Interleukin-17A stimulates granulocyte-macrophage colony-stimulating factor release by murine osteoblasts in the presence of 1,25-dihydroxyvitamin D(3) and inhibits murine osteoclast development in vitro.

OBJECTIVE: To investigate the effects of interleukin-17A (IL-17A) on osteoclastogenesis in vitro. METHODS: Bone marrow cells (BMCs) were isolated from the excised tibia and femora of wild-type C57BL/6J mice, and osteoblasts were obtained by sequential digestion of the calvariae of ddY, C57BL/6J, and granulocyte-macrophage colony-stimulating factor-knockout (GM-CSF(-/-)) mice. Monocultures of BMCs or cocultures of BMCs and osteoblasts were supplemented with or without 1,25-dihydroxyvitamin D(3)(1,25[OH](2)D(3)), recombinant human macrophage colony-stimulating factor (M-CSF), RANKL, and IL-17A. After 5-6 days, the cultures were fixed with 4% paraformaldehyde and subsequently stained for the osteoclast marker enzyme tartrate-resistant acid phosphatase (TRAP). Osteoprotegerin (OPG) and GM-CSF expression were measured by enzyme-linked immunosorbent assay, and transcripts for RANK and RANKL were detected by real-time polymerase chain reaction. RESULTS: In both culture systems, IL-17A alone did not affect the development of osteoclasts. However, the addition of IL-17A plus 1,25(OH)(2)D(3) to cocultures inhibited early osteoclast development within the first 3 days of culture and induced release of GM-CSF into the culture supernatants. Furthermore, in cocultures of GM-CSF(-/-) mouse osteoblasts and wild-type mouse BMCs, IL-17A did not affect osteoclast development, corroborating the role of GM-CSF as the mediator of the observed inhibition of osteoclastogenesis by IL-17A. CONCLUSION: These findings suggest that IL-17A interferes with the differentiation of osteoclast precursors by inducing the release of GM-CSF from osteoblasts.

Synthesis, characterisation and bioimaging of a fluorescent rhenium-containing PNA bioconjugate.

A new rhenium tricarbonyl complex of a bis(quinoline)-derived ligand (2-azido-N,N-bis((quinolin-2-yl)methyl)ethanamine, L-N(3)), namely [Re(CO)(3)(L-N(3))]Br was synthesized and characterized in-depth, including by X-ray crystallography. [Re(CO)(3)(L-N(3))]Br exhibits a strong UV absorbance in the range 300-400 nm with a maximum at 322 nm, and upon photoexcitation, shows two distinct emission bands at about 430 and 560 nm in various solvents (water, ethylene glycol). [Re(CO)(3)(L-N(3))]Br could be conjugated, on a solid phase, to a peptide nucleic acid (PNA) oligomer using the copper(I)-catalyzed azide-alkyne cycloaddition reaction (Cu-AAC, "click" chemistry) and an alkyne-containing PNA building block to give Re-PNA. It was demonstrated that upon hybridisation with a complementary DNA strand (DNA), the position of the maxima and emission intensity for the hybrid Re-PNA·DNA remained mainly unchanged compared to those of the single strand Re-PNA. The rhenium-containing PNA oligomer Re-PNA could be then mediated in living cells where they have been shown to be non-toxic contrary to the general notion that organometallic compounds are usually unstable under physiological conditions and/or cytotoxic. Furthermore, Re-PNA could be detected in living cells using fluorescent microscopy.

The complex clinical picture of side effects to biologicals.

Biologicals are proteins used as drugs. Biologicals target clearly defined molecular structures, being part of established pathogenetic pathways. Therefore, their focused mode of action seems to render them superior to classic small molecular drugs regarding "off-target" adverse drug reactions (ADR). Nevertheless, the increasing use of biologicals for the treatment of different diseases has revealed partially unexpected adverse reactions. The often direct interaction of a biological with the immune system provides a clue to most side effects, which have consequently been subclassified, based on pathogenetic principles, into 5 subtypes named alpha, beta, gamma, delta, and epsilon, reflecting overstimulation (high cytokine values, type alpha), hypersensitivity (type beta), immune deviation (including immunodeficiency, type gamma), cross-reactivity (type delta), and nonimmune mediated side effects (type epsilon). This article presents typical clinical manifestations of these subtypes of ADR to biologicals, proposes general rules for treating them, and provides a scheme for a thorough allergological workup. This approach should help in future handling of these often very efficient drugs.

Plasma vaporisation of the prostate: initial clinical results.

BACKGROUND: Laser vaporisation of the prostate has had a considerable impact in recent years. In an attempt to achieve tissue vaporisation with bipolar high-frequency generators, plasma vaporisation was recently introduced. OBJECTIVE: To provide the first clinical information on bipolar plasma vaporisation of the prostate for patients with lower urinary tract symptoms (LUTS) due to bladder outlet obstruction (BOO). DESIGN, SETTING, AND PARTICIPANTS: Thirty patients were included in this prospective bicentre study. INTERVENTION: All patients underwent bipolar plasma vaporisation with a novel electrode (Olympus Winter & Ibe GmbH, Hamburg, Germany). MEASUREMENTS: International Prostate Symptom Score (IPSS), bother score, maximum flow rate (Q(max)), and postvoid residual were evaluated at baseline and at the time of discharge as well as at 1, 3, and 6 mo after the intervention. RESULTS AND LIMITATIONS: Mean preoperative prostate volume was 59±32 ml (range: 30-170), and mean operating time was 61±26 min (range: 20-140). Besides one reoperation (conventional transurethral prostatectomy) due to persistent obstruction, no major complication occurred intra- or postoperatively and no blood transfusion was required. Catheterisation time averaged 41±35 h (range: 18-192). Transient mild to moderate dysuria was noted in four patients (13%). At 1, 3, and 6 mo, Q(max) increased from 6.6±2.7 ml/s preoperative to 17.3±4.7 ml/s (p<0.01), 18.5±4.6 ml/s (p<0.01), and 18.1±5.0 ml/s (p<0.01), respectively. The IPSS decreased from 20.8±3.6 to 10.4±3.5 (p<0.01), 8.2±2.9 (p<0.01), and 8.1±3.1 (p<0.01), respectively. These data represent a small nonrandomised study cohort with limited follow-up. CONCLUSIONS: Our initial experience indicates that bipolar plasma vaporisation might be a safe and effective treatment option for patients with LUTS due to BOO. To define the potential role of this novel technique, randomised trials with longer follow-up are mandatory.

Preliminary evaluation of a novel side-fire diode laser emitting light at 940 nm, for the potential treatment of benign prostatic hyperplasia: ex-vivo and in-vivo investigations.

OBJECTIVES: To evaluate, ex vivo and in vivo, the tissue-removal capacity and coagulation properties of a diode laser emitting light at 940 nm, as in the search for potential therapeutic strategies for benign prostatic hyperplasia that cause less morbidity than transurethral resection of the prostate (TURP), various types of lasers have been tested. MATERIALS AND METHODS: A diode laser system (prototype; wavelength 940 nm, Dornier MedTech, Wessling, Germany) was evaluated in an isolated, blood-perfused ex-vivo porcine kidney model at 10-60 W (five kidneys). An in-vivo beagle model was used to investigate the effects on six prostate lobes at a generator output power level of 200 W. After the laser treatment tissue were examined histologically to compare the depth of coagulation and vaporization. RESULTS: With increasing generator output power levels there was an increasing vaporization and coagulation ability for the diode laser at 940 nm in the ex-vivo model. At 60 W the mean (sd) vaporization depth was 1.72 (0.47) mm with a coagulation zone of 9.56 (0.26) mm. In vivo, the diode laser caused rapid ablation with no intraoperative haemorrhage. Histologically, the zone of coagulation had a mean (sd) depth of 4.25 (0.15) mm at 200 W. The tissue removal capacity was estimated at 0.874-1.583 g/min in vivo. CONCLUSIONS: Our findings indicate that diode-laser vaporization at 940 nm is feasible and might be effective for acutely relieving bladder outlet obstruction in an in-vivo setting. Due to its mean coagulation zone of 4.25 mm the diode laser seems to have effective haemostatic properties.

Comparison of potassium-titanyl-phosphate laser vaporization of the prostate and transurethral resection of the prostate: update of a prospective non-randomized two-centre study.

OBJECTIVES: To evaluate the intermediate-term clinical efficacy and the rate of complications in 80 W photoselective vaporization of the prostate (PVP) with the potassium-titanyl-phosphate laser (Greenlight, (AMS, Minnetonka, MN, USA) compared with transurethral resection of the prostate (TURP) in a prospective non-randomised two-centre study. PATIENTS AND METHODS: From December 2003 to August 2006, 396 patients (PVP 269, TURP 127) with lower urinary tract symptoms secondary to benign prostatic hyperplasia were included in the study. There was a significant difference in mean age (72 years for PVP vs 68 for TURP, P = 0.001). Patients were therefore stratified in age categories (<70, 70-80, >80 years) and compared for perioperative variables, functional outcome and complications, with a follow-up of up to 24 months. RESULTS: The mean prostate size was greater (overall, 62 vs 48 mL, P < 0.001) and mean operative duration longer (overall 72 vs 53 min; P = 0.001) for PVP in all age categories. The rate of intraoperative bleeding (3% vs 11%), blood transfusions (0% vs 5.5%) and capsule perforations (0.4% vs 6.3%), and early postoperative clot retention (0.4% vs 3.9%) was significantly lower for PVP. Hospitalization time was significantly shorter in the PVP group for patients aged <70 years (3.0 vs 4.7 days) and 70-80 years (4.0 vs 5.0 days; P = 0.001). The improvement of peak urinary flow rate was higher after TURP for any age category. The International Prostate Symptom Score and postvoid residual volume during the follow-up showed no significant difference. After 12 months the overall prostate size reduction was 63% (-30 mL) after TURP and 44% (-27 mL) after PVP. The rate of repeat TURP/PVP was higher in the PVP group (6.7% vs 3.9%, not significant) within the follow-up of up to 2 years. The incidence of urethral and bladder neck strictures was comparable. CONCLUSIONS: PVP was more favourable in terms of perioperative safety. Although patients assigned for PVP were older and had larger prostates, PVP resulted in a similar functional outcome. Further follow-up is needed to draw final conclusions about the long-term efficacy of PVP.

Morbidity, mortality and early outcome of transurethral resection of the prostate: a prospective multicenter evaluation of 10,654 patients.

PURPOSE: Transurethral resection of the prostate has for decades been the standard surgical therapy for lower urinary tract symptoms secondary to benign prostatic hyperplasia, the most common benign neoplasm in men. To generate a contemporary reference for evolving medical and minimally invasive therapies we analyzed complications and immediate outcomes of transurethral prostate resection in a statewide multicenter study. MATERIALS AND METHODS: We prospectively evaluated 10,654 patients undergoing transurethral prostate resection in the state of Bavaria, Germany from January 1, 2002 until December 31, 2003. Case records containing 54 items concerning preoperative status, operation details, complications and immediate outcome, were recorded for each patient. RESULTS: The mortality rate for transurethral prostate resection was 0.10%. The cumulative short-term morbidity rate was 11.1%. The most relevant complications were failure to void (5.8%), surgical revision (5.6%), significant urinary tract infection (3.6%), bleeding requiring transfusions (2.9%) and transurethral resection syndrome (1.4%). The resected tissue averaged 28.4 gm. Incidental carcinoma of the prostate was diagnosed by histological examination in 9.8% of patients. Urinary peak flow rate increased significantly to 21.6 +/- 9.4 ml per second (baseline 10.4 +/- 6.8 ml per second, 1 tail p <0.0001), while post-void residual decreased to 31.1 +/- 73.0 ml (baseline 180.3 +/- 296.9 ml, 1-tail p <0.0001). CONCLUSIONS: In a large scale evaluation comprising 44 mostly nonacademic urological departments in Bavaria, unique real-world data for transurethral prostate resection were prospectively generated. This most contemporary information should be of use to potential patients and facilitate subsumption of emerging surgical and nonsurgical benign prostatic hyperplasia treatment options.