Written education about central sensitization and pain physiology alone is insufficient. Nevertheless, an educational booklet about pain physiology is highly appreciated

by fibromyalgia patients (Ittersum et al., in press), indicating that it can be used in conjunction with face-to-face educational meetings. From the available evidence it is concluded that face-to-face sessions of pain physiology education, in conjunction with written educational material, are effective for changing pain perceptions and health status in patients with various chronic musculoskeletal pain disorders, including those with chronic low back pain, chronic whiplash, fibromyalgia and chronic fatigue syndrome. Practice guidelines on how to apply pain physiology education in patients with chronic musculoskeletal pain are provided below (and are summarized in Fig. 1). Prior http://www.selleckchem.com/products/GDC-0980-RG7422.html to commencing pain physiology education, it is important firstly to ascertain that pain physiology education is indicated in the chronic pain patient. Pain

physiology education is indicated when: 1) the clinical picture is characterized and dominated by central sensitization; and 2) maladaptive pain cognitions, illness perceptions or coping strategies are present. Both indications are prerequisites for commencing pain physiology education. Some (acute) musculoskeletal pain patients may not fulfil these requirements Cabozantinib initially, but will do so later on during their course of treatment (e.g. a patient receiving physiotherapy for an acute Phosphoribosylglycinamide formyltransferase muscle strain experiencing a whiplash trauma). To examine whether central sensitization is present, clinicians can use guidelines for the recognition of central sensitization in patients with chronic musculoskeletal pain (Nijs et al., 2010). In the assessment of illness perceptions patients must be asked about their perceptions

about the cause of pain, the consequences, the treatment and the timeline of pain. Maladaptive pain cognitions include ruminating about pain, and hypervigilance to somatic signs, each of which can be easily assessed with short self-reported measures with excellent psychometric properties (e.g. the Pain Catastrophizing Scale1, Pain Vigilance and Awareness Questionnaire2, etc.) (Sullivan et al., 1995, Van Damme et al., 2002 and Kraaimaat and Evers, 2003). Likewise, illness perception can be questioned or can be assessed by use of the brief Illness Perception Questionnaire3 (Broadbent et al., 2006). This information addressing pain perceptions and coping strategies should be used by the therapist to tailor the individual education sessions (remember that pain physiology education aims to reconceptualise pain). It is essential for clinicians to explain the treatment rationale and discuss the practical issues of the treatment with the patient. In case of central sensitization and chronic musculoskeletal pain, explaining the treatment rationale is of prime importance. Basically, patients should understand the mechanism of central sensitization.

Use Navitoclax of

IG biopsy coupled with deformable image registration should permit improved longitudinal sampling [12]. All of the above work could have significant clinical implications, not just for identifying a more effective therapeutic drug target, but also for monitoring treatment response. Identifying molecular targets with specific imaging markers should lead to development of better chemotherapeutic agents with less toxicity. Early detection of a favorable response or failure of a treatment regimen using combined imaging and genomic markers could potentially help expedite drug approval, generating substantial cost savings for clinical trials. Mouse and human-in-mouse Afatinib solubility dmso models of malignancies (e.g., patient-derived xenografts, transgenic) are routinely used for drug efficacy and toxicity testing [49] and [50].

The mouse model research strategies prove to be promising for understanding biological factors in prediction and response to therapy, as direct access to tissues during longitudinal studies is possible. In addition, a growing body of evidence shows that reliable preclinical data can be merged with patient data and used to determine what therapy may be used to treat specific malignancies [51]. This newer approach to integrated cross-species testing, termed co-clinical trials, involves concurrent assessment of novel drug combinations in mouse and human-in-mouse models of tumors, and in patients with recurrent or metastatic disease with whom the mice are genotypically matched [52] and [53]. Recent published literature demonstrates that well-documented, integrated cross-species approaches are of value for clinical decision making [54]. Radiogenomics will clearly play an important role in co-clinical trial studies where imaging phenotypes will be correlated with genomics

signatures. A powerful component of both pre- and co-clinical testing is the use of various in vivo imaging modalities that either mirror medical imaging practices or provide additional biological information [52], [53] and [55]. Imaging is a key to success in co-clinical Etofibrate investigations, providing real-time monitoring of the animal subjects for response, disease progression, recurrence, or metastasis, and ready access to longitudinal tissue samples for genomic analysis using image guidance. The evolving pre- and co-clinical approaches require development and incorporation of data and semantic standards to ensure reliability of interpretation and use of research resources such as data archiving and the implementation of quality improvement methods as reviewed later.

Gridscale noise in regions where the flow should be relatively quiescent might be an indicator of this type of instability; further testing in other GCMs is necessary to check whether this is true. The unphysical mixing effect occurred in both the nonhydrostatic solver and the MITgcm, and as such the authors consider it a general numerical issue that may arise when using anisotropic Selleckchem BMS 354825 viscosity. To explore further, another set of five simulations was run with an isotropic grid (Δx=Δz=1Δx=Δz=1 m)

and stratification parameters as in Taylor and Ferrari (2009), except that the horizontal viscosity and diffusivity were set to νh=κh=10-4,10-3,10-2,10-1,1νh=κh=10-4,10-3,10-2,10-1,1 m2 s−1. This configuration was chosen because in their original paper Taylor and Ferrari (2009) used isotropic viscosity and diffusivity with νh=κh=10-4νh=κh=10-4 m2 s−1 on an isotropic grid, and obtained full restratification to q=0q=0 and Ri=1Ri=1. The linear stability calculator predicts that full restratification would also be achieved for any choice of νhνh in the set above. Therefore, if the vertical viscosity is held fixed at νv=10-4νv=10-4 m2 s−1 and the horizontal viscosity is increased, any overshoot in either Ri or q can be attributed to anisotropic

viscosity. Indeed, Fig. 7 demonstrates a progressively mTOR inhibitor larger overshoot in both Ri   and q  , as well as more energetic inertial oscillations, as νhνh is increased away from νv=10-4νv=10-4 m2 s−1. These results suggest that the use of anisotropic viscosity is at least partly responsible for the excessive restratification, though this effect does seem to be amplified as the grid aspect ratio Δz/ΔxΔz/Δx becomes smaller ( Fig. 5(b)). The converse scenario (isotropic viscosity and anisotropic grid) was not tested due to the prohibitively small timestep it would require – in order to permit SI the vertical viscosity (and thus horizontal viscosity) must be kept very small, which makes modelling of this situation prohibitively expensive. As the stratification of the mixed layer plays a key role

in communicating atmospheric forcing to the interior of the ocean, excessive or improperly represented restratification 4��8C could negatively impact climate prediction on long time scales. Further investigation of this numerical issue is beyond the scope of this paper. To the authors’ knowledge this effect has not been previously documented, but due to the ubiquity of using anisotropic viscosity in GCMs it is possible that this it would occur in non-SI flow regimes as well. In this paper a set of 2D numerical simulations have been conducted to demonstrate how a combination of model viscosity and grid resolution can affect mixed layer restratification by symmetric instability. Linear theory is used to predict the growth and restratification potential of SI modes resolved in the model.

2). To overcome the inherent problems and establish the clinical significance

of transcranial ultrasound perfusion imaging, we have clinically introduced the Sonopod for TCDS monitoring [10] and [11] and evaluated acetazolamide (ACZ) vasoreactivity [12] and [13]. The objective of this study is to clarify clinical usefulness and identify problems in TCDS-Sonopod monitoring in the evaluation of brain tissue perfusion. Brain tissue perfusion monitoring was evaluated in 11 patients (ages 31–94, mean 66). Details of patient demographics are shown in Table 1. After a 5 ml-bolus Levovist® injection (2.5 g, 400 mg/ml) via the antecubital vein, power modulation imaging (PMI) in all cases in comparison with second harmonic imaging (SHI) in the initial two cases were evaluated in the supine position via TWs NU7441 chemical structure (Fig. 3). Both imaging types were visualized by an integrated backscatter method. The transmitting and receiving frequencies Pexidartinib manufacturer of PMI and SHI were 1.7/1.7 MHz and 1.3/2.6 MHz, respectively. The investigation depth was 16 cm with a focus of 8 cm. Settings were mechanical index 1.6, system gain 75, and compression 70. ACZ cerebral vasoreactivity, before and after 500 mg Diamox® intravenous injection,

was evaluated in 10 cases utilizing a SONOS5500 S3 transducer (Philips Electronics Japan, Ltd.) installed in the Sonopod. Time–intensity curves (TICs) on the diencephalic horizontal Clomifene plain were evaluated

before and after ACZ in five regions of interest (ROI); bilateral basal ganglia (BG) and thalamus (Th), and contra-lateral temporal lobe (TL). A total of 30 TICs with a duration of 10 min via the bilateral (five cases) and unilateral (five cases) TWs were analyzed before and after ACZ. Conventional SHI and PMI utilizing hand-held monitoring were compared in two cases. In the visualization of the contralateral hemispheres via the unilateral TWs, PMI was superior to SHI as shown in the upper panels of Fig. 4a and b. As shown in the lower panels of the quantitative TIC evaluations in both PMI and SHI, peak intensity (PI) in the contralateral hemisphere ROIs was lower than in the ipsilateral hemisphere ROIs. During hand-held monitoring, TICs were not always stable in all cases and drifted from the base-line due to patients’ movements as shown in the lower panels of Fig. 4. All patients could be fitted and monitored continuously by one examiner. Brain tissue perfusion could be precisely quantified before/after ACZ in the same ROI as shown in Fig. 5. Due mainly to patient’s movements, drifts from the base-line were observed in the TICs of 4 (seven TIC analyses) out of 10 (30 TIC analyses) patients. However, fixed-probe shifts due to patients’ movements during monitoring were easily re-adjustable and the TICs could be returned to the baseline in all patients as shown in Fig. 6.

63, 87.18, 57.36 and 75.06 times greater than that in Wuyujing 3 at 24, 36, 48 and 72 hpi, respectively ( Fig. 2). The relative expression levels of EDS1 and PAD4 were also higher in Kasalath than in Wuyujing 3 at 24 hpi ( Fig. 2). Meanwhile, the NPR1 (nonexpressor of pathogenesis-related genes 1) is a key regulatory gene Ku-0059436 price in SA-dependent SAR reaction. The relative expression level of NPR1 was remarkably higher in Kasalath than in Wuyujing

3 after SBPH feeding with expression of 6.47, 4.84, 8.92 and 5.49 times in Kasalath greater than that in Wuyujing 3 at 12, 24, 36 and 72 hpi, respectively ( Fig. 2). Another gene, PR1b, encodes a pathogenesis-related protein that inhibits growth, reproduction and communication of pathogens in plants. The PR1b gene expression level was significantly higher in susceptible Wuyujing 3 than in resistant Kasalath after SBPH feeding. The

relative expression of PR1b in Wuyujing 3 was 13.38, 89.82, 71.01 and 46.66 times greater than that in Kasalath at 24, 36, 48 and 72 hpi, respectively ( Fig. 2). The up-regulated PR1b gene expression in the susceptible Wuyujing 3 rice was likely to have been induced by the physical injuries caused by SBPH foraging. The above results showed that SBPH feeding activated the SA-dependent resistance pathway in Kasalath and that the expression levels of PAL and NPR1 played key roles in regulating resistance to SBPH. The expression levels of the JA synthesis-related genes LOX (lipoxygenase) and AOS2 (allene Doxorubicin in vivo oxide synthase 2) were lower in the resistant cultivar Kasalath than in the susceptible cultivar Pifithrin�� Wuyujing 3 after SBPH feeding. There was a significant difference in transcription level at 36 hpi by the insect when comparing Kasalath and Wuyujing 3. Furthermore, the expression level was substantially lower in Kasalath at subsequent time points. The relative expression of LOX in Wuyujing

3 was 4.06, 4.17, 3.06 and 12.43 times greater than that in Kasalath at 24, 36, 48 and 72 hpi, respectively. AOS2 transcript accumulation was much greater in Wuyujing 3 and the relative expression level was 4.63, 12.38, 22.72 and 60.72 times greater than that in Kasalath at 36, 48 and 72 hpi with SBPH, respectively ( Fig. 2). Similarly, the relative expression level of P450 was higher in Wuyujing 3 than in Kasalath ( Fig. 2). In addition, the expression level of the receptor gene EIN2 (ethylene insensitive 2) in the ethylene signaling pathway was higher in Wuyujing 3 than in Kasalath after SBPH feeding. The relative expression of EIN2 in Wuyujing 3 was 2.55, 2.81 and 2.53 times greater than that in Kasalath at 36, 48 and 72 hpi, respectively, which indicated that SBPH feeding induced defense responses in the susceptible Wuyujing 3 rice associated with a JA/ET-dependent signaling pathway ( Fig. 2). The PAL activity in Kasalath was almost identical to that in Wuyujing 3 without SBPH attack and increased in both after SBPH feeding.

, Ltd., Ningbo, China), 4.5 m × 1.5 m × 1.7 m (length × width × height) in size. The air

temperature and relative humidity in the chamber were controlled using Fluorouracil electric resistance heaters and a bubbling system. The air temperature in the chamber at nighttime (19:00 to 7:00) was maintained at 25–28 °C with a wind speed of 0.5 m s− 1. The relative humidity was maintained at 75%–85%, similar to that of the unwarmed control environment. The air temperatures in the rice canopy in the chamber and the ambient environment were monitored every 10 min at night with a Thermo Recorder (ZDR-41, Zeda Instrument Co., Ltd., Hangzhou, China). The differences in rice canopy air temperatures at nighttime were automatically adjusted to approximately 3.0–3.5 °C higher in the chamber than in the ambient control environment (Fig. 1). Germinated rice seeds were sown in plastic boxes on 13 May 2010. After one month of growth, rice seedlings were transplanted to screening assay the plastic pots. There were two holes seedlings for each pot and two seedlings for each hole. Fertilizer was applied as 0.75 g N, 0.38 g P2O5 and 0.38 g K2O per pot. All of the P2O5 and K2O and 50% of the N were applied

as basal dressing. Half of the remaining N was applied as side dressing at the early tillering stage in the latter of June, and the rest of the N was applied at panicle initiation in the latter part of August. Water depth in all pots was maintained at about 5 cm above the soil surface during the entire rice growing cycle. All pots were kept under ambient conditions outside the chamber before rice anthesis. During the post-anthesis phase, half of the pots were

placed in the chamber for 12 h at night (from 19:00 to 7:00) and moved outside after 7:00 every day. The warmed and unwarmed pots were kept in the same ambient environment at the daytime from 7:00 to 19:00 every day during the post-anthesis phase. At the anthesis and maturity stages, plants from three pots of each treatment were sampled and divided into leaf, stem, and panicle. All plant samples were oven-dried at 80 °C for 24 h and weighed. Post-anthesis biomass accumulation was calculated as the difference in total aboveground dry matter between the anthesis stage and harvest. Nine pots from each treatment were harvested to determine grain yield and its components. At 0, 21 and Etomidate 35 days post-anthesis (DPA), fifteen flag leaves of main stems were selected for measurements of net photosynthesis rate (from 9:00 to 11:00) and night respiration rate (from 22:00 to 23:00) with a portable photosynthesis system (Li-6400; Li-Cor, Inc., Lincoln, NE, USA). Another fifteen flag leaves were sampled in each treatment at 7, 14, 21, 28 and 35 DPA for measurements of chlorophyll a and b contents by the method of aqueous acetone extraction [13]. At the anthesis stage, approximately 200 rice panicles were labeled for the determination of grain filling rate.

Thus, in continuation of our previous work, which led to selleck products the development of a prototype ECC ergocycle,5 and in the absence of any specific device to measure power output for the ECC ergometer, we decided to test a simplified procedure using a prior CON exercise to determine the

plantar pressure that corresponded to a comfortable pedaling power (CPP) and to use this CPP workload to start ECC training. The aims of this study, conducted on healthy subjects, were therefore (1) to evaluate the feasibility and safety of this simplified procedure to determine an intensity level of exercise corresponding to a moderate demand in ECC training, with this level based on the rate of perceived exertion (RPE) during prior CON exercise; and (2) to study the acute cardiocirculatory, respiratory, and metabolic responses to this level of ECC exercise using the prototype ergocycle, and to compare these data with similar data in CON exercise. Eighteen subjects (15 men, 3 women) were recruited

in this study (see Supplemental Appendix 1, available online only at http://www.archives-pmr.org/, for detailed description of participants) according to the following inclusion criteria: men or women selleck aged between 18 and 40 years; no musculoskeletal, cardiovascular, mafosfamide or neurologic disorder; stable anthropometric characteristics for at least 1 year; and no other activities with a large amount of ECC contraction for at least 6 months before the study (running was tolerated except for prolonged downhill running). The main characteristics of the participants are shown in table 1. Informed consent was obtained from all participants after they were informed of all the potential risks and benefits of participating in the study, as required by the Declaration of Helsinki. The study was registered in French “Agence Nationale de Sécurité du Médicament”

(ANSM) database under reference no. 2009-A01265-52. Participants came to the laboratory for 2 sessions, for a total of 3 bouts of exercise. We aimed to determine a comfortable level of CON exercise to then adapt the intensity to ECC pedaling. We used the 6- to 20-point Borg scale,17 which has been shown to be reliable for assessing subjective RPE in a healthy population.18 After making sure the participants understood the instructions for the RPE rating, they were asked to perform a CON exercise on a standard CON ergocycle,a to determine a CPP. The exercise consisted of pedaling at 60 revolutions per minute (rpm), starting at an initial power of 50W, followed by an incremental increase of 25W every minute.

Miejscowe NOP, w tym silny ból w miejscu wstrzyknięcia, znamiennie częściej występowały po szczepionce Cervarix niż Silgard [48]. W badaniach klinicznych po szczepionce Cervarix nieco częściej niż w grupie kontrolnej obserwowano również ból stawów i mięśni w ciągu kilku dni po szczepieniu [36]. W żadnym przypadku objawy nie spowodowały jednak przerwania cyklu szczepienia [36, 48]. Monitorowanie ciężkich NOP po zastosowaniu szczepionki Cervarix

w ramach badań klinicznych (ponad 37 000 zaszczepionych pacjentów i ponad GSK1120212 chemical structure 32 000 w grupie kontrolnej; okres obserwacji do 6,4 roku) wykazało, że ryzyko nowych zachorowań na choroby przewlekłe, w tym autoimmunizacyjne, po szczepieniu i w grupie kontrolnej się nie różni [26, 34]. Przypadkowe zaszczepienie Selleckchem Androgen Receptor Antagonist kobiet w ciąży lub zajście w ciążę podczas cyklu szczepienia szczepionką Cervarix nie wiązało się ze zwiększeniem ryzyka negatywnych następstw dla płodu, ale obserwacje dotyczące bezpieczeństwa w tej grupie nie są jeszcze wystarczające, aby zalecać szczepienie ciężarnych [52]. Monitorowanie bezpieczeństwa szczepionki Silgard podczas jej masowego stosowania w ramach powszechnych szczepień w USA (ponad 23 miliony dawek do końca 2008 r.) wykazało, że najczęściej występującym zdarzeniem niepożądanym po szczepieniu było omdlenie wazowagalne (8,2 przypadków/100 tys. dawek). Ponadto u niewielkiego odsetka

zaszczepionych osób (<2 przypadki/100 tys. dawek) zarejestrowano obwodowe neuropatie/porażenia wiotkie (w tym zespół Guillaina-Barrégo), jednak ryzyko ich wystąpienia po szczepieniu było mniejsze niż w populacji ogólnej w danym wieku (odpowiednio: 0,3 vs 1,57/100 tys. osób rocznie) [53]. Raport VAERS (Vaccine Adverse Events Reporting System) nie wykazał statystycznie istotnego

związku pomiędzy ciężkimi zdarzeniami niepożądanymi a podaniem Silgardu [53]. Raport bezpieczeństwa wydany w Wielkiej Brytanii przez MHRA (Medicines and Healthare products Regulatory Agency) informuje, że podanie 3,5 mln dawek szczepionki Cervarix w ramach Narodowego Programu Szczepień dziewcząt potwierdziło korzystny profil bezpieczeństwa tej Plasmin interwencji [54]. Bilans korzyści i ryzyka potencjalnych działań niepożądanych jest w przypadku obu szczepionek dodatni [53, 54]. Szczepionki przeciwko wirusowi HPV są przeciwwskazane [20, 21, 29, 30]: 1. w przypadku nadwrażliwości w stopniu anafilaksji uogólnionej (np. wstrząs anafilaktyczny lub objawy anafilaktyczne z co najmniej 2 układów) na którykolwiek składnik preparatu, Szczepionki domięśniowe należy podawać ostrożnie pacjentom z małopłytkowością lub jakimikolwiek zaburzeniami krzepnięcia [20, 21, 29, 30]. Szczepienie należy odłożyć do czasu poprawy stanu ogólnego i ustąpienia objawów klinicznych u osób z ostrą infekcją przebiegającą z wysoką gorączką lub podczas zaostrzenia choroby przewlekłej. Łagodna choroba infekcyjna nie jest natomiast przeciwwskazaniem do szczepienia [20, 21, 29, 30].

Previous studies have also indicated that myosin-Va is found in synaptic vesicle preparations and forms stable complexes between synaptic vesicle membrane proteins (Mani et al., 1994 and Prekeris and Terrian, 1997). In the vertebrate brain, 5–15% of the total zinc is concentrated in synaptic vesicles

(Frederickson, 1989 and Frederickson and Moncrieff, 1994), which has been studied using the Neo-Timm method (Babb et al., 1991). Moreover, zinc serves as an endogenous neuromodulator of several important receptors, including N-methyl-d-aspartate (NMDA) ( Smart et al., 1994). Functional studies of honey bee myosin-Va have not been carried out until now. In this study, we addressed the effects of intracerebral injections of melittin www.selleckchem.com/products/ly2109761.html and NMDA on the honey bee. Melittin is a polypeptide present in bee venom (Habermann, 1972) and a potent calmodulin

antagonist (Steiner et al., 1986). Calmodulin is the most extensively studied member of the intracellular calcium-binding proteins, which includes myosin-Va. Additionally, NMDA is a glutamate-gated ion channel agonist present in both mammals and insects (Paoletti and Neyton, 2007). The see more NMDA receptor is involved in delayed neuronal death (Choi, 1988) and excitatory synaptic transmission in the central nervous system, which results in learning and memory (Albensi, 2007). A critical role of the NMDA receptor was recently demonstrated in olfactory learning and memory in Drosophila melanogaster ( Xia et al.,

2005) and A. mellifera ( Locatelli et al., 2005 and Si et al., 2004). The aims of this study were to elucidate some of the biochemical properties and the distribution of myosin-Va and to describe the expression patterns of molecular motors and SNARE proteins in the honey bee (A. mellifera L.) brain. Moreover, we evaluated the alterations in myosin-Va expression after intracerebral injections of melittin and NMDA. Rabbit affinity-purified polyclonal antibodies were used in this study. Anti-chicken brain myosin-Va (α-myosin-Va) head domain recombinant protein (Espreafico et al., 1992 and Suter et al., 2000), anti-pig myosin-VI (α-myosin-VI) tail fusion protein (Hasson and Mooseker, 1994) and anti-myosin-IXb Phospholipase D1 heavy chain tail domain recombinant protein (Post et al., 1998) were all from the Mooseker Laboratory (Yale University, New Haven, CT, USA). Anti-rabbit myosin-IIb (α-myosin-IIb) was produced in the Larsons Laboratory (USP, Ribeirão Preto, SP, Brazil). The dynein light chain (α-DYNLL1/LC8) antibody was generated against the Chlamydomonas LC8 recombinant protein ( King et al., 1996). Mouse monoclonal antibodies used included anti-cytoplasmic dynein intermediate chain IC74 (α-DIC; Chemicon International Inc.

The latter were at least twice as long as wide. In order to determine the thickness of the collagen layer in the resorption lacunae, maximum resorption depths were measured before and after treatment with NaOCl and the difference between these PD0325901 nmr two depth measurements was calculated as an assessment of the thickness of the collagen

layer, as previously described [17]. Removal of organic matrix prior to seeding of OCs for resorption was performed in a similar fashion. Each bone slice was transferred into 500 μl 5–7% NaOCl and incubated at room temperature for 15 min while shaking in a thermomixer. Subsequently, the bone slices were washed individually in 50 ml sterile ddH2O while shaking for 30 min. The bone slices were stored for

up to a week in sterile ddH2O at 4 °C until use. Differentiated OCs were obtained as explained above. The cells were lyzed, RNA purified, cDNA generated and TaqMan Q-RT-PCR performed as described previously [24]. The following kits and primer/probes were used: Trizol Plus RNA Purification kit selleck chemical (RNA purification) (Invitrogen, Taastrup, Denmark), iScript kit (cDNA synthesis) (Bio-Rad, Copenhagen, Denmark), hGUS, Hs99999908_m1, hAbl, Hs00245443_m1, and hCatK Hs00166156_m1. All TaqMan primer⁄probe sets were inventoried and used according to the instructions by the supplier (Applied Biosystems, Naerum, Denmark). Each Q-RT-PCR run was normalized to the cDNA preparation of one single randomly chosen donor to enable comparisons between donors and between the different Q-RT-PCR runs. In addition to this, the expression levels of CatK were subsequently normalized to the average expression level of the house Bumetanide keeping genes hGUS and hAbl. All Q-RT-PCR reactions were run as triplicates. Excavations were generated by OCs in three different conditions: (i) the control condition; (ii) the presence of a low concentration of ethoxyzolamide to slightly decrease the demineralization rate; and (iii)

the presence of E64 to decrease the collagenolysis rate. The maximum resorption depths were measured both before and after removal of collagen left in the excavations, by using NaOCl (Figs. 2A and B). This procedure allowed us to monitor both the thickness of the layer of collagen left-over (Figs. 2C and D) and the depths to which bone was demineralized (Figs. 2A and B, hatched bars). NaOCl treatment of the excavations obtained under control conditions, made depths increasing from 5 to 9 μm (Fig. 2A), thus revealing a layer of collagen left-over of about 4 μm thickness (Fig. 2C), and a demineralization depth of 9 μm (Fig. 2A). This effect of NaOCl is in accordance with the repeated reports that demineralized collagen is left behind by the OC under control conditions, and means that the rate of collagen degradation is on average slower than the rate of demineralization in control conditions (Fig. 1, average control condition).