An experimental model for the measurement of renal function after temporary ureteral obstruction in the rat

We present the results obtained with a ureterovesical implant after ipsilateral ureteral obstruction in the rat, suitable for the study of renal function after deobstruction in these animals. Thirty-seven male Wistar rats weighing 260 to 300 g were submitted to distal right ureteral ligation and divided into 3 groups, A (N = 13, 1 week of obstruction), B (N = 14, 2 weeks of obstruction) and C (N = 10, 3 weeks of obstruction). The animals were then submitted to ureterovesical implantation on the right side and nephrectomy on the left side. During the 4-week follow-up period serum levels of urea and creatinine were measured on the 2nd, 7th, 14th, 21st and 28th day and compared with preoperative levels. The ureterovesical implantation included a psoas hitch procedure and the ureter was pulled into the bladder using a transvesical suture. During the first week of the postoperative period 8 animals died, 4/13 in group A (1 week of obstruction) and 4/14 in group B (2 weeks of obstruction). When compared to preoperative serum levels, urea and creatinine showed a significant increase (P<0.05) on the 2nd postoperative day in groups A and B, with a gradual return to lower levels. However, the values in group B animals were higher than those in group A at the end of the follow-up. In group C, 2/10 animals (after 3 weeks of obstruction) were sacrificed at the time of ureterovesical implantation due to infection of the obstructed kidneys. The remaining animals in this group were operated upon but all of them died during the first week of follow-up due to renal failure. This technique of ureterovesical implantation in the rat provides effective drainage of the upper urinary tract, permitting the development of an experimental model for the study of long-term renal function after a period of ureteral obstruction

Assessing the diversity of the virulence potential ofEscherichia coli isolated from bacteremia in São Paulo, Brazil

Most of the knowledge of the virulence determinants of extraintestinal pathogenicEscherichia coli (ExPEC) comes from studies with human strains causing urinary tract infections and neonatal meningitis and animal strains causing avian colibacillosis. In this research, we analyzed the phylogenetic background, the presence of 20 ExPEC virulence factors, and the intrinsic virulence potential of 74 E. coli strains isolated in São Paulo, Brazil, from 74 hospitalized patients (43 males and 31 females) with unknown-source bacteremia. Unlike other places in the world, the bacteremic strains originated equally from phylogroups B2 (35%) and D (30%). A great variability in the profiles of virulence factors was noted in this survey. Nevertheless, 61% of the strains were classified as ExPEC, meaning that they possessed intrinsic virulent potential. Accordingly, these strains presented high virulence factor scores (average of 8.7), and were positively associated with 12 of 17 virulence factors detected. On the contrary, the non-ExPEC strains, isolated from 39% of the patients, presented a generally low virulence capacity (medium virulence factor score of 3.1), and were positively associated with only the colicin cvaC gene. These results show the importance of discriminating E. coli isolates that possess characteristics of true pathogens from those that may be merely opportunistic in order to better understand the virulence mechanisms involved in extraintestinalE. coli infections. Such knowledge is essential for epidemiological purposes as well as for development of control measures aimed to minimize the incidence of these life-threatening and costly infections.

Pain determinants of pain in autosomal dominant polycystic kidney disease

Pain is the most common symptom reported by ADPKD patients, afflicting approximately 60% of cases and may result from renal hemorrhage, calculi, urinary tract infections, cyst rupture, or due to stretching of the capsule or traction of the renal pedicle. We have recently investigated pain patterns in AD-PKD patients using a translated version of a pain questionnaire specific for AD-PKD population. The questionnaire revealed that 67% patients with ADPKD exhibited some type of pain. The findings of that study emphasized that pain appeared early in the course of ADPKD, when patients still exhibited preserved renal function. In the present study, a multivariate logistic regression analysis disclosed that renal volume (9-fold increased risk) and nephrolithiasis (4-fold increased risk) were the most important determinant factors for pain in ADPKD patients with preserved renal function, after adjustments for the presence of hypertension and duration of the disease.

Five years results after intrafamilial kidney post-transplant in a case of familial hypomagnesemia due to a claudin-19 mutation

Introduction: Familial Hypomagnesaemia with hypercalciuria and nephrocalcinosis, with severe ocular impairment secondary to claudin-19 mutation, is a rare recessive autossomic disorder. Its spectrum includes renal Mg2+ wasting, medullary nephrocalcinosis and progressive chronic renal failure in young people. Objective: To report a case of kidney transplantation father to daughter in a familial occurrence of severe bilateral nephrocalcinosis associated with ocular impairment in a non-consanguineous Brazilian family, in which two daughters had nephrocalcinosis and severe retinopathy. Methods: The index case, a 19 years-old female, had long-lasting past medical history of recurrent urinary tract infections, and the abdominal X-ray revealed bilateral multiple renal calcifications as well as ureteral lithiasis, and she was under haemodialysis. She had the diagnosis of retinitis pigmentosa in the early neonatal period. The other daughter (13 years-old) had also nephrocalcinosis with preserved kidney function, retinopathy with severe visual impairment, and in addition, she exhibited hypomagnesaemia = 0.5 mg/dL and hypercalciuria. The other family members (mother, father and son) had no clinical disease manifestation. Mutation analysis at claudin-19 revealed two heterozygous missense mutations (P28L and G20D) in both affected daughters. The other family members exhibited mutant monoallelic status. In despite of that, the index case underwent intrafamilial living donor kidney transplantation (father). Conclusion: In conclusion, the disease was characterized by an autosomal recessive compound heterozygous status and, after five years of donation the renal graft function remained stable without recurrence of metabolic disturbances or nephrocalcinosis. Besides, donor single kidney Mg2+ and Ca2+ homeostasis associated to monoallelic status did not affect the safety and the usual living donor post-transplant clinical course.

Purple urine bag syndrome in end-stage chronic kidney disease

Introduction: When faced with violet, purple or purplish-blue urine, clinicians should consider urinary tract infection in their differential diagnosis. Case report: A 60-year-old woman with end-stage kidney disease and non-adherence to renal replacement therapy was admitted to our hospital for placement of hemodialysis catheter. During her hospitalization she had purple urine, and purple urine bag syndrome (PUBS) was diagnosed. She was effectively treated with antibiotics and her urine returned to a dark yellow color. Discussion: Although this condition is often easily treated, diagnosing PUBS in chronic renal patients probably means an increased serum concentration of indoxyl sulfate, metabolite that is involved in the progression of both CKD and cardiovascular disease. Conclusion: Hence, in the context of our renal patients, perhaps PUBS is not as benign as supposed.

Cryptosporidiosis of the biliary tract mimicking pancreatic cancer in an AIDS patient

Diarrhea caused by Cryptosporidium sp is frequent in patients with AIDS, but involvement of other organs of the digestive tract is uncommon. We report a case of Cryptosporidium-associated obstruction of the biliary tract mimicking cancer of the head of the pancreas in a 43-year-old woman with AIDS.

Anal squamous carcinoma: a new AIDS-defining cancer? Case report and literature review

Squamous anal cell carcinoma is a rare malignancy that represents the 1.5% to 2% of all the lower digestive tract cancers. However, an increased incidence of invasive anal carcinoma is observed in HIV-seropositive population since the widespread of highly active antiretroviral therapy. Human papillomavirus is strongly associated with the pathogenesis of anal cancer. Anal intercourse and a high number of sexual partners appear to be risk factors to develop anal cancer in both sexes. Anal pain, bleeding and a palpable lesion in the anal canal are the most common clinical features. Endo-anal ultrasound is the best diagnosis method to evaluate the tumor size, the tumor extension and the infiltration of the sphincter muscle complex. Chemoradiotherapy plus antiretroviral therapy are the recommended treatments for all stages of localized squamous cell carcinoma of the anal canal in HIV-seropositive patients because of its high rate of cure. Here we present an HIV patient who developed a carcinoma of the anal canal after a long time of HIV infection under highly active antiretroviral therapy with a good virological and immunological response.

Analysis of molecular biology techniques for the diagnosis of human papillomavirus infection and cervical cancer prevention

The objective of the present study was to evaluate the usefulness of molecular methodologies to access human papillomavirus genome in the genital tract. Samples from 136 women aged 17 to 52 years old obtained from the Dr. Sérgio Franco Laboratories between 2000 and 2001, were analyzed by the hybrid capture assay and amplified by PCR with generic primers MY09/MY11 and specific primers for types 16, 18, 31, 33, 35, 58. Viral genome was detected in 71.3% of the samples by hybrid capture and 75% by amplification. When cytopathology was used as a reference method for screening lesions, hybrid capture (p=0) and amplification (p=0.002) presented positive association. The 3 methods showed absolute agreement when cytopathology confirmed papillomavirus infection and high grade intraepithelial lesion. Disagreements occurred for 10 cases: seven inflammatory cases positive by PCR and negative for hybrid capture and 3 low squamous intraepithelial lesions positive for hybrid capture but negative for amplification. In conclusion, hybrid capture was shown to be sensitive and specific enough for use in clinical routines. Moreover, the evaluation of viral load values obtained by this method were shown to be related to the severity of the lesion and merit further studies to analyze the possible association with risk of progression to malignancy.

Epithelial effects of proteinase-activated receptors in the gastrointestinal tract

The intestinal epithelium plays a crucial role in providing a barrier between the external environment and the internal milieu of the body. A compromised mucosal barrier is characteristic of mucosal inflammation and is a key determinant of the development of intestinal diseases such as Crohn's disease and ulcerative colitis. The intestinal epithelium is regularly exposed to serine proteinases and this exposure is enhanced in numerous disease states. Thus, it is important to understand how proteinase-activated receptors (PARs), which are activated by serine proteinases, can affect intestinal epithelial function. This review surveys the data which demonstrate the wide distribution of PARs, particularly PAR-1 and PAR-2, in the gastrointestinal tract and accessory organs, focusing on the epithelium and those cells which communicate with the epithelium to affect its function. PARs have a role in regulating secretion by epithelia of the salivary glands, stomach, pancreas and intestine. In addition, PARs located on subepithelial nerves, fibroblasts and mast cells have important implications for epithelial function. Recent data outline the importance of the cellular site of PAR expression, as PARs expressed on epithelia may have effects that are countered by PARs expressed on other cell types. Finally, PARs and their ability to promote epithelial cell proliferation are discussed in terms of colon cancer.

Microbiological and host features associated with corynebacteriosis in cancer patients: a five-year study

During a five-year period, 932 clinical isolates from cancer patients treated in a Brazilian reference centre were identified as corynebacteria; 86% of the cultures came from patients who had been clinically and microbiologically classified as infected and 77.1% of these patients had been hospitalised (71.1% from surgical wards). The adult solid tumour was the most common underlying malignant disease (66.7%). The univariate and multivariate analyses showed that hospitalised patients had a six-fold greater risk (OR = 5.5, 95% CI = 1.15-26.30 p = 0.033) related to 30-day mortality. The predominant species were Corynebacterium amycolatum (44.7%), Corynebacterium minutissimum (18.3%) and Corynebacterium pseudodiphtheriticum (8.5%). The upper urinary tracts, surgical wounds, lower respiratory tracts, ulcerated tumours and indwelling venous catheters were the most frequent sources of C. amycolatum strains. Corynebacterium jeikeium infection occurred primarily in neutropenic patients who have used venous catheters, while infection caused by C. amycolatum and other species emerged mainly in patients with solid tumours.

In vitro and in vivo studies of pirarubicin-loaded SWNT for the treatment of bladder cancer

Intravesical chemotherapy is an important part of the treatment for superficial bladder cancer. However, the response to it is limited and its side effects are extensive. Functional single-walled carbon nanotubes (SWNT) have shown promise for tumor-targeted accumulation and low toxicity. In the present study, we performed in vivo and in vitro investigations to determine whether SWNT-based drug delivery could induce high tumor depression in rat bladder cancer and could decrease the side effects of pirarubicin (tetrahydropyranyl-adriamycin, THP). We modified SWNT with phospholipid-branched polyethylene glycol and constructed an SWNT-THP conjugate via a cleavable ester bond. The cytotoxicity of SWNT-THP against the human bladder cancer cell line BIU-87 was evaluated in vitro. Rat bladder cancer in situ models constructed by N-methyl-N-nitrosourea intravesical installation (1 g/L, 2 mg/rat once every 2 weeks for 8 weeks) were used for in vivo evaluation of the cytotoxicity of SWNT and SWNT-THP. Specific side effects in the THP group including urinary frequency (N = 12), macroscopic hematuria (N = 1), and vomiting (N = 7) were identified; however, no side effects were observed with SWNT-THP treatment. Flow cytometry was used to assess the cytotoxicity in vitro and in vivo. Results showed that SWNT alone did not yield significant tumor depression compared to saline (1.74 ± 0.56 and 1.23 ± 0.42%) in vitro. SWNT-THP exhibited higher tumor depression than THP-saline in vitro (74.35 ± 2.56 and 51.24 ± 1.45%) and in vivo (52.46 ± 2.41 and 96.85 ± 0.85%). The present findings indicate that SWNT delivery of THP for the treatment of bladder cancer leads to minimal side effects without loss of therapeutic efficacy. Therefore, this nanotechnology may play a crucial role in the improvement of intravesical treatment of bladder cancer.