, 2004) ECV, treated or not with venom, were lysed in 50 mM Tris

, 2004). ECV, treated or not with venom, were lysed in 50 mM Tris–HCl, pH 7.4, 150 mM NaCl, 1.5 mM MgCl2, 1.5 mM EDTA, Triton X-100 (1%, v/v), glycerol (10%, v/v), aprotinin (10 μg/μl), leupeptin (10 μg/μl), pepstatin (2 μg/μl), and 1 μM PMSF. Lysates (2 μg of protein/μl) were incubated overnight at 4 °C with rabbit polyclonal anti-FAK Ab (1:200). After that, protein A/G-agarose (20 μl/sample) was added, and samples were incubated at 4 °C in a rotatory shaker for 2 h (Nascimento-Silva et al., 2007). The contents

of signaling pathway FAK and actin associated to FAK were analyzed by immunoblotting as described below. The translocation of NF-kB to cell nucleus was analyzed by immunofluorecence microscopy and also by western blot detection of NF-kB p65-subunit in ECV nuclear extracts. For immunofluorescence studies, the ECV grown on glass coverslips and fixed with paraformaldehyde as described above, were blocked with 5% BSA/PBS for 30 min, and then incubated with rabbit polyclonal anti-p65 NF-κB Ab (1:50; Santa Cruz, sc-372; CA, USA) overnight at 4 °C. Subsequently, cells were washed three times with PBS and incubated with biotin-conjugated anti-mouse or anti-rabbit IgG (1:50) followed Protein Tyrosine Kinase inhibitor by incubation with Cy3-conjugated streptavidin (1:50)

for 1 h at room temperature. Coverslips were mounted on a slide using a solution of 20 mM N-propylgalate and 80% glycerol in PBS and examined under an Olympus BX40 microscope equipped for epifluorescence ( Nascimento-Silva et al., 2007). Nuclear extracts of ECV treated or not with L. obliqua venom were obtained as described. Briefly, cells were lysed in ice-cold buffer A (10 mM HEPES, pH 7.9, 10 mM KCl, 0.1 mM EDTA, 0.1 mM EGTA, 1 mM DTT, and 0.5 mM PMSF), and DOCK10 after a 15-min incubation on ice, Nonidet P-40 was added to a final concentration of 0.5% (v/v). Nuclei were collected by centrifugation (1810 × g; 5 min at 4 °C). The nuclear pellet was suspended

in ice-cold buffer C (20 mM HEPES, pH 7.9, 400 mM NaCl, 1 mM EDTA, 1 mM EGTA, 1 mM DTT, 1 mM PMSF, 1 μg/ml pepstatin, 1 μg/ml leupeptin, and 20% (v/v) glycerol) and incubated for 30 min. Nuclear proteins were collected in the supernatant after centrifugation (12,000 × g; 10 min at 4 °C), and the nuclear extracts were denatured in sample buffer (50 mM Tris–HCl, pH 6.8, 1% SDS, 5% 2-ME, 10% glycerol and 0.001% bromophenol blue) and heated in a boiling water bath for 3 min and assayed in SDS-PAGE ( Nascimento-Silva et al., 2007). Samples (30 μg total protein) were resolved by 12% SDS-PAGE and proteins were transferred to PVDF membranes for western blot analysis (Nascimento-Silva et al., 2007). Molecular weight markers were run in parallel to estimate molecular weights. Membranes were blocked with Tween-TBS (20 mM Tris–HCl, pH 7.5; 500 mM NaCl; 0.

However,

the absolute

However,

the absolute GSK1120212 solubility dmso necessity for this additional prophylaxis therapy has not been established for patients being treated with a PNA as monotherapy. Furthermore, patients being treated with more than one agent (e.g., combined chemo-immunotherapy) or those receiving multiple cycles of therapy may be at an increased risk for infection. There is currently no data to guide the use of prophylactic antibacterial or antifungal medications and in our practice these are not routinely administered. The routine use of growth factor support such as filgrastim is not supported by available data showing a lack of significant clinical benefit [36], however this agent may be useful in some situations (e.g., as an adjunct for treating patients with active infection). Clinical research to define the optimal strategy for managing and preventing the infections encountered in these patients is clearly needed. The administration of immunizations has not been studied specifically in patients with HCL, however guidelines exist for the immunization of immunocompromised individuals [45]. The humoral response to immunization following PNA therapy is unknown but would be expected to be significantly lower than the general population, as was demonstrated

in rheumatoid Alectinib chemical structure arthritis patients who had received prior rituximab [46]. We routinely administer immunizations to eligible patients including seasonal influenza immunization, adult booster immunizations for tetanus and pertussis, and pneumococcal vaccines every five years as scheduled.

We discourage HCL patients from Tacrolimus (FK506) receiving live vaccines such as varicella zoster, influenza nasal mist, or measles/mumps/rubella, as these could result in acquisition of viral disease. One study which evaluated the long-term risk of infection in patients with HCL found that the increased risk appeared to be confined to the first year following diagnosis, with infection risk approaching that of the general population subsequent to this [47]. Long-term data with either purine nucleoside analog show that at least 40% of patients will relapse from the initial hematologic remission and require further treatment for the leukemia [48]. The occurrence of chronic bacterial or fungal infection during initial therapy raises serious difficulties for providing subsequent therapy with a purine analog if the patient should relapse. The long-term improvement in survival as a result of purine analog therapy paradoxically increases the risk that these challenging therapeutic questions will be encountered [49]. Patients with hairy cell leukemia can also experience auto-immune complications associated with their underlying disease [5]. Vasculitis presenting as leukocytoclastic vasculitis has been associated with infection. A recurrent inflammatory arthropathy similar to rheumatoid arthritis has been observed [50]. The autoimmune complications may not improve in parallel with treatment of HCL.

Coefficient bbpis computed by using the MODIS

Coefficient bbpis computed by using the MODIS

selleck kinase inhibitor standard products of Rrs(531), Rrs(547) and Kd(490) (http://oceancolor.gsfc.nasa.gov); a brief description of the algorithm is given at (http://optics.ocean.ru) and in more detail by Burenkov et al. (2001). The regression equation TSM vs. bbp was derived from our field data of 2012 and 2013; the combined data set included 39 stations (15 in 2012, 24 in 2013). The TSM concentration varied from 1.0 mg 1−1 (St. 19F) to 5.5 mg 1−1 (St. 3L) in 2012 and from 1.7 mg 1−1 (St. 10F and 33F) to 4.4 mg 1−1 (St. 3FG) in 2013. The regression equation was derived in logarithmic form: equation(3) logTSM=0.79logbbp+1.95,where TSM is expressed in mg 1−1, bbp in m−1.

Figure 8 shows the regression line TSM vs. bbp on a logarithmic scale; Figure 9 is a scatterplot showing TSMcalc vs. TSMmeas. As seen from the figure, the agreement is rather good: the coefficient of determination r2 = 0.61, the standard error of the regression is equal to 0.62 mg 1−1; the averages of TSMcalc and TSMmeas are close to each other at 2.56 and 2.62 mg 1−1 respectively; the averaged ratio of TSMcalc/TSMmeas is equal to 1.03, and the ratio range is 0.72-1.5. Figure 10 shows the spatial distributions of TSM concentration calculated from MODIS-Aqua data Entinostat in vivo on 22 July 2012 and 27 July 2013 using (3). One can see a general similarity of these distributions with the distributions of chlorophyll concentration in Figure 7. Such a similarity is to be expected, because Thymidine kinase there is a common factor determining the distribution of both TSM and chlorophyll: the River

Neva carries suspended particles and phytoplankton with chlorophyll and nutrients for primary bioproduction. We evaluated the applicability of the regional Baltic algorithms by Darecki & Stramski (2004) and Woźniak et al. (2008) for determining chlorophyll concentrations in the Gulf of Finland by using our data set of 2012–2013. The input parameter of the second of them (the DESAMBEM algorithm – Development of a Satellite Method for Baltic Ecosystem Monitoring) is the ratio XR = [Rrs(490) —Rrs(665)]/[Rrs(550) —Rrs(665)], which is completely unsuitable for the Gulf of Finland because of the abnormally high values of Rrs(665). The regional parameterisation of MODIS algorithms for chlorophyll retrieval in the Baltic was presented by Darecki & Stramski (2004) in two versions: #9 Baltic_chlor_MODIS: Chl = 100.4692–20.6802X, where X = log[Lwn(443) + Lwn(488)/Lwn(551)], The values of Lwn are related to Rrs by a simple formula: Lwn(λ) = F0(λ) Rrs(λ), where F0(λ) is the mean extra-terrestrial solar irradiance (http://oceancolor.gsfc.nasa.gov). The results of the evaluation of these algorithms are presented in Table 2 and can be compared with the results for algorithms #4 and #8 from Table 1.

According to Teixeira et al (2007), this particular behavior can

According to Teixeira et al. (2007), this particular behavior can be attributed selleck kinase inhibitor to the fact that sucrose has

a higher number of OH groups than other sugars and, therefore, is more hydrophilic and is a more efficient plasticizing agent. In the second phase of the work, as can be observed in Table 3, an increase of clay and glycerol contents caused a decrease of TS. For each content of clay nanoparticles, an increase of glycerol content from 0.75 g to 1.25 g caused a significant decrease of TS (P < 0.05). The same tendency can be observed for each glycerol content: an increase of clay nanoparticles content decreases significantly the TS of the films (P < 0.05). The regression analysis applied on results, using the response surface methodology, Selleckchem Saracatinib indicated that both glycerol (G) and clay nanoparticles (C) content, as well as their interaction, influenced significantly this property and the fitted model, in real values is (r2 = 72%): equation(4) TS=(5.62−1.83×G+21×C−28×G×C)±0.59(0.75≤G≤1.25)(0.00≤C≤0.10)wherein

TS is the tensile strength of films [MPa]; G is the glycerol content [g/100 g of filmogenic solution]; and C is the clay nanoparticles content [g/100 g of filmogenic solution]. As can be observed in Fig. 2(a), higher contents of glycerol and clay yield films with lower TS. For films formulated without clay nanoparticles, the E decreased as glycerol content increased, as Anidulafungin (LY303366) expected, confirming the results obtained in the first phase. An opposite effect was observed for films produced with clay nanoparticles, i.e., for each clay content, with increasing glycerol content, E of the films increased. This effect was more pronounced and significant (P < 0.05)

with higher clay nanoparticles content (0.10 g/100 g). ANOVA applied on results of water vapor permeability and oxygen permeability coefficient indicated that the glycerol content influenced significantly these properties (P < 0.05), since a rise in glycerol content caused an increase in both permeabilities ( Table 2). As mentioned earlier, glycerol is a relatively small hydrophilic molecule, which can be entrapped between adjacent polymeric chains, decreasing intermolecular attractions and increasing molecular mobility, facilitating migration of water vapor and oxygen molecules ( Rodríguez, Osés, Ziani, & Maté, 2006). Similar tendencies have been reported for BF based on potato starch (Rodríguez et al., 2006 and Talja et al., 2007), yam starch (Mali, Grossmann, García, Martino, & Zaritzky, 2004), corn starch (Bertuzzi et al., 2007) and cassava starch (Alves et al., 2007 and Chillo et al., 2008). In Table 3, the positive influence caused by the addition of clay nanoparticles on water vapor permeability and oxygen permeability coefficient can be noticed.

B (i) Radar plot indicating differential Dek expression througho

B. (i) Radar plot indicating differential Dek expression throughout myeloid specific normal murine hematopoietic differentiation. Each radius represents a particular hematopoietic cell stage. (ii) Bar chart highlighting Dek expression during normal LY294002 mw differentiation from the common myeloid cells towards the granulocytic

(G) and monocytic (M) lineages. *** p < 0.001. Abbreviations as follows: long-term hematopoietic stem cells (LT-HSC), short-term hematopoietic stem cells (ST-HSC), lymphoid primed multipotent progenitor (LMPP), common lymphoid progenitor (CLP), early T-cell progenitor (ETP), immunoglobulin M positive side population cells (IgM + SP), natural killer (NK), granulocyte macrophage (GM), granulocyte monocyte progenitor (GMP), megakaryocyte erythroid precursor (MkE) megakaryocyte precursor (MkP) and colony forming units erythroid cell (CFUE). This study was supported and funded by Leukaemia & Lymphoma NIR2561CNR (GEL, KIM, MJP), the START-Program of the Faculty of Medicine, RWTH Erastin ic50 Aachen University (to F.K.) and the German Research Foundation

(DFG; KA 2799/1 to F.K.). “
“Neurosurgical stimulation studies are an important source of information about cortical function (Penfield and Rasmussen, 1950). Patients may undergo pre-surgical implantation of subdural electrodes for functional mapping, to inform subsequent surgery. By direct electrical stimulation (DES) between specific pairs of electrodes (or by equivalent intraoperative stimulation with movable electrodes), clinicians can assess the functional role of a given cortical region, and thus guide neurosurgical interventions. Because DES can be performed in awake patients, it provides a crucial insight into the contribution of diverse cortical regions to conscious experience (Desmurget et al., 2009, Fritsch and Hitzig, 1870 and Penfield and Rasmussen, 1950). In particular, the clinician can stimulate a particular cortical region and assess the impact on the patient’s behaviour, and subjectively reported sensation. Penfield and Boldrey (Penfield and

Boldrey, 1937) classically mapped the human motor cortex in this way. Their work is known primarily for the ‘positive’ sensorimotor signs they evoked in specific muscles, leading aminophylline to the famous motor homunculus. Interestingly, stimulation of some cortical sites has ‘negative’ effects, causing inhibition of an ongoing movement. These sites have been termed ‘negative motor areas’ (NMAs) in the neurosurgical literature (Lüders et al., 1995). In his early studies, Penfield (Penfield and Boldrey, 1937, Penfield and Jasper, 1954 and Penfield and Rasmussen, 1950) had already described speech arrest following stimulation at some sites within the supplementary motor area (SMA). However, this aspect of Penfield’s data has been neglected, in comparison to the attention paid to the positive motor homunculus.

In GGE biplot the ranks were assigned as follows: (i) the yield r

In GGE biplot the ranks were assigned as follows: (i) the yield ranks were determined by giving the best rank (rank of 1) to the ideal genotype, found at the far right-hand side, and the check details last rank to the genotype on the far left-hand side of the biplot; (ii) the stability ranks were determined as the visual ratings of the projections of genotypes on the AEC ordinate, with a shorter projection corresponding to a higher stability ranking; and (iii) the yield–stability ranks were determined as the sums of GGE yield and stability ranks [16]. Yield–stability is also equal to GGE distance, which is a measure of the distance to the “ideal” genotype. Genotypes are evaluated in terms

of both mean performance and stability

[22]. For the YSi statistic, the yield ranks were obtained from the phenotypic adjusted yield data [19]. The stability ranks were obtained by assigning the best rank (rank of 1) to the genotype with the lowest Shukla’s [24] stability variance (σ2); and the yield–stability ranking were determined as the sums of yield and stability ranks. The combined analysis GDC-0449 solubility dmso of variance (ANOVA) revealed that the grain yield was significantly affected by the environment, followed by GE interaction and genotype effects (Table 1). Environment accounted for 75.9% of the total sum of squares (TSS), followed by the GE and G effects accounting for 7.7 and 4.4, respectively. Most of the TSS was explained by the environment, reflecting a much wider range of environment main

effects than genotype main effects. About one fifth of the significant GE interaction was attributed to heterogeneity among regressions, while the remaining variance was attributed to deviation mean squares (S2di) (Table 1). A large proportion of the GE interaction was due to a nonlinear component, which maybe regarded as a very important parameter very for the selection of stable genotypes. The average grain yield of genotypes over 24 environments varied from 1.891(corresponding to G6) to 2.682 t ha–1 (corresponding to G4). According to the Finlay and Wilkinson method, genotypes G15, G17, and G18 were identified as highly stable genotypes, as their regression coefficients were within one standard error (SE) of the overall average coefficient of regression (Fig. 1). Genotypes G18 and G17 would be considered well suited to the environments tested, as they had the highest grain yield within the range of stability. According to Fig. 1, genotypes G4, G10, G1, G20, and G8 with b > (1.0 + 1SE) had below-average stability and were adapted specifically to high-performing environments, while genotypes G9, G6, G13, and G2 with b < (1.0 − 1SE) had below-average stability and were poorly adapted to all environments owing to their low mean yield performance.

Surface currents were recorded as moving to the east and north in

Surface currents were recorded as moving to the east and north in July–August 2006, with velocities ranging from 20 to 30 cm/s in water temperatures as high as 30 °C (Coppini et al., 2011). The high-frequency SKIRON wind forecast system showed winds varying Z-VAD-FMK price from north-westerly to south-westerly, a pattern that remained steady for most of the summer of 2006, with wind strength varying between 2 and 7 m/s

(Lardner et al., 2006). For these meteorological and oceanographic conditions, oil spill impacts on shoreline regions were observed to be heaviest from Jieh up to south of Beirut, i.e., closer to the spill source. Significant impacts between Beirut and Chekka and northward along the Syrian coast were also reported, and subsequently confirmed several weeks after the oil spill event (Coppini

et al., 2011). Adler and Inbar (2007) found that sandy shorelines show moderate to low susceptibility to oil spills in areas exposed to significant wave and wind action, i.e., with important natural cleaning processes. LY294002 ic50 Regions with the lower shoreline susceptibility in Israel comprise relatively straight and smooth profiles without deep and complex bays and headlands, preferably low, flat and sandy in nature (Adler and Inbar, 2007). Shoreline susceptibility increases in Israel, and throughout the Mediterranean Sea, with the presence of important ecosystems, specific habitats, coastal resources and shoreline types that must be preserved in case of oil spills. A contrasting setting is that associated Farnesyltransferase with oil refineries. In Syria and Lebanon, oil refineries were found to be a controlling factor to As and Cr values in seafloor sediment regardless of local wave and meteorological conditions (Othman et al., 2000). Arsenium and Chromium were found to be

above natural levels offshore Syria, whereas elements such as Al, Ca, Fe, K, Mg, Mn, Na, Ba and Br and some trace metals (Pb, Zn and Cu) were naturally cleaned and kept under defined limits in the same region. This poses the interesting problem of secondary pollutants in oil spills and, particularly, in industrial (chemical) spills that occur during drilling operations. In this latter case, the North Sea is one of the best documented regions in the literature, and where drilling muds contaminated with hydrocarbons and heavy metal elements are known to be an important polluter (Davies et al., 1984 and Grant and Briggs, 2002). Here, hydrocarbon concentration levels were found to be as much as 1000 times normal background levels close to drilling platforms (i.e., at distances < 250 m), but show a rapid decline with distance (Davies et al., 1984). Background levels were found to be reached some 2000–3000 m from the platform, with the shape and extent of polluted zones being largely determined by current regimes and scale of the drilling operations (Davies et al., 1984 and Elliot, 1986).

This technique has been shown to be reproducible between radiolog

This technique has been shown to be reproducible between radiologic readers and its precision was demonstrated with a strong correlation with tumor necrosis as measured on histopathology [20] and [25]. In contrast to most tumors, uveal melanoma liver metastasis

may be heterogeneous depicting high signal intensity on baseline precontrast T1-weighted images due to hemorrhage with the presence of methemoglobin Selleck Dolutegravir and/or melanin [21] and [22]. Furthermore, as shown by our results, uveal melanoma lesions treated with TACE exhibited more high signal intensities on precontrast T1-weighted images compared to baseline imaging, making oftentimes challenging the assessment of tumor enhancement, even when image subtraction is used. This might explain why a quantitative measurement may be more precise in assessing these lesions in comparison to a more subjective method such as EASL, in that the calculation of volume eliminates potential variability in the assessment based on slice selection. The aggressiveness of the disease with potential changes in non-target lesions already seen in the short interval between the baseline and after TACE MR imaging provided the rationale to investigate the effect of the untreated lesions in the overall response. Our study demonstrated that the analysis based on the target lesions provided similar results as when including target and non-target lesions in the assessment of early tumor

response. This may potentially lead to simplification of imaging assessment DAPT in vitro after one session of TACE. There were several limitations Resveratrol to this study. First, the sample of the study was relatively small. However, uveal melanoma is a rare disease, and even in centers with high patient volume, it is unlikely to have a large sample from a single institution. Thus, a multi-institutional study with a larger cohort is needed to confirm our data.

Moreover, a thorough statistical analysis was performed including exact permutation distribution in the calculations to overcome this limitation. Second, this study included only patients with pretreatment and posttreatment MR imaging, leading to a selection bias. However, accumulation of iodized oil (as used in TACE) into treated lesions limits the reliability of contrast enhancement on computed tomography scans; thus, only contrast-enhanced MR imaging is used in our institution in a post-TACE setting. Third, the quantitative volumetric measurements used in this study lack radiologic-pathologic validation [20]. However, this is unrealistic as patients with uveal melanoma metastatic to the liver were not considered appropriate candidates for any surgical treatment and were referred for TACE. Fourth, this study did not investigate the potential role of quantitative volumetric diffusion-weighted MR imaging. Diffusion-weighted MR imaging is increasingly used to evaluate tumor response to therapy [26]. Buijs et al.

To explore evolutionary relationships we constructed a phylogenet

To explore evolutionary relationships we constructed a phylogenetic tree on the basis of the aa sequences of mature plant isoamylases. All monocots gathered in a single cluster (Fig. 4). There is 98% sequence homology between Ae. tauschii wDBE1 and wheat iso1. On the phylogenetic tree of the deduced mature protein sequences, Sorafenib rye ISA shares 96% sequence homologies with Ae. tauschii wDBE1 and wheat iso1, and 92%

homology with barley ISA1, indicating that rye isoamylase is more closely related to Ae. tauschii wDBE1 and wheat iso1. In this study, we isolated and characterized genomic DNA and cDNA and also predicted the corresponding protein sequence of the rye isoamylase gene. By comparing isoamylase genes and their proteins among rye and other plant species, we found that plant isoamylase genes are highly homologous in the exon regions and rye isoamylase is most closely homologous in aa sequence to wheat and Ae. tauschii than to barley in terms of phylogenetic relationship. Our real-time PCR results indicated that the rye isoamylase gene is mainly expressed in seed endosperms with a maximum

level at the mid-development stage (15 DPA). Starch synthesis is a complicated metabolic system in plants and characterization of starch synthesis genes is essential for establishing a basis to explore starch structure, function, and accumulation. Isoamylase genes have been isolated and characterized from different plant species, but their precise roles in starch synthesis and granule initiation are not yet clear. The rye isoamylase isolated and characterized in this study has provided new and essential information BMN 673 order to explore its function in amylopectin accumulation in rye and triticale grains and also its effects on subsequent

development of new triticale genotypes for novel starch granule see more types leading to higher or lower amylopectin contents. This study was supported by the MOE-AAFC PhD Research Program and partial A-Base funding from Agriculture and Agri-Food Canada. “
“Rice (Oryza sativa L.), as the most important staple food, feeds about 50% of the world population [1]. However, world rice production has to increase by at least 70% by 2050 in order to meet the demand of the population. Historically, at least 50% of the increases in rice productivity have resulted from development and wide adoption of new cultivars, which included benefits of the Green Revolution in the 1960s and hybrid rice technology from the late 1970s. Nowadays, it is a priority to improve yield potential in almost all rice breeding programs worldwide. Meanwhile, rice production is facing more and more challenges, such as water scarcity resulting from urban and industrial demands and pollution [2] and [3], dramatically declining arable lands and land degradation [4], and more frequent and dramatic climate changes from global warming [5], [6], [7] and [8].

The treatment algorithm and clinical guidance, which this panel w

The treatment algorithm and clinical guidance, which this panel wishes to support, aim to treat men at a similar 10-year fracture risk as in women, because the morbidity and mortality associated with major osteoporotic fractures in men are substantial. Available evidence suggests that treatment algorithms in women are also applicable to men. In practice, this is likely to involve the use of FRAX and clinical risk factors (Table 1). The use of fixed intervention thresholds is viewed as counter-intuitive to current practice, because the risk is to exclude too many younger patients and, conversely, to include too many older patients above a threshold

value. The available level of evidence that Metformin supplier treatment decreases the risk of fracture in men is lower than for women. As such, the US Endocrine Society is of the opinion that there is currently not enough information in men to make a recommendation, because too few fractures have been recorded in men to link BMD changes selleck with anti-fracture efficacy. Additional fracture data are needed to endorse the clinical care of osteoporosis in men. However, this panel believes that this view can be countered, based on available epidemiological and clinical efficacy data in male subjects, which display similarities with data acquired in women, in terms of treatment effects on BMD, biochemical markers

of bone turnover, and fracture endpoint, despite the recorded differences in pathophysiology of bone loss and bone microarchitecture. Overall, empirical data from men and women are so similar that differences in morphology may not be clinically relevant. Despite the wealth of available data from numerous studies in women, the current strategy of drug development for the treatment of osteoporosis in men is such that there is a delay of several years before clinical trial data in men become available. Perhaps the lag between comparable treatments becoming available for female and for male osteoporosis can be reduced. The situation is not unlike coronary artery disease, which was initially thought to be principally a male disease, oxyclozanide but for which female treatment was made

more rapidly available. A logical conclusion would eventually be to design mixed studies, as recommended by the WHO [111]. From a pragmatic point of view, it is unlikely that drugs for the specific treatment of osteoporosis in men will be developed. One area of research that deserves more attention is the hormonal and non-hormonal factors influencing bone loss in men. There appears to be potential in measuring serum oestradiol levels, in addition to testosterone levels in men with low BMD. We wish to encourage the development of standardised mass spectroscopy assays for the assessment of sex steroid contribution in male osteoporosis. Awareness of osteoporosis in men is improving, although it remains under-diagnosed and under-treated.