Integrated toxicity evaluation of a pulp deposit using organisms of different trophic levels

Purpose: In order to assess possible adverse effects originating from pulp deposits in a Swiss lake, a sediment quality triad approach was applied with chemical, ecotoxicological and ecological assessment methods. Materials and methods: To obtain an integrative picture of the potential ecotoxicological effects on organisms of different trophic levels, four test procedures were applied. The acute effects of pulp deposit pore water on a decomposer, the amphipod Gammarus fossarum, were monitored. Chronic toxicity of the pore water was evaluated on primary producers via a growth inhibition test with unicellular green algae (Pseudokirchneriella subcapitata) and on secondary consumers in a reproduction test with the water flea Ceriodaphnia dubia. To evaluate the effects of the pulp deposit on sediment inhabitants, a whole-life-cycle test with the non-biting midge Chironomus riparius was undertaken. Chemical assessment included dissolved organic carbon, extractable organic halogenic compounds, polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs) and heavy metals. The composition of the macrozoobenthos community was analysed in order to assess the ecological effects. Results and discussion: G. fossarum displayed increased locomotor activity at 12.5% but not at 25% sample concentration during a short-time exposure of 20h. Chronic effects compromised the reproduction and growth of C. dubia (lowest observed effect concentration, 12.5% sample concentration) with zero population growth in 100% pulp deposit pore water. In 100% pulp deposit, C. riparius exhibited increased mortality at 10 and 17days after oviposition. Pulp deposits of 50% and 100% concentration caused a significantly lower emergence compared with the reference treatments (lake sediment and quartz sand). Additionally, the locomotor activity of chironomids decreased significantly in 25-100% pulp deposit. No chronic effects of pulp deposit pore water on algae photosynthesis and growth could be detected. The bioassay results were in accordance with an elevated content of PAHs, PCBs and metals in the pulp deposit. Significantly more organisms known to be tolerant to organic pollution were present within the macrozoobenthos community. Conclusions: In general, for sediment inhabitants such as chironomids, the pulp deposit has to be classified toxic. In the present test setup, the toxicity of the pulp deposit was reflected better by the chronic test systems applied than by the acute ones. The applied testing framework could be a suitable tool to assess the risk of contaminated sites, and this information will help decide whether risk mitigation measures should be taken. In addition, with a similar approach, the success of any mitigation measures taken can be assesse

NY-BR-1 protein expression in breast carcinoma: a mammary gland differentiation antigen as target for cancer immunotherapy

NY-BR-1 is a recently identified differentiation antigen of the mammary gland. To use NY-BR-1 for T-cell-based immunotherapy, analysis of its co-expression with HLA class I antigens is required. In the present tissue microarray study, primary breast cancers (n=1,444), recurrences (n=88), lymph node (n=525) and distant metastases (n=91) were studied for NY-BR-1 expression using a novel monoclonal antibody. NY-BR-1 expression was compared with prognosis, estrogen receptor, HER2-status, EGFR and HLA class I antigen expression. NY-BR-1 was more frequently expressed in grade 1 (82%) than in grade 2 (69%) and grade 3 (46%) carcinomas (P<0.0001). Moreover, NY-BR-1 expression correlated directly with estrogen receptor expression (P<0.0001) and inversely correlated with HER2-status and EGFR expression (P<0.0001 for both). Considering high expression level of co-expression, 198/1,321 (15%) primary breast carcinomas and 4/65 (6%) distant metastases expressed NY-BR-1 and HLA class I, suggesting that active immunotherapy can be applied to about 10% of breast cancer patients. Survival analysis showed an association of NY-BR-1 expression with better patient outcome (P=0.015). No difference between NY-BR-1 expression of primary tumors and metastases could be found, indicating that the presence of NY-BR-1 in metastases can be deduced from their corresponding primary. Forty-three paired biopsies taken from patients before and after chemotherapy suggest that NY-BR-1 expression is not influenced by preceding chemotherapy (κ=0.89, P<0.0001). In summary, the co-expression of NY-BR-1 with HLA class I antigens and its expression in metastases without modification by chemotherapy suggest that NY-BR-1 targeted immunotherapy represents a viable strategy in addition to other targeted cancer drug therapies of breast cance

Initial steps in the degradation of benzene sulfonic acid, 4-toluene sulfonic acids, and orthanilic acid in Alcaligenes sp. strain O-1

Alcaligenes sp. strain O-1 grew with benzene sulfonate (BS) as sole carbon source for growth with either NH4 + or NH4 + plus orthanilate (2-aminobenzene sulfonate, OS) as the source(s) of nitrogen. The intracellular desulfonative enzyme did not degrade 3- or 4-aminobenzene sulfonates in the medium, although the enzyme in cell extracts degraded these compounds. We deduce the presence of a selective permeability barrier to sulfonates and conclude that the first step in sulfonate metabolism is transport into the cell. Cell-free desulfonation of BS in standard reaction mixtures required 2 mol of O2 per mol. One mol of O2 was required for a catechol 2,3-dioxygenase. When meta ring cleavage was inhibited with 3-chlorocatechol in desalted extracts, about 1 mol each of O2 and of NAD(P)H per mol of BS were required for the reaction, and SO3 2- and catechol were recovered in high yield. Catechol was shown to be formed by dioxygenation in an experiment involving 18O2. 4-Toluene sulfonate was subject to NAD(P)H-dependent dioxygenation to yield SO3 2- and 4-methylcatechol, which was subject to meta cleavage. OS also required 2 mol of O2 per mol and NAD(P)H for degradation, and SO3 2- and NH4 + were recovered quantitatively. Inhibition of ring cleavage with 3-chrorocatechol reduced the oxygen requirement to 1 mol per mol of OS SO3 2- (1 mol) and an unidentified organic intermediate, but no NH4 +, were observed

Vestibular Aqueduct Morphology Correlates With Endolymphatic Sac Pathologies in Menièreʼs Disease—A Correlative Histology and Computed Tomography Study

HYPOTHESIS: The vestibular aqueduct (VA) in Menière's disease (MD) exhibits different angular trajectories depending on the presenting endolymphatic sac (ES) pathology, i.e., 1) ES hypoplasia or 2) ES degeneration. BACKGROUND: Hypoplasia or degeneration of the ES was consistently found in inner ears affected by MD. The two etiologically distinct ES pathologies presumably represent two disease "endotypes," which may be associated with different clinical traits ("phenotypes") of MD. Recognizing these endotypes in the clinical setting requires a diagnostic tool. METHODS: 1) Defining the angular trajectory of the VA (ATVA) in the axial plane. 2) Measuring age-dependent normative data for the ATVA in postmortem temporal bone histology material from normal adults and fetuses. 3) Validating ATVA measurements from normative CT imaging data. 4) Correlating the ATVA with different ES pathologies in histological materials and CT imaging data from MD patients. RESULTS: 1) The ATVA differed significantly between normal adults and MD cases with ES degeneration, as well as between fetuses and MD cases with ES hypoplasia; 2) a strong correlation between ATVA measurements in histological sections and CT imaging data was found; 3) a correlation between the ATVA, in particular its axial trajectory in the opercular region (angle αexit), with degenerative (αexit  140°) was demonstrated. CONCLUSION: We established the ATVA as a radiographic surrogate marker for ES pathologies. CT-imaging-based determination of the ATVA enables endotyping of MD patients according to ES pathology. Future studies will apply this method to investigate whether ES endotypes distinguish clinically meaningful subgroups of MD patients.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

Patterns of care and economic consequences of using bone-targeted agents for castration-sensitive prostate cancer patients with bone metastases to prevent skeletal-related events in Switzerland - the SAKK 95/16 prostate study

International guidelines state that bone-targeted agents such as denosumab or zoledronic acid at doses used for bone metastasis are not indicated for patients with metastatic castration-sensitive prostate cancer (mCSPC) with bone metastases. Whereas denosumab has never been studied in this patient population, zoledronic acid has been shown to be ineffective in decreasing the risk for skeletal-related events. This study estimates the prevalence and economic consequences of real-world use of bone-targeted agents for mCSPC patients in Switzerland.; To estimate the frequency of bone-targeted agent administration and skeletal-related events, data from a non-interventional, cross-sectional survey involving oncologists across Switzerland (SAKK 95/16) was combined with data from the Swiss National Institute for Cancer Epidemiology and Registration (NICER). Economic parameters were calculated from the perspective of the healthcare system over the median time to prostate-specific antigen (PSA) progression for the extrapolated patient group, using data from NICER. The cost calculation covered costs for bone-targeted agents, their administration and skeletal-related events. The time to PSA progression (33.2 months), as well as the probability and cost of skeletal-related events were derived from the literature.; The survey was answered by 86 physicians treating 417 patients, of whom 106 (25.4%) had prostate cancer, with 36 (34.0%) of these mCSPC. The majority of mCSPC patients (52.8%, n = 19) received bone-targeted agents monthly. Denosumab was the treatment of choice in 84.2% of patients (n = 16). Extrapolation using data from NICER indicated that 568 mCSPC patients may be treated with bone-targeted agents at doses used for bone metastasis every year in Switzerland, leading to estimated total costs of more than CHF 8.3 million over 33.2 months. Because of its more frequent prescription and higher price, it appears that almost 93% of the total costs can be attributed to denosumab. For both denosumab and zoledronic acid, the most expensive components were the cost of administration and the drug cost, making up more than 90% of the total costs, with the rest being costs of skeletal-related events.; This study found that the administration of bone-targeted agents in doses used for bone-metastatic diseases to prevent skeletal-related events is frequent in the setting of mCSPC and results in significant costs for the healthcare system

NY-BR-1 protein expression in breast carcinoma: a mammary gland differentiation antigen as target for cancer immunotherapy

NY-BR-1 is a recently identified differentiation antigen of the mammary gland. To use NY-BR-1 for T-cell-based immunotherapy, analysis of its co-expression with HLA class I antigens is required. In the present tissue microarray study, primary breast cancers (n = 1,444), recurrences (n = 88), lymph node (n = 525) and distant metastases (n = 91) were studied for NY-BR-1 expression using a novel monoclonal antibody. NY-BR-1 expression was compared with prognosis, estrogen receptor, HER2-status, EGFR and HLA class I antigen expression. NY-BR-1 was more frequently expressed in grade 1 (82%) than in grade 2 (69%) and grade 3 (46%) carcinomas (P < 0.0001). Moreover, NY-BR-1 expression correlated directly with estrogen receptor expression (P < 0.0001) and inversely correlated with HER2-status and EGFR expression (P < 0.0001 for both). Considering high expression level of co-expression, 198/1,321 (15%) primary breast carcinomas and 4/65 (6%) distant metastases expressed NY-BR-1 and HLA class I, suggesting that active immunotherapy can be applied to about 10% of breast cancer patients. Survival analysis showed an association of NY-BR-1 expression with better patient outcome (P = 0.015). No difference between NY-BR-1 expression of primary tumors and metastases could be found, indicating that the presence of NY-BR-1 in metastases can be deduced from their corresponding primary. Forty-three paired biopsies taken from patients before and after chemotherapy suggest that NY-BR-1 expression is not influenced by preceding chemotherapy (kappa = 0.89, P < 0.0001). In summary, the co-expression of NY-BR-1 with HLA class I antigens and its expression in metastases without modification by chemotherapy suggest that NY-BR-1 targeted immunotherapy represents a viable strategy in addition to other targeted cancer drug therapies of breast cancer