„Neko bi pomislio da se barem delimično sačuva dogma o monarhiji”: Antilatinski traktati Varlaama Kalabrijskog u srpskoslovenskom prevodu 14. veka

Die antilateinischen Traktate von Gregorios Palamas und Barlaam von Kalabrien stellten für die serbischen Übersetzer des 14. Jahrhunderts eine grosse Herausforderung dar – nicht nur wegen ihres dogmatischen Inhalts, sondern auch wegen des ausgeprägt polemischen Charakters ihrer Argumentation. In diesem Aufsatz wird die argumentative Form der zwei Traktate („opuscula“ ) Barlaams von Kalabrien analysiert, die in cod. Dečani 88 enthalten sind (fol. 38r-81r). Der zweite von ihnen (fol. 69v-81r) richtet sich an ein griechisches (orthodoxes) Auditorium; die Anreden an die Lateiner, die sich darin finden, haben rein rhetorischen Charakter. Der erste Traktat (fol. 39r-69r), der während der Unionsverhandlungen des Jahres 1334/1335 entstand, hat jedoch eine für die byzantinische Unionspolemik eher ungewöhnliche Form: der Dialog mit der Gegenseite ist hier keine rhetorische Fiktion, sondern ein ernstes Anliegen des Autors. Dies hat bereits bei der Rezeption des Traktats im griechisch-athonitischen Milieu den Verdacht geweckt, Barlaam habe den Lateinern unzulässige Zugeständnisse gemacht. Barlaam hat versucht, diesen Verdacht durch metakommunikative Kommentare zu entkräften, die ausschliesslich in der serbisch-kirchenslavischen Übersetzung von Dečani 88 enthalten sind. Der Übersetzer der Traktate hat deren argumentative Form im wesentlichen nicht angetastet und nur gelegentlich versucht, die Zugehörigkeit der einzelnen Argumente dem Leser durch Marginalscholien deutlich zu machen.

Active intestinal calcium transport in the absence of transient receptor potential vanilloid type 6 and calbindin-D9k

To study the role of the epithelial calcium channel transient receptor potential vanilloid type 6 (TRPV6) and the calcium-binding protein calbindin-D9k in intestinal calcium absorption, TRPV6 knockout (KO), calbindin-D9k KO, and TRPV6/calbindin-D(9k) double-KO (DKO) mice were generated. TRPV6 KO, calbindin-D9k KO, and TRPV6/calbindin-D9k DKO mice have serum calcium levels similar to those of wild-type (WT) mice ( approximately 10 mg Ca2+/dl). In the TRPV6 KO and the DKO mice, however, there is a 1.8-fold increase in serum PTH levels (P < 0.05 compared with WT). Active intestinal calcium transport was measured using the everted gut sac method. Under low dietary calcium conditions there was a 4.1-, 2.9-, and 3.9-fold increase in calcium transport in the duodenum of WT, TRPV6 KO, and calbindin-D9k KO mice, respectively (n = 8-22 per group; P > 0.1, WT vs. calbindin-D9k KO, and P < 0.05, WT vs. TRPV6 KO on the low-calcium diet). Duodenal calcium transport was increased 2.1-fold in the TRPV6/calbindin-D9k DKO mice fed the low-calcium diet (P < 0.05, WT vs. DKO). Active calcium transport was not stimulated by low dietary calcium in the ileum of the WT or KO mice. 1,25-Dihydroxyvitamin D3 administration to vitamin D-deficient null mutant and WT mice also resulted in a significant increase in duodenal calcium transport (1.4- to 2.0-fold, P < 0.05 compared with vitamin D-deficient mice). This study provides evidence for the first time using null mutant mice that significant active intestinal calcium transport occurs in the absence of TRPV6 and calbindin-D9k, thus challenging the dogma that TRPV6 and calbindin-D9k are essential for vitamin D-induced active intestinal calcium transport.

Allopurinol hypersensitivity is primarily mediated by dose-dependent oxypurinol-specific T cell response

BACKGROUND Allopurinol is a main cause of severe cutaneous adverse reactions (SCAR). How allopurinol induces hypersensitivity remains unknown. Pre-disposing factors are the presence of the HLA-B*58:01 allele, renal failure and possibly the dose taken. OBJECTIVE Using an in vitro model, we sought to decipher the relationship among allopurinol metabolism, HLA-B*58:01 phenotype and drug concentrations in stimulating drug-specific T cells. METHODS Lymphocyte transformation test (LTT) results of patients who had developed allopurinol hypersensitivity were analysed. We generated allopurinol or oxypurinol-specific T cell lines (ALP/OXP-TCLs) from allopurinol naïve HLA-B*58:01(+) and HLA-B*58:01(-) individuals using various drug concentrations. Their reactivity patterns were analysed by flow cytometry and (51) Cr release assay. RESULTS Allopurinol allergic patients are primarily sensitized to oxypurinol in a dose-dependent manner. TCL induction data show that both the presence of HLA-B*58:01 allele and high concentration of drug are important for the generation of drug-specific T cells. The predominance of oxypurinol-specific lymphocyte response in allopurinol allergic patients can be explained by the rapid conversion of allopurinol to oxypurinol in vivo rather than to its intrinsic immunogenicity. OXP-TCLs do not recognize allopurinol and vice versa. Finally, functional avidity of ALP/OXP-TCL is dependent on both the induction dose and HLA-B*58:01 status. CONCLUSIONS AND CLINICAL RELEVANCE This study establishes the important synergistic role of drug concentration and HLA-B*58:01 allele in the allopurinol or oxypurinol-specific T cell responses. Despite the prevailing dogma that Type B adverse drug reactions are dose independent, allopurinol hypersensitivity is primarily driven by oxypurinol-specific T cell response in a dose-dependent manner, particular in the presence of HLA-B*58:01 allele.

Collingwood on religious atonement

R. G. Collingwood’s philosophical analysis of religious atonement as a dialectical process of mortal repentance and divine forgiveness is explained and criticized. Collingwood’s Christian concept of atonement, in which Christ TeX the Atonement (and also TeX the Incarnation), is subject in turn to another kind of dialectic, in which some of Collingwood’s leading ideas are first surveyed, and then tested against objections in a philosophical evaluation of their virtues and defects, strengths and weaknesses. Collingwood’s efforts to synthesize objective and subjective aspects of atonement, and his proposal to solve the soteriological problem as to why God becomes flesh, as a dogma of some Christian belief systems, is finally exposed in adversarial exposition as inadequately supported by one of his main arguments, designated here as Collingwood’s Dilemma. The dilemma is that sin is either forgiven or unforgiven by God. If God forgives sin, then God’s justice is lax, whereas if God does not forgive sin, then, also contrary to divine nature, God lacks perfect loving compassion. The dilemma is supposed to drive philosophy toward a concept of atonement in which the sacrifice of Christ is required in order to absolve God of the lax judgment objection. God forgives sin only when the price of sin is paid, in this case, by the suffering and crucifixion of God’s avatar. The dilemma can be resolved in another way than Collingwood considers, undermining his motivation for synthesizing objective and subjective facets of the concept of atonement for the sake of avoiding inconsistency. Collingwood is philosophically important because he asks all the right questions about religious atonement, and points toward reasonable answers, even if he does not always deliver original philosophically satisfactory solutions.

Prognostic Relevance of Palliative Primary Tumor Removal in 37,793 Metastatic Colorectal Cancer Patients: A Population-Based, Propensity Score-Adjusted Trend Analysis

OBJECTIVE To assess whether palliative primary tumor resection in colorectal cancer patients with incurable stage IV disease is associated with improved survival. BACKGROUND There is a heated debate regarding whether or not an asymptomatic primary tumor should be removed in patients with incurable stage IV colorectal disease. METHODS Stage IV colorectal cancer patients were identified in the Surveillance, Epidemiology, and End Results database between 1998 and 2009. Patients undergoing surgery to metastatic sites were excluded. Overall survival and cancer-specific survival were compared between patients with and without palliative primary tumor resection using risk-adjusted Cox proportional hazard regression models and stratified propensity score methods. RESULTS Overall, 37,793 stage IV colorectal cancer patients were identified. Of those, 23,004 (60.9%) underwent palliative primary tumor resection. The rate of patients undergoing palliative primary cancer resection decreased from 68.4% in 1998 to 50.7% in 2009 (P < 0.001). In Cox regression analysis after propensity score matching primary cancer resection was associated with a significantly improved overall survival [hazard ratio (HR) of death = 0.40, 95% confidence interval (CI) = 0.39-0.42, P < 0.001] and cancer-specific survival (HR of death = 0.39, 95% CI = 0.38-0.40, P < 0.001). The benefit of palliative primary cancer resection persisted during the time period 1998 to 2009 with HRs equal to or less than 0.47 for both overall and cancer-specific survival. CONCLUSIONS On the basis of this population-based cohort of stage IV colorectal cancer patients, palliative primary tumor resection was associated with improved overall and cancer-specific survival. Therefore, the dogma that an asymptomatic primary tumor never should be resected in patients with unresectable colorectal cancer metastases must be questioned.