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.

Pentavalent antimonial nephrotoxicity in the rat

Aspects of the renal function were assessed in rats treated with the pentavalent antimonials Glucantime (Meglumine Antimoniate, Rhodia) or Pentostam (Sodium Stibogluconate, Wellcome). In dose of 30 mg of Sb v (Glucantime or Pentostam) by 100 mg of weight by day for 30 days, renal functional changes were observed consisting of disturbances in urine concentrating capacity. Such disturbances were expressed by significantly low values of urine osmolality as compared to the basal values previous to the drugs. The decrease in urine osmolality was associated to a significant increase in urinary flow and in negative free-water clearance. There was no alteration in osmolar clearance and in fractional excretion of sodium. These observations suggest an interference of the drugs in the action of the antidiuretic hormone. The disturbance in urine concentration was reversible after a seven days period without the drugs administration. No significant histopathological alterations were observed in the kidneys of the rats treated with the drugs. On the other hand, the rats treated with a high dose of Pentostam (200 mg/100 grams of weight/day) showed the functional and the histopathological alterations of the acute tubular necrosis.

The use of botulinum toxin type A in the treatment of HTLV-1-associated overactive bladder refractory to conventional therapy

Urinary symptoms occur in 19% of human T-cell lymphotropic virus type 1 (HTLV-1)-infected patients who do not fulfill criteria for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and in almost 100% of HAM/TSP patients. Few studies have evaluated therapies for overactive bladder (OAB) caused by HTLV-1 infection. This case report describes the effect of onabotulinum toxin A on the urinary manifestations of three patients with HAM/TSP and OAB symptoms. The patients were intravesically administered 200 units of Botox®. Their incontinence episodes improved, and their OAB symptoms scores (OABSS) reduced significantly. These data indicate that Botox® should be a treatment option for OAB associated with HTLV-1 infection.

Urinary tract infection in full-term newborn infants: value of urine culture by bag specimen collection

OBJETIVE: to evaluate the efficacy of urine culture by bag specimen for the detection of neonatal urinary tract infection in full-term newborn infants. Retrospective study (1997) including full-term newborn infants having a positive urine culture (>100,000 CFU/ml) by bag specimen collection. The urinary tract infection diagnosis was confirmed by positive urine culture (suprapubic bladder aspiration method). The select cases were divided into three groups, according to newborn infant age at the bag specimen collection: GI (< 48 h, n = 17), GII (48 h to 7 d, n = 35) and GIII (> 7 d, n = 9). Sixty one full-term newborn infants were studied (5.1 % of total infants). The diagnosis was confirmed on 19/61 (31.1 %) of full-term infants born alive. Distribution among the groups was: GI = 2/17 (11.8 %), GII = 10//35 (28.6 %), and GIII = 7/9 (77.7 %). The most relevant clinical symptoms were: fever (GI - 100 %, GII - 91.4 %) and weight loss (GI - 35.3 %, GII - 45.7 %). Urine culture results for specimens collected by suprapubic aspiration were: E. coli GI (100 %), GII (40 %) and GIII (28.6 %), E. faecalis GI (30%), Staphylococcus coagulase-negative GII (20 %) and GIII (42.8 %), and Staphylococcus aureus GII (10 %). Correlation between positive urine culture collection (bag specimen method) and urinary tract infection diagnosis, using relative risk analysis, produced the following results: GI=0.30 (CI95% 0.08-1.15), GII=0.51 (CI 95% 0.25-1.06) and GIII=3.31 (CI95% 1.8-6.06) The most frequent urinary tract infection clinical signs in the first week were fever and weight loss, while non-specific symptomatology occurred later. E. coli was most frequent infectious agent, although from the 7th day of life, staphylococcus was noted. The urine culture (bag specimen method) was effective in detecting urinary tract infection only after the 7th day of life.

Elimination of biliary stones through the urinary tract: a complication of the laparoscopic cholecystectomy

The introduction and popularization of laparoscopic cholecystectomy has been accompanied with a considerable increase in perforation of gallbladder during this procedure (10%--32%), with the occurrence of intraperitoneal bile spillage and the consequent increase in the incidence of lost gallstones (0.2%--20%). Recently the complications associated with these stones have been documented in the literature. We report a rare complication occurring in an 81-year-old woman who underwent laparoscopic cholecystectomy and developed cutaneous fistula to the umbilicus and elimination of biliary stones through the urinary tract. During the cholecystectomy, the gall bladder was perforated, and bile and gallstones were spilled into the peritoneal cavity. Two months after the initial procedure there was exteriorization of fistula through the umbilicus, with intermittent elimination of biliary stones. After eleven months, acute urinary retention occurred due to biliary stones in the bladder, which were removed by cystoscopy. We conclude that efforts should be concentrated on avoiding the spillage of stones during the surgery, and that no rules exist for indicating a laparotomy simply to retrieve these lost gallstones.

Urinary tract infection in full-term newborn infants: risk factor analysis

OBJECTIVE: To analyze the correlation of risk factors to the occurrence of urinary tract infection in full-term newborn infants. PATIENTS AND METHODS: Retrospective study (1997) including full-term infants having a positive urine culture by bag specimen. Urine collection was based on: fever, weight loss > 10% of birth weight, nonspecific symptoms (feeding intolerance, failure to thrive, hypoactivity, debilitate suction, irritability), or renal and urinary tract malformations. In these cases, another urine culture by suprapubic bladder aspiration was collected to confirm the diagnosis. To compare and validate the risk factors in each group, the selected cases were divided into two groups: Group I - positive urine culture by bag specimen collection and negative urine culture by suprapubic aspiration, and Group II - positive urine culture by bag specimen collection and positive urine culture by suprapubic aspiration . RESULTS: Sixty one infants were studied, Group I, n = 42 (68.9%) and Group II, n = 19 (31.1%). The selected risk factors (associated infectious diseases, use of broad-spectrum antibiotics, renal and urinary tract malformations, mechanical ventilation, parenteral nutrition and intravascular catheter) were more frequent in Group II (p<0.05). Through relative risk analysis, risk factors were, in decreasing importance: parenteral nutrition, intravascular catheter, associated infectious diseases, use of broad-spectrum antibiotics, mechanical ventilation, and renal and urinary tract malformations. CONCLUSION: The results showed that parenteral nutrition, intravascular catheter, and associated infectious diseases contributed to increase the frequency of neonatal urinary tract infection, and in the presence of more than one risk factor, the occurrence of urinary tract infection rose up to 11 times.

Evaluation and treatment of the overactive bladder

The overactive bladder is characterized by symptoms of frequency, urgency, and urge incontinence, substantially affecting the quality of life of millions of people throughout the world. The symptoms are associated with significant social, psychological, occupational, domestic, physical, and sexual problems. Despite the considerable impact of this condition on quality of life, sufferers are often unwilling to discuss their problem with family members or health care professionals. This situation is unfortunate, for much can be done to alleviate the symptoms of this distressing condition. It is therefore of utmost importance that medical education about symptoms of the overactive bladder and other related problems be improved to help health care professionals identify and treat patients who will benefit from therapy. This article reviews current thinking regarding definition, epidemiology, quality of life effects, evaluation, and management of the overactive bladder.

Induction of experimental mammary carcinogenesis in rats with 7,12-dimethylbenz(a)anthracene

PURPOSE: To test an experimental model of chemical mammary carcinogenesis induction in rats. METHODS: Twenty young virgin Sprague-Dawley female rats, aged 47 days, received 20 mg of 7,12-dimethylbenz(a)anthracene (DMBA) intragastrically by gavage. Afterwards, at 8 and 13 weeks, their mammary glands were examined. At the end of the experiment, the animals were sacrificed, and the mammary tumors were measured and weighed. Tumor fragments were analyzed using light microscopy. RESULTS: Eight weeks after DMBA injection, 16 rats presented at least 1 breast tumor (80%). After 13 weeks, all of them (100%) developed breast carcinomas that were confirmed by histopathological analysis. CONCLUSION: This experimental animal model of chemical mammary induced carcinogenesis is feasible and can be used in further experiments on the role of tumorigenic biomodulator substances.

Medium-term protocols for in vivo evaluation of chemical modifiers of carcinogenesis

Cancer development is a long-term multistep process which allows interventional measure before the clincial disease emerges. the detection of natural substances which can block the process of carcinogenesis is a important as the identification of anti-tumoral drugs since they might be used in chemoprevention of cancer in high-risk groups. In vivo rodent models of chemical caecinogenesis have been used to study plant-derived inhibitors of carcinofenesis such as indols, coumarins, isothiocyanates, flavones, phenols and allyl-sulfides. Since the standard in vivo rodent bioassay is prolonged and expensive, shorter reliable protocols are needed. Two in vivo medium-term protocols for evaluation of modifiers of carcinogenesis are presented, one related to liver and the other to bladder cancer. Both protocols use rats, last 8 and 36 weeks and are based on the two-step concept of carcinogenesis: initiation and promotion. The protocols use respectively the development of altered foci of hepatocytes expressing immunochistochemically the placental form of gluthation S-transferase and the appearence of pre-neoplastic urothelium and papillomas as the "end-points". the use of these protocols for detection of plantpderived inhibitors of carcinogenesis appear warranted.

Age-targeted chemotherapy for control of urinary schistosomiais in endemic populations

Severity of urinary tract morbidity increases with intensity and duration of Schistosoma haematobium infection. We assessed the ability of yearly drug therapy to control infection intensity and reduce S. haematobium-associated disease in children 5-21 years old in an endemic area of Kenya. In year I, therapy resulted in reduced prevalence (66% to 22%, P < 0.001) and intensity of S. haematobium infection (20 to 2 eggs/10 mL, urine), with corresponding reductions in the prevalence of hematuria (52% to 19%, P < 0.001). There was not, however, a significant first-year effect on prevalence of urinary tract abnormalities detected by ultrasound. Repeat therapy in years 2 and 3 resulted in significant regression of hydronephrosis and bladder abnormalities (41% to 6% prevalence, P< 0.001), and further reductions in proteinuria. Repeat age-targeted therapy was associated with decreased prevalence of infection among young children (< 5yr) entering into the target age group. Two years after discontinuation of therapy, intensity of S. haematobium infection and ultrasound abnormalities remained suppressed, but hematuria prevalence began to increase (to 33% in 1989). Reinstitution of annual therapy in 1989 and 1990 reversed this trends. We conclude that annual oral therapy provides an effective strategy for control of morbidity due to S. haematobium on population basis, both through regression of disease in treated individuals, and prevention of infection in untreated subjects.

Ultrasound monitoring of structural urinary tract disease in Schistosoma haematobium infection

A major advance in our understanding of the natural history of Schistosoma haematobium-related morbidity has come through the introduction of the portable ultrasound machines for non-invasive examination of the kidneys and bladder. With the use of generators or battery packs to supply power in non-clinical field settings, and with the use of instant photography or miniaturized thermal printers to record permanent images, it is possible to examine scores of individuals in endemic communities every day. Broad-based ultrasound screening has allowed better definition of age-specific disease risks in urinary schistosomiasis. Results indicate that urinary tract abnormalities are common (18% overall prevalence) in S. haematobium transmission areas, with a 2-4% risk of either severe bladder abnormality or advanced ureteral obstruction. In longitudinal surveys, ultrasound studies have shown that praziquantel and metrifonate therapy are rapidly effective in reversing urinary tract abnormalities among children. The benefits of treating adults are less well known, but research in progress should help to define this issue. Similarly, the prognosis of specific ultrasound findings needs to be clarified, and the ease of sonographic examination will make such long-term follow-up studies feasible. In summary, the painless, quick, and reproducible ultrasound examination has become an essential tool in the study of urinary schistosomiasis.

Long-term outcomes of school-based treatment for control of urinary schistosomiasis: a review of experience in Coast Province, Kenya

Urinary schistosomiasis remains a significant burden for Africa and the Middle East. The success of population-based control programs will depend on their impact, over many years, on Schistosoma haematobium reinfection and associated disease. In a multi-year (1984-1992) control program in Kenya, we examined risk for S. haematobium reinfection and late disease during and after annual school-based treatment. In this setting, long-term risk of new infection was independently associated with location, age, hematuria, and incomplete treatment, but not with sex or frequency of water contact. Thus, very local environmental features and age-related factors played an important role in S. haematobium transmission, such that population-based control programs should optimally tailor their efforts to local conditions on a village-by-village basis. In 2001-2002, the late benefits of earlier participation in school-based antischistosomal therapy were estimated in a cohort of formerly-treated adult residents compared to never-treated adults from the same villages. Among age-matched subjects, current infection prevalence was lower among those who had received remote therapy. In addition, prevalence of bladder abnormality was lower in the treated group, who were free of severe bladder disease. Treatment of affected adults resulted in rapid resolution of infection and any detectable bladder abnormalities. We conclude that continued treatment into adulthood, as well as efforts at long-term prevention of infection (transmission control) are necessary to achieve optimal morbidity control in affected communities.

Urinary incontinence nursing diagnoses in patients with stroke

Abstract OBJECTIVE Identifying the prevalence of Stress urinary incontinence (SUI), Urge urinary incontinence (UUI), Functional urinary incontinence (FUI), Overflow urinary incontinence (OUI) and Reflex urinary incontinence (RUI) nursing diagnoses and their defining characteristics in stroke patients. METHOD A cross-sectional study with 156 patients treated in a neurological clinic. Data were collected through interviews and forwarded to nurses for diagnostic inference. RESULTS 92.3% of the patients had at least one of the studied diagnoses; OUI showed the highest prevalence (72.4%), followed by FUI (53.2%), RUI (50.0%), UUI (41.0%) and SUI (37.8%). Overdistended bladder and reports of inability to reach the toilet in time to avoid urine loss were the most prevalent defining characteristics. A statistically significant association of the defining characteristics with the studied diagnosis was verified. CONCLUSION The five incontinence diagnoses were identified in the evaluated patients, with different prevalence.

Modified pubovaginal sling technique in the surgical management of female stress urinary incontinence

Objective: To assess the application of aponeurotic sling by a modified technique with direct visualization of needles in patients with stress urinary incontinence. Methods: we applied the Kings Health Questionnaire (KHQ) for quality of life, gynecological examination, urinalysis I and urine culture approximately seven days prior to the urodynamic study (UDS) and the one-hour PAD test in patients undergoing making aponeurotic sling with its passing through the retropubic route with direct visualization of the needle, PAD test and King's Helth Questionnaire before and after surgery. Results: The mean age was 50.6 years, BMI of 28 and Leak Pressure (LP) 58,5cm H2O; 89% were Caucasian. Forty-six of them were monitored for three and six months, 43 for 12 months. The objective cure rate at 12 months postoperatively was approximately 93.5%. In evaluating quality of life, we observed a significant improvement in 12 months postoperatively compared with the preoperative period. There was no no urethral/bladder injury. As adverse results, we had one persistent urinary retention (2.3%), who was submitted to urethrolysis, currently without incontinence. Conclusion: The proposed procedure is safe as for the risk of bladder or urethral injuries, promoting significant improvement in quality of life and objective cure.

Effects of microcystin-LR in isolated perfused rat kidney

Microcystin is a hepatotoxic peptide which inhibits protein phosphatase types 1 and 2A. The objective of the present study was to evaluate the physiopathologic effects of microcystin-LR in isolated perfused rat kidney. Adult Wistar rats (N = 5) of both sexes (240-280 g) were utilized. Microcystin-LR (1 µg/ml) was perfused over a period of 120 min, during which samples of urine and perfusate were collected at 10-min intervals to determine the levels of inulin, sodium, potassium and osmolality. We observed a significant increase in urinary flow with a peak effect at 90 min (control (C) = 0.20 ± 0.01 and treated (T) = 0.32 ± 0.01 ml g-1 min-1, P<0.05). At 90 min there was a significant increase in perfusate pressure (C = 129.7 ± 4.81 and T = 175.0 ± 1.15 mmHg) and glomerular filtration rate (C = 0.66 ± 0.07 and T = 1.10 ± 0.04 ml g-1 min-1) and there was a significant reduction in fractional sodium tubular transport at 120 min (C = 78.6 ± 0.98 and T = 73.9 ± 0.95%). Histopathologic analysis of the perfused kidneys showed protein material in the urinary space, suggestive of renal toxicity. These data demonstrate renal vascular, glomerular and urinary effects of microcystin-LR, indicating that microcystin acts directly on the kidney by probable inhibition of protein phosphatases.