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1.
Drug Chem Toxicol ; 45(4): 1558-1564, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33198524

RESUMO

The ß-adrenoceptor blockers may have anti-oxidant properties or induce ß-arrestin recruitment beyond classical desensitization of receptor/G protein coupling, offering potential therapeutic benefits. Here, we investigated the effects of carvedilol, metoprolol and propranolol in an animal model of cisplatin-induced nephrotoxicity. Rats received the ß-blockers (3 or 12 mg/kg/day) with or without cisplatin, and kidney function was investigated using renal scintigraphy, histopathology, and serum variables. Metoprolol and propranolol as well as low-dose carvedilol did not alter kidney function, per se. Meanwhile, high-dose carvedilol reduced renal accumulation of Technetium-99m (99mTc)-labeled dimercaptosuccinic acid (99mTc-DMSA) without significant effect on other variables. Furthermore, low-dose carvedilol prevented cisplatin-induced reduction of tracer uptake, but high-dose of this drug aggravated the situation. In this regard, both low and high -doses of carvedilol significantly inhibited cisplatin effects on kidney histology, BUN and creatinine levels. Also, high-dose propranolol inhibited cisplatin adverse effects on radiotracer uptake, histological manifestations, BUN and creatinine levels, while metoprolol failed to cause a notable effect. Taken together, carvedilol and high-dose propranolol may offer potential benefits in cisplatin nephrotoxicity.


Assuntos
Metoprolol , Propranolol , Antagonistas Adrenérgicos beta/farmacologia , Animais , Carvedilol , Cisplatino/toxicidade , Creatinina/metabolismo , Rim/patologia , Metoprolol/farmacologia , Propranolol/farmacologia , Ratos , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacologia
2.
J Pediatr Urol ; 15(5): 514.e1-514.e6, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31285138

RESUMO

BACKGROUND: Primary vesicoureteral reflux (VUR) is the most common urological anomaly in children. Voiding cystourethrography (VCUG) is considered the reference standard for the diagnosis of VUR. Even if it is a secure and standardized technique, it is still an invasive method, hence, the effort to find an alternative method to diagnose VUR. The aim of the study is to evaluate the diagnostic accuracy of 99mTC-MAG3 scintigraphy with indirect cystography in detecting VUR and to estimate any interobserver variability in 99mTC-MAG3 scintigraphy interpretation. METHODS: The authors retrospectively reviewed all the pediatric patients who underwent both a VCUG and a 99mTC-MAG3 renal scintigraphy at the study institution between 2012 and 2016. RESULTS: A total of 86 children (and 168 renal units) were included. MAG3 scan revealed a sensitivity of 54% and a specificity of 90% with positive predictive value of 79% and negative predictive value of 73%. Each MAG3 scintigraphy was then independently and blindly evaluated by a pediatric urologist and two nuclear physicians. After revision, the concordance between VCUG and MAG3 in reflux cases dropped from 54% to 27% (on average), and the reviewers reclassified most examinations as non-conclusive. CONCLUSIONS: 99mTC-MAG3 renal scintigraphy with indirect cystography showed low sensitivity in detecting VUR of any grade and cannot, therefore, be proposed as completely alternative to VCUG in the diagnosis of VUR. Moreover, MAG3 scintigraphy interpretation for the diagnosis of VUR has a very high interobserver variability, mostly because of the lack of a correct and complete voiding phase.


Assuntos
Cistografia/métodos , Cintilografia/métodos , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacologia , Bexiga Urinária/diagnóstico por imagem , Refluxo Vesicoureteral/diagnóstico , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Curva ROC , Compostos Radiofarmacêuticos/farmacologia , Estudos Retrospectivos , Micção , Urodinâmica/fisiologia , Refluxo Vesicoureteral/fisiopatologia
3.
J Pediatr Urol ; 14(3): 269.e1-269.e7, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29588142

RESUMO

INTRODUCTION: Static renal scintigraphy is the gold standard for detection of inflammatory changes in the renal parenchyma in acute pyelonephritis. Our aim was to determine whether diffusion-weighted magnetic resonance imaging (DW-MRI) was comparable with static renal scintigraphy (DMSA-SRS) to demonstrate acute renal parenchymal lesions. OBJECTIVE: To compare 99mTc-dimercaptosuccinic acid static renal scintigraphy (DMSA-SRS) with diffusion-weighted magnetic resonance imaging (DW-MRI) for detecting acute inflammatory changes in the renal parenchyma in children with febrile urinary tract infection. METHODS: Thirty-one children (30 girls) aged 3-18 years with a first episode of febrile UTI without a previously detected congenital malformation of the urinary tract, were prospectively included. DMSA-SRS and DW-MRI were performed within 5 days of diagnosis to detect renal inflammatory lesions. The DW-MRI examination was performed without contrast agent and without general anesthesia. Late examinations were performed after 6 months using both methods to detect late lesions. RESULTS: DW-MRI confirmed acute inflammatory changes of the renal parenchyma in all 31 patients (100%), mostly unilateral. DMSA-SRS detected inflammatory lesions in 22 children (71%; p = 0.002). The lesions were multiple in 26/31 children (84%) on DW-MRI and in 9/22 (40%) on DMSA-SRS. At the control examination, scarring of the renal parenchyma was found equally by DW-MRI and DMSA-SRS in five patients (16%), three of whom were the same patients. The overall concordance of positive and negative late findings occurred in 87% of patients. There was correspondence in the anatomical location of acute and late lesions. DISCUSSION: The clinical significance of acute and late parenchymal findings on DWI-MR is yet to be determined. A limitation of our study is the age of the patients (older than 3 years) who are less sensitive to scar development; therefore, a smaller number of patients with scars could be analyzed during control examination. Further studies using the DW-MRI should confirm its reliability to detect acute and late lesions in younger children and infants and determine the clinical consequences. CONCLUSION: DW-MRI has higher sensitivity for detecting acute renal inflammatory lesions and multifocal lesions than DMSA-SRS. The incidence of scars was low and corresponded with the anatomical location of acute and late lesions.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Rim/patologia , Pielonefrite/diagnóstico , Cintilografia/métodos , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacologia , Doença Aguda , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos , Compostos Radiofarmacêuticos/farmacologia , Reprodutibilidade dos Testes
4.
Ren Fail ; 38(9): 1496-1502, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27604130

RESUMO

BACKGROUND: The aim of the current study was to investigate whether agmatine (AGM) has a protective effect against cisplatin-induced nephrotoxicity. MATERIALS AND METHODS: Thirty-two rats were randomly divided into four groups: (1) Saline (control); (2) Cisplatin (CDDP; 7.5 mg/kg intraperitoneally); (3) Agmatine (AGM; 10 mg/kg intraperitoneally); (4) Cisplatin plus agmatine (CDDP + AGM). Agmatine was given before and two consecutive days after cisplatin injection. All the animals underwent renal scintigraphy with 99mTc-DMSA. The levels of serum creatinine, cystatin C, and blood urea nitrogen (BUN) were measured in addition to examination of the tissue samples with light microscopy. Acute renal injury was assessed with biochemical analyses, scintigraphic imaging, and histopathological evaluation. RESULTS: In the cisplatin group, the levels of BUN, creatinine, and cystatin C were significantly higher than that of the controls. Histopathological examination showed remarkable damage of tubular and glomerular structures. Additionally, cisplatin caused markedly decreased renal 99mTc-DMSA uptake. AGM administration improved renal functions. Serum creatinine, BUN, and cystatin C levels had a tendency to normalize and, scintigraphic and histopathological findings showed significantly less evidence of renal toxicity than those observed in animals receiving cisplatin alone. CONCLUSIONS: Our data indicate that AGM has a protective effect against cisplatin-induced nephrotoxicity. Therefore, it may improve the therapeutic index of cisplatin. In addition, the early renal damage induced by cisplatin and protective effects of AGM against cisplatin nephrotoxicity was accurately demonstrated with 99mTc-DMSA renal scintigraphy.


Assuntos
Injúria Renal Aguda/prevenção & controle , Agmatina/farmacologia , Cistatina C/farmacologia , Rim/diagnóstico por imagem , Cintilografia/métodos , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Animais , Cisplatino/toxicidade , Modelos Animais de Doenças , Feminino , Compostos Radiofarmacêuticos/farmacologia , Ratos , Ratos Wistar
5.
Pediatr Nephrol ; 30(9): 1375-7, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26037738

RESUMO

In this issue of Pediatric Nephrology, Gebäck et al. from Gothenburg, Sweden, show that after a mean follow-up after childhood urinary tract infection of 41 years, kidney function decreases from a mean of 93 ml/min/1.73m(2) to 81 ml/min/1.73m(2). This was found in women with severe bilateral renal scarring. They had experienced their UTI during childhood in the 1950s and 1960s and had been drawn from a population-based cohort of more than 1,000 children. A previous paper on this same group of women had shown a higher systolic blood pressure of 3 mmHg during the day and 5 mmHg during the night compared with a control group. This contrasted with a follow-up study published earlier by the same group on two different cohorts in which no impairment of kidney function or increase in hypertension could be found. The present follow-up time was 13 years longer than that of any previous studies. Data on the long-term outcome of children who have had one or several urine infections is very important, as the fear of long-term complications has been driving the extensive investigations to which these children have traditionally been subjected. Further population-based follow-up data can help us to outline modern guidance on imaging after UTI.


Assuntos
Rim , Insuficiência Renal Crônica , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacologia , Infecções Urinárias , Feminino , Humanos
6.
J Pediatr Urol ; 11(5): 252.e1-7, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25979215

RESUMO

OBJECTIVE: In a historical cohort of children with a urinary tract infection (UTI) who had already undergone all the imaging procedures, the aim was to determine renal tract abnormalities which would have been missed had we implemented the new guidelines from the National Institute for Health and Care Excellence in the United Kingdom (NICE) or the American Academy of Pediatrics (AAP). MATERIAL AND METHODS: After a UTI episode, forty-three children (28 females, 65%) aged between 2 months and 2 years presenting at two general hospitals with a febrile UTI before 2008 underwent all the recommended imaging studies predating the new guidelines. Hydronephrosis was defined and graded according to the Society for Fetal Urology (SFU) classification. Hydronephrosis grade II (mild pelvicalyceal dilatation), grade III (moderate dilatation), and grade IV (gross dilatation with thinning of the renal cortex), duplication, vesicoureteral reflux (VUR) grade II and above, renal scarring and reduced renal uptake (<45%) on technetium-99m-labeled dimercaptosuccinic acid (DMSA) scintigraphy were considered significant abnormalities. We calculated the proportion of abnormalities which would have been missed had the new guidelines been used instead. RESULTS: The median of age was 7.6 months (mean 8.7, range 2-24 months), with the majority (n = 37, 86%) being under 1 year of age. Ultrasound (US) showed hydronephrosis in 14 (32%), all grade II. A voiding cystourethrogram (VCUG) was performed in all and showed VUR ≥ grade II in 16 (37%), including eight children (19%) where it was bilateral. DMSA scan showed scarring in 25 children (58%) of whom 11 (26%) had bilateral scars. Reduced differential renal uptake was present in 10 children (23%). Of the 29 children with normal US, 18 (62%) had renal scarring and nine (31%) had VUR ≥ grade II. The NICE guidelines would have missed 63% of the children with VUR ≥ grade II, including a high proportion of grades IV and V VUR, 44% of the children with renal scarring, and 20% of the children with decreased renal uptake, including some children with bilateral renal scarring and with decreased renal uptake. The AAP guidelines would have missed 56% of the children with VUR ≥ grade II, including a high proportion of grades IV and V VUR, and all children with renal scarring as well as those with decreased renal uptake. CONCLUSION: The prevalence of renal tract abnormalities missed by the new guidelines is high. They should be used with full awareness of their limitations.


Assuntos
Diagnóstico por Imagem/normas , Rim/anormalidades , Guias de Prática Clínica como Assunto , Sociedades Médicas , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacologia , Infecções Urinárias/etiologia , Anormalidades Urogenitais/diagnóstico por imagem , Pré-Escolar , Feminino , Humanos , Lactente , Rim/diagnóstico por imagem , Masculino , Cintilografia , Compostos Radiofarmacêuticos/farmacologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Reino Unido , Estados Unidos , Infecções Urinárias/diagnóstico por imagem , Anormalidades Urogenitais/complicações
7.
Pediatr Nephrol ; 30(9): 1493-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25814208

RESUMO

BACKGROUND: The risk of deterioration of renal function in patients with urinary tract infection (UTI)-associated renal damage over several decades is incompletely known but of importance in regard to follow-up. METHODS: A population-based cohort of women followed from their first UTI in childhood was studied at median age of 27 years and now at 41 years. Renal damage was evaluated by (99m)Tc-dimercaptosuccinic acid scan and glomerular filtration rate (GFR) by (51)Cr-edetic acid clearance. Extent of individual kidney damage was graded as class 1 to 3. RESULTS: Eighty-six women completed the investigation, 58 with renal damage, and 28 without. Of those with damage, one had chronic kidney disease (CKD) stage 3, 14 stage 2, and 43 stage 1. Women with bilateral damage had lower GFR than those with no or unilateral damage (p < 0.0001). Women with class 3 damage had numerically but not significantly lower GFR than the others with damage (p = 0.07). Between the two studies there was significant decrease of GFR in the group with bilateral damage (p = 0.01). CONCLUSIONS: Women with UTI-associated renal damage had remarkably well preserved renal function, but those with bilateral or severe individual kidney damage may be considered for regular monitoring of GFR and blood pressure.


Assuntos
Rim , Insuficiência Renal Crônica , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacologia , Infecções Urinárias , Adulto , Criança , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/diagnóstico por imagem , Rim/fisiopatologia , Estudos Longitudinais , Pessoa de Meia-Idade , Radiografia , Compostos Radiofarmacêuticos/farmacologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/fisiopatologia , Índice de Gravidade de Doença , Suécia/epidemiologia , Infecções Urinárias/complicações , Infecções Urinárias/epidemiologia
8.
Ren Fail ; 37(2): 280-4, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25540869

RESUMO

BACKGROUND: In this study, we investigated the protective effect of thymol as a natural compound against cisplatin-induced nephrotoxicity by quantitative renal 99mTc-DMSA uptake and compared its effect with histopathology in mice. MATERIALS AND METHODS: Mice were divided into six groups as control, cisplatin (7.5 mg/kg, intraperitoneally), thymol+cisplatin (thymol; 50 and 150 mg/kg+cisplatin; 7.5 mg/kg) and thymol (50 and 150 mg/kg). Thymol was orally administrated for two days before cisplatin injection and continued for 4 days. (99m)Tc-DMSA was injected through the tail of mice after the drug administration. The percentage of the injected dose per gram of kidney tissue (%ID/g) was calculated. In other experiment, kidneys of treated mice were assessed for histopathology. RESULTS: 99mTc-DMSA uptake per gram tissue of the kidneys as %ID/g was 85.27±21.81, 45.55±5.50, 65.02±32.21 and 88.46±20.46 in the control, cisplatin, thymol (50 mg/kg)+cisplatin and thymol (150 mg/kg)+cisplatin. Thymol administration with cisplatin resulted in a significant increase in the level of %ID/g. Histopathological examinations showed a protective effect of thymol against cisplatin nephrotoxicity in mice. CONCLUSION: The results showed that thymol significantly attenuates the cisplatin-induced nephrotoxicity in mice, and 99mTc-DMSA uptake in kidney is a suitable method for assessment of nephrotoxicity in mice.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Cisplatino , Nefropatias , Rim , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacologia , Timol/farmacologia , Animais , Antineoplásicos Alquilantes/administração & dosagem , Antioxidantes/farmacologia , Cisplatino/farmacocinética , Cisplatino/toxicidade , Creatinina/análise , Relação Dose-Resposta a Droga , Rim/diagnóstico por imagem , Rim/fisiopatologia , Nefropatias/induzido quimicamente , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Masculino , Camundongos , Substâncias Protetoras/farmacologia , Cintilografia , Compostos Radiofarmacêuticos/farmacologia , Resultado do Tratamento
9.
Biomed Res Int ; 2014: 134940, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25105116

RESUMO

OBJECTIVES: This study aimed to demonstrate if the addition of anti-inflammatory treatment to antibiotic therapy shows any superiority to the treatment with antibiotic only. METHODS: Forty-nine Wistar rats were divided into 7 groups. Pyelonephritis was performed by E. coli injection to upper pole of kidneys except control group. Group 2 was not treated. Ceftriaxone, ketoprofen, "ceftriaxone + ketoprofen," methylprednisolone, and "ceftriaxone + methylprednisolone" were given in the groups. The technetium-99m-dimercaptosuccinic acid scintigraphies were performed in 3rd day to detect pyelonephritis and 10th week to detect renal scarring. All kidneys were also histopathologically evaluated. RESULTS: When 3rd day and 10th week scintigraphies were compared, initial 2.00 ± 0.30 point pyelonephritis score resulted in 0.71 ± 0.36 renal scar score in "ceftriaxone + ketoprofen" group (P = 0.039). Initial 2.00 ± 0.43 point pyelonephritis score resulted in 0.86 ± 0.26 renal scar score in "ceftriaxone + methylprednisolone" group (P = 0.041). Renal scar score was declined in "ceftriaxone + ketoprofen" group and "ceftriaxone + methylprednisolone" group compared with no-treatment group on 10th week of the study (P = 0.026, P = 0.044). On histopathological evaluation, it was seen that renal scar prevalence and expansion declined significantly in "ceftriaxone + ketoprofen and ceftriaxone + methylprednisolone" (P = 0.011, P = 0.023). CONCLUSION: It was evidenced that ceftriaxone treatment in combination with ketoprofen or methylprednisolone declined scar formation in scintigraphic and histopathologic examinations of the kidneys.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Ceftriaxona/farmacologia , Cicatriz/prevenção & controle , Infecções por Escherichia coli/tratamento farmacológico , Cetoprofeno/farmacologia , Metilprednisolona/farmacologia , Pielonefrite/tratamento farmacológico , Doença Aguda , Animais , Cicatriz/diagnóstico por imagem , Cicatriz/etiologia , Quimioterapia Combinada/métodos , Escherichia coli , Infecções por Escherichia coli/patologia , Pielonefrite/diagnóstico por imagem , Pielonefrite/microbiologia , Cintilografia , Compostos Radiofarmacêuticos/farmacologia , Ratos , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacologia
10.
Urology ; 77(6): 1404-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20570320

RESUMO

OBJECTIVES: To measure the renal parenchymal volume (RPV) before and after unilateral nephrectomy and investigate the relationship between the RPV and single kidney glomerular filtration rate (GFR). METHODS: From November 2003 to August 2009, 183 patients who had undergone unilateral nephrectomy were enrolled in the present study. All patients had undergone preoperative technetium-99m dimercaptosuccinic acid renal scintigraphy. Contrast-enhanced computed tomography was performed before and 6 months after surgery. RPV was calculated as the normally functioning tissue, excluding tumors or nonenhanced areas, using a 3-dimensional image reconstruction program. RESULTS: The mean split GFR of the remaining kidney increased by 21.2%, from 41.6 to 49.5 mL/min/1.73 m(2) at 6 months after nephrectomy. The mean RPV of the remaining kidney increased by 9.3%, from 164.2 to 178.8 cm(3) after nephrectomy. The preoperative relative RPV of the remaining kidney was 58.8% (range 37.2%-97.9%) and the technetium-99m dimercaptosuccinic acid uptake was 62.2% (range 39.6%-100%), indicating a significant linear correlation (R = 0.865, P <.001). RPV correlated well with the single kidney GFR and patient age, both preoperatively and postoperatively. The postoperative GFR could be predicted by combining the preoperative factors. Multivariate regression analysis revealed that the RPV was positively associated with the single kidney GFR and negatively associated with patient age. CONCLUSIONS: The differential renal function correlated well with the RPV and can be estimated by calculating the RPV. Even without using renal scintigraphy, the postoperative GFR can be predicted using our established formula.


Assuntos
Taxa de Filtração Glomerular , Rim/metabolismo , Rim/patologia , Nefrectomia/métodos , Idoso , Meios de Contraste/farmacologia , Creatinina/metabolismo , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Oncologia/métodos , Pessoa de Meia-Idade , Cintilografia/métodos , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacologia , Tomografia Computadorizada por Raios X/métodos
11.
Singapore Med J ; 49(1): 19-22, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18204763

RESUMO

INTRODUCTION: Medullary thyroid carcinoma (MTC) is a rare disease. Serum calcitonin levels and Tc-99m DMSA (V) scans are used in the follow-up of these patients after surgical resection. We present our experience in the follow-up of these patients at a tertiary institution. METHODS: A retrospective review of the medical records was performed. Patients with histologically-proven MTC, and who had serum calcitonin assays and DMSA (V) scans in their postoperative follow-up, were included. RESULTS: There were 17 patients with 56 DMSA (V) scans. Four out of seven patients with elevated preoperative calcitonin measurements had calcitonin normalisation within six months of surgery, and have remained disease-free. Two patients had persistently elevated calcitonin levels after six months, which predated positive DMSA (V) scans. Results of DMSA (V) scans and serum calcitonin levels were concordant in 38 of 48 instances (79.2 percent) and discordant in 10 of 48 instances (20.8 percent). Sensitivity of DMSA (V) scans for detecting recurrence was 71.4 percent. There were no false-positive scans. CONCLUSION: Serum calcitonin level is a sensitive and specific indicator of disease recurrence in postoperative follow-up of patients with MTC. Early (within six months) normalisation of calcitonin levels postsurgery may predict subsequent disease-free status. Discordant results between serum calcitonin levels and DMSA (V) scans may be due to undetectable lesions and follow-up scans or alternative radionuclide imaging may be required.


Assuntos
Calcitonina/análise , Carcinoma Medular/diagnóstico , Compostos Radiofarmacêuticos/farmacologia , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacologia , Neoplasias da Glândula Tireoide/diagnóstico , Adulto , Idoso , Carcinoma Medular/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Oncologia/métodos , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia , Resultado do Tratamento
12.
Mol Cell Biochem ; 308(1-2): 35-42, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17899318

RESUMO

Erdosteine is a mucolytic agent having antioxidant properties through its active metabolites in acute injuries induced by pharmacological drugs. This study was designed to investigate the renoprotective potential of Erdosteine against gentamicin (GM)-induced renal dysfunction by using Technetium-99 m dimercaptosuccinic acid (Tc-99 m DMSA) uptake and scintigraphy in rats. For this purpose, male Wistar rats were randomly allotted into one of the four experimental groups: Control, Erdosteine, GM, and GM + Erdosteine groups. GM and GM + Erdosteine groups received 100 mg/kg GM intramuscularly for 6 days. In addition, Erdosteine and GM + Erdosteine groups received 50 mg/kg Erdosteine orally for 6 days. Renal function tests were assessed by serum blood urea nitrogen (BUN), creatinine levels, as well as scintigraphic and tissue radioactivity measurements with Tc-99 m DMSA. Renal oxidative damage was determined by renal malondialdehyde (MDA) levels, by antioxidant enzyme activities; superoxide dismutase (SOD) and catalase (CAT) and activities of oxidant enzymes; xanthine oxidase (XO) and myeloperoxidase (MPO). GM administration resulted in marked renal lipid peroxidation, increased XO and MPO activities and decreased antioxidant enzyme activities. GM + Erdosteine group significantly had lower MDA levels, higher SOD and CAT activities and lower XO and MPO activities, when compared to GM. Also GM + Erdosteine had lower levels of serum BUN, creatinine and higher renal tissue Tc-99 m DMSA uptake and radioactivity with respect to GM. In conclusion, our results supported a protective role of Erdosteine in nephrotoxicity associated with GM treatment.


Assuntos
Gentamicinas/toxicidade , Rim/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacocinética , Tioglicolatos/farmacologia , Tiofenos/farmacologia , Animais , Antioxidantes/metabolismo , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Rim/diagnóstico por imagem , Rim/enzimologia , Masculino , Malondialdeído/metabolismo , Oxidantes/metabolismo , Cintilografia , Ratos , Ratos Wistar , Ácido Dimercaptossuccínico Tecnécio Tc 99m/administração & dosagem , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacologia
13.
Cancer Biother Radiopharm ; 22(1): 40-9, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17627412

RESUMO

UNLABELLED: In peptide receptor radionuclide therapy (PRRT), the dose-limiting organ is, most often, the kidney. However, the precise mechanism as well as the exact localization of kidney damage during PRRT have not been fully elucidated. We studied renal damage in rats after therapy with different amounts of [(177)Lu-DOTA(0), Tyr(3)]octreotate and investigated (99m)Tc-DMSA (dimercaptosuccinic acid) as a tool to quantify renal damage after PRRT. EXPERIMENTAL DESIGN: Twenty-nine (29) rats were divided into 3 groups and injected with either 0, 278, or 555 MBq [(177)Lu-DOTA(0), Tyr(3) ]octreotate, leading to approximately 0, 46, and 92 Gy to the renal cortex. More than 100 days after therapy, kidney damage was investigated using (99m)Tc-DMSA single-photon emission computed tomography (SPECT) autoradiography, histology, and blood analyses. RESULTS: In vivo SPECT with (99m)Tc-DMSA resulted in high-resolution (<1.6-mm) images. The (99m)Tc-DMSA uptake in the rat kidneys was inversely related with the earlier injected activity of [(177)Lu-DOTA(0), Tyr(3)]octreotate and correlated inversely with serum creatinine values. Renal ex vivo autoradiograms showed a dose-dependent distribution pattern of (99m)Tc-DMSA. (99m)Tc-DMSA SPECT could distinguish between the rats that were injected with 278 or 555 MBq [(177)Lu-DOTA(0), Tyr(3) ]octreotate, whereas histologic damage grading of the kidneys was nearly identical for these 2 groups. Histologic analyses indicated that lower amounts of injected radioactivity caused damage mainly in the proximal tubules, whereas as well the distal tubules were damaged after high-dose radioactivity. CONCLUSIONS: Renal damage in rats after PRRT appeared to start in a dose-dependent manner in the proximal tubules and continued to the more distal tubules with increasing amounts of injected activity. In vivo SPECT measurement of (99m)Tc-DMSA uptake was highly accurate to grade renal tubular damage after PRRT.


Assuntos
Nefropatias/metabolismo , Nefropatias/patologia , Receptores de Peptídeos/metabolismo , Ácido Dimercaptossuccínico Tecnécio Tc 99m/efeitos adversos , Animais , Peso Corporal/efeitos dos fármacos , Peso Corporal/efeitos da radiação , Creatinina/sangue , Relação Dose-Resposta à Radiação , Imageamento por Ressonância Magnética , Masculino , Ratos , Ratos Endogâmicos Lew , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacologia , Tomografia Computadorizada de Emissão de Fóton Único
14.
Ann Nucl Med ; 21(5): 275-83, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17634845

RESUMO

OBJECTIVE: To define the role of Tc-99m (V) dimercaptosuccinic acid (DMSA) scanning in the detection of lung cancer (LC) and its metastases, and monitoring the response of LC lesions (LCL) to chemo/radiotherapy (TH). METHODS: Tc-99m (V) DMSA whole-body scans, planar thorax views, and thorax Single-photon emission computed tomography (SPECT) images were obtained both 30 min (early) and 5 h (late) after Tc-99m (V) DMSA administration in 12 small/nonsmall cell LC patients (11 men, 1 woman; mean age 59 years). Five patients also had bone scans. The same scintigraphic protocol was performed in 7 of 12 patients, 3 weeks after first-line TH. TH response was evaluated visually in all LCL and semiquantitatively in primary tumors (PT) of six patients, by comparing the tumor uptake ratios (TUR) of pre-TH and post-TH Tc-99m (V) DMSA SPECT [TUR = mean counts of region of interests (ROI) in PT/mean counts in contralateral ROI]. In seven patients, a 6-month survival was determined. RESULTS: Tc-99m (V) DMSA accumulated in 34 LCL (11 PT, 19 bone metastases, 1 suprarenal mass, 1 axillary node, 2 supraclavicular nodes). A total of 11 patients displayed Tc-99m (V) DMSA uptake in LCL and one patient did not show uptake. In six patients, SPECT imaging showed deeply located PT in the lung parenchyma better than planar views. In five patients, both planar and SPECT views revealed peripherally located PT in the lungs. Early scans showed 18 LCL and late scans displayed all the LCL. Nine bone metastases on pre-TH Tc-99m (V) DMSA scans revealed matched areas of increased Tc-99m methylene diphosphonate (MDP) uptake on bone scans; six bone metastases were additionally detected on Tc-99m (V) DMSA scans when compared with bone scans, and four bone metastases on Tc-99m (V) DMSA scans could not be compared with bone scans because bone scan was not performed. In one patient, Tc-99m (V) DMSA scans became positive for bone metastases on post-TH later than the bone scans for some of the bone metastases. Neither planar nor SPECT imaging showed mediastinal lesions defined on thorax CT in nine patients. On TH monitoring, 17 LCL showed diminished Tc-99m (V) DMSA uptake, one disappeared, four were unchanged, three displayed increased uptake, and five new lesions were established. Of the six patients, TUR in PT increased in two (one survived), decreased in one (exitus), was unchanged in two (two exitus) on post-TH scans, and PT totally disappeared in one (survived) patient. CONCLUSIONS: Tc-99m (V) DMSA scans are useful in detecting LCL, except for those around the blood pool regions, making it a promising modality to monitor TH response. Obtaining a single fifth hour late Tc-99m (V) DMSA scan is appropriate. SPECT should be applied to all patients for the detection of deeply located lesions.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma de Células Pequenas/diagnóstico por imagem , Carcinoma de Células Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Compostos Radiofarmacêuticos/farmacologia , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacologia , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Idoso , Osso e Ossos/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Cintilografia/métodos , Ácido Dimercaptossuccínico Tecnécio Tc 99m/química , Imagem Corporal Total
15.
Ann Nucl Med ; 21(5): 285-91, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17634846

RESUMO

OBJECTIVE: Gallium-67 (Ga-67) and labeled leukocytes are useful in the detection of an unknown infectious source. However, the delay in the diagnosis of a Ga-67 citrate scan (gallium scan) and the complicated labeling technique of a leukocyte scan are major drawbacks to their clinical use. Recently, Tc-99m (V) dimercaptosuccinic acid (DMSA) has been found to be very useful in the detection of infection. Tc-99m (V) DMSA is inexpensive, easy to prepare, and provides a result within hours. In this study, we evaluated the potential of Tc-99m (V) DMSA scan (DMSA scan) in the detection of intra-abdominal infection. METHODS: A total of 33 patients who suffered from an unknown cause of fever after colorectal surgery were enrolled in this study. All patients received both a gallium scan and a DMSA scan. DMSA scintigraphy was performed 3-4 h after an injection of 740 MBq (20 mCi) of Tc-99m DMSA. After completion of the DMSA image, 111 MBq (3 mCi) of Ga-67 citrate was injected intravenously. Gallium scintigraphy was performed after 24 h and later as needed. RESULTS: Of the 33 patients, 17 (51.5%) were diagnosed with intra-abdominal abscesses. For DMSA scans, the sensitivity, specificity, and overall accuracy were 88.2%, 93.7%, and 90.9%, respectively. For gallium scans, the diagnostic sensitivity, specificity, and accuracy were 100%, 87.5%, and 93.9%, respectively. No statistical difference was found in the diagnostic accuracy between these two diagnostic modalities using Fisher's exact test. CONCLUSIONS: DMSA scan is a useful alternative to gallium scan in the detection of intra-abdominal infection in patients with colorectal surgery because Tc-99m DMSA is inexpensive, easy to prepare, and most importantly the result can be obtained within hours.


Assuntos
Radioisótopos de Gálio/farmacologia , Infecções/diagnóstico por imagem , Compostos Radiofarmacêuticos/farmacologia , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacologia , Idoso , Citratos/farmacologia , Colo/cirurgia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgia , Feminino , Febre/diagnóstico , Gálio/farmacologia , Humanos , Infecções/diagnóstico , Masculino , Pessoa de Meia-Idade , Cintilografia , Sensibilidade e Especificidade , Infecção da Ferida Cirúrgica/diagnóstico
16.
Semin Dial ; 15(4): 269-76, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12191027

RESUMO

Nuclear medicine (scintigraphy) studies that are performed in patients being prepared for regular dialysis treatment include the measurement of renal clearance and dynamic studies of renal perfusion and function. Static scintigraphy with 99mTc-DMSA may be used in the evaluation of children at risk of renal damage and further functional deterioration. In patients on peritoneal dialysis, nuclear medicine procedures enable the diagnosis of structural complications such as intra-abdominal herniations and leaks. Diagnosis of infections of the vascular access sites in patients on hemodialysis and of the catheter tunnel in patients on peritoneal dialysis can be made with high diagnostic accuracy using radiolabeled, autologous leukocytes. Scintigraphy is valuable in delineating the extent of deposits of amyloid and parenchymal microcalcifications, and may be helpful in the functional evaluation of organs and tissues involved in the pathophysiology of renal impairment and dialysis. If radioiodine therapy with 131I is performed in patients on hemodialysis with benign or malignant thyroid disease, then pretherapeutic dosimetry is necessary to avoid over- and undertreatment. Radioiodine therapy in the dialysis patient leads to only insignificant contamination of dialysis equipment and marginal exposure to the medical staff.


Assuntos
Falência Renal Crônica/diagnóstico por imagem , Falência Renal Crônica/terapia , Diálise Peritoneal/efeitos adversos , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacologia , Adulto , Criança , Feminino , Seguimentos , Humanos , Testes de Função Renal , Masculino , Medicina Nuclear , Diálise Peritoneal/métodos , Cintilografia , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença
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