Recent Advances in Organic Dyes for Application in Dye-Sensitized Solar Cells under Indoor Lighting Conditions.

Among the emerging photovoltaic (PV) technologies, Dye-Sensitized Solar Cells (DSSCs) appear especially interesting in view of their potential for unconventional PV applications. In particular, DSSCs have been proven to provide excellent performances under indoor illumination, opening the way to their use in the field of low-power devices, such as wearable electronics and wireless sensor networks, including those relevant for application to the rapidly growing Internet of Things technology. Considering the low intensity of indoor light sources, efficient light capture constitutes a pivotal factor in optimizing cell efficiency. Consequently, the development of novel dyes exhibiting intense absorption within the visible range and light-harvesting properties well-matched with the emission spectra of the various light sources becomes indispensable. In this review, we will discuss the current state-of-the-art in the design, synthesis, and application of organic dyes as sensitizers for indoor DSSCs, focusing on the most recent results. We will start by examining the various classes of individual dyes reported to date for this application, organized by their structural features, highlighting their strengths and weaknesses. On the basis of this discussion, we will then draft some potential guidelines in an effort to help the design of this kind of sensitizer. Subsequently, we will describe some alternative approaches investigated to improve the light-harvesting properties of the cells, such as the co-sensitization strategy and the use of concerted companion dyes. Finally, the issue of measurement standardization will be introduced, and some considerations regarding the proper characterization methods of indoor PV systems and their differences compared to (simulated) outdoor conditions will be provided.

Partitioning of discrete proton arcs into interlaced subplans can bring proton arc advances to existing proton facilities.

BACKGROUND: Proton arcs have shown potential to reduce the dose to organs at risks (OARs) by delivering the protons from many different directions. While most previous studies have been focused on dynamic arcs (delivery during rotation), an alternative approach is discrete arcs, where step-and-shoot delivery is used over a large number of beam directions. The major advantage of discrete arcs is that they can be delivered at existing proton facilities. However, this advantage comes at the expense of longer treatment times. PURPOSE: To exploit the dosimetric advantages of proton arcs, while achieving reasonable delivery times, we propose a partitioning approach where discrete arc plans are split into subplans to be delivered over different fractions in the treatment course. METHODS: For three oropharyngeal cancer patients, four different arc plans have been created and compared to the corresponding clinical IMPT plan. The treatment plans are all planned to be delivered in 35 fractions, but with different delivery approaches over the fractions. The first arc plan (1×30) has 30 directions to be delivered every fraction, while the others are partitioned into subplans with 10 and 6 beam directions, each to be delivered every third (3×10), fifth fraction (5×6), or seventh fraction (7×10). All plans are assessed with respect to delivery time, target robustness over the treatment course, doses to OARs and NTCP for dysphagia and xerostomia. RESULTS: The delivery time (including an additional delay of 30 s between the discrete directions to simulate manual interaction with the treatment control system) is reduced from on average 25.2 min for the 1×30 plan to 9.2 min for the 3×10 and 7×10 plans and 5.7 min for the 5×6 plans. The delivery time for the IMPT plan is 7.9 min. When accounting for the combination of delivery time, target robustness, OAR sparing, and NTCP reduction, the plans with 10 directions in each fraction are the preferred choice. Both the 3×10 and 7×10 plans show improved target robustness compared to the 1×30 plans, while keeping OAR doses and NTCP values at almost as low levels as for the 1×30 plans. For all patients the NTCP values for dysphagia are lower for the partitioned plans with 10 directions compared to the IMPT plans. NTCP reduction for xerostomia compared to IMPT is seen in two of the three patients. The best results are seen for the first patient, where the NTCP reductions for the 7×10 plan are 1.6 p.p. (grade 2 xerostomia) and 1.5 p.p. (grade 2 dysphagia). The corresponding NTCP reductions for the 1×30 plan are 2.7 p.p. (xerostomia, grade 2) and 2.0 p.p. (dysphagia, grade 2). CONCLUSIONS: Discrete proton arcs can be implemented at any proton facility with reasonable treatment times using a partitioning approach. The technique also makes the proton arc treatments more robust to changes in the patient anatomy.

Proton arc therapy increases the benefit of proton therapy for oropharyngeal cancer patients in the model based clinic.

BACKGROUND AND PURPOSE: In the model-based approach, patients qualify for proton therapy when the reduction in risk of toxicity (ΔNTCP) obtained with IMPT relative to VMAT is larger than predefined thresholds as defined by the Dutch National Indication Protocol (NIPP). Proton arc therapy (PAT) is an emerging technology which has the potential to further decrease NTCPs compared to IMPT. The aim of this study was to investigate the potential impact of PAT on the number of oropharyngeal cancer (OPC) patients that qualify for proton therapy. MATERIALS AND METHODS: A prospective cohort of 223 OPC patients subjected to the model-based selection procedure was investigated. 33 (15%) patients were considered unsuitable for proton treatment before plan comparison. When IMPT was compared to VMAT for the remaining 190 patients, 148 (66%) patients qualified for protons and 42 (19%) patients did not. For these 42 patients treated with VMAT, robust PAT plans were generated. RESULTS: PAT plans provided better or similar target coverage compared to IMPT plans. In the PAT plans, integral dose was significantly reduced by 18% relative to IMPT plans and by 54% relative to VMAT plans. PAT decreased the mean dose to numerous organs-at-risk (OARs), further reducing NTCPs. The ΔNTCP for PAT relative to VMAT passed the NIPP thresholds for 32 out of the 42 patients treated with VMAT, resulting in 180 patients (81%) of the complete cohort qualifying for protons. CONCLUSION: PAT outperforms IMPT and VMAT, leading to a further reduction of NTCP-values and higher ΔNTCP-values, significantly increasing the percentage of OPC patients selected for proton therapy.

Spot scanning proton arc therapy reduces toxicity in oropharyngeal cancer patients.

BACKGROUND: Proton arc technology has recently shown dosimetric gains for various treatment indications. The increased number of beams and energy layers (ELs) in proton arc plans, increases the degrees of freedom in plan optimization and thereby flexibility to spare dose in organs at risk (OARs). A relationship exists between dosimetric plan quality, delivery efficiency, the number of ELs -and beams in a proton arc plan. PURPOSE: This work aims to investigate the effect of the number of beams and ELs in a proton arc plan, on toxicity and delivery time for oropharyngeal cancer patients (OPC) selected for intensity modulated proton therapy (IMPT) based on the Dutch model-based approach. METHODS: The EL reduction algorithm iteratively selects ELs from beams equidistantly spaced over a 360° arc. The beams in the final plan may contain multiple ELs, making them suited for static delivery on the studied treatment machine. The produced plans can therefore be called "step and shoot" proton arc plans. The number of beams and ELs were varied to determine the relationship with the planning cost function value, normal tissue complication probability (NTCP) and delivery time. Proton arc plans with robust target coverage and optimal energy layer reduction (ELR) settings to reduce NTCP, were generated for 10 OPC patients. Proton arc plans were compared to clinical volumetric modulated arc therapy (VMAT) and IMPT plans in terms of integral dose, OAR dose, NTCP for xerostomia and dysphagia and delivery time. Furthermore, dose-weighted average linear energy transfer (LETd ) distributions were compared between the IMPT and proton arc plans. A dry run delivery of a plan containing 20 beams and 360 ELs was performed to evaluate delivery time and accuracy. RESULTS: We found 360 ELs distributed over 30 beams generated proton arc plans with near minimal expected plan toxicity. Relative to corresponding IMPT and VMAT plans, an average reduction of 21 ± 3% and 58 ± 10% in integral dose was observed. D m e a n $_{mean}$ was reduced most in the pharyngeal constrictor muscle (PCM) medius structure, with on average 9.0 ± 4.2 Gy(RBE) (p = 0.0002) compared to the clinical IMPT plans. The average NTCP for grade≥2 and grade≥3 xerostomia at 6 months after treatment significantly decreased with 4.7 ± 1.8% (p = 0.002) and 1.7 ± 0.8% (p = 0.002), respectively, while the average NTCP for grade≥2 and grade≥3 dysphagia decreased with 4.4 ± 2.9% (p = 0.002) and 0.9 ± 0.4% (p = 0.002), respectively, increasing the benefit of protons relative to VMAT. For a "step and shoot" proton arc delivery with auto beam sequencing the estimated delivery time is 11 min, similar to the delivery time of a 6-field IMPT treatment. Gamma analysis between the planned and delivered dose distribution resulted in a 99.99% pass rate using 1mm/1% dose difference/distance to agreement criteria. CONCLUSIONS: "Step and shoot" proton arc demonstrates potential to further reduce toxicity compared to IMPT and VMAT in OPC treatment. By employing 360 ELs and 30 beams in the proposed ELR method, delivery time can reach clinically acceptable levels without compromising plan toxicity when automatic beam sequencing is available.

Comparison of the suitability of CBCT- and MR-based synthetic CTs for daily adaptive proton therapy in head and neck patients.

Cone-beam computed tomography (CBCT)- and magnetic resonance (MR)-images allow a daily observation of patient anatomy but are not directly suited for accurate proton dose calculations. This can be overcome by creating synthetic CTs (sCT) using deep convolutional neural networks. In this study, we compared sCTs based on CBCTs and MRs for head and neck (H&N) cancer patients in terms of image quality and proton dose calculation accuracy. A dataset of 27 H&N-patients, treated with proton therapy (PT), containing planning CTs (pCTs), repeat CTs, CBCTs and MRs were used to train two neural networks to convert either CBCTs or MRs into sCTs. Image quality was quantified by calculating mean absolute error (MAE), mean error (ME) and Dice similarity coefficient (DSC) for bones. The dose evaluation consisted of a systematic non-clinical analysis and a clinical recalculation of actually used proton treatment plans. Gamma analysis was performed for non-clinical and clinical treatment plans. For clinical treatment plans also dose to targets and organs at risk (OARs) and normal tissue complication probabilities (NTCP) were compared. CBCT-based sCTs resulted in higher image quality with an average MAE of 40 ± 4 HU and a DSC of 0.95, while for MR-based sCTs a MAE of 65 ± 4 HU and a DSC of 0.89 was observed. Also in clinical proton dose calculations, sCTCBCT achieved higher average gamma pass ratios (2%/2 mm criteria) than sCTMR (96.1% vs. 93.3%). Dose-volume histograms for selected OARs and NTCP-values showed a very small difference between sCTCBCT and sCTMR and a high agreement with the reference pCT. CBCT- and MR-based sCTs have the potential to enable accurate proton dose calculations valuable for daily adaptive PT. Significant image quality differences were observed but did not affect proton dose calculation accuracy in a similar manner. Especially the recalculation of clinical treatment plans showed high agreement with the pCT for both sCTCBCT and sCTMR.

Factors affecting the harmonization of disease-related metabolic brain pattern expression quantification in [18F]FDG-PET (PETMETPAT).

INTRODUCTION: The implementation of spatial-covariance [18F]fluorodeoxyglucose positron emission tomography-based disease-related metabolic brain patterns as biomarkers has been hampered by intercenter imaging differences. Within the scope of the JPND-PETMETPAT working group, we illustrate the impact of these differences on Parkinson's disease-related pattern (PDRP) expression scores. METHODS: Five healthy controls, 5 patients with idiopathic rapid eye movement sleep behavior disorder, and 5 patients with Parkinson's disease were scanned on one positron emission tomography/computed tomography system with multiple image reconstructions. In addition, one Hoffman 3D Brain Phantom was scanned on several positron emission tomography/computed tomography systems using various reconstructions. Effects of image contrast on PDRP scores were also examined. RESULTS: Human and phantom raw PDRP scores were systematically influenced by scanner and reconstruction effects. PDRP scores correlated inversely to image contrast. A Gaussian spatial filter reduced contrast while decreasing intercenter score differences. DISCUSSION: Image contrast should be considered in harmonization efforts. A Gaussian filter may reduce noise and intercenter effects without sacrificing sensitivity. Phantom measurements will be important for correcting PDRP score offsets.

Single-Crystal Pt-Decorated WO3 Ultrathin Films: A Platform for Sub-ppm Hydrogen Sensing at Room Temperature.

Hydrogen-related technologies are rapidly developing, driven by the necessity of efficient and high-density energy storage. This poses new challenges to the detection of dangerous gases, in particular the realization of cheap, sensitive, and fast hydrogen sensors. Several materials are being studied for this application, but most present critical bottlenecks, such as high operational temperature, low sensitivity, slow response time, and/or complex fabrication procedures. Here, we demonstrate that WO3 in the form of single-crystal, ultrathin films with a Pt catalyst allows high-performance sensing of H2 gas at room temperature. Thanks to the high electrical resistance in the pristine state, this material is able to detect hydrogen concentrations down to 1 ppm near room temperature. Moreover, the high surface-to-volume ratio of WO3 ultrathin films determines fast sensor response and recovery, with characteristic times as low as 1 s when the concentration exceeds 100 ppm. By modeling the hydrogen (de)intercalation dynamics with a kinetic model, we extract the energy barriers of the relevant processes and relate the doping mechanism to the formation of oxygen vacancies. Our results reveal the potential of single-crystal WO3 ultrathin films toward the development of sub-ppm hydrogen detectors working at room temperature.

Optimizing sharing of hospital biobank samples.

Implementing technical guidelines and standards as well as ways to boost cooperation should facilitate sharing of hospital biobank samples.

Impact of dietary n-3 polyunsaturated fatty acids on cognition, motor skills and hippocampal neurogenesis in developing C57BL/6J mice.

Maternal intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) is critical during perinatal development of the brain. Docosahexaenoic acid (DHA) is the most abundant n-3 PUFA in the brain and influences neuronal membrane function and neuroprotection. The present study aims to assess the effect of dietary n-3 PUFA availability during the gestational and postnatal period on cognition, brain metabolism and neurohistology in C57BL/6J mice. Female wild-type C57BL/6J mice at day 0 of gestation were randomly assigned to either an n-3 PUFA deficient diet (0.05% of total fatty acids) or an n-3 PUFA adequate diet (3.83% of total fatty acids) containing preformed DHA and its precursor α-linolenic acid. Male offspring remained on diet and performed cognitive tests during puberty and adulthood. In adulthood, animals underwent (31)P magnetic resonance spectroscopy to assess brain energy metabolites. Thereafter, biochemical and immunohistochemical analyses were performed assessing inflammation, neurogenesis and synaptic plasticity. Compared to the n-3 PUFA deficient group, pubertal n-3 PUFA adequate fed mice demonstrated increased motor coordination. Adult n-3 PUFA adequate fed mice exhibited increased exploratory behavior, sensorimotor integration and spatial memory, while neurogenesis in the hippocampus was decreased. Selected brain regions of n-3 PUFA adequate fed mice contained significantly lower levels of arachidonic acid and higher levels of DHA and dihomo-γ-linolenic acid. Our data suggest that dietary n-3 PUFA can modify neural maturation and enhance brain functioning in healthy C57BL/6J mice. This indicates that availability of n-3 PUFA in infant diet during early development may have a significant impact on brain development.

Translational cancer research: balancing prevention and treatment to combat cancer globally.

Cancer research is drawing on the human genome project to develop new molecular-targeted treatments. This is an exciting but insufficient response to the growing, global burden of cancer, particularly as the projected increase in new cases in the coming decades is increasingly falling on developing countries. The world is not able to treat its way out of the cancer problem. However, the mechanistic insights from basic science can be harnessed to better understand cancer causes and prevention, thus underpinning a complementary public health approach to cancer control. This manuscript focuses on how new knowledge about the molecular and cellular basis of cancer, and the associated high-throughput laboratory technologies for studying those pathways, can be applied to population-based epidemiological studies, particularly in the context of large prospective cohorts with associated biobanks to provide an evidence base for cancer prevention. This integrated approach should allow a more rapid and informed translation of the research into educational and policy interventions aimed at risk reduction across a population.

Fit for purpose frozen tissue collections by RNA integrity number-based quality control assurance at the Erasmus MC tissue bank.

About 5000 frozen tissue samples are collected each year by the Erasmus Medical Center tissue bank. Two percent of these samples are randomly selected annually for RNA isolation and RNA Integrity Number (RIN) measurement. A similar quality assessment was conducted during centralization of a 20-year-old tissue collection from the cancer institute, a 15-year-old liver sample archive (-80°C), and a 13-year-old clinical pathology frozen biopsy archive (Liquid Nitrogen). Samples were divided into either high-quality (RIN ≥6.5) or low-quality overall categories, or into four "fit-for-purpose" quality groups: RIN <5: not reliable for demanding downstream analysis; 5 ≤RIN <6: suitable for RT-qPCR; 6 ≤RIN <8: suitable for gene array analysis; and RIN ≥8: suitable for all downstream techniques. In general, low RIN values were correlated with fatty, fibrous, pancreatic, or necrotic tissue. When the percentage of samples with RIN ≥6.5 is higher than 90%, the tissue bank performance is adequate. The annual 2011 quality control assessment showed that 90.3% (n=93) of all samples had acceptable RIN values; 97.4% (n=39) of the cancer institute collection had RIN values above 6.5; and 88.6% (n=123) of samples from the liver sample archive collection had RIN values higher than 6.5. As the clinical pathology biopsy collection contained only 58.8% (n=24) acceptable samples, the procurement protocols used for these samples needed immediate evaluation. When the distribution of RIN values of the different collections were compared, no significant differences were found, despite differences in average storage time and temperature. According to the principle of "fit-for-purpose" distribution, the vast majority of samples are considered good enough for most downstream techniques. In conclusion, an annual tissue bank quality control procedure provides useful information on tissue sample quality and sheds light on where and if improvements need to be made.

Histological assessment of PAXgene tissue fixation and stabilization reagents.

Within SPIDIA, an EC FP7 project aimed to improve pre analytic procedures, the PAXgene Tissue System (PAXgene), was designed to improve tissue quality for parallel molecular and morphological analysis. Within the SPIDIA project promising results were found in both genomic and proteomic experiments with PAXgene-fixed and paraffin embedded tissue derived biomolecules. But, for this technology to be accepted for use in both clinical and basic research, it is essential that its adequacy for preserving morphology and antigenicity is validated relative to formalin fixation. It is our aim to assess the suitability of PAXgene tissue fixation for (immuno)histological methods. Normal human tissue specimens (n = 70) were collected and divided into equal parts for fixation either with formalin or PAXgene. Sections of the obtained paraffin-embedded tissue were cut and stained. Morphological aspects of PAXgene-fixed tissue were described and also scored relative to formalin-fixed tissue. Performance of PAXgene-fixed tissue in immunohistochemical and in situ hybridization assays was also assessed relative to the corresponding formalin-fixed tissues. Morphology of PAXgene-fixed paraffin embedded tissue was well preserved and deemed adequate for diagnostics in most cases. Some antigens in PAXgene-fixed and paraffin embedded sections were detectable without the need for antigen retrieval, while others were detected using standard, formalin fixation based, immunohistochemistry protocols. Comparable results were obtained with in situ hybridization and histochemical stains. Basically all assessed histological techniques were found to be applicable to PAXgene-fixed and paraffin embedded tissue. In general results obtained with PAXgene-fixed tissue are comparable to those of formalin-fixed tissue. Compromises made in morphology can be called minor compared to the advantages in the molecular pathology possibilities.

Changes in bladder wall blood oxygen saturation in the overactive obstructed bladder.

PURPOSE: Several studies suggest that hypoxia of the bladder wall contributes to bladder dysfunction but the exact relation between bladder function and blood oxygen saturation, a surrogate marker for hypoxia, is not known. We determined bladder wall blood oxygen saturation in vivo in an animal model of bladder outlet obstruction to establish the exact relation between blood oxygen saturation and bladder function. MATERIALS AND METHODS: In 8 sham operated and 8 urethrally obstructed guinea pigs we measured blood oxygen saturation of the bladder wall by differential path length spectroscopy before surgery and 8 weeks postoperatively. Urodynamic investigations performed during the whole 8-week period provided data on bladder function. RESULTS: Before surgery and 8 weeks after sham surgery blood oxygen saturation in the bladder wall was between 88% and 95% during filling. It decreased during voiding and returned to greater than 90% within 30 seconds. Eight weeks after obstruction saturation was significantly lower than in the sham operated group during filling and voiding. The decrease was positively related to bladder pressure during filling and voiding, and was more pronounced when overactivity was present. Local bladder contractions occurred without a measurable increase in bladder pressure but were associated with a decrease in saturation. CONCLUSIONS: A normal bladder maintains a high oxygen saturation level during filling. Bladder obstruction compromises this ability, especially when it involves overactivity. Local bladder contractions without a measurable increase in bladder pressure were associated with a decrease in blood saturation.

The Organization of European Cancer Institute Pathobiology Working Group and its support of European biobanking infrastructures for translational cancer research.

BACKGROUND: Today's translational cancer research increasingly depends on international multi-center studies. Biobanking infrastructure or comprehensive sample exchange platforms to enable networking of clinical cancer biobanks are instrumental to facilitate communication, uniform sample quality, and rules for exchange. METHODS: The Organization of European Cancer Institutes (OECI) Pathobiology Working Group supports European biobanking infrastructure by maintaining the OECI-TuBaFrost exchange platform and organizing regular meetings. This platform originated from a European Commission project and is updated with knowledge from ongoing and new biobanking projects. This overview describes how European biobanking projects that have a large impact on clinical biobanking, including EuroBoNeT, SPIDIA, and BBMRI, contribute to the update of the OECI-TuBaFrost exchange platform. RESULTS: Combining the results of these European projects enabled the creation of an open (upon valid registration only) catalogue view of cancer biobanks and their available samples to initiate research projects. In addition, closed environments supporting active projects could be developed together with the latest views on quality, access rules, ethics, and law. CONCLUSIONS: With these contributions, the OECI Pathobiology Working Group contributes to and stimulates a professional attitude within biobanks at the European comprehensive cancer centers. IMPACT: Improving the fundamentals of cancer sample exchange in Europe stimulates the performance of large multi-center studies, resulting in experiments with the desired statistical significance outcome. With this approach, future innovation in cancer patient care can be realized faster and more reliably.

Higher capillary electrophoresis injection settings as an efficient approach to increase the sensitivity of STR typing.

Evidentiary traces may contain low quantities of DNA, and regularly incomplete short tandem repeat (STR) profiles are obtained. In this study, higher capillary electrophoresis injection settings were used to efficiently improve incomplete STR profiles generated from low-level DNA samples under standard polymerase chain reaction (PCR) conditions. The method involves capillary electrophoresis with higher injection voltage and extended injection time. STR peak heights increased six-fold. Inherent to the analysis of low-level DNA samples, we observed stochastic amplification artifacts, mainly in the form of allele dropout and heterozygous peak imbalance. Increased stutter ratios and allele drop-in were rarely seen. Upon STR typing of 10:1 admixed samples, the profile of the major component did not become overloaded when using higher injection settings as was observed upon elevated cycling. Thereby an improved profile of the minor component was obtained. For low-level DNA casework samples, we adhere to independent replication of the PCR amplification and boosted capillary electrophoresis.

Changes in the penile arteries of the rat after fractionated irradiation of the prostate: a pilot study.

INTRODUCTION: External beam radiotherapy for prostate cancer leads to erectile dysfunction in 36%-43% of patients. The underlying mechanism is largely unknown, although some clinical studies suggest that the arterial supply to the corpora cavernosa is responsible. Two animal experimental studies reported on the effects of a single fraction of prostate irradiation on the penile structures. However, irradiation in multiple fractions is more representative of the actual clinical treatment. AIM: The present prospective, controlled study was initiated to investigate the effect of fractionated prostate irradiation on the arteries of the corpora cavernosa. MAIN OUTCOME MEASURES: Histological evaluation of the penile tissue in comparison with control rats at 2, 4, and 9 weeks after irradiation. METHODS: The prostate of twelve rats was treated with external beam radiation in 5 daily fractions of 7.4 gray. Three control rats were treated with sham irradiation. Prostatic and penile tissue was evaluated for general histology (hematoxylin-eosin). The penile tissue was further evaluated after combined staining for collagen (resorcin fuchsin) and alpha-smooth muscle actin (SMA) (Biogenex). RESULTS: The prostate showed adequate irradiation with fibrosis occurring at 9 weeks after irradiation. The corpora cavernosa showed arteries that had developed loss of smooth muscle cells expressing SMA, thickening of the intima, and occlusions. All the control rats maintained normal anatomy. CONCLUSION: This is the first animal experimental study that demonstrates changes in the arteries of the corpora cavernosa after fractionated irradiation to the prostatic area. The preliminary data suggests that erectile dysfunction after radiotherapy might be caused by radiation damage to the arterial supply of the corpora cavernosa.

The detrusor glycogen content of a de-obstructed bladder reflects the functional history of that bladder during PBOO.

AIMS: To determine if detrusor glycogen content in a bladder after removal of a urethral obstruction reflects the situation of bladder dysfunction as it existed during the period of obstruction. METHODS: The glycogen content of the detrusor was scored using a Periodic Acid Schiff's (PAS) staining. It was related to the functional history of the bladder. Bladder tissue was obtained from a guinea-pig model for posterior urethral valves where animals had been obstructed for up to 10 weeks, de-obstructed and allowed to recover for 2--8 weeks. Bladder urodynamic function had been documented with multiple measurements for the complete period of obstruction and de-obstruction. RESULTS: The degree of glycogen deposition in a bladder after de-obstruction correlated directly with bladder function during obstruction. The strongest glycogen deposition was found in bladders having experienced the highest pressures, most instabilities, lowest compliance and highest contractility. In contrast, the bladder glycogen content was not related to the function of the bladder at the day the tissue was obtained, except for a relation between high glycogen content and continuing low compliance. CONCLUSIONS: The glycogen content of a bladder reflects the history of bladder dysfunction, also when measured during a recovery period. This window on the functional history of a bladder may be of clinical value for picking out potential bad-responders to therapy in patients with incomplete data on bladder function during a previous period of bladder obstruction.

The effect of oxybutynin on structural changes of the obstructed guinea pig bladder.

PURPOSE: Oxybutynin is used clinically to lower intravesical pressure and detrusor overactivity. In vitro it inhibits stretch induced bladder smooth muscle cell proliferation. We tested whether oxybutynin also prevents hypertrophic bladder changes in vivo in a model of partial bladder obstruction. MATERIALS AND METHODS: Subvesical obstruction was induced in immature guinea pigs by a silver ring around the urethra. Eight animals received 0.4 mg oxybutynin per kg body weight per day in 2 doses. Control groups were obstructed without oxybutynin treatment or sham operated. Urodynamic pressure flow studies were performed at 1-week intervals for 10 weeks in all animals under anesthesia with ketamine/xylazine. After 10 weeks the animals were sacrificed and the bladder was removed for structural analysis with periodic acid-Schiff stain, in which the number of glycogen granules was also scored as a measure of previous ischemia. RESULTS: Compared to the sham treated group obstructed animals had significantly higher intravesical pressure and detrusor overactivity, lower compliance and increased contractility. Obstructed animals that received oxybutynin retained normal intravesical pressure, detrusor overactivity and compliance. Their bladder contractility increased as in obstructed animals. The oxybutynin group showed less collagen infiltration in the detrusor and fewer glycogen granules compared to those in obstructed animals. CONCLUSIONS: Our results demonstrate that oxybutynin has a protective effect on bladder function and structure. Prevention of hypertrophic and ischemic bladder changes is an argument for an early start of oxybutynin treatment in children with inborn neurogenic bladder dysfunction, such as spina bifida, or in patients with urethral valves.

Detrusor glycogen reflects the functional history of bladders with partial outlet obstruction.

OBJECTIVE: To assess the relationship between glycogen content in bladder detrusor tissue and historical bladder function in a guinea-pig model of partial bladder outlet obstruction (PBOO). MATERIALS AND METHODS: In male immature guinea pigs PBOO was created with a silver ring around the proximal urethra; a control group had a sham operation for comparison. Longitudinal individual urodynamic data were obtained weekly, so that guinea pigs were killed at different levels of bladder dysfunction. Bladder sections were stained with periodic acid-Schiff (PAS) to assess overall morphology and glycogen granule density, scored from 0 (no glycogen) to 3. Glycogen scores were related to both the end-stage and historical extremes of bladder function values. RESULTS: Glycogen granules were seen only in the detrusor; as their number increased their location expanded from only close to the serosa (glycogen score 1), through the detrusor (score 2) up to the urothelium (score 3). A glycogen score of 0 correlated with normal values for all urodynamic variables. Compared with a glycogen score of 0 a score of 1 correlated with significant (P < 0.05) changes in end-stage compliance (decrease) and contractility (increase) and significantly higher historical values for contractility, pressure and number of unstable contractions (NUC). In the group with a glycogen score of 2 there were significant changes in both the end-stage values and historical extremes for compliance, pressure, contractility and NUC (all P < 0.05). In the group with a glycogen score of 3 all these changes were even more dramatic, except for the end-stage contractility, for which the increase was not significant. From glycogen score 0 to score 3 all changes increased in magnitude. CONCLUSION: A high glycogen content reflects a history of abnormal urodynamic function. This finding exemplifies the added value of structural analysis to urodynamic studies. Further studies are needed to relate bladder structure to the potential for functional recovery.

Tubular and interstitial nephrocalcinosis.

PURPOSE: We determined whether nephrocalcinosis is common and whether its detection is influenced by renal tissue processing. MATERIALS AND METHODS: Renal cortical and papillary tissue was obtained from the unaffected parts of 15 kidneys removed due to an oncological indication. The effect of tissue processing on the loss of crystals was studied in a kidney with nephrocalcinosis due to chronic pyelonephritis. Immediately frozen and formaldehyde fixed sections were analyzed by polarized light and Raman spectroscopy, and stained for calcium (Yasue) and hyaluronan. RESULTS: Although 13 of 15 snap-frozen sections from tumor kidneys contained birefringent particles (mean +/- SD 3.2 +/- 2.9 particles per cm(2)) in the renal tubules, this was not considered nephrocalcinosis because the crystals were not attached to the epithelial lining. Interstitial nephrocalcinosis was found on Yasue stain in 3 of 15 kidneys with tumor (20%). Calcium deposits were found in the papillary interstitium only, always together with hyaluronan. Formaldehyde fixed sections from the pyelonephritis kidney contained fewer renal tubular cell associated birefringent particles than immediately frozen sections (9.4 +/- 1.9 vs 41.6 +/- 1.2 per cm(2)). Particles were composed of calcium oxalate monohydrate (Yasue and Raman). CONCLUSIONS: There are 2 distinct forms of nephrocalcinosis, including tubular nephrocalcinosis, which seems to be reserved for specific conditions such as chronic pyelonephritis, and interstitial nephrocalcinosis. The incidence of tubular calcium oxalate nephrocalcinosis could be underestimated due to the loss of crystals during tissue processing for routine histology. The crystal binding molecule hyaluronan may have a role in the 2 forms of nephrocalcinosis.