Toll-like receptors are key players in initiation of innate immune response of the host. In addition to innate immunity they can also induce adaptive immune responses. The concept that inflammation ...can promote chronic prostatic diseases, such as benign prostatic hyperplasia or prostate carcinoma is supported by several new findings. Epidemiological data have correlated prostatitis with an increased risk of prostate cancer, while PCR-based analyses of bacterial colonization in prostate cancer specimens and normal prostate tissue showed high correlation of bacterial colonization and chronic inflammation with a diagnosis of prostate carcinoma. Even evidence from genetic studies support the hypothesis that prostate inflammation may be a cause of prostate cancer. From these points of view identification of factors, such as SNPs in TLR genes, associated with risk for prostate carcinoma development seems reasonable. Consequently, there are many investigations showing the connection between SNPs in TLR genes and pronounced susceptibility to different diseases. In this article we review the key findings about the genetic variability of TLR genes and prostate cancer risk.
•Successful Transplantation of a Kidney from a Living Donor.•Mentally Disabled Recipient Following Unilateral Nephrectomy.•Massive Hemorrhage and Imminent Hemorrhage in the Normally Functioning ...Kidney.
Many centers do not perform transplantation in mentally disabled people. Our patient with progressive psychomotor developmental delay had bilateral angiomyolipomas.
Three years ago she underwent a right nephrectomy for massive spontaneous hemorrhage. The left kidney had a large, well-vascularized angiomyolipoma ready at any moment to bleed spontaneously was functioning normally. Two renal transplantation centers in Croatia refused to transplant from the patient's donor mother. The transplantation team had concerns whether to transplant a kidney to a person unable to care for herself, about who would take complete care of the patient, including regular immunosuppressive therapy, and whether it was ethically justified to explant a functioning kidney, although affected by angiomyolipomas, from a patient who required no renal replacement therapy at the time.
We presented a successful kidney transplant in a mentally disabled person, clinical and ethical justifications for such a procedure, and a four-year post-transplant evaluation. Furthermore, in our opinion, renal transplantation in the mentally challenged needs to be referred to in literature exclusively as a relative contraindication instead of an absolute one, as has been practiced to date. This would facilitate transplantation teams deciding on kidney transplantation in mentally incapacitated individuals.
Frequency and mortality of renal cell carcinoma (RCC) are increasing for decades. However, the molecular background of RCC tumorigenesis is still poorly understood. In current study we investigated ...the expression of TCF/LEF and SFRP family members (SFRP1 and SFRP3) to gain a better understanding of biological signaling pathways responsible for epidemiology and clinical parameters of clear cell RCC (cRCC). Thirty-six pairs of paraffin-embedded clear cRCC and adjacent nontumoral tissues samples using immunohistochemistry (IHC) were analyzed and compared with corresponding clinicopathological parameters. Immunohistochemistry indicated statistically significant decreased SFRP3 expression in tumor tissues but no consistency in SFRP1 expression in analyzed normal and tumor tissue. The TCF1 expression level was significantly weaker in normal tissue compared to tumor samples while LEF1 protein levels were significantly weaker in tumor tissue. To our knowledge, this is the first report on analysis of the expression of transcription factors TCF1 and LEF1 in clear cell renal cell carcinoma and their comparison with Wnt signal pathway antagonists belonging to SFRP family.
Objectives Chronic transplant dysfunction after kidney transplantation is a major reason of kidney graft loss and is caused by immunological and non-immunological factors. There is evidence that ...mycophenolate mofetil (MMF) may exert a positive effect on renal damage in addition to immunosuppression, by its direct antifibrotic properties. The aim of our study was to retrospectively investigate the role of MMF doses on progression of chronic allograft dysfunction and fibrosis and tubular atrophy (IF/TA). Setting Retrospective, cohort study. Participants Patients with kidney transplant in a tertiary care institution. This is a retrospective cohort study that included 79 patients with kidney and kidney–pancreas transplantation. Immunosuppression consisted of anti-interleukin 2 antibody induction, MMF, a calcineurin inhibitor±steroids. Primary outcome measures An association of average MMF doses over 1 year post-transplant with progression of interstitial fibrosis (Δci), tubular atrophy (Δct) and estimated-creatinine clearance (eCrcl) at 1 year post-transplant was evaluated using univariate and multivariate analyses. Results A higher average MMF dose was significantly independently associated with better eCrcl at 1 year post-transplant (b=0.21±0.1, p=0.04). In multiple regression analysis lower Δci (b=−0.2±0.09, p=0.05) and Δct (b=−0.29±0.1, p=0.02) were independently associated with a greater average MMF dose. There was no correlation between average MMF doses and incidence of acute rejection (p=0.68). Conclusions A higher average MMF dose over 1 year is associated with better renal function and slower progression of IF/TA, at least partly independent of its immunosuppressive effects.
Renal biopsy is a gold standard for establishing diagnosis of acute rejection of the renal allograft. However, being invasive, renal biopsy has potential significant complications and ...contraindications. Therefore, possibility to noninvasively diagnose acute rejection would improve follow-up of kidney transplant patients. The purpose of this study was to evaluate urine immunocytology for T cells as a method for noninvasive identification of patients with acute renal allograft rejection in comparison to renal biopsy. In this prospective study a cohort of 56 kidney, or kidney-pancreas transplant recipients was included. Patients either received their transplant at the University Hospital "Merkur", or have been followed at the "Merkur" Hospital. Patients were subject to either protocol or indication kidney biopsy (a total of 70 biopsies), with simultaneous urine immunocytology (determination of CD3-positive cells in the urine sediment). Acute rejection was diagnosed in 24 biopsies. 23 episodes were T-cell mediated (6 grade IA, 5 grade IB, 1 grade IIA, 1 grade III and 10 borderline), while in 1 case acute humoral rejection was diagnosed. 46 biopsies did not demonstrate acute rejection. CD3-positive cells were found in 21% of cases with acute rejection and in 13% of cases without rejection (n.s.). A finding of CD3-positive cells in urine had a sensitivity of 21% and specificity of 87% for acute rejection (including borderline), with positive predictive value of 45% and negative predictive value of 68%. Although tubulitis is a hallmark of acute T cell-mediated rejection, detection of T cells in urine sediment was insufficiently sensitive and insufficiently specific for diagnosing acute rejection in our cohort of kidney transplant recipients.
Since 2003 when the international norm for implementation of quality management in medical laboratories (EN ISO 15189, Medical laboratories--Particular requirements for quality and competence) was ...established and accepted, accreditation has become practical, generally accepted method of quality management and confirmation of technical competence of medical laboratories in the whole world. This norm has been translated into Croatian and accepted by the Croatian Institute for Norms as Croatian norm. Accreditation is carried out on voluntary basis by the Croatian Accreditation Agency that has up to now accredited two clinical medical biochemical laboratories in the Republic of Croatia. Advantages of accredited laboratory lie in its documented management system, constant improvement and training, reliability of test results, establishing users' trust in laboratory services, test results comparability and interlaboratory (international) test results acceptance by adopting the concept of metrological traceability in laboratory medicine.
Childhood infection with polyomaviruses leads to a life-long latent infection of renal and urinary tract epithelia. Replication in the reno-urinary epithelium is associated with viral cytopathic ...changes such as nuclear inclusions and decoy cells. During the 2005-2009 period, cytological urine analysis was performed in 154 samples (94 male and 60 female) from patients with kidney transplantation (n = 19), simultaneous pancreas-kidney transplantation (SPKT) (n = 9) and simultaneous kidney and liver transplantation (n = 2). Urine samples were analyzed monthly following transplantation according to the protocol. The period from transplantation to the first occurrence of decoy cells in the urine and the period of decoy cell persistence in the urine were assessed. The presence of decoy cells (< 10 and > 10 decoy cells) and red blood cells (< 20 E, 20-100 E and > 100 E) per cytospin smear was semiquantitatively determined, along with analysis of inflammatory cells (neutrophilic granulocytes) and fungi. In patients with decoy cells detected, their sensitivity, specificity, and negative and positive predictive value for BK virus nephropathy were calculated. Correlation of the study parameters was estimated by use of Kruskal-Wallis test (Statistica 7.1, StatSoft Inc., Tulsa, USA). Decoy cells were found in 30 patients (20 male and 10 female), age median 40 (range 16-69) years, at a mean of day 115 (range day 5-747) post transplantation, whereas their presence was recorded for a mean of 141 (range 77-771) days. Immunohistochemical staining of kidney biopsy sample for polyomavirus (SV40 large T-antigen) yielded positive reaction in 2/30 (7%) patients. Erythrocyturia was present in 29/30 patients with decoy cells. The number of decoy cells per cytospin smear generally ranged less than 10 in 25/30 patients, whereas more than 10 decoy cells per cytospin smear were only recorded in 5/30 patients. Immunohistochemistry produced positive finding for BK virus in one patient with SPKT and simultaneous kidney and liver transplantation each, which was statistically significantly more common as compared with patients with kidney transplantation alone (p = 0.0244). Immunohistochemical positivity for BK virus was more significant in cases with more than 10 decoy cells detected in cytospin smear (p = 0.013). In BK nephropathy, the finding of urinary decoy cells showed a 100% sensitivity, 84% specificity, 100% negative predictive value and 6% positive predictive value. BK virus nephropathy remains a significant post transplantation complication.
Enterotoxigenic Escherichia coli (ETEC) strains expressing F4 and F18 fimbriae are the most common causative agents of post-weaning diarrhoea (PWD) in pigs. The growing global restriction on the use ...of antibiotics in food animals has encouraged research into the development of nutritional and feeding strategies as well as vaccination against PWD. The aim of this study was to evaluate the efficacy of a live oral F4ac+ F18ac+ non-ETEC vaccine candidate (VAC) to stimulate gut and systemic cellular immunity in 4-week old pigs over 5 weeks following immunization. The onset and duration of protective immunity against on-farm occurring PWD, growth performance, diarrhoea scoring and mortality, as well as the phenotypic proportions of immune cells, were determined. Faecal and ileal samples were taken for determining the microbial composition or phenotyping of naïve/memory T cells. Also, the effect of prebiotic supplement mannan oligosaccharide (MOS) in the prevention of small intestinal colonization by ETEC, and its potential adjuvanticity in combination with the vaccine (VAC+MOS) were assessed. The pigs supplemented with MOS or that received VAC had significantly higher body weight (BW) (P<0.05) on Day 14, whereas the VAC+MOS treated pigs had significantly lower BW on Day 35. Treatment with VAC+MOS resulted in considerably reduced clinical PWD, in particular the incidence and severity of diarrhoea and mortality. The total bacterial load in the ileum was much lower in the pigs from all 3 principal groups (MOS, VAC, and VAC+MOS) than in the control (CON) group (19 x 107, 17 x 107 and 12 x 107 vs. 23 x 108 CFU/mL, respectively) on Day 35. The pigs from the principal groups had significantly higher proportions of tested immune cells (P<0.05) on Days 28 and 35. The localization and frequency of naive CD45RA+ and memory CD45RC+ T lymphocytes indicated their different distribution patterns within particular tissue structures, such as the villi, crypts, epithelium, lamina propria and areas (interfollicular follicular and Peyer’s patches) of ileal mucosa. This may indicate their different functions in intestinal immune responses to intraluminal microbes and their products, vaccinal immunogens and/or immunomodulators/adjuvants. To conclude, active mucosal immunity is needed to protect pigs against PWD. Hence, oral vaccination of pigs against both F4 and F18 ETEC, in combination with prebiotic supplementation represents a sustainable, practical and effective approach in PWD control.
This study was performed to examine the adequacy of biological inert patches as a substitute material for the construction of urinary bladder replacement tissue. An animal model experiment was ...conducted in six sheep and six swine. In all animals partial resection of the urinary bladder was performed; round or oval-shaped, 5–6 cm in diameter. Patches of the same shape, 4–5 cm in diameter were used. Two types of patches, polytetrafluorethylene and small intestinal submucosa were tested in the experiment, sewn with an absorbable 4-0 polydioxanone suture. Following 16 weeks the animals were euthanized followed by autopsy and histologic analysis. All animals showed evidence of bladder regeneration at the replaced segment. The patches were found to be contracted to 12–20 mm in length and 8–10 mm in width, attached to the bladder mucosa with their smaller base and protruding into the bladder lumen. In some animals, no shrunk patches were found, suggesting they had been passed out by urine. Histologically, fibrous tissue completely replacing the substitute tissue was identified with endothelial-lined luminal surface and submucosal and serosal ingrowth of new blood vessels. The replacement tissue showed no evidence of muscle layer ingrowth. Bladder capacity was also measured and no significant decrease was recorded. Our experiment demonstrated the formation of replacement tissue at the site of graft implantation, which allows the resection of a larger portion of bladder without decreasing its capacity and thus constitutes a very good method for surgical treatment of urinary bladder tumours and other defects.
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