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1.
Article in English | MEDLINE | ID: mdl-38765540

ABSTRACT

Objective: To present a series of cases with our initial experience and short-term outcomes of a modified vaginal mucosal flap urethroplasty. Methods: Patients diagnosed with urethral stricture and operated by the same operative technique between January 2012 and January 2018 were followed for at least 6 months. Uroflowmetry and clinical outcomes were evaluated. Results: Nineteen patients were included with an average age of 56.4 years, mean preoperative Qmax of 5.3 ml/s, and PVR of 101.4 mL. After 6 months of the procedure, the mean Qmax improved to 14.7 mL/s (p<0.05), PVR decreased to 47.3 mL (p<0.05), and 84.2% of all patients reported improvement in clinical self-reported symptoms. There was an improvement in symptoms such as voiding effort in 84.2% of patients, weak stream (89.5%), and recurrent urinary tract infection (85.7%). The success rate (absence of symptoms and normal Qmax with no significant PVR) of the procedure was 84.2%. Conclusion: The described technique was considered effective for the treatment of female urethra stricture, with a high clinical success rate and an objective improvement of Qmax and decrease in PVR after 6 months of the procedure.


Subject(s)
Urethra , Urethral Stricture , Humans , Urethral Stricture/surgery , Female , Middle Aged , Treatment Outcome , Urethra/surgery , Adult , Aged , Retrospective Studies , Urologic Surgical Procedures/methods , Surgical Flaps , Vagina/surgery
2.
J Pediatr Urol ; 16(5): 719-720, 2020 10.
Article in English | MEDLINE | ID: mdl-32828684

ABSTRACT

Appendicovesicostomy is an established continent urinary conduit. The development of minimally invasive techniques and the reduction of operative time instigated the search for new techniques. In this video we show the laparoscopic transabdominal technique for appendicovesicostomy using U-stitch technique as proposed by Santiago Weller et al. We present a case of a teenager with neurogenic bladder and intolerance for urethral catheterization. The procedure was performed using a transperitoneal approach. The appendix was detached from the colon preserving its pedicle. The proximal appendix was spatulated and pulled through a hiatus created in the distal vesical mucosa into the bladder using a U-stitch, on a Shanfield fashion anastomosis in the anterior wall of the bladder. Detrusor was approximated over the appendix creating an antireflux mechanism. The tip of the appendix was brought out to the right iliac fossa and ostomy was fashioned. The operative time was 180 min. A Foley catheter was placed through the conduit. The case was done without any intraoperative or postoperative complications. Laparoscopic appendicovesicostomy with U-stitch technique is feasible and can be easily done in a short operative time in centers with expertise in laparoscopic surgeries with low complexity and high reproducibility.


Subject(s)
Appendix , Laparoscopy , Urinary Diversion , Adolescent , Appendix/surgery , Cystostomy , Humans , Reproducibility of Results
3.
Acta Cir Bras ; 33(5): 396-407, 2018 May.
Article in English | MEDLINE | ID: mdl-29924210

ABSTRACT

PURPOSE: To evaluate whether combining hypothermia and remote ischemic preconditioning (RIPC) results in protection from ischemia-reperfusion (IR). METHODS: Thirty-two Wistar rats underwent right nephrectomy and were randomly assigned to four experimental protocols on the left kidney: warm ischemia (group 1), cold ischemia (group 2), RIPC followed by warm ischemia (group 3), and RIPC followed by cold ischemia (group 4). After 240 minutes of reperfusion, histological changes in the left kidney, as well as lipid peroxidation and antioxidant enzyme activity, were analyzed. The right kidney was used as the control. Serum creatinine was collected before and after the procedures. RESULTS: RIPC combined with hypothermia during IR experiments revealed no differences on interventional groups regarding histological changes (p=0.722). Oxidative stress showed no significant variations among the groups. Lower serum creatinine at the end of the procedure was seen in animals exposed to hypothermia (p<0.001). CONCLUSIONS: Combination of RIPC and local hypothermia provides no renal protection in IR injury. Hypothermia preserves renal function during ischemic events. Furthermore, RIPC followed by warm IR did not show benefits compared to warm IR alone or controls in our experimental protocol.


Subject(s)
Hypothermia, Induced/methods , Ischemic Preconditioning/methods , Kidney/blood supply , Oxidative Stress/physiology , Reperfusion Injury/prevention & control , Animals , Cold Ischemia , Combined Modality Therapy , Disease Models, Animal , Kidney/pathology , Male , Rats , Rats, Wistar , Superoxide Dismutase/metabolism , Warm Ischemia
4.
Acta cir. bras ; 33(5): 396-407, May 2018. tab, graf
Article in English | LILACS | ID: biblio-949345

ABSTRACT

Abstract Purpose: To evaluate whether combining hypothermia and remote ischemic preconditioning (RIPC) results in protection from ischemia-reperfusion (IR). Methods: Thirty-two Wistar rats underwent right nephrectomy and were randomly assigned to four experimental protocols on the left kidney: warm ischemia (group 1), cold ischemia (group 2), RIPC followed by warm ischemia (group 3), and RIPC followed by cold ischemia (group 4). After 240 minutes of reperfusion, histological changes in the left kidney, as well as lipid peroxidation and antioxidant enzyme activity, were analyzed. The right kidney was used as the control. Serum creatinine was collected before and after the procedures. Results: RIPC combined with hypothermia during IR experiments revealed no differences on interventional groups regarding histological changes (p=0.722). Oxidative stress showed no significant variations among the groups. Lower serum creatinine at the end of the procedure was seen in animals exposed to hypothermia (p<0.001). Conclusions: Combination of RIPC and local hypothermia provides no renal protection in IR injury. Hypothermia preserves renal function during ischemic events. Furthermore, RIPC followed by warm IR did not show benefits compared to warm IR alone or controls in our experimental protocol.


Subject(s)
Animals , Male , Rats , Reperfusion Injury/prevention & control , Oxidative Stress/physiology , Ischemic Preconditioning/methods , Hypothermia, Induced/methods , Kidney/blood supply , Superoxide Dismutase/metabolism , Rats, Wistar , Combined Modality Therapy , Disease Models, Animal , Cold Ischemia , Warm Ischemia , Kidney/pathology
5.
Acta Cir Bras ; 33(3): 197-206, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29668777

ABSTRACT

PURPOSE: To evaluate whether their combination was more effective than either alone in decreasing renal damage due to ischemia/reperfusion (I/R) injury in rats. METHODS: Thirty-two Wistar rats were assigned to four groups. Following right nephrectomy, their left kidneys were subjected to warm ischemia (IR), cold ischemia (TH+IR), intraperitoneal injection of 10 mg/kg melatonin (MEL+IR), or injection of 10 mg/kg melatonin followed by cold ischemia (MEL+TH+IR). Eight randomly assigned right kidneys constituted the control group. After 240 min of reperfusion, left nephrectomy was performed for histopathological evaluation, lipid peroxidation, and measurement of antioxidant enzyme activity. Serum was collected to measure urea and creatinine concentrations. RESULTS: Histopathological damage induced by ischemia and reperfusion was more attenuated in the MEL+TH+IR group than in the MEL+IR and TH+IR groups (p<0.037). Superoxide dismutase activity was significantly higher (p<0.029) and creatinine (p<0.001) and urea (p<0.001) concentrations were significantly lower in the MEL+TH+IR group than in the MEL+IR and TH+IR groups. CONCLUSION: The combination of melatonin (MEL) and topical hypothermia (TH) better protects against renal I/R injury than does MEL or TH alone.


Subject(s)
Hypothermia, Induced/methods , Kidney/blood supply , Melatonin/therapeutic use , Reperfusion Injury/prevention & control , Animals , Combined Modality Therapy , Disease Models, Animal , Male , Malondialdehyde/metabolism , Oxidative Stress , Rats , Rats, Wistar , Reperfusion Injury/pathology , Superoxide Dismutase/metabolism
6.
Acta cir. bras ; 33(3): 197-206, Mar. 2018. graf
Article in English | LILACS | ID: biblio-886272

ABSTRACT

Abstract Purpose: To evaluate whether their combination was more effective than either alone in decreasing renal damage due to ischemia/reperfusion (I/R) injury in rats. Methods: Thirty-two Wistar rats were assigned to four groups. Following right nephrectomy, their left kidneys were subjected to warm ischemia (IR), cold ischemia (TH+IR), intraperitoneal injection of 10 mg/kg melatonin (MEL+IR), or injection of 10 mg/kg melatonin followed by cold ischemia (MEL+TH+IR). Eight randomly assigned right kidneys constituted the control group. After 240 min of reperfusion, left nephrectomy was performed for histopathological evaluation, lipid peroxidation, and measurement of antioxidant enzyme activity. Serum was collected to measure urea and creatinine concentrations. Results: Histopathological damage induced by ischemia and reperfusion was more attenuated in the MEL+TH+IR group than in the MEL+IR and TH+IR groups (p<0.037). Superoxide dismutase activity was significantly higher (p<0.029) and creatinine (p<0.001) and urea (p<0.001) concentrations were significantly lower in the MEL+TH+IR group than in the MEL+IR and TH+IR groups. Conclusion: The combination of melatonin (MEL) and topical hypothermia (TH) better protects against renal I/R injury than does MEL or TH alone.


Subject(s)
Animals , Male , Rats , Reperfusion Injury/prevention & control , Hypothermia, Induced/methods , Kidney/blood supply , Melatonin/therapeutic use , Superoxide Dismutase/metabolism , Reperfusion Injury/pathology , Rats, Wistar , Combined Modality Therapy , Oxidative Stress , Disease Models, Animal , Malondialdehyde/metabolism
7.
Acta Cir Bras ; 32(10): 816-826, 2017 Oct.
Article in English | MEDLINE | ID: mdl-29160368

ABSTRACT

PURPOSE: Topical hypothermia and local ischemic preconditioning have been shown to reduce renal ischemia-reperfusion (I/R) injury individually. We examined whether combination of both strategies lessens renal I/R injury. METHODS: Post right nephrectomy, 40 male Wistar rats were randomly assigned to five experimental protocols performed in the left kidney: topical hypothermia without ischemia (TH), warm ischemia (IR), ischemic preconditioning followed by warm ischemia (IPC+IR), cold ischemia (TH+IR), and ischemic preconditioning followed by cold ischemia (IPC+TH+IR). Eight randomly assigned right kidneys constituted the control group. After 240 min of reperfusion, the left kidney was retrieved to evaluate histological changes, lipid peroxidation and antioxidant enzymes activity. Serum was collected to evaluate urea and creatinine. RESULTS: IPC+TH+IR group revealed no difference to any other group subjected to ischemia in relation to histological changes, lipid peroxidation and antioxidant enzymes activity. Creatinine was lower in IPC+TH+IR group compared with IPC+IR, but showed no difference compared to TH+IR group. CONCLUSIONS: Combination of local ischemic preconditioning (IPC) and topical hypothermia conferred no protection in renal I/R injury. Moreover, local IPC solely followed by warm ischemia impaired renal function more than warm ischemia alone.


Subject(s)
Hypothermia, Induced/methods , Ischemic Preconditioning/methods , Kidney/pathology , Reperfusion Injury/prevention & control , Animals , Disease Models, Animal , Kidney/blood supply , Kidney/chemistry , Lipid Peroxidation , Male , Nephrectomy , Random Allocation , Rats , Rats, Wistar , Reperfusion Injury/blood , Reperfusion Injury/pathology
8.
Acta cir. bras ; 32(10): 816-826, Oct. 2017. tab, graf
Article in English | LILACS | ID: biblio-886169

ABSTRACT

Abstract Purpose: Topical hypothermia and local ischemic preconditioning have been shown to reduce renal ischemia-reperfusion (I/R) injury individually. We examined whether combination of both strategies lessens renal I/R injury. Methods: Post right nephrectomy, 40 male Wistar rats were randomly assigned to five experimental protocols performed in the left kidney: topical hypothermia without ischemia (TH), warm ischemia (IR), ischemic preconditioning followed by warm ischemia (IPC+IR), cold ischemia (TH+IR), and ischemic preconditioning followed by cold ischemia (IPC+TH+IR). Eight randomly assigned right kidneys constituted the control group. After 240 min of reperfusion, the left kidney was retrieved to evaluate histological changes, lipid peroxidation and antioxidant enzymes activity. Serum was collected to evaluate urea and creatinine. Results: IPC+TH+IR group revealed no difference to any other group subjected to ischemia in relation to histological changes, lipid peroxidation and antioxidant enzymes activity. Creatinine was lower in IPC+TH+IR group compared with IPC+IR, but showed no difference compared to TH+IR group. Conclusions: Combination of local ischemic preconditioning (IPC) and topical hypothermia conferred no protection in renal I/R injury. Moreover, local IPC solely followed by warm ischemia impaired renal function more than warm ischemia alone.


Subject(s)
Animals , Male , Rats , Reperfusion Injury/prevention & control , Ischemic Preconditioning/methods , Hypothermia, Induced/methods , Kidney/pathology , Lipid Peroxidation , Reperfusion Injury/pathology , Reperfusion Injury/blood , Random Allocation , Rats, Wistar , Disease Models, Animal , Kidney/blood supply , Kidney/chemistry , Nephrectomy
9.
Acta Cir Bras ; 30(7): 445-51, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26270135

ABSTRACT

PURPOSE: To evaluate whether topical renal hypothermia (TRH) at different levels of temperature has protective effects on lung tissue after renal I/R, through an analysis of organ histology and inflammatory markers in lung tissue. METHODS: Twenty-eight male Wistar rats were randomly allocated across four groups and subjected to renal ischemia at different levels of topical renal temperature: normothermia (no cooling, 37°C), mild hypothermia (26°C), moderate hypothermia (15°C), and deep hypothermia (4°C). To induce I/R, the vessels supplying the left kidney of each animal were clamped for 40 minutes, followed by reperfusion. After four hours, another procedure was performed to harvest the tissues of interest. TNF-α, IL-1ß and myeloperoxidase activity were measured in lung tissue. Histological analysis was performed in hematoxylin and eosin-stained lung specimens. RESULTS: Induction of renal I/R under deep topical hypothermia resulted in a significant decrease in lung concentrations of TNF-α compared with normothermic I/R (p<0.05). A trend toward significant correlation was found between lung IL-1ß concentration and intensity of hypothermia (Spearman r=-0.37; p=0.055). No difference was found in myeloperoxidase activity or histologic injury between groups. CONCLUSION: Topical renal hypothermia reduces activation of the inflammatory cascade in the lung parenchyma. However, tissue-protective effects were not observed.


Subject(s)
Hypothermia, Induced/methods , Interleukin-1beta/metabolism , Kidney/blood supply , Lung/blood supply , Peroxidase/metabolism , Reperfusion Injury/metabolism , Tumor Necrosis Factor-alpha/metabolism , Animals , Cold Temperature , Enzyme-Linked Immunosorbent Assay , Kidney/pathology , Lung/pathology , Male , Random Allocation , Rats, Wistar , Reperfusion Injury/etiology , Reproducibility of Results , Time Factors
10.
Acta cir. bras ; 30(7): 445-451, 07/2015. graf
Article in English | LILACS | ID: lil-754978

ABSTRACT

PURPOSE: To evaluate whether topical renal hypothermia (TRH) at different levels of temperature has protective effects on lung tissue after renal I/R, through an analysis of organ histology and inflammatory markers in lung tissue. METHODS: Twenty-eight male Wistar rats were randomly allocated across four groups and subjected to renal ischemia at different levels of topical renal temperature: normothermia (no cooling, 37°C), mild hypothermia (26°C), moderate hypothermia (15°C), and deep hypothermia (4°C). To induce I/R, the vessels supplying the left kidney of each animal were clamped for 40 minutes, followed by reperfusion. After four hours, another procedure was performed to harvest the tissues of interest. TNF-α, IL-1β and myeloperoxidase activity were measured in lung tissue. Histological analysis was performed in hematoxylin and eosin-stained lung specimens. RESULTS: Induction of renal I/R under deep topical hypothermia resulted in a significant decrease in lung concentrations of TNF-α compared with normothermic I/R (p<0.05). A trend toward significant correlation was found between lung IL-1β concentration and intensity of hypothermia (Spearman r=−0.37; p=0.055). No difference was found in myeloperoxidase activity or histologic injury between groups. CONCLUSION: Topical renal hypothermia reduces activation of the inflammatory cascade in the lung parenchyma. However, tissue-protective effects were not observed. .


Subject(s)
Animals , Male , Hypothermia, Induced/methods , Interleukin-1beta/metabolism , Kidney/blood supply , Lung/blood supply , Peroxidase/metabolism , Reperfusion Injury/metabolism , Tumor Necrosis Factor-alpha/metabolism , Cold Temperature , Enzyme-Linked Immunosorbent Assay , Kidney/pathology , Lung/pathology , Random Allocation , Rats, Wistar , Reproducibility of Results , Reperfusion Injury/etiology , Time Factors
11.
Acta cir. bras ; 28(8): 568-573, Aug. 2013. ilus, graf
Article in English | LILACS | ID: lil-680610

ABSTRACT

PURPOSE:To design an animal model of ischemia-reperfusion (I/R) in kidneys and evaluate the role that predetermined ranges of local hypothermia plays on markers of stress-oxydative as well as on histologic sections. METHODS: Twenty eight male rats Wistar, under general anesthesia, undergone right nephrectomy (G0, control group) followed by left kidney ischemia during 40 min. Four temperatures groups were designed, with seven animals randomized for each group: normothermic (G1, ±37ºC), mild hypothermia (G2, 26ºC), moderate hypothermia (G3, 15ºC) and deep hypothermia (G4, 4ºC). Left kidney temperature was assessed with an intraparenchymal probe. Left nephrectomy was performed after 240 min of reperfusion. After I/R a blood sample was obtained for f2-IP. Half of each kidney was sent to pathological evaluation and half to analyze CAT, SOD, TBARS, NO3, NO2. RESULTS:Histopathology showed that all kidneys under I/R were significantly more injured than the G0 (p<0.001). TBARS had increased levels in all I/R groups compared with the G0 (p<0.001). CAT had a significant difference (p<0.03) between G1 and G4. Finally, no difference was found on SOD, NO3, NO2 nor on f2-IP. CONCLUSION: This model of I/R was efficient to produce oxidative-stress in the kidney, showing that 4ºC offered significant decrease in free radicals production, although tissue protection was not observed.


Subject(s)
Animals , Male , Rats , Hypothermia, Induced , Ischemia/metabolism , Kidney/blood supply , Oxidative Stress/physiology , Reperfusion Injury/metabolism , Biomarkers , Free Radicals/metabolism , Kidney/metabolism , Kidney/pathology , Lipid Peroxidation , Models, Animal , Nephrectomy , Nitric Oxide/metabolism , Random Allocation , Rats, Wistar , Reperfusion Injury/pathology , Time Factors
12.
Acta Cir Bras ; 28(8): 568-73, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23896835

ABSTRACT

PURPOSE: To design an animal model of ischemia-reperfusion (I/R) in kidneys and evaluate the role that predetermined ranges of local hypothermia plays on markers of stress-oxydative as well as on histologic sections. METHODS: Twenty eight male rats Wistar, under general anesthesia, undergone right nephrectomy (G0, control group) followed by left kidney ischemia during 40 min. Four temperatures groups were designed, with seven animals randomized for each group: normothermic (G1, ±37ºC), mild hypothermia (G2, 26ºC), moderate hypothermia (G3, 15ºC) and deep hypothermia (G4, 4ºC). Left kidney temperature was assessed with an intraparenchymal probe. Left nephrectomy was performed after 240 min of reperfusion. After I/R a blood sample was obtained for f2-IP. Half of each kidney was sent to pathological evaluation and half to analyze CAT, SOD, TBARS, NO3, NO2. RESULTS: Histopathology showed that all kidneys under I/R were significantly more injured than the G0 (p<0.001). TBARS had increased levels in all I/R groups compared with the G0 (p<0.001). CAT had a significant difference (p<0.03) between G1 and G4. Finally, no difference was found on SOD, NO3, NO2 nor on f2-IP. CONCLUSION: This model of I/R was efficient to produce oxidative-stress in the kidney, showing that 4ºC offered significant decrease in free radicals production, although tissue protection was not observed.


Subject(s)
Hypothermia, Induced , Ischemia/metabolism , Kidney/blood supply , Oxidative Stress/physiology , Reperfusion Injury/metabolism , Animals , Biomarkers , Free Radicals/metabolism , Kidney/metabolism , Kidney/pathology , Lipid Peroxidation , Male , Models, Animal , Nephrectomy , Nitric Oxide/metabolism , Random Allocation , Rats , Rats, Wistar , Reperfusion Injury/pathology , Time Factors
13.
J. bras. nefrol ; 34(4): 387-391, out.-dez. 2012. ilus
Article in Portuguese | LILACS | ID: lil-660553

ABSTRACT

Recentemente, o transplante renal passou a ser uma modalidade terapêutica aceita para o tratamento de pacientes renais crônicos terminais infectados pelo HIV. Para tal, há necessidade de estabilidade de parâmetros clínicos e laboratoriais relacionados à infecção pelo HIV e do uso de terapia antiretroviral de elevada eficiência. Neste relato, apresentamos os dois primeiros casos no Brasil de pacientes portadores de infecção pelo HIV transplantados com órgãos de doadores falecidos realizados com sucesso em nossa instituição. As interações entre os imunossupressores e as drogas antiretrovirais, as coinfecções, o perfil de risco cardiovascular e a elevada incidência de rejeição aguda permanecem os maiores problemas a serem equacionados nestes pacientes.


Recently kidney transplantation has become an accepted treatment modality for the treatment of HIV infected patients with end-stage renal diseases. For such treatment it is required stability of clinical and laboratory parameters related to HIV infection and the use of highly active antiretroviral therapy. In this report we present the first two cases in Brazil of patients with HIV infection transplanted with organs from deceased donors performed successfully in our institution. The interactions between immunosuppressive and antiretroviral drugs, the co-infections, cardiovascular risk profile and the high incidence of acute rejection remain the major problems to be dealt with in these patients.


Subject(s)
Adult , Female , Humans , Middle Aged , HIV Seropositivity/complications , Kidney Transplantation , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/surgery , Hospitals
14.
J Bras Nefrol ; 34(4): 387-91, 2012.
Article in Portuguese | MEDLINE | ID: mdl-23318828

ABSTRACT

Recently kidney transplantation has become an accepted treatment modality for the treatment of HIV infected patients with end-stage renal diseases. For such treatment it is required stability of clinical and laboratory parameters related to HIV infection and the use of highly active antiretroviral therapy. In this report we present the first two cases in Brazil of patients with HIV infection transplanted with organs from deceased donors performed successfully in our institution. The interactions between immunosuppressive and antiretroviral drugs, the co-infections, cardiovascular risk profile and the high incidence of acute rejection remain the major problems to be dealt with in these patients.


Subject(s)
HIV Seropositivity/complications , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/surgery , Kidney Transplantation , Adult , Female , Hospitals , Humans , Middle Aged
15.
Appl. cancer res ; 29(2): 65-68, Apr.-June 2009. ilus
Article in English | LILACS, Inca | ID: lil-547667

ABSTRACT

Objectives: We are proposing the adaptation of a method for the assessment of the activity of 5 alpha-reductase type 1 and type 2 isoenzymes in human prostate tissue to be used in studies of the relationship of enzymatic activity and cancer. Material and Methods: We have been developing a method, based on Thomas et al., 2003 which consists of collecting human prostate samples and performing 5 alpha-reductase activity assessment. We are proposing a method based on samples obtained from prostate biopsies, according to a pilot study developed by Oliveira et al. 2006. We have obtained two samples of the same prostate area, and our idea is to send one of these samples for pathological examination and another for 5 alpha-reductase evaluation. Herein we have showed the feasibility of this assay. Through a thin layer chromatography with 14C-testosterone and NADPH (nicotinamide adenine dinucleotide phosphate) cofactor, we have obtained radioactive spots which were detected by autoradiography. The areas associated with testosterone and its metabolite DHT (dihydrotestosterone) were scrapped and counted with a scintillation chamber. Results: We believe that it is possible to demonstrate the activity of 5 alpha-reductase through the adaptation of this biochemistry method. Conclusions: This method is feasible and can be utilized to assess 5 alpha-reductase type 1 and type 2 activity in prostate tissue samples.


Subject(s)
Humans , Male , Adult , Androgens , Prostatectomy , Prostatic Neoplasms
16.
Neoplasia ; 10(9): 996-1003, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18714401

ABSTRACT

The tyrosine kinase receptor c-kit and its ligand stem cell factor (SCF) have not been explored in prostate cancer (PC) bone metastasis. Herein, we found that three human PC cell lines and bone marrow stromal cells express a membrane-bound SCF isoform and release a soluble SCF. Bone marrow stromal cells revealed strong expression of c-kit, whereas PC cells showed very low levels of the receptor or did not express it all. Using an experimental model of PC bone metastasis, we found that intraosseous bone tumors formed by otherwise c-kit-negative PC3 cells strongly expressed c-kit, as demonstrated using immunohistochemical and Western blot analyses. Subcutaneous PC3 tumors were, however, c-kit-negative. Both bone and subcutaneous PC3 tumors were positive for SCF. Immunohistochemical analysis of human specimens revealed that the expression frequency of c-kit in epithelial cells was of 5% in benign prostatic hyperplasia, 14% in primary PC, and 40% in PC bone metastases, suggesting an overall trend of increased c-kit expression in clinical PC progression. Stem cell factor expression frequency was more than 80% in all the cases. Our data suggest that the bone microenvironment up-regulates c-kit expression on PC cells, favoring their intraosseous expansion.


Subject(s)
Bone Neoplasms/genetics , Prostatic Neoplasms/genetics , Proto-Oncogene Proteins c-kit/biosynthesis , Stem Cell Factor/metabolism , Up-Regulation , Animals , Bone Neoplasms/secondary , Cell Culture Techniques , Gene Expression Regulation, Neoplastic , Humans , Ligands , Male , Mice , Prostatic Neoplasms/pathology , Reverse Transcriptase Polymerase Chain Reaction
17.
Int J Cancer ; 122(11): 2482-90, 2008 Jun 01.
Article in English | MEDLINE | ID: mdl-18324629

ABSTRACT

At the cellular level, the process of bone metastasis involves many steps. Circulating cancer cells enter the marrow, proliferate, induce neovascularization, and ultimately expand into a clinically detectable, often symptomatic, metastatic deposit. Although the initial establishment and later expansion of the metastatic deposit in bone require tumor cells to possess invasive capability, the exact proteases responsible for this phenotype are not well known. The objective of our study was to take an unbiased approach to determine which proteases were expressed and functional during the initial interactions between prostate cancer cells and bone marrow stromal (BMS) cells. We found that the combination of human prostate cancer PC3 and BMS cells stimulates the invasive ability of cancer cells through type I collagen. The use of inhibitors for each of the major protease families indicated that 1 or more MMPs was/were responsible for the BMS-induced invasion. Gene profiling and semiquantitative RT-PCR analysis revealed an increased expression of several MMP genes because of PC3/BMS cell interaction. However, only MMP-12 showed an increase in protein expression. Downregulation of MMP-12 expression in PC3 cells by siRNA inhibited the enhanced invasion induced by PC3/BMS cell interaction. In vivo, MMP-12 was found to be primarily expressed by prostate cancer cells growing in bone. Our data suggest that BMS cells induce MMP-12 expression in prostate cancer cells, which results in invasive cells capable of degradation of type I collagen.


Subject(s)
Bone Marrow Cells/pathology , Collagen Type I/metabolism , Matrix Metalloproteinase 12/metabolism , Prostatic Neoplasms/enzymology , Prostatic Neoplasms/pathology , Stromal Cells/pathology , Blotting, Western , Cell Line, Tumor , Coculture Techniques , Down-Regulation , Flow Cytometry , Gene Expression Profiling , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Keratins/analysis , Male , Matrix Metalloproteinases/metabolism , Neoplasm Invasiveness , RNA, Small Interfering , Reverse Transcriptase Polymerase Chain Reaction , Transfection , Up-Regulation
18.
Clin Chim Acta ; 391(1-2): 36-40, 2008 May.
Article in English | MEDLINE | ID: mdl-18328817

ABSTRACT

BACKGROUND: The conversion of testosterone (T) to the more potent metabolite dihydrotestosterone (DHT) by prostate-specific steroid 5 alpha-reductase isoenzymes is a key mechanism in the action of androgens in the prostate and it is important in the promotion and progression of prostate diseases. We described an adaptation of a sensitive method for evaluation of the 5 alpha-reductase type 2 (5 alpha-R2) activity using a small quantity of protein. METHODS: We used 29 human prostate transrectal ultrasound-guided core biopsies obtained from patients (median age 70, range 55-86 y) undergoing this procedure for diagnostic purposes. 4-[(14)C]testosterone and NADPH were incubated with biopsy homogenate. Reaction products were extracted, separated by thin layer chromatography and revealed by autoradiography. Areas correspondent to T and DHT were scraped into vials and their radioactivity determined. RESULTS: The 5 alpha-R2 activity was expressed as ln (natural logarithm). The assay was validated according to the protein concentration and incubation time linearities. The 5 alpha-R2 activity showed a significant difference between normal and neoplastic tissues with significance level set at P<0.05, mainly in the left prostate lobe. This was independent from the PSA levels. CONCLUSIONS: Determination of 5 alpha-R2 activity, using the conditions reported herein, could be utilized as an efficient biochemical parameter of prostate neoplastic processes.


Subject(s)
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism , Dihydrotestosterone/metabolism , Prostate/enzymology , Prostatic Hyperplasia/enzymology , Prostatic Neoplasms/enzymology , Testosterone/metabolism , Aged , Aged, 80 and over , Biopsy , Humans , Male , Middle Aged
19.
Rev. AMRIGS ; 40(2): 136-41, abr.-jun. 1996. tab
Article in Portuguese | LILACS | ID: lil-181841

ABSTRACT

Estudos prévios sugerem que o tempo de lazer diminui progressivamente durante o curso médico, e que a reduçäo de qualidade de vida pode se refletir na reduçäo do desempenho curricular. Näo há relatos de associaçäo entre a quantidade de lazer e a performance acadêmica. Para avaliar essa associaçäo, foi realizdo estudo de corte transversal controlado, onde se aferiram as horas semanais de lazer e o escore de desempenho acadêmico de 77 estudantes da Faculdade de Medicina da Universidade Federal do Rio Grande do Sul. Observou-se ausência de associaçäo entre lazer e desempenho (risco relativo de 1,1 e P=0,9553). Houve uma discreta correlaçäo positiva entre a valorizaçäo do conceito e as horas semanais de lazer (r=-0,23 +/-0,22). Estes resultados permitem concluir que näo foi observada associaçäo entre horas semanais de lazer e desempenho


Subject(s)
Humans , Adult , Leisure Activities , Students, Medical/psychology , Employee Performance Appraisal , Cross-Sectional Studies , Quality of Life
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