Systemic infusion of autologous adipose tissue-derived mesenchymal stem cells in peritoneal dialysis patients: feasibility and safety

Objective: Using mesenchymal stem cells [MSCs] is regarded as a new therapeutic approach for improving fibrotic diseases.The aim of this study to evaluate the feasibility and safety of systemic infusion of autologous adipose tissue-derived MSCs [AD-MSCs] in peritoneal dialysis [PD] patients with expected peritoneal fibrosis

Materials and Methods: This study was a prospective, open-label, non-randomized, placebo-free, phase I clinical trial. Case group consisted of nine eligible renal failure patients with more than two years of history of being on PD. Autologous AD-MSCs were obtained through lipoaspiration and expanded under good manufacturing practice conditions. Patients received 1.2 +/- 0.1×106 cell/kg of AD-MSCs via cubital vein and then were followed for six months at time points of baseline, and then 3 weeks, 6 weeks, 12 weeks, 16 weeks and 24 weeks after infusion. Clinical, biochemical and peritoneal equilibration test [PET] were performed to assess the safety and probable change in peritoneal solute transport parameters

Results: No serious adverse events and no catheter-related complications were found in the participants. 14 minor reported adverse events were self-limited or subsided after supportive treatment. One patient developed an episode of peritonitis and another patient experienced exit site infection, which did not appear to be related to the procedure. A significant decrease in the rate of solute transport across peritoneal membrane was detected by PET [D/P cr=0.77 vs. 0.73, P=0.02]

Conclusion: This study, for the first time, showed the feasibility and safety of AD-MSCs in PD patients and the potentials for positive changes in solute transport. Further studies with larger samples, longer follow-up, and randomized blind control groups to elucidate the most effective route, frequency and dose of MSCs administration, are necessary [Registration Number: IRCT2015052415841N2]

Assessing the diagnostic value of plasma-Free DNA in prostate cancer screening

Background: Prostate cancer is the second form of cancer among men worldwide. For early cancer detection, we should identify tumors in initial stages before the physical signs become visible. The present study aims to evaluate the diagnostic value of cell-free DNA [cfDNA], its comparison with prostate-specific antigen [PSA] level in prostate cancer screening and also in patients with localized prostate cancer, metastatic form, and benign prostatic hyperplasia [BPH]

Methods: The participants of this study were selected from 126 patients with genitourinary symptoms suspected prostate cancer, rising PSA, and/or abnormal rectal examination results and 10 healthy subjects as controls. Peripheral blood plasma before any treatment measures was considered. cfDNA was extracted using a commercial kit, and PSA levels were measured by ELISA. The ANOVA test was used to compare the average serum level of PSA and plasma concentration of cfDNA between the groups. The correlation between variables was measured by the Pearson test

Results: The subgroups consisted of 50 patients with localized prostate cancer, 26 patients with metastatic prostate cancer, 50 patients with BPH, and 10 healthy subjects; the average concentrations of cfDNA in these subgroups were 15.04, 19.62, 9.51, and 8.7 ng/Mul, respectively. According to p < 0.0001 obtained from multivariate test, there was a significant difference between all the groups

Conclusion: Our findings indicated significant differences between cfDNA levels of patients with localized and metastatic prostate cancer, and differences of these two groups from BPH and healthy cases show the importance of this biomarker in non-invasive diagnostic procedures

Developmental potential of vitrified mouse testicular tissue after ectopic transplantation

Objective: Cryopreservation of immature testicular tissue should be considered as an important factor for fertility preservation in young boys with cancer. The objective of this study is to investigate whether immature testicular tissue of mice can be successfully cryopreserved using a simple vitrification procedure to maintain testicular cell viability, proliferation, and differentiation capacity

Materials and Methods: In this experimental study, immature mice testicular tissue fragments [0.5-1 mm[2]] were vitrified-warmed in order to assess the effect of vitrification on testicular tissue cell viability. Trypan blue staining was used to evaluate developmental capacity. Vitrified tissue [n=42] and fresh [control, n=42] were ectopically transplanted into the same strain of mature mice [n=14] with normal immunity. After 4 weeks, the graft recovery rate was determined. Hematoxylin and eosin [H and E] staining was used to evaluate germ cell differentiation, immunohistochemistry staining by proliferating cell nuclear antigen [PCNA] antibody, and terminal deoxynucleotidyl transferase [TdT] dUTP Nick-End Labeling [TUNEL] assay for proliferation and apoptosis frequency

Results: Vitrification did not affect the percentage of cell viability. Vascular anastomoses was seen at the graft site. The recovery rate of the vitrified graft did not significantly differ with the fresh graft. In the vitrified graft, germ cell differentiation developed up to the secondary spermatocyte, which was similar to fresh tissue. Proliferation and apoptosis in the vitrified tissue was comparable to the fresh graft

Conclusion: Vitrification resulted in a success rates similar to fresh tissue [control] in maintaining testicular cell viability and tissue function. These data provided further evidence that vitrification could be considered an alternative for cryopreservation of immature testicular tissue

[Urinary tract infection in renal transplant patients in Sina university hospital]

Renal transplantation is the treatment of choice in patients with end-stage renal disease. Urinary tract infection [UTI] is one of the most common complications after renal transplantation and it has serious consequences. The aim of this study was assessing UTIs in renal transplanted patients and evaluation of risk factors associated with post-transplant UTI. In this prospective study, 173 patients [48 hospitalized patients and 125 outpatients] were enrolled in this study. These renal transplant recipients evaluated for bacterial urinary tract infection in urology research center at Sina Hospital. After collecting urine samples from symptomatic and asymptomatic patients, urinalysis and colony count were performed. Identification of bacteria was performed by routine microbiological tests in the Department of Pathobiology, School of Public Health, Tehran, Iran, in 2011. UTI was observed in 47 patients and the most prevalent microorganism was Escherichia coli [E.coli] 18 [38.2%]. Nearly 71% of UTI cases were diagnosed during the first three months post transplantation. Risk factors for post transplant UTI were female gender, age, length of hospitalization and diabetes mellitus. Female patients were more susceptible than males [OR=0.50 and P=0.047] to infection. There were no significant difference between diabetes mellitus and UTI. Most of the isolated bacteria were susceptible to imipenem and resistant to tetracycline and trimethoprim-sulfamethoxazole. Our study confirmed that bacterial infections remain as the most common infectious complication in the early post-transplant period, and antibiogram rather than empirical treatment is needed to find the best effective antibiotics. Moreover, risk factors such as female gender, increased age and length of hospitalization are predisposing factors to increased urinary tract infection in renal transplantation.

Renal actinomycosis in presence of renal stones in a patient with end stage renal disease

Renal actinomycosis is a rare infection, and actinomycosis mostly acts as a normal flora in mouth, colon and vagina. We present a case of 56 years old man, who referred to our center for renal transplantation with kidney stone and diagnosed with renal actinomycosis. This case has risen possibility of rare infection that can be considered in the setting of renal transplantation

Anti-HLA antibodies and kidney allograft outcomes in recipients with donor bone marrow cell infusion

Anti-HLA-antibodies are known to affect the allograft survival in transplant recipient patients. The aim of this study was to evaluate the association between anti-HLA antibodies and kidney allograft outcomes, particularly in recipients with concurrent donor bone marrow cell infusion [DBMI]. Between June 2006 and May 2007, forty living unrelated donor kidney transplants consisting of 20 recipients with DBMI and 20 without infusion entered into the study and were monitored prospectively for one year. Pre-and post-transplant [days 14, 30, and 90] sera were screened for the presence of anti-HLA class-I and II antibodies, and subsequently positive sera retested with ELISA specific panel for antibody specification. Of 40 patients, 9 [22.5%] experienced acute rejection episodes [ARE] [6/20 cases in non-infused versus 3/20 in DBMI patients]. The prevalence of anti-HLA antibodies before and after transplantation were higher in patients with ARE compared to non-rejecting ones [88.8% vs. 38.7%, p=0.01 and 66.6% vs. 25.8%, p=0.04, respectively]. A total of 10% [4/40] of patients developed donor specific anti-HLA antibodies [DSA] and in this regard 2 patients from the control group experienced ARE. All 3 rejecting patients in DBMI group were negative for DSA and positive for non-DSA. The lower titer of post-transplant anti-HLA antibodies were shown in DBMI patients compared to pre-transplantation titer. Additionally, the average serum creatinine levels during one year follow up and even in those patients with ARE were lower compared to controls. Our findings reveal an association between pre-and post-transplant anti-HLA antibodies, and ARE and also early allograft dysfunction. It suggests that lower incidence of ARE, undetectable DSA, lower titer of antibodies concomitant with a decrease in serum creatinine level, better allograft function and lower percentages of PRA in DBMI patients, could be the probable manifestations of partial hypo-responsiveness against allografts

Mutations of RAS gene family in specimens of bladder cancer

Studies have shown different types of RAS mutations in human bladder tumors with a wide range of mutation frequencies in different patient populations. This study aimed to assess the frequency of specific-point mutations in the RAS gene family of a group of Iranian patients with bladder cancer. We examined the tumor specimens of 35 consecutive patients with transitional cell carcinoma. The DNA samples were evaluated for the occurrence of HRAS, KRAS, and NRAS activation using a polymerase chain reaction-restriction fragment length polymorphism technique. None of the patients had mutations in the RAS gene family "hot spots" including codons 12, 13, and 61. We failed to find RAS mutations in our bladder tumor samples. These observations may reflect the involvement of different etiological factors in the induction of bladder tumor of which RAS mutation might not be present in all populations

Role of PTEN gene in progression of Prostate Cancer

The aim of this study was to clarify the role of PTEN gene in progression of prostate cancer. A total of 51 formalin-fixed paraffin-embedded specimens of prostate cancer were analyzed for PTEN mutations. Tissue microdissection and polymerase chain reaction/ single-strand conformation polymorphism methods were used. Clinical and pathologic data of the patients were reviewed with regard to PTEN mutation. The Gleason score [GS] was less than 7 in 29 [56.8%], 7 in 11 [21.6%], and greater than 7 in 11 [21.6%]. Tumor stage was IIa, IIb, IIc, and IV in 14 [27.4%], 4 [7.8%], 21 [41.2%], and 12 [23.6%] patients, respectively. Eleven of 12 stage IV tumors had metastases at the time of presentation. Six of 51 cases [11.6%] showed mutation in PTEN which had involved exones 1,2, and 5. Two of these cases had localized and the others had advanced prostate cancer. One case of the tumors with PTEN mutation had a GS of 7 and 5 had GSs greater than 7. Patients with a positive mutation of PTEN had a significantly greater GS [P<.001], lower survival rate [P=.001], higher tendency to metastasis [P=.002], and higher prostate-specific antigen [p=.03]. Cox proportional hazard model showed that only GS was significantly correlated with mortality [P=.03]. Patients with prostate cancer who had PTEN mutation had also a significantly greater GS, poorer prognosis, and higher rate of metastasis. However, this mutation cannot predict the prognosis and the GS is a more precise factor

Posttransplant infectious complications: a prospective study on 142 kidney allograft recipients

We evaluated the posttransplant complications resulting from infections and their association with graft function, immunosuppressive drugs, and mortality. A total of 142 kidney allograft recipients were followed for 1 year after transplantation. The patients' status was assessed during regular visits, and data including clinical characteristics, infections, serum creatinine level, acute rejection episodes, immunosuppressive regimen, graft function, and mortality were recorded and analyzed. Infections occurred in 77 patients [54%]. The lower urinary [42%] and respiratory [6.3%] tracts were the most common sites of infection. The most frequent causative organisms were Klebsiella in 34 [24%] and cytomegalovirus in 25 patients [18%]. Wound infection occurred in 7 patients [5%]. The mortality rate was 7.7% and infection-related death was seen in 5 patients [3.5%] who developed sepsis. Graft loss was seen in 16 patients [11%], of whom 2 developed cytomegalovirus infection, 2 experienced urinary tract infection, and 5 developed sepsis and died. Mycobacterial and hepatitis C infections were noticeably rare [0.7% and 2.8%, respectively]. This study showed that infections are important causes of morbidity and mortality during the posttransplant period. We recommend that serologic tests be performed before and after transplantation to recognize and meticulously follow those who are at risk. In our study, high-risk patients were those with elevated serum creatinine levels who received high doses of immunosuppressive drugs. As the urinary tract is the most common site of infection, early removal of urethral catheter is recommended to reduce the risk of infection

Correlation of sperm nuclear chromatin condensation staining method with semen parameters and sperm functional tests in patients with spinal cord injury, varicocele, and idiopathic infertility

Our aim was to investigate sperm nuclear chromatin condensation and its correlation with semen parameters and vitality test in infertile patients with spinal cord injury [SCI], varicocele, and idiopathic infertility. Sperm chromatin condensation was determined by aniline blue staining in 22 SCI-injured infertile men, 20 with varicocele, and 28 with idiopathic infertility. The results were compared with the semen analysis parameters and the hypo-osmotic swelling test results. Three grades of staining for sperm heads were distinguished: unstained, showing sperm maturity [G0]; partially stained [G1]; and completely stained, showing sperm immaturity [G2]. The total score was calculated as: [G0 * 0] + [G1 * 1] + [G2 * 2]. In all groups, the total staining score was higher than 75%, corresponding to a high degree of immaturity of sperm. Patients with SCI had a less sperm nuclear chromatin condensation and chromatin stability than patients with idiopathic infertility and varicocele [total scores, 98% versus 89% and 88%, respectively; P <.01]. All of the patients had normal hypo-osmotic swelling test results. Sperm counts for all patients were within the reference range. The mean percentages for normal motility and morphology of the sperm were 15.5% and 15% for patients with SCI, 43% and 15% for patients with varicocele, and 62.5% and 54% for patients with idiopathic infertility. There was no correlation between sperm nuclear chromatin condensation and semen analysis parameters. Aniline blue staining for sperm nuclear chromatin condensation is a method independent of semen analysis and demonstrates the internal structural defects of sperm. This method may have a predictive value in assessing fertility

Improvement of erectile dysfunction after kidney transplantation the role of the associated factors

The aim of this study was to evaluate erectile dysfunction [ED] in hemodialysis patients and the factors influencing ED after a successful kidney transplantation. A total of 64 patients on hemodialysis were evaluated before and 6 months after the kidney transplantation. They were all recipients of their first kidney allografts from living unrelated donors and had a functional kidney allograft during the follow-up. The 5-item version of the International Index of Erectile Function [IIEF-5] was used to assess their erectile function. A group of age-matched controls were compared with them before transplantation. The effects of pretransplant IIEF-5 score, age at transplantation, the artery used for anastomosis, and duration of the dialysis prior to transplantation on ED were also studied. Fifty-six of the patients [87.5%] and 23 of the controls [35.9%] had ED [P < .001]. The prevalence of ED was 87.5% in the hemodialysis patients. There was no relationship between the duration of dialysis and the severity of ED. Successful transplantation improved IIEF-5 score significantly [13.6 +/- 5.2 before and 19.2 +/- 5.0 after transplantation; P < .001]. Based on the IIEF-5 scores, the severity of ED increased in 6 [9.4%] patients; 8 [12.5%] experienced no change in their erectile function; and 50 [78.1%] reported an improved erectile function. Preoperative IIEF-5 score and age at transplantation had statistically significant associations with ED improvement [P < .001; P = .02]. Erectile dysfunction is highly prevalent in hemodialysis patients and significantly improves after successful kidney transplantation. Younger patients with a less severe ED have the most improvement after transplantation

Urinary Tamm-Horsfall protein and citrate: a case-control study of inhibitors and promoters of calcium stone formation

This study aimed to compare urinary Tamm-Horsfall protein [THP], citrate, and other inhibitors and promoters of stone formation in calcium stone formers with those in healthy individuals. From January 2002 to June 2004, 100 calcium stone formers [mean age, 38.6 +/- 10.3 years] who had at least 2 episodes of calcium stone formation were compared with 100 healthy individuals [mean age, 33.8 +/- 9.7 years]. Their 24-hour urine THP [using the sodium dodecyl sulfate polyacrylamide gel electrophoresis method], citrate, calcium, uric acid, oxalate, and magnesium values were measured and compared. The mean 24-hour urine THP was 3.3 +/- 8.1 mg in patients in the study group and 4.6 +/- 19.2 mg in controls [P=0.5]. However, THP in individuals with and without bacteriuria was significantly different [15.8 +/- 33.6 versus 2.6 +/- 10.2, P<0.001]. Mean 24-hour urinary calcium, citrate, and oxalate values were 232.6 +/- 95.3 mg and 177.8 +/- 82.7 mg [P<0.001], 132 +/- 103.2 mg and 395 +/- 258.5 mg [P<0.001], and 18.9 +/- 22.5 mg and 10.4 +/- 8.5 mg [P<0.001] in patients in the study and control groups, respectively. There was a significant positive correlation between urinary citrate and promoters of stone formation, including urinary calcium, oxalate, and uric acid, in patients in the control group, but not in patients in the study group. THP in the urine of stone formers is not quantitatively different from that of healthy individuals, but it is different in patients with bacteriuria. Increased urinary excretion of calcium, oxalate, and uric acid in stone formers with no increase in urine citrate may play a role in the pathogenesis of recurrent stone formation

Buccal mucosal graft in repeat urethroplasty

Our aim was to evaluate the efficacy of a tubed buccal mucosal graft in repeat urethroplasty for patients with urethral stricture and failed previous operations. Ten patients [aged 12 to 47 years] with urethral stricture were entered into the study. All had a history of failed previous urethroplasties, and 5 had failed internal urethrotomies, too. Repeat urethroplasties were performed by excising the fibrous tissue around the stricture; buccal mucosa was then harvested from the inner cheek, made into graft tubing, and interposed into the defect. The patients were followed at 1, 6, and 12 months. The procedure was technically successful in all the patients. The mean operative time was 150 minutes. The stricture sites were in the posterior urethra in 8 and the anterior urethra in 2 patients. The mean urethral defect length was 4.9 cm. The primary etiology was pelvic fracture in 7 patients. Strictures recurred postoperatively in 3 patients, all of whom had a urethral defect longer than 5 cm, and 2 of whom had more than 1 previous failed urethroplasties [compared with 1 out of 7 in the successful cases]. Urinary flow rate increased significantly [from 0 to 10.4 +/- 7.33 mL/s] postoperatively [P = .018]. Longer strictures produced signifcantly poorer graft urethroplasty outcomes [P = .001]. Urethroplasty with buccal mucosal grafts is tough, resilient, easy to harvest, and leaves no scar. It appears to be an optimal substitute for anterior and posterior urethral strictures longer than 3 cm