 35 ratos machos, distribuídos em sete grupos (n=5): Grupo 1: sem esplenectomia; Grupo 2: esplenectomia total sem implante; Grupo 3: esplenectomia total e implante autógeno imediato; Grupo 4: esplenectomia total, preservação do baço em Ringer-lactato à temperatura ambiente, em seguida, fatiado e implantado; Grupo 5: esplenectomia total, baço fatiado e preservado em Ringer-lactato à temperatura ambiente antes de ser implantado; Grupo 6: esplenectomia total com preservação do baço em Ringer-lactato a 4°C e, em seguida, fatiado e implantado; Grupo 7: esplenectomia total e baço fatiado, para preservação em Ringer-lactato a 4°C antes de ser implantado. Após 90 dias, realizaram-se estudos cintilográficos com estanho coloidal-Tc99m (fígado, pulmão, baço ou implante e coágulo), hematológicos (eritrograma, leucometria, plaquetas), bioquímicos (eletroforese de proteínas) e anatomopatológicos. Resultados: ocorreu regeneração dos implantes esplênicos autógenos nos animais dos grupos com preservação do baço a 4ºC. A captação de estanho coloidal foi superior nos grupos 1, 3, 6 e 7 em relação aos demais. Não houve diferença nos valores hematimétricos nos sete grupos. A eletroforese de proteínas mostrou diminuição da fração gama no grupo de animais esplenectomizados em relação aos grupos operados. Conclusão: o tecido esplênico conservado em solução de Ringer-lactato à temperatura de 4ºC mantém sua estrutura morfológica e permite a recuperação funcional após ser implantado sobre o omento maior.
Тема - темы
Animals , Male , Rats , Spleen/transplantation , Organ Preservation Solutions , Isotonic Solutions , Spleen/anatomy & histology , Spleen/physiology , Random Allocation , Rats, Sprague-Dawley , Ringer's LactateРеферат
Abstract Purpose: To compare the influence of two metallic implants in the diagnosis of periprosthetic infection using 99m technetium-labeled ceftizoxime. Methods: Twenty rats were randomly divided into four groups, which received sterile and contaminated titanium and stainless steel implants. After 3 weeks, scintilographic images were obtained using a gamma chamber. Radioactivity counts were obtained for the region of interest (ROI) on the operated and non-operated paws. Results: Groups A, B, and C showed homogenous distribution of the radiopharmaceutical. Hyper uptake was observed in the operated paw from group D. The ROI target count was higher in the two groups with stainless steel implants. Among the control groups, the count was higher in the stainless steel group. Furthermore, among the contaminated groups, the uptake was higher in the stainless steel group, with a significant difference. The target: non-target ratio was significantly lower in the control and contaminated groups with both titanium and stainless steel, but the comparison between control groups and contaminated groups was only significant in the former. The cpm/g observed after a decay of 48h showed statistically significant differences between groups. Conclusion: Different biomaterials used in implants have an influence on the results of scintigraphy with 99mTc-CFT.
Тема - темы
Animals , Stainless Steel/radiation effects , Titanium/radiation effects , Ceftizoxime/analogs & derivatives , Organotechnetium Compounds , Prosthesis-Related Infections/diagnostic imaging , Radiopharmaceuticals , Radioactivity , Reference Values , Stainless Steel/chemistry , Time Factors , Titanium/chemistry , Biocompatible Materials/chemistry , Random Allocation , Radionuclide Imaging , Reproducibility of Results , Prosthesis-Related Infections/microbiology , Rats, WistarРеферат
Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with 99mTc. Methods Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with 99mTc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl2. 2H2O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values 0.05). Results Both LyeTx I derivatives were suitably synthesized and purified, as shown by RP-HPLC and MALDI-ToF-MS analysis. The microbiological test showed that HYNIC-LyeTx I (N-terminal modification) did not inhibit bacterial growth, whereas LyeTx I-K-HYNIC (C-terminal modification) showed a MIC of 5.05 mol.L1 (S. aureus) and 10.10 mol.L1 (E. coli). Thus, only the latter was radiolabeled with 99mTc. The radiochemical purity analysis of LyeTx I-K-HYNIC-99mTc showed that the optimal radiolabeling conditions (10 g of LyeTx I-K-HYNIC; 250 g of SnCl2. 2H2O; pH = 7; heating for 15 min) yielded a radiochemical purity of 87 ± 1 % (n= 3). However, RP-HPLC data suggested 99mTc transchelation from LyeTx I-K-HYNIC to the co-ligands (tricine and EDDA). Conclusions The binding of HYNIC to the N-terminal portion of LyeTx I seems to affect its activity against bacteria. Nevertheless, the radiolabeling of the C-terminal derivative, LyeTx I-K-HYNIC, must be better investigated to optimize the radiolabeled compound, in order to use it as a specific imaging agent to distinguish septic and aseptic inflammation.
Тема - темы
Anti-Infective Agents/analysis , Anti-Infective Agents/chemistry , Intercellular Signaling Peptides and Proteins/analysisРеферат
Background Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with 99mTc. Methods Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with 99mTc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl2. 2H2O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values < 0.05). Results Both LyeTx I derivatives were suitably synthesized and purified, as shown by RP-HPLC and MALDI-ToF-MS analysis. The microbiological test showed that HYNIC-LyeTx I (N-terminal modification) did not inhibit bacterial growth, whereas LyeTx I-K-HYNIC (C-terminal modification) showed a MIC of 5.05 μmol.L−1 (S. aureus) and 10.10 μmol.L−1 (E. coli). Thus, only the latter was radiolabeled with 99mTc. The radiochemical purity analysis of LyeTx I-K-HYNIC-99mTc showed that the optimal radiolabeling conditions (10 μg of LyeTx I-K-HYNIC; 250 μg of SnCl2. 2H2O; pH = 7; heating for 15 min) yielded a radiochemical purity of 87 ± 1 % (n= 3). However, RP-HPLC data suggested 99mTc transchelation from LyeTx I-K-HYNIC to the co-ligands (tricine and EDDA). Conclusions The binding of HYNIC to the N-terminal portion of LyeTx I seems to affect its activity against bacteria. Nevertheless, the radiolabeling of the C-terminal derivative, LyeTx I-K-HYNIC, must be better investigated to optimize the radiolabeled compound, in order to use it as a specific imaging agent to distinguish septic and aseptic inflammation.(AU)
Тема - темы
Peptides , Chelating Agents , Anti-Infective Agents , Technetium/analysisРеферат
PURPOSE:To evaluate whether scintigraphy with technetium-99m-labeled ceftizoxime (99mTc-CFT) can differentiate mediastinitis from aseptic inflammation associated with sternotomy.METHODS:Twenty female Wistar rats were randomly distributed into four groups: S (control) -partial upper median sternotomy with no treatment; SW (control) - sternotomy and treatment of sternal wounds with bone wax; SB - sternotomy and infection with Staphylococcus aureus; SWB - sternotomy with bone wax treatment and bacterial infection. Scintigraphy with 99mTc-CFT was performed eight days after surgery and images were collected 210 and 360 min after infusion of the radiopharmaceutical.RESULTS: No animals exhibited clinical signs of wound infection at the end of the experiment, although histological data verified acute inflammatory response in those experimentally infected with bacteria. Scintigraphic images revealed that tropism of 99mTc-CFT to infected sternums was greater than to their non-infected counterparts. Mean counts of radioactivity in bacteria-infected sternal regions (SB and SWB) were significantly higher (p = 0.0007) than those of the respective controls (S and SW).CONCLUSION:Scintigraphy with technetium-99m-labeled ceftizoxime is a method that can potentially detect infection post sternotomy and differentiate from aseptic inflammation in animals experimentally inoculated with S. aureus.
Тема - темы
Animals , Female , Ceftizoxime/analogs & derivatives , Mediastinitis , Organotechnetium Compounds , Sternotomy/adverse effects , Sternum , Surgical Wound Infection , Disease Models, Animal , Random Allocation , Rats, Wistar , Reproducibility of Results , Staphylococcus aureus , Staphylococcal Infections , Sternum/microbiology , Surgical Wound Infection/microbiologyРеферат
Leishmaniasis is one of the six major tropical diseases targeted by the World Health Organization. It is a life-threatening disease of medical, social and economic importance in endemic areas. No vaccine is yet available for human use, and chemotherapy presents several problems. Pentavalent antimonials have been the drugs of choice to treat the disease for more than six decades; however, they exhibit high toxicity and are not indicated for children, for pregnant or breastfeeding women or for chronically ill patients. Amphotericin B (AmpB) is a second-line drug, and although it has been increasingly used to treat visceral leishmaniasis (VL), its clinical use has been hampered due to its high toxicity. This review focuses on the development and in vivo usage of new delivery systems for AmpB that aim to decrease its toxicity without altering its therapeutic efficacy. These new formulations, when adjusted with regard to their production costs, may be considered new drug delivery systems that promise to improve the treatment of leishmaniasis, by reducing the side effects and the number of doses while permitting a satisfactory cost-benefit ratio.
Тема - темы
Animals , Dogs , Humans , Amphotericin B/administration & dosage , Antiprotozoal Agents/administration & dosage , Drug Delivery Systems , Leishmaniasis, Visceral/drug therapy , Chemistry, Pharmaceutical , Nanoparticles , NanotechnologyРеферат
OBJECTIVE: To verify the effectiveness of coconut water in preserving tissues for transplant. METHODS: Fifty male Wistar rats were randomly distributed in five groups, according to the following preservation solutions for tissue grafts: Group 1: Lactated Ringer; Group 2: Belzer solution; Group 3: mature coconut water; Group 4: green coconut water; Group 5: modified coconut water. In Group 5, the green coconut water has been modified like the Belzer solution. From each animal we harvasted the spleen, ovaries and skin of the back segment. These tissues were preserved for six hours in one of the solutions. Then, the grafts were reimplanted. The recovery of the function of the implanted tissues was assessed 90 days after surgery, by splenic scintigraphy and blood exame. The implanted tissues were collected for histopathological examination. RESULTS: The serum levels did not differ among groups, except for the animals in Group 5, which showed higher levels of IgG than Group 1, and differences in relation to FSH between groups 1 and 2 (p <0.001), 4 and 2 (p = 0.03) and 5 and 2 (p = 0.01). The splenic scintigraphy was not different between groups. The ovarian tissue was better preserved in mature coconut water (p <0.007). CONCLUSION: the coconut water-based solutions preserves spleen, ovary, and rat skin for six hours, maintaining their normal function.
OBJETIVO: Verificar a eficácia da água de coco na preservação de tecidos para transplante. MÉTODOS: cinquenta ratas Wistar foram distribuídas aleatoriamente em cinco grupos, de acordo com as seguintes soluções de preservação para enxertos teciduais: Grupo 1- Ringer lactato, Grupo 2- Solução de Belzer, Grupo 3- Água de coco maduro, Grupo 4- Água de coco verde, Grupo 5- Água de coco modificada. No Grupo 5, a água de coco verde foi modificada à semelhança da solução de Belzer. De cada animal, retirou-se o baço, os ovários e um segmento de pele do dorso. Esses tecidos foram preservados durante seis horas em uma das soluções. Em seguida, os enxertos foram reimplantados. A recuperação da função dos tecidos implantados foi avaliada 90 dias após a cirurgia, por meio de cintilografia esplênica, exames de sangue. Os tecidos implantados foram coletados para estudo anatomopatológico. RESULTADOS: as dosagens séricas não apresentaram diferença entre os cinco grupos, exceto pelos animais do Grupo 5, que apresentaram valores mais elevados de IgG do que o Grupo 1,e pelas diferenças em relação ao FSH entre os grupos 1 e 2 (p<0,001), 4 e 2 (p=0,03), 5 e 2 (p=0,01). A cintilografia esplênica não foi diferente entre os grupos. O tecido ovariano foi melhor preservado em água de coco maduro (p<0,007). CONCLUSÃO: as soluções à base de água de coco preservam baço, ovário e pele de rato durante seis horas, mantendo sua função normal.
Тема - темы
Humans , Cocos , Organ Preservation Solutions , Ovary , Skin , Spleen , TransplantationРеферат
Objective: To evaluate the splenic parenchymal blood distribution through scintigraphic study. Methods: Thirty Wistar rats were randomly divided into six groups (n = 5). Group 1 (spleen - 30 minutes) and Group 2 (spleen - 90 minutes) underwent laparotomy with direction of blood flow to the spleen by ligature of the aorta near the iliac bifurcation and splanchnic vessels, keeping blood flow only in the splenic artery; Group 3 (spleen and stomach - 30 minutes) and Group 4 (spleen and stomach - 90 minutes) underwent laparotomy with direction of blood flow to the spleen and stomach by ligature of the aorta near the iliac bifurcation and splanchnic vessels, maintaining the flow through the splenic, gastric and splenogastric vessels; Group 5 (control - 30 minutes) and Group 6 (control - 90 minutes) underwent laparotomy and ligation of the aorta near the iliac bifurcation, keeping the flow to the abdominal organs. After arterial ligation, the animals received an injection of 0.2 ml of sodium pertechnetate in the aorta. Scintigraphic images were taken and the animals had their spleens removed for radioactivity counting with an automatic counter device. Results: There was no difference in the amounts of radiation from the spleen between groups, indicating retention of the radioisotope by the spleen, even after the period of 90 minutes. Conclusion: The blood flow through the spleen is not continuous. The blood diffuses through the splenic parenchyma and its venous drainage is slow, not following a predictable sequence. .
Objetivo: avaliar a distribuição sanguínea vasculoparenquimatosa do baço, por meio de estudo cintilográfico. Métodos: trinta ratos da raça Wistar foram distribuídos aleatoriamente em seis grupos (n=5). Grupo 1 (baço - 30 minutos) e Grupo 2 (baço - 90 minutos): submetidos à laparotomia com direcionamento do fluxo sanguíneo para o baço, por meio de ligadura da aorta próxima à bifurcação das ilíacas e dos vasos esplâncnicos, mantendo apenas a artéria esplênica; Grupo 3 (baço e estômago - 30 minutos) e Grupo 4 (baço e estômago - 90 minutos): submetidos à laparotomia com direcionamento do fluxo sanguíneo para baço e estômago, por meio de ligadura da aorta próxima da bifurcação das ilíacas e dos vasos esplâncnicos, com manutenção do fluxo pelas artérias esplênica, gástrica e vasos esplenogástricos; Grupo 5 (controle - 30 minutos) e Grupo 6 (controle - 90 minutos): submetidos à laparotomia e ligadura da aorta próxima à bifurcação das ilíacas, mantendo o fluxo para os órgãos abdominais. Após as ligaduras arteriais, os animais receberam injeção de 0,2ml de pertecnetato de sódio na aorta. Foram realizadas imagens cintilográficas, e os animais tiveram o baço retirado para contagem radioativa em aparelho contador automático. Resultados: não houve diferença nos valores de radiação do baço entre os grupos, indicando retenção do radioisótopo pelo baço, mesmo após o período de 90 minutos. Conclusão: o fluxo sanguíneo através do baço não é contínuo. O sangue difunde-se pelo parênquima esplênico e sua drenagem venosa é lenta, não seguindo sequência previsível. .
Тема - темы
Animals , Female , Rats , Regional Blood Flow , Spleen/blood supply , Random Allocation , Radionuclide Imaging , Rats, WistarРеферат
PURPOSE: To evaluate the effectiveness of the use of the povidone-iodine (PVI) added to the liquid of wash of the peritoneal cavity in the reduction of bacterial absorption and in the remainder non-phagocyted bacteria in the circulating blood of rat. METHODS: Thirty four Wistar females rats were used, distributed in the following groups: A (n=10), non-treated; B (n=9), wash of the peritoneal cavity with solution of PVI to 1 percent in saline solution; C (n=15), wash of the cavity with saline solution. After anesthesia, it was made intraperitoneal infusion of solution of Escherichia coli labeled with 99mTc containing 10(8) CFU/ml. After 40 minutes, it was made the treatment, in the group A, manipulation of the viscera; in the group B, irrigation of the peritoneal cavity with warm solution of 1 percent PVPI to 37,5ºC, and in the group C irrigation with warm saline (37,5ºC). After 15 minutes of the treatment, blood samples and fragments of liver, spleen and lung was obtained for count of the radioactivity, and animals killed by abdominal aorta section. There were determined the bacterial absorption index and the remainder index in the bloodstream. RESULTS: Of the total of bacteria infused in the peritoneum, there was absorption of 0,92 percent (0,14 percent to 2,13 percent) in the animals of the group A (controls), 0,49 percent (0,18 percent to 0,71 percent) after use of topical PVPI (group B) and 0,80 percent (0,04 percent to 3,8 percent) after wash with saline solution (group C). There was significant reduction of the absorption when compared the treated animals with PVPI and the controls (p=0,003). Of the total of bacteria absorbed for the circulatory current, the percentile amount of bacteria non-phagocyted in the outlying blood was of 2,9 percent (1,1 percent to 17,7 percent) in the control group, 15,2 percent (8,3 percent to 21,4 percent) in those treated with PVPI (group B) and 6,9 percent (0,8 percent to 29,7 percent) after wash...
OBJETIVO: Avaliar a eficácia do uso do polivinilpirrolidona-iodo (PVPI) acrescido ao líquido de lavagem da cavidade peritoneal na redução da absorção bacteriana e no remanescente bacteriano não fagocitado no sangue periférico de ratos. MÉTODOS: Estudou-se 34 ratos Wistar fêmeas, distribuídos aleatoriamente nos seguintes grupos: controle (n=10), nenhum tratamento; PVPI (n=9), lavagem da cavidade peritoneal com solução de PVPI a 10 por cento em solução salina; salina (n=15), lavagem da cavidade com solução salina. Após anestesia, fez-se inoculação intraperitoneal de solução de Escherichia coli marcadas com 99mTc contendo 10(8) UFC/ml. Após 40 minutos, realizou-se o tratamento que foi, no grupo controle, manipulação das vísceras; no grupo PVPI, irrigação da cavidade peritoneal com solução de PVPI aquecido a 37,5ºC na concentração de 1 por cento, e no grupo salina irrigação com solução salina aquecida a 37,5ºC. Após 15 minutos do tratamento, os animais foram mortos por secção da aorta abdominal e colhidas amostras do sangue, do fígado, do baço e do pulmão para contagem da radioatividade. Foram determinados o índice de absorção bacteriano e o índice de remanescente no sangue periférico. RESULTADOS: Do total de bactérias inoculadas no peritôneo, houve absorção de 0,92 por cento (0,14 por cento a 2,13 por cento) nos animais do grupo controle, 0,49 por cento (0,18 por cento a 0,71 por cento) após uso do PVPI tópico e 0,80 por cento (0,04 por cento a 3,8 por cento) após lavagem com solução salina. Houve redução significativa da absorção quando comparados os animais tratados com o PVPI e os controles não tratados (p=0,03). Do total de bactérias absorvidas para a corrente circulatória, o percentual de bactérias não fagocitadas presentes no sangue periférico foi de 2,9 por cento (1,1 por cento a 17,7 por cento) nos animais controle 15,2 por cento (8,3 por cento a 21,4 por cento) naqueles tratados com PVPI e 6,9 por cento (0,8 por cento a 29,7 por...
Тема - темы
Animals , Female , Rats , Anti-Infective Agents, Local/therapeutic use , Escherichia coli Infections/drug therapy , Peritoneal Lavage , Peritonitis/drug therapy , Povidone-Iodine/therapeutic use , Disease Models, Animal , Drug Evaluation, Preclinical , Macrophages, Peritoneal , Peritoneal Cavity , Phagocytosis , Peritonitis/microbiology , Rats, Wistar , SolutionsРеферат
The diagnosis of inflammatory and infectious processes is an important goal in medicine. The use of radiopharmaceuticals for identification of inflammation and infection foci has received considerable attention. The aim of this work was to evaluate the uptake and the imaging potential of stealth pH-sensitive liposomes radiolabelled with 99mTechnetium (99mTc) to identify infection sites in mice. The liposomes containing glutathione were labeled with 99mTc-Hexamethylpropyleneamine oxime (HMPAO) complex. The 99mTc-labeled stealth pH-sensitive liposomes (99mTc-SpHL) were injected in mice bearing infection in the right thigh muscle induced by Staphylococcus aureus. Biodistribution studies and scintigraphic imaging were performed at different times after injection of radiopharmaceutical. The 99mTc-SpHL was significantly uptaken by abscess when compared to the respective control. The abscess was visualized as early as 0.5 hours after injection of 99mTc-SpHL becoming more prominent with the time. These results indicate that 99mTc-SpHL is a promising radiopharmaceutical for visualizing infection foci in patients.
O diagnóstico de processos inflamatórios e infecciosos é um objetivo importante em medicina. O uso de radiofármacos para identificação de focos de inflamação e infecção tem recebido considerável atenção. O objetivo deste trabalho foi avaliar a captação e o potencial de imagem de lipossomas pH-sensíveis furtivos radiomarcados com 99mTecnécio (99mTc) para identificar sítios de infecção em camundongos. Os lipossomas contendo glutationa foram marcados com o complexo 99mTc-hexametilpropilenoamina oxima (HMPAO). Os lipossomas pH-sensíveis furtivos marcados com 99mTc (99mTc-LpHS) foram injetados em camundongos com infecção induzida por Staphylococcus aureus no músculo da coxa direita. Estudos de biodistribuição e imagem cintilográfica foram realizados em diferentes tempos após injeção do radiofármaco. Os 99mTc-LpHS foram captados significativamente pelo abscesso quando comparado ao respectivo controle. O abscesso foi visualizado rapidamente (0,5 horas) após injeção do 99mTc-LpHS tornando-se mais evidenciado com o tempo. Estes resultados indicam que 99mTc-LpHS é um promissor radiofármaco para identificação de focos inflamatórios e infecciosos em pacientes.
Реферат
OBJETIVO: O objetivo deste estudo foi identificar processos inflamatórios na articulação temporomandibular empregando leucócitos autólogos marcados com tecnécio-99m hexametilpropilenoaminooxima (99mTc-HMPAO). MATERIAIS E MÉTODOS: Foi utilizado um modelo experimental de indução de artrite na articulação temporomandibular de dez coelhos machos da raça Nova Zelândia, por meio da injeção intra-articular de ovalbumina na articulação temporomandibular esquerda de cada animal. Para controle, na articulação contralateral foi injetada solução salina. Após a marcação dos leucócitos com 99mTc-HMPAO e injeção endovenosa deste complexo nos coelhos, imagens cintilográficas foram obtidas. RESULTADOS: Observou-se captação aumentada dos 99mTc-HMPAO-leucócitos na articulação temporomandibular esquerda quando comparada à direita. A análise estatística foi realizada utilizando-se o teste não-paramétrico de Wilcoxon. Houve diferença estatisticamente significativa dos valores das contagens por minuto de radioatividade, relativos à articulação inflamada quando comparados aos valores obtidos na articulação contralateral (p = 0,0073). CONCLUSÃO: O método empregando leucócitos autólogos marcados com 99mTc-HMPAO é capaz de identificar focos inflamatórios de forma precoce e precisa, o que poderá contribuir na conduta terapêutica dos pacientes, antes que alterações estruturais sejam instaladas.
OBJECTIVE: The present study was aimed at identifying temporomandibular joint inflammatory processes employing technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO)-labelled autonomous leukocytes. MATERIALS AND METHODS: We have utilized an experimental model of arthritis induction in ten adult male New Zealand rabbits by means of ovalbumin intra-articular injection into each left temporomandibular joint. For control purposes, saline solution was injected. After leukocytes radiolabelling with 99mTc-HMPAO and injection into rabbits, scintigraphic images were obtained. RESULTS: A higher 99mTcHMPAO-leukocytes uptake was observed in left temporomandibular joint in comparison with the contralateral joint. Wilcoxon non-parametric test was applied for statistical analysis. There was a statistically significant difference between counts of radioactivity per minute in the inflammed joint and the contralateral one (p = 0.0073). CONCLUSION: The method employing 99mTc-HMPAO-labelled autologous leukocytes allows an early and accurate detection of inflammatory processes, contributing to the adoption of a therapeutic conduct for patients before structural alterations have occurred.
Тема - темы
Animals , Male , Rabbits , Arthritis/diagnosis , Technetium , Temporomandibular Joint Disorders , Temporomandibular Joint Disorders/chemically induced , TechnetiumРеферат
Clinical images are worthwhile in Health Sciences and their analysis and correct interpretation aid the professionals,such as physicians, physiotherapists and occupational therapists, to make decisions and take subsequent therapeutic and/or rehabilitation measures. Other factors, besides the state of the disease, may interfere and affect the bioavailability of the radiopharmaceuticals (radiobiocomplexes) and the quality of the SPECT and PET images. Furthermore, the labeling of some of these radiobiocomplexes, such as plasma proteins, white blood cells and red blood cells, with 99mT, can also be modified. These factors include drugs (synthetic and natural) and dietary conditions, as well as some medical procedures (invasive or non-invasive), such as radiation therapy, surgical procedures, prostheses, cardioversion, intubation, chemoperfusion, external massage, immunotherapy, blood transfusion and hemodialysis. In conclusion, the knowledge about these factors capable of interfering with the bioavailability of the radiobiocomplexes is worthwhile for secure diagnosis. Moreover, the development of biological models to study these phenomena is highly relevant and desirable.
Imagens clínicas são valiosas em Ciências da Saúde e a análise e a interpretação correta das mesmas auxiliam os profissionais, como médico, fisioterapeuta, terapeuta ocupacional, na tomada de decisões e subseqüentes ações terapêuticas e/ou de reabilitação. Além das doenças outros fatores podem interferir e afetar a biodisponibilidade dos radiofármacos (radiobiocomplexos) e a qualidade das imagens (SPECT e PET). Além disso, a marcação de alguns desses radiobiocomplexos com Tc-99m, como proteínas plasmáticas, leucócitos e hemácias, também pode ser modificada. Entre esses fatores, estão drogas (sintéticas e naturais) e condições alimentares, assim como alguns procedimentos médicos (invasivos e não invasivos), como a radioterapia, processos cirúrgicos, próteses, cardioversão, intubação, quimioperfusão, massagem externa, imunoterapia, transfusão sanguínea e hemodiálise. Em conclusão, o conhecimento sobre esses efeitos capazes de interferir na biodisponibilidade de radiobiocomplexos é altamente relevante para diagnósticos precisos. Além disso, o desenvolvimento de modelos biológicos para estudar esses fenômenos é de elevada importância e desejável.
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Infections and endotoxemia continue to be the principal causes of morbidity and mortality of patients with obstructions of the bile duct. The objective of the present work was the investigation of the phagocitary capacity of the mononuclear system in an experimental model of obstructive jaundice utilizing Tc-99m E.coli. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were significantly higher in jaundiced rats than in the control animals (p < 0.001). The liver of the jaundiced animals presented a significant reduction in Tc-99m E.coli uptake when compared to the controls (p < 0.001). The data also showed that there was a significant increase in the uptake of Tc-99m E.coli by the lungs of jaundiced rats (p < 0.01). The histological analyses of the liver of jaundiced rats showed an intense and diffuse proliferation of the bile ducts and an intensified polyploidy of the hepatocytes (mean volume = 843 µm³), but no significant alterations were observed in the lungs of either group. This dates could contribute to a better understanding of the mechanisms involved in cases of bacteremia, renal failure and pulmonary dysfunction observed in clinical analyses of obstructive jaundice.
Nos pacientes com obstrução do ducto biliar, as infecções e a endotoxemia continuam sendo uma das principais causas de morbidade e mortalidade. O objetivo desse trabalho foi investigar a capacidade fagocitária do sistema mononuclear, em um modelo experimental de icterícia obstrutiva, utilizando Tc-99m E.coli. Os níveis de aspartato aminotransferase (AST), alanina aminotransferase (ALT) e fosfatase alcalina (PAL) nos ratos com ligadura do ducto biliar comum (CBD) encontram-se significativamente mais elevados do que nos ratos sham. (p < 0.001). O fígado dos animais ictéricos apresentou uma significativa redução na captação da Tc-99m E.coli quando comparado com o controle. Os dados mostraram também, que houve um aumento significativo na captação da Tc-99m E.coli pelo pulmão dos ratos ictéricos (p < 0.01). O exame histológico dos cortes de fígado dos animais ictéricos apresentou proliferação intensa e difusa dos ductos biliares e uma acentuada poliploidia dos hepatócitos (volume médio: 843 µm³), Não foram observadas alterações significativas nos pulmões de nenhum grupo.
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In obstructive jaundice, the passage of bacteria and endotoxins through the intestine wall to reach the systemic circulation is associated with septicemia, renal failure and pulmonary dysfunction. The aim of this work was to investigate bacterial translocation utilizing 99mTc-E.coli in an experimental model of obstructive jaundice. The levels of bilirubin in rats that were subjected to ligature of the bile duct were significantly increased when compared to control animals (p < 0.001). The biodistribution results did not show any translocation of 99mTc-E.coli to the mesenteric lymphatic nodules, liver, spleen or lungs of the rats that suffered ligature of the bile duct (p > 0.05). The evaluation of the intestinal permeability using "per os" administration of 99mTc-DTPA showed 1.61 ± 0.57 percent and 1.39 ± 0.72 percent of radioactivity in the urine of the control and jaundice animals, respectively. The histological analysis of the distal wall of the ileum showed that the covering epithelium and the crypt were morphologically preserved in both groups. The seven-day period after the ligature of the bile duct may not have been long enough to promote modifications in intestinal wall to occur so as to permit the passage of Tc-99m E.coli.
Na icterícia obstrutiva, a passagem de bactérias e endotoxinas através da parede intestinal alcançando a circulação sistêmica está associada com septicemia, falência renal e disfunção pulmonar. A proposta deste trabalho foi investigar a translocação bacteriana, empregando a Tc-99m E.coli, em um modelo experimental de icterícia obstrutiva. Os níveis de bilirrubina nos ratos que sofreram a ligadura do ducto biliar estavam significativamente aumentados quando comparados com os valores dos animais controles (p<0,001). Os resultados de biodistribuição não mostraram translocação da Tc-99m E.coli para os nódulos linfáticos mesentéricos, fígado, baço e pulmões dos ratos que sofreram ligadura do ducto biliar (p>0,05). A avaliação da permeabilidade intestinal usando a administração "per os" de 99mTc-DTPA mostrou um percentual de eliminação deste radiofármaco na urina de 1,61±0,57 e 1,39±0,72 para os animais controles e ictéricos, respectivamente. A análise histológica da parede distal do íleo mostrou que tanto o epitélio de revestimento quanto as criptas apresentaram morfologicamente conservados em ambos os grupos. O tempo transcorrido, 7 dias, após a ligadura do ducto biliar talvez não tenha sido longo o suficiente para promover modificações na parede intestinal de modo a permitir a passagem da 99mTc-E.coli.
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This work presents the preparation of radiolabelled cis-dichlorodiammineplatinum (II), CDDP*, from its direct irradiation into a cadmium capsule, using the TRIGA MARK I IPR R-1 research reactor of the CDTN. The ability to detect CDDP* in Ehrlich tumour-bearing mice after administration via an intravenous route was evaluated. After 24 hours, blood and some organs were collected to determine the incorporated activity. The CDDP* showed a great chemical purity and high specific activity that resulted in an optimum in vivo detection. The CDDP* was taken up principally by liver, spleen and kidney. The CDDP* obtained from this condition was shown to be a good tool for biodistribution studies.
O presente trabalho refere-se à obtenção de cis-diclorodiaminoplatina (II) radiomarcada, CDDP*, a partir de sua irradiação direta numa cápsula de cádmio. A irradiação foi realizada no reator de pesquisa TRIGA MARK I IPR R-1. Em seguida, foi avaliada a capacidade de detecção da radioatividade emitida por CDDP* após sua administração intravenosa em camundongos acometidos por tumor de Ehrlich. Após 24 horas, fez-se a coleta de amostras de sangue e de alguns órgãos, a fim de se avaliar o nível de radioatividade presente nos mesmos. A CDDP* obtida apresentou uma ótima pureza química e elevada atividade específica que permitiu um excelente nível de detecção. A CDDP* foi captada principalmente pelo fígado, baço e rins. Portanto, a CDDP* obtida na condição de bombardeamento supracitada mostrou ser uma ferramenta útil para a realização de estudos de biodistribuição.
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The aim of this work was to prepare a kit of 99mTc-ceftizoxime (99mTc-CFT), with stability and biological activity preserved, able to identify a septic focus (E. coli) in the experimental infection model in rats. The preparation of the CFT kit involved the use of lyophilized solutions containing the antibiotic ceftizoxime and the sodium dithionite reducing agent (6.0 mg/mL). After lyophilization, the kit was reconstituted with 1.0 mL of sodium 99mTc-pertechnetate solution (Na99mTcO4-) with an activity of 370 MBq. The solution was boiled for 10 min and filtered through a cellulose ester filter. The labeling efficiency was on the order of 92 percent, remaining stable for six hours and the kit remained stable for two months. The biological activity of the 99mTc-CFT was evaluated by diffusion in agar impregnated with E.coli and S. aureus. Seven Wistar rats, weighing from 200 to 250 g, were used for the development of the septic focus. After 24 hours from the induction of the infectious site (E.coli), the animals were anesthetized and 0.1 mL of 99mTc-CFT (37 MBq) was injected into the tail veins of the animals. The images were obtained with a gamma camera one, two and six hours after injection and the regions of interest (ROIs) were calculated. The diameters of the inhibition halos for 99mTc-CFT were 27.16 ± 0.23 and 27.17 ± 0.20 for S.aureus and E.coli, respectively, while those for the unlabeled CFT were 30.4 ± 0.33 and 29.43 ± 0.26, respectively. The results for the biodistribution of 99mTc-CFT in infected animals furnished a ratio of 1.97 ± 0.31, 2.10 ± 0.42 and 2.01 ± 0.42 for cpm-target/cpm-no target for the one, two and six-hour periods, respectively. The images showed a clear uptake of labeled antibiotic (99mTc-CFT) by the infectious site during the experiment. The results attest to the viability of producing a kit with 99m technetium-labeled ceftizoxime for the investigation of infectious processes.
O objetivo deste trabalho foi preparar um kit de Tc-99m Ceftizoxima (99mTc-CFT), com estabilidade e atividade biológica preservadas, capaz de identificar um foco séptico (E.coli) em um modelo experimental de infecção em ratos. A preparação do kit de CFT baseou-se em uma mistura de soluções contendo o antibiótico ceftizoxima (2,5mg/mL) e o agente redutor ditionito de sódio (6,0mg/mL) que foram submetidos a um processo de liofilização. Após a liofilização, o kit foi reconstituído with 1,0 mL de solução de pertecnetato de sódio (Na99mTcO4 -), contendo uma atividade de 370 MBq. Em seguida, a solução foi incubada, por 10 min, em banho fervente (1000C) e, posteriormente, foi resfriada em água corrente por 5 min. A eficiência de marcação foi da ordem de 92 por cento permanecendo estável por 6 horas e o kit permaneceu estável por 2 meses. A atividade biológica do 99mTc-CFT foi avaliada por difusão em ágar impregnado com E.coli e S. aureus. Foram utilizados 07 ratos Wistar, pesando entre 200 a 250 g, para o desenvolvimento do foco séptico. Após 24 horas da indução do foco infeccioso (E.coli), os animais foram anestesiados e 0,1 mL da 99mTc-CFT (37 MBq) foi injetado na veia da cauda dos animais. As imagens de 1, 2 e 6 horas após a injeção foram adquiridas em uma gama câmara e as regiões de interesse (ROIS) foram calculadas. Os valores obtidos dos diâmetros dos halos de inibição para 99mTc-CFT foram 27,16±0,23 e 27,17±0,20 para S. aureus e E.coli, respectivamente, sendo que para CFT não marcada foram 30,4±0,33 e 29,43±0,26, respectivamente. Os resultados obtidos da biodistribuição da 99mTc-CFT nos animais com focos infecciosos mostraram uma relação alvo/não alvo de 1,97±0,31, 2,10±0,42 e 2,01±0,42 para os tempos de 1, 2 e 6 horas, respectivamente. As imagens obtidas mostraram nítida captação do antibiótico marcado (99mTc-CFT) pelo foco infeccioso ao longo do experimento. Os resultados obtidos neste...
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The oral administration of proteic antigens, like ovalbumin, may result in the induction of oral tolerance or immunization. The aim of this work was to label a protein antigen with 99mTechnetium, encapsulate it in liposomes and investigate its absorption and tissue distribution after oral administration in mice. Ovalbumin was labeled with 99mTechnetium and encapsulated in small unilamellar vesicles. 99mTc-OVA encapsulated or not in liposomes was administrated to mice that were sacrificed after different times. The radioactivity was measured in various organs of the animals. Differences concerning the biodistribution of 99mTc-OVA were noticed. The technique may represent alternatives for the induction of immunization or oral tolerance.
A administração oral de antígenos protéicos pode levar a indução ou supressão da resposta imune. A indução da resposta imune é de grande importância para o desenvolvimento de vacinas orais. Já a supressão, denominada de tolerância oral, pode vir a representar uma solução terapêutica a numerosas enfermidades. O objetivo deste trabalho foi de compreender o comportamento in vivo de um antígeno modelo, a ovalbumina (OVA), marcado com um radioisótopo, o 99m tecnécio (99mTc), e administrado por via oral na sua forma livre e encapsulado em lipossomas de pequeno tamanho (SUV). As amostras foram administradas por gavagem à camundongos, sacrificados após 30, 60, 90, 120, 180 e 360 minutos. A radioatividade foi medida no estômago, intestinos, placas de Peyer, linfonodos mesentéricos, baço, fígado e sangue dos animais. Os resultados mostraram que a OVA livre ou encapsulada em lipossomas SUV apresenta biodistribuições distintas. As diferenças encontradas na biodistribuição da OVA livre ou encapsulada podem representar mecanismos diferentes para a indução ou não de tolerância oral.
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PURPOSE: Ischemia and reperfusion of the small intestine disrupts gut barrier, causes bacterial translocation and activates inflammatory responses. An experimental study was planned to evaluate if 99mTc labelled Escherichia coli translocates to mesenteric lymph nodes, liver, spleen, lung and serum of rats submitted to mesenteric ischemia/reperfusion. Additionally, it was observed if the time of reperfusion influences the level of translocation. METHODS: Forty male Wistar rats underwent 45 minutes of gut ischemia by occlusion of the superior mesenteric artery. The translocation of labelled bacteria to different organs and portal serum was determined in rats reperfused for 30 minutes, 24 hours, sham(S) and controls(C), using radioactivity count and colony forming units/g (CFU). RESULTS: All the organs from rats observed for 24 hours after reperfusion had higher levels of radioactivity and positive cultures (CFU) than did the organs of rats reperfused for 30 minutes, C and S, except in the spleen (p<0,01). CONCLUSION: The results of this study indicated that intestinal ischemia/reperfusion led to bacterial translocation, mostly after 24 hours of reperfusion.
Тема - темы
Animals , Male , Rats , Bacterial Translocation , Escherichia coli , Intestines , Ischemia , Reperfusion , Technetium , Mesenteric Artery, Superior/physiopathology , Rats, WistarРеферат
O efeito da irradiação gama nos níveis de aflatoxina B1 e na infecção fúngica foram investigadas em amostras de amendoim, cultivar Tatu Vermelho. Dose de irradiação gama (60Co) de 10 KGy inibiu completamente o crescimento de fungos. Doses de 15, 20, 25 e 30 KGy foram suficientes para destruição de aflatoxina B1 de 55 a 74%. Pode-se concluir do presente trabalho, que a descontaminação de fungos por irradiação gama antes da produção de aflatoxina B1 é o método apropriado na preservação de amendoim.