Concomitant transrectal ultrasound-guided biopsy and transurethral resection of prostate in patients with urinary retention and elevated serum prostate-specific antigen levels.

BACKGROUND: There was no consensus about the management of patients with urinary retention and elevated serum prostate-specific antigen (PSA) levels. This study aimed to determine whether concomitant transrectal ultrasound (TRUS)-guided biopsy and transurethral resection of prostate (TURP) is practical in patients with urinary retention and elevated serum PSA levels. METHODS: From March 2007 to May 2015, a total of 34 patients with urinary retention and elevated PSA (≥ 4 ng/mL) underwent concomitant TRUS-guided biopsy and TURP. The medical records were evaluated retrospectively, and data including PSA, prostate volume, TURP results, TRUS-guided biopsy results, length of hospitalization, and complications were collected. These patients were then compared with 40 patients with urinary retention who underwent TURP alone. RESULTS: The mean age of the patients was 71.6 years. The mean PSA levels were 16.9 ng/mL. Prostate cancer was detected in eight cases (23.5%): one case by TRUS-guided biopsy alone, two cases by TURP alone, and five cases by both TRUS-guided biopsy and TURP. Complications included fever in five patients (14.7%), recatheterization for urine retention in two patients (5.9%), urinary tract infection in two patients (5.9%), and de novo urge incontinence in seven patients (20.6%). The complication rate was not significantly increased compared with that of the patients who underwent TURP alone. CONCLUSION: This study showed that concomitant TRUS-guided biopsy and TURP was safe and of possible clinical significance in urinary retention patients with elevated serum PSA.

Mutations in pseudohypoparathyroidism 1a and pseudopseudohypoparathyroidism in ethnic Chinese.

An inactivating mutation in the GNAS gene causes either pseudohypoparathyroidism 1a (PHP1A) when it is maternally inherited or pseudopseudohypoparathyroidism (PPHP) when it is paternally inherited. We investigated clinical manifestations and mutations of the GNAS gene in ethnic Chinese patients with PHP1A or PPHP. Seven patients from 5 families including 4 girls and 2 boys with PHP1A and 1 girl with PPHP were studied. All PHP1A patients had mental retardation. They were treated with calcitriol and CaCO3 with regular monitoring of serum Ca levels, urinary Ca/Cr ratios, and renal sonography. Among them, 5 patients also had primary hypothyroidism suggesting TSH resistance. One female patient had a renal stone which was treated with extracorporeal shockwave lithotripsy. She had an increased urinary Ca/Cr ratio of 0.481 mg/mg when the stone was detected. We detected mutations using PCR and sequencing as well as analysed a splice acceptor site mutation using RT-PCR, sequencing, and minigene construct. We detected 5 mutations: c.85C>T (Q29*), c.103C>T (Q35*), c.840-2A>G (R280Sfs*21), c.1027_1028delGA (D343*), and c.1174G>A (E392K). Mutations c.840-2A>G and c.1027_1028delGA were novel. The c.840-2A>G mutation at the splice acceptor site of intron 10 caused retention of intron 10 in the minigene construct but skipping of exon 11 in the peripheral blood cells. The latter was the most probable mechanism which caused a frameshift, changing Arg to Ser at residue 280 and invoking a premature termination of translation at codon 300 (R280Sfs*21). Five GNAS mutations in ethnic Chinese with PHP1A and PPHP were reported. Two of them were novel. Mutation c.840-2A>G destroyed a spice acceptor site and caused exon skipping. Regular monitoring and adjustment in therapy are mandatory to achieve optimal therapeutic effects and avoid nephrolithiasis in patients with PHP1A.

Primary prostatic Wilms' tumor: a case report.

BACKGROUND: Extrarenal Wilms' tumors (EWTs) are very rare, and a single case of prostatic EWT has been reported in the English-language literature. CASE: A 46-year-old man presenting with lower urinary tract symptoms was diagnosed with a prostatic tumor histologically proven to be a EWT. CONCLUSION: During the evaluation of a patient with a prostatic tumor, more common prostatic neoplasms such as adenocarcinoma, transitional cell carcinoma and carcinosarcoma must first be considered. However, the presence of a primary prostatic Wilms' tumor must also be taken into consideration.

Simvastatin attenuates testicular injury induced by torsion-detorsion.

PURPOSE: The lipid lowering agent simvastatin has potent anti-oxidation capacity. We elucidated the potential of simvastatin to attenuate testicular injury induced by testicular torsion-detorsion. We also investigated simvastatin effects on nuclear factor-kappaB expression. MATERIALS AND METHODS: We allocated 60 adult male Sprague-Dawley(R) rats to testicular torsion-detorsion, torsion-detorsion plus simvastatin (1 or 5 mg/kg), sham operation or sham operation plus simvastatin (5 mg/kg). There were 12 rats per group. Simvastatin was administered immediately after detorsion or immediately after sham operation. Testes were harvested 30 minutes and 24 hours after detorsion to facilitate the evaluation of nuclear factor-kappaB and testicular injury, respectively. RESULTS: Histological findings revealed severe injury in testes of the torsion-detorsion and torsion-detorsion-simvastatin (1 mg/kg) groups while testes in the torsion-detorsion-simvastatin (5 mg/kg) group showed moderate injury. Myeloperoxidase activity, and cytokines, nitric oxide and malondialdehyde in testes in the torsion-detorsion-simvastatin (5 mg/kg) group were significantly lower than in the torsion-detorsion group. Values were comparable in the torsion-detorsion-simvastatin (1 mg/kg) and torsion-detorsion groups. Testicular concentrations of nuclear factor-kappaB in nuclear extracts and phosphorylated inhibitor-kappaB in cytosolic extracts in the torsion-detorsion-simvastatin (5 mg/kg) group were significantly lower than in the torsion-detorsion group. Values were comparable in the torsion-detorsion-simvastatin (1 mg/kg) and torsion-detorsion groups. CONCLUSIONS: Simvastatin protected testes from torsion-detorsion injury in a dose dependent manner. Mechanisms may involve attenuating nuclear factor-kappaB activation and decreasing oxidative stress induced by torsion-detorsion.

Common variants at 8q24 are associated with prostate cancer risk in Taiwanese men.

BACKGROUND: Recently, independent genome-wide scans have found multiple genetic variants at 8q24 to be associated with prostate cancer risk. This study was performed to determine whether two of the variants more strongly associated with prostate cancer risk in European and American populations, specifically rs16901979 and rs6983561, were also associated with prostate cancer risk in Taiwanese men. METHODS: We conducted a case-control study comprising of 340 prostate patients and 336 healthy controls. Genotyping was performed for rs16901979 and rs6983561. Their association with disease stage, tumor grade, PSA level and disease aggressiveness was also determined. RESULTS: The risk allele A of rs16901979 was associated with a 1.28-fold increase in prostate cancer risk (P = 0.046), and the risk allele C of rs6983561 was associated with a 1.40-fold increase in prostate cancer risk (P = 0.006). When compared with controls, the risk allele of rs6983561 was more frequent in patients with more aggressive disease. Analysis of the cumulative risk of rs1447295, a confirmed risk variant, and one of these markers showed that compared to men who do not have any of these risk variants, men who carry any combination of 1 or 2 risk genotypes have a gradually increased prostate cancer risk (P for trend <0.001). CONCLUSION: The variants rs16901979 and rs6983561 at 8q24 are associated with prostate cancer risk in Taiwanese men.

The rs1447295 at 8q24 is a risk variant for prostate cancer in Taiwanese men.

OBJECTIVES: To determine the association of a common variant, rs1447295, at the 8q24 region with prostate cancer (PCa) risk in Taiwanese men. Common variants at the 8q24 region have been shown to be associated with PCa risk. The variant rs1447295 has shown the strongest association. Most of the studies have been performed in European and American populations. METHODS: This case-control study comprised 340 PCa patients and 337 controls. Genotyping was performed for rs14417295 to test for the association between its risk allele and PCa. Its association with disease stage, Gleason score, PSA level, and disease aggressiveness was also determined. RESULTS: The A allele of rs1447295 was significantly associated with increased PCa risk (odds ratio = 1.49, 95% CI = 1.12-1.99). When compared with controls, the risk allele A was more frequent in PCa patients of both stages I+II (P = .028) and stages III+IV (P = .023), in patients of all Gleason scores (P < .05 in all subgroups), in patients with PSA levels >20 ng/mL (P = .001), and in patients with aggressive disease (P = .005). CONCLUSIONS: This study confirmed that the A allele of rs1447295 is associated with a high risk of PCa in Taiwanese men.

Catheter-assisted transurethral resection of the prostate: a novel approach.

INTRODUCTION: The aim of the study was to compare the safety and efficacy of catheter-assisted transurethral resection of the prostate (TURP) with traditional TURP in the treatment of benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 61 men were randomized to either catheter-assisted TURP (30 patients) or traditional TURP (31), both performed with a monopolar device. Measurements included the duration of Foley catheterization, length of hospital stay, symptom score and urinary flow rate. All patients were followed for at least 1 year after surgery. RESULTS: The catheter-assisted group had a significantly shorter operative time, duration of postoperative catheterization and length of stay. There were no significant differences in changes in serum sodium and hemoglobin level on postoperative day 1. At 1 year postoperatively, none of the patients suffered from urethral stricture and the 2 groups did not differ significantly in terms of prostatic volume, peak flow rate or International Prostate Symptom Score. CONCLUSIONS: Catheter-assisted TURP is safe and produced results at 1 year similar to traditional TURP. This new method for TURP appears to be a better and more effective approach than the traditional method, although a longer period of observation is needed to assess the durability of the results.

Hemin induced heme oxygenase-1 over expression involves nuclear factor-E2 related factor-2, nuclear factor-kappaB and extracellular regulated kinase: an experimental study in a testicular torsion-detorsion rodent model.

PURPOSE: Nrf2 (nuclear factor-E2 related factor-2), nuclear factor-kappaB and mitogen-activated protein kinase, including extracellular regulated kinase, c-jun N-terminal kinase and p38 mitogen-activated protein kinase, are crucial for signal transduction. We previously reported that heme oxygenase-1 over expression induced by the heme oxygenase-1 inducer hemin protected testes from torsion-detorsion injury. In this study we elucidated which of these enzymes is involved in hemin induced heme oxygenase-1 over expression in testicular tissues after torsion-detorsion injury. MATERIALS AND METHODS: Adult male Sprague-Dawley rats (National Science Council, Taipei, Taiwan, Republic of China) were allocated to undergo testicular torsion-detorsion immediately followed by injection of normal saline, hemin or hemin plus tin protoporphyrin, a heme oxygenase-1 inhibitor. Another set of rats that underwent sham operation were used as controls. Testes were harvested 0 and 30 minutes after detorsion and enzyme expression was analyzed. RESULTS: Hemin alone caused no significant effects on the expression of Nrf2, nuclear factor-kappaB, extracellular regulated kinase and c-jun N-terminal kinase. Similarly testicular torsion-detorsion injury caused no significant effects on Nrf2 expression. In the presence of torsion-detorsion injury hemin significantly up-regulated Nrf2 expression. Moreover, this effect was not affected by tin protoporphyrin. Unlike Nrf2, the expression of nuclear factor-kappaB, extracellular regulated kinase and c-jun N-terminal kinase was significantly up-regulated by testicular torsion-detorsion. Hemin significantly attenuated the testicular torsion-detorsion induced up-regulation of nuclear factor-kappaB and extracellular regulated kinase but not c-jun N-terminal kinase. The effects of hemin on nuclear factor-kappaB and extracellular regulated kinase were significantly reversed by tin protoporphyrin. However, the expression of p38 mitogen-activated protein kinase in rodent testes was not affected by these interventions. CONCLUSIONS: Hemin induced heme oxygenase-1 over expression in rodent testes after torsion-detorsion injury involves Nrf2, nuclear factor-kappaB and extracellular regulated kinase.

CYP19 TCT tri-nucleotide Del/Del genotype is a susceptibility marker for prostate cancer in a Taiwanese population.

OBJECTIVES: The CYP19 gene encodes aromatase--a key enzyme involved in the conversion of androstenedione/testosterone to estrone/estradiol. In this study, we analyzed the association between the TCT insertion (Ins)/deletion (Del) and TTTA repeat polymorphisms of CYP19 and prostate cancer (PCa). METHODS: Automated sequencer with GeneScan software was used to determine the CYP19 gene polymorphisms in peripheral blood mononuclear cell DNA from 244 patients with PCa and 261 age-matched healthy male controls. The distribution of Stage I to IV was 3.4%, 23.8%, 19.6%, and 53.2%, respectively. The Gleason score was 2 to 5 in 22.9%, 6 to 7 in 53.2%, and 8 to 10 in 23.8%. RESULTS: The frequency of the TCT Del/Del genotype in the Taiwanese patients with PCa (12.3%) was significantly greater than that in the controls (5.4%; P = 0.015, odds ratio [OR] 2.43, 95% confidence interval [CI] 1.23 to 4.80). Individuals with a homozygous A1 (seven TTTA repeats) genotype had a significantly greater risk of developing PCa (OR 1.59, 95% CI 1.04 to 2.44, P = 0.044). The frequency of the Ins-A6 (12 TTTA repeats) haplotype was significantly greater in the control group than in the patient group (9.8% versus 6.1%, OR 0.61, 95% CI 0.38 to 0.97). The OR of developing PCa for men with the homozygous Del-A1 diplotype was 2.31 (95% CI 1.10 to 4.83). CONCLUSIONS: The results of our study have shown that the CYP19 TCT Del/Del genotype might be a susceptibility marker for PCa. Men with the Ins-A6 haplotype had a lower risk of developing PCa.

The protective role of heme oxygenase-1 induction on testicular tissues after testicular torsion and detorsion.

PURPOSE: Testicular torsion-detorsion has been identified as an ischemia-reperfusion type of injury. We elucidated the protective role of heme oxygenase-1 super induction on testicular torsion-detorsion injury. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were randomly allocated to undergo testicular torsion-detorsion, immediately followed by injection of normal saline, the heme oxygenase-1 inducer hemin or hemin plus the heme oxygenase-1 inhibitor tin protoporphyrin. Another set of rats that underwent sham operation, immediately followed by injection of normal saline, hemin or hemin plus tin protoporphyrin, served as controls. Testes were harvested 4 and 24 hours after detorsion, respectively, in the experimental groups or at comparable time points in the control groups. RESULTS: Histological evaluation confirmed that torsion-detorsion caused significant testicular tissue injury. Torsion-detorsion also caused significant increases in the testicular levels of nitric oxide, malondialdehyde, myeloperoxidase activity and heme oxygenase-1. The heme oxygenase-1 inducer hemin significantly enhanced the heme oxygenase-1 expression induced by torsion-detorsion and in turn attenuated testicular injury, and increases in nitric oxide, malondialdehyde and myeloperoxidase activity. In addition, the protective effects of hemin were significantly offset by the heme oxygenase-1 inhibitor tin protoporphyrin. CONCLUSIONS: Super induction of heme oxygenase-1 protects testes from torsion-detorsion injury.

Haplotypes, loss of heterozygosity, and expression levels of glycine N-methyltransferase in prostate cancer.

PURPOSE: Glycine N-methyltransferase (GNMT) affects genetic stability by regulating DNA methylation and interacting with environmental carcinogens. In a previous study, we showed that GNMT acts as a susceptibility gene for hepatocellular carcinoma. Here, we report on our efforts to characterize the haplotypes, loss of heterozygosity (LOH), and expression levels of the GNMT in prostate cancer. EXPERIMENTAL DESIGN: Peripheral blood mononuclear cell DNA collected from 326 prostate cancer patients and 327 age-matched controls was used to determine GNMT haplotypes. Luciferase reporter constructs were used to compare the promoter activity of different GNMT haplotypes. GNMT LOH rates in tumorous specimens were investigated via a comparison with peripheral blood mononuclear cell genotypes. Immunohistochemical staining was used to analyze GNMT expression in tissue specimens collected from 5 normal individuals, 33 benign prostatic hyperplasia patients, and 45 prostate cancer patients. RESULTS: Three major GNMT haplotypes were identified in 92% of the participants: A, 16GAs/DEL/C (58%); B, 10GAs/INS/C (19.9%); and C, 10GAs/INS/T (14.5%). Haplotype C carriers had significantly lower risk for prostate cancer compared with individuals with haplotype A (odds ratio, 0.68; 95% confidence interval, 0.48-0.95). Results from a phenotypic analysis showed that haplotype C exhibited the highest promoter activity (P < 0.05, ANOVA test). In addition, 36.4% (8 of 22) of the prostatic tumor tissues had LOH of the GNMT gene. Immunohistochemical staining results showed abundant GNMT expression in normal prostatic and benign prostatic hyperplasia tissues, whereas it was diminished in 82.2% (37 of 45) of the prostate cancer tissues. CONCLUSIONS: Our findings suggest that GNMT is a tumor susceptibility gene for prostate cancer.

Prophylactic intravesical instillation of epinephrine prevents cyclophosphamide-induced hemorrhagic cystitis in rats.

The objective of this study is to investigate the potential protective effects of intravesical instillation of epinephrine in cyclophosphamide-induced hemorrhagic cystitis. In an earlier study, we have shown that epinephrine promotes hemostasis on established hemorrhagic cystitis induced by cyclophosphamide. Female Sprague-Dawley rats were divided into seven groups as follows: group 1: positive control (150 mg/kg, cyclophosphamide, i.p.), group 2: negative control (10 microg/ml, epinephrine, intravesical), co-administration of cyclophosphamide (150 mg/kg, i.p.), group 3: saline (intravesical), groups 4-6: epinephrine (2.5, 5, and 10 mu g/ml, intravesical), and group 7: mesna (50 mg/kg, i.p.). Rats were sacrificed on 3 consecutive days and the urinary bladders were removed, weighed, and evaluated. The vesical vascular permeability was determined by wet bladder weight and Evan's blue dye absorbance. After 24 hours of cyclophosphamide administration, severe hemorrhagic cystitis was induced with marked edema, hemorrhage, and inflammation. In the epinephrine-treated groups, symptoms of hemorrhagic cystitis (such as edema, inflammation, and hemorrhage) were reduced significantly. Intravesical instillation of epinephrine prevents edema, hemorrhage, and inflammation in rats with cyclophosphamide-induced hemorrhagic cystitis.

Testicular metastasis from hepatocellular carcinoma.

We document a case of testicular metastasis from hepatocellular carcinoma. The patient suffered from bilateral testicular painful swelling for 6 months. Scrotal ultrasonography showed bilateral testicular tumors and the whole abdominal computed tomography revealed a huge tumor in the left lobe of the liver. Bilateral orchiectomy and postoperative ultrasound-guided liver biopsy were done. Pathological examination revealed metastatic hepatocellular carcinoma. Hepatocellular carcinoma with testicular metastases is a very rare disease.

HO-1 mediates the effects of HBO pretreatment against sepsis.

BACKGROUND: We have recently shown that attenuation of sepsis-induced lung injury by hyperbaric oxygen (HBO) pretreatment involves expression regulation of inducible nitric oxide synthase (iNOS) and heme oxygenase (HO)-1. This study was performed to determine the effects of HBO pretreatment on acute kidney and liver injuries in septic rats and the roles of iNOS and HO-1. MATERIALS AND METHODS: One group of adult male rats (n = 48) were pretreated with HBO. The other group of rats (n = 48) breathed air at normal atmospheric pressure instead. Rats in each group were randomly allocated to receive injection of lipopolysaccharide (LPS), normal saline (N/S), LPS plus hemin (a HO-1 inducer), hemin, LPS plus SnPP (a HO-1 inhibitor), SnPP, LPS plus hemin plus SnPP, or hemin plus SnPP. Hemin and SnPP were injected at 1 h before HBO or air pretreatment. Rats were maintained for 6 h before sacrifice. RESULTS: LPS caused prominent kidney and liver injuries as well as iNOS and HO-1 expression in stimulated rats. HBO pretreatment significantly attenuated LPS-induced kidney but not liver injury. However, in conjunction with hemin (a HO-1 inducer), HBO pretreatment did attenuate LPS-induced liver injury. In addition, the inhibition of iNOS expression by HBO pretreatment was associated with "super-induction" (i.e., further enhancement) of LPS-induced HO-1 expression. Furthermore, the therapeutic effect of HBO could be counteracted by SnPP (a HO-1 inhibitor). CONCLUSIONS: HBO pretreatment significantly attenuates LPS-induced acute organ injuries in septic rats. The beneficial effect of HBO pretreatment against sepsis is mediated, at least in part, by "super-induction" of HO-1.

Ureteral carcinoid tumor.

Most ureteral tumors are transitional cell neoplasms. Neuroendocrine tumors of the genitourinary tract are extremely rare. To our knowledge, only one ureteral carcinoid tumor has been reported before. We report a second case of ureteral carcinoid tumor found in a 70-year-old female.

Renal cell carcinoma producing granulocyte colony-stimulating factor.

Severe neutrophilia caused by renal cell carcinoma secreting granulocyte colony-stimulating factor (G-CSF) is a rare manifestation of renal cancer. A 70-year-old woman presented with a 2-year history of severe anemia, severe neutrophilia and elevated serum G-CSF, which completely resolved after radical nephrectomy. Histologic study revealed a histologically high-grade, stage pT1N0M0 renal cell carcinoma. Serum G-CSF level was elevated preoperatively and returned to normal postoperatively. Immunohistochemical study of the tumor tissue using anti-G-CSF monoclonal antibody revealed positive staining in the cancer cells. Careful follow-up of white blood cell count and physical examination for neck lymph node enlargement led to the timely identification of tumor recurrence 17 months after surgery, which resulted in prompt and successful salvage immunotherapy. In this case, G-CSF appeared to contribute to the leukocytosis, as both serum G-CSF level and white blood cell count closely correlated with the clinical tumor growth. White blood cell count should be closely monitored as an indicator of disease activity in patients with G-CSF-producing renal cell carcinoma.

Epinephrine promotes hemostasis in rats with cyclophosphamide-induced hemorrhagic cystitis.

OBJECTIVES: To evaluate the hypothesis that intravesical instillation of epinephrine would attenuate bladder hemorrhage in a rat model of cyclophosphamide (CYP)-induced hemorrhagic cystitis. METHODS: Female Sprague-Dawley rats were divided into seven treatment groups: positive control (CYP, 150 mg/kg), negative control (epinephrine, 10 microg/mL), intravesical instillation of normal saline (vehicle) and epinephrine (2.5, 5, and 10 microg/mL), and intraperitoneal administration of mesna (50 mg/kg). Rats were killed on days 1, 2, and 3, and the urinary bladders were removed, weighed, and evaluated by gross and histologic analysis. Vesical vascular permeability was determined by wet bladder weight and Evan's blue dye absorbance. RESULTS: Cyclophosphamide administration induced severe hemorrhagic cystitis with marked edema, hemorrhage, and inflammation. All three epinephrine-treated groups had marked attenuation of hemorrhagic cystitis compared with the positive and negative control and mesna-treated groups. Epinephrine was also associated with significant inhibition of tissue edema, indicating decreased vesical vascular permeability. CONCLUSIONS: In this rat model of CYP-induced hemorrhagic cystitis, intravesical instillation of epinephrine inhibited edema, hemorrhage, and inflammation.

Modulation of monocyte-derived dendritic cell differentiation is associated with ischemic acute renal failure.

BACKGROUND: Dendritic cells (DCs) play a central role in both stimulating and suppressing immune responses and are impacted by surgical injury, exercise, and other physiological stressors. This study aims to determine whether renal ischemia/reperfusion (I/R) injury alters the differentiation, maturation, and activation of DCs from peripheral blood monocytes (PBMo). MATERIALS AND METHODS: Sprague-Dawley (SD) rats were subjected to I/R injury or sham-operated. Creatinine clearance (CCr) was monitored daily during the 14 days of reperfusion that followed the ischemic insult. At 2 and 14 days of reperfusion, the following properties of PBMo derived-DCs were assessed: the amount of generated DCs, surface markers [CD11c, CD80, CD86, and MHC-II (IA)], and functional status including magnitude of mixed lymphocyte reaction (MLR), production of IL-12 p70 by DCs, and production of IFN-gamma and IL-4 by DC-stimulated T cells. RESULTS: CCr was greatly reduced in the injured rats 0 to 4 days after ischemia. Two days after I/R injury to kidney, the numbers of DCs differentiated from PBMo, IL-12 production by DCs, expression of MHC-II (IA), and IFN-gamma production by DC-stimulated T cells were significantly increased in the I/R injured group (compared to the sham-operated group). After 14 days of reperfusion, there was no between-group differences in the numbers of DCs derived from PBMo, MLR, expression of CD80, CD86, and MHC-II (IA), and production of IL-12, IFN-gamma, and IL-4. CONCLUSIONS: The increases seen at 2 days of reperfusion may reflect a preparatory step in the renal I/R injury pathway. The relationship between up-regulation of DC differentiation and ischemic acute renal failure (ARF) remains to be elucidated.

Renal ischemia/reperfusion injury inhibits differentiation of dendritic cells derived from bone marrow monocytes in rats.

Dendritic cells (DCs) are impacted by surgical injury, exercise, and other physiological stressors. This study aims to determine whether renal I/R injury affects 1) the differentiation of myeloid DCs from bone marrow monocytes (BMMos) and the maturation and activation state of these DCs and 2) DC infiltration of kidney. Sprague-Dawley rats were subjected to I/R injury or sham-operated. Creatinine clearance was monitored daily during the 14 d of reperfusion that followed the ischemic insult. At 2 and 14 d of reperfusion, the following were assessed 1) properties of BMMo-derived DCs (i.e., the amount of generated DCs, differentiation state markers [CD11c, CD80, CD86, and Ia], and functional state [MLR and amount of IL-12 produced]), and 2) the presence of DCs in the kidney. Numbers of BMMo-derived DCs were significantly decreased in the I/R injured group (compared with the sham-operated group) at 2 d but not 14 d. A comparison of the their functionality found mixed lymphocyte response [MLR] and IL-12 production were similar in the two groups at both time points. Also, immunohistochemistry showed infiltrating DCs in the outer medulla of the I/R injured kidney at 2 d but not 14 d of reperfusion. Thus, I/R stress reduces the number of DCs differentiated from BMMos but not the functional activity of these DCs. This decrease may reflect a stress-induced downshift in the capacity of BMMos to differentiate into DCs and a parallel upshift in the capacity of DCs to infiltrate the kidney.