Glomerular proteinuria induces heme oxygenase-1 gene expression within renal epithelial cells

To clarify the patterns of heme oxygenase-1 (HO-1) production within the human kidney, we examined HO-1 mRNA expression in various renal diseases and compared the patterns with those of HO-1 protein expression and these data with the clinical features. The degrees of hematuria and proteinuria and the levels of urinary N-acetyl-beta-D-glucosaminidase (NAG), beta(2)-microglobulin (beta(2)-mg), and creatinine were determined. In situ hybridization and immunohistochemical studies were performed to evaluate HO-1 expression. HO-1 mRNA was detectable within tubular, glomerular, and Bowman's epithelial cells and infiltrating macrophages. Within the proximal tubuli, there was a correlation between expression of HO-1 protein and mRNA, but the intensity of HO-1 mRNA expression was much less than expected from the levels of protein. In contrast, both HO-1 protein and mRNA were expressed at significant levels within distal tubuli. Furthermore, there was no correlation with both expressions within distal tubuli. HO-1 mRNA expression within tubular, glomerular, and Bowman's epithelial cells tended to be more intense with greater degrees of proteinuria. However, there was little correlation between the intensity of HO-1 mRNA expression and the degree of hematuria, NAG, and beta(2)-mg. HO-1 plays important roles in maintaining renal functions by protecting renal epithelial cells from glomerular proteinuria, which can become a cause of oxidative stress. Furthermore, from the different expression pattern of HO-1 gene between within the proximal tubuli and within the distal tubuli, renal expression of HO-1 is regulated in a segment-specific manner, with HO-1 thereby playing distinct roles in different segments of the nephron to maintain renal functions.     

IL-15 and HIV infection: lessons for immunotherapy and vaccination

IL-15 is a pleiotropic and multifunctional cytokine that has a diverse array of distinct biological effects in the body. It plays a crucial role in host defense from viral and non-viral intracellular pathogens. The cytokine is essential for the development and differentiation of NK cells and for homeostatic expansion of CD8+ memory T cells, NKT cells and certain subsets of intestinal intra-epithelial lymphocytes (iIEL). It acts as a survival factor and inhibits spontaneous apoptosis in T, B and NK cells by increasing expression of different anti-apoptotic proteins. Several studies have shown that IL-15 production is compromised in HIV-infected AIDS patients and exogenous IL-15 drastically enhances functions of immune cells from these patients. Considering these distinct immune enhancing effects, relative safety in animal models, and minimal effects on HIV replication, IL-15 may represent a better cytokine for immune reconstitution in these patients. Furthermore, IL-15 may also act as a better adjuvant in eliciting antiviral immunity in anti-HIV vaccine strategies.     

Dual role of orphan nuclear receptor pregnane X receptor in bilirubin detoxification in mice

The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are implicated in xenobiotic and endobiotic detoxification, including the clearance of toxic bilirubin. Previous studies have suggested both overlapping and preferential regulation of target genes by these receptors, but the mechanism of cross-talk remains elusive. Here we reveal a dual role of PXR in bilirubin detoxification in that both the loss and activation of PXR led to protection from hyperbilirubinemia induced by bilirubin infusion or hemolysis. The increased bilirubin clearance in PXR-null mice was associated with selective upregulation of detoxifying enzymes and transporters, and the pattern of regulation is remarkably similar to that of transgenic mice expressing the activated CAR. Interestingly, the increased bilirubin clearance and associated gene regulation were absent in the CAR-null or double-knockout mice. In cell cultures, ligand-free PXR specifically suppressed the ability of CAR to induce the multidrug resistance associated protein 2 (MRP2), a bilirubin-detoxifying transporter. This suppression was, at least in part, the result of the disruption of ligand-independent recruitment of coactivator by CAR. In conclusion, PXR plays both positive and negative roles in regulating bilirubin homeostasis, and this provides a novel mechanism that may govern receptor cross-talk and the hierarchy of xenobiotic and endobiotic regulation. PXR is a potential therapeutic target for clinical treatment of jaundice. (HEPATOLOGY 2005;41:497-505.).     

Effect of iodine supplementation on goiter prevalence among the pediatric population in a severely iodine deficient area

We evaluated goiter status and urinary iodine excretion (UIC) of 304 school-children (7-12 years old) 3 years after a law was passed for mandatory production of iodinated salt in an area previously characterized by severe iodine deficiency in Zonguldak, a mountainous city in the West Black Sea region in Turkey. We examined all the children for goiter by palpation, measured sonographic thyroid volumes (STV) and UIC. Eighty-two percent of families had been using iodinated salt. UIC was above 100 microg/l in 71.2% of the children and median UIC was sufficient (143.5 microg/l). The prevalence of goiter was lower at ultrasound (14.6%) than by palpation (19.4%). Median STV values were within recommended normal limits at all ages. Although Zonguldak had been a highly endemic region, it became mildly endemic 3 years after mandatory iodination of salt, with decrease of goiter prevalence.     

Bronchoscopic lung volume reduction in patients with severe emphysema: anesthetic management

Bronchoscopic lung volume reduction is a novel approach to the treatment of severe emphysema. Its objective is to achieve the same improvements in lung function and exercise tolerance as lung volume reduction surgery while avoiding the surgical morbidity and mortality. We describe the anesthetic experience in a series of seven patients who underwent a total of eight procedures (one patient underwent a second procedure on the contralateral side). The technique used was one of total IV anesthesia using remifentanil and propofol, with a ventilatory strategy aimed at avoiding gas trapping and dynamic hyperinflation. To achieve this pressure, limited ventilation with a prolonged expiratory phase was provided by a Draeger Evita 2 ventilator. This technique resulted in intraoperative hypercapnia (Paco(2) 6.75 kPa) compared with baseline values (median Paco(2) 5.1 kPa; P < 0.05), but 2 h postoperatively the arterial partial pressure of CO(2) was returning to baseline (median Paco(2) 5.6 kPa; P < 0.01 compared with intraoperative data). There were no deaths or admissions to the intensive care unit after the procedure. One patient developed a pneumothorax that required drainage, three patients had acute exacerbations of chronic obstructive pulmonary disease, and one patient developed a cough that resolved spontaneously. Total hospital stay did not exceed 5 days for any of these patients.     

Chondrosarcoma of the hand: is a wide surgical resection necessary?

Chondrosarcomas of the hand are rare and generally treated with surgical resection. Thirteen patients with Grade 1 chondrosarcoma of the small bones of the hand were followed up for a mean of 99.8 months (range, 26-293 months). In eight patients (Group 1) curettage and reconstruction with cancellous bone was done and in five patients (Group 2) a wide resection was done. No patient experienced relapse in Group 2. In Group 1 one patient had a local relapse 18 months after intralesional resection. Using the Musculoskeletal Tumor Society score for evaluation, the clinical results showed an average of 98% and 95% of the normal function in Groups 1 and 2, respectively. None of the patients had evidence of systemic spread of the disease. With a relapse rate of 12.5% and no distant metastases after curettage, intralesional resection is the preferred method of treatment in Grade 1 chondrosarcoma of the hand, allowing the patient to avoid amputation and major loss of function.     

Trisacryl Gelatin Microspheres Versus Polyvinyl Alcohol Particles in the Preoperative Embolization of Bone Neoplasms

The aim of this study was to compare the efficacy of trisacryl gelatin microspheres versus polyvinyl alcohol particles (PVA) in the preoperative embolization of bone neoplasms, on the basis of intraoperative blood loss quantified by the differences in preoperative and postoperative hematic levels of hemoglobin, hematocrit and erythrocytes count. From January 1997 to December 2002, preoperative embolization of bone tumors (either primary or secondary) was carried out in 49 patients (age range 12/78), 20 of whom were treated with trysacril gelatin microspheres (group A) and 29 with PVA particles (group B). The delay between embolization and surgery ranged from 1 to 13 days in group A and 1 to 4 days in group B. As used in international protocols, we considered hematic levels of hemoglobin, hematocrit and erythrocytes count for the measurement of intraoperative blood loss then the differences in pre- and postoperative levels were used as statistical comparative parameters. We compared the values of patients treated with embospheres (n = 10) and PVA (n = 18) alone, and patients treated with (group A = 10; group B = 11) versus patients treated without other additional embolic materials in each group (group A = 10; group B = 18). According to the Students t-test (p < 0.05), the difference of hematic parameters between patients treated by embospheres and PVA alone were significant; otherwise there was no significant difference between patients treated with only one embolic material (embospheres and PVA) versus those treated with other additional embolic agents in each group. The patients treated with microspheres had a minor quantification of intraoperative blood loss compared to those who received PVA particles. Furthermore, they had a minor increase of bleeding related to the delay time between embolization and surgery. The use of additional embolic material did not improve the efficacy of the procedure in either group of patients.     

Retroperitoneoscopic live donor nephrectomy: extended experience in a single center

INTRODUCTION: Retroperitoneoscopic live donor nephrectomy (RPLDN) was performed because it is considered to be less invasive than open live donor-nephrectomy (OLDN) or transperitoneal laparoscopic live donor nephrectomy. PATIENTS AND METHODS: Between July 2001 and May 2003, 118 consecutive live donor kidney grafts were procured using RPLDN or OLDN. The patients who underwent RPLDN were divided into 2 groups: an initial group 1 (n = 38) and a subsequent group 2 (n = 48).Thirty-two patients who underwent OLDN during the same period were used as controls (group 3). The patients were placed in the lateral position. Three retroperitoneoscopic ports were inserted. The kidneys were retrieved through a 5-cm flank incision just below the 11th rib in group 1. In group 2, a 5-cm Pfannenstiel incision was used to extract the kidney. RESULTS: The operative time was 307 +/- 88 minutes, 245 +/- 42 minutes, and 215 +/- 70 minutes in groups 1, 2, and 3, respectively (group 1 vs group 2 or 3, P < .01). The mean postoperative pentazocine (painkiller) requirements were 12 mg, 4.4 mg, and 22 mg in groups 1, 2, and 3, respectively (group 2 vs group 1 or 3, P < .01). The hospital stay was 6.6 +/- 1.6, 4.9 +/- 0.7, and 7.0 +/- 0.1 days in groups 1, 2, and 3, respectively (group 2 vs group 1 or 3, P < .01). There were no serious complication, such as massive bleeding or bowel injury. CONCLUSIONS: RPLDN may be safer and less invasive than open donor nephrectomy.     

Comparison of the ImmunoCyt test and urinary cytology with other urine tests in the detection and surveillance of bladder cancer

Despite several new urine markers urinary cytology remains the gold standard for the non-invasive detection of bladder carcinoma. The use of monoclonal antibodies against tumor associated antigens offers a promising approach to improve urinary cytology. The aim of this study was to compare fluorescence immunocytology (ImmunoCyt/Ucyt+ test), alone and in combination with the conventional cytology, with other urine markers. Urine samples from 126 patients undergoing cystoscopy were included in the study. Among them, 42 patients had urothelial carcinoma, two dysplasia, two other malignancies, and 78 had no evidence of bladder cancer. Urine samples were taken before any manipulation. We used the ImmunoCyt test and Papanicolaou staining for conventional cytology. The ImmunoCyt slides were examined under a fluorescence microscope. Evaluations of the tests were blinded to clinical and pathological data and were carried out by three independent observers. The results of cytology and ImmunoCyt were compared with the BTAstat, NMP22, Lewis X, 486p3/12, and Urovision tests. The sensitivity for the ImmunoCyt test was 78.3% and for conventional cytology 84.6%. The combination of ImmunoCyt and cytology showed a sensitivity of 89.1%. The specificity was 73.8% for the ImmunoCyt alone, 80.0% for the cytology, and 72.5% for the combination of ImmunoCyt and cytology. Sensitivities for the other tests were 68.8% for (FISH), 66.6% (BTA-Stat), 68.8% (486p3/12), 95.5% (Lewis X), and 71.1% for (NMP22). Specificity was 89.1% for (FISH), 78.2% (BTA-Stat), 76.4% (486p3/12), 32.8% (Lewis X), and 65.5% for (NMP22). Urinary cytology can be improved by immunostaining with monoclonal antibodies against tumor-associated antibodies. The combination of ImmunoCyt with conventional cytology offers a superior sensitivity to other commercial tests. The ImmunoCyt test provides a useful supplement to urinary cytology in the diagnosis of bladder cancer.M.I. Toma, M.G. Friedrich contributed equally to this study