Effect of a BK Receptor Antagonist (R‐954) in Experimental Endometriosis
Bibliographic record
Abstract
Endometriosis is a gynecological condition characterized by the growth of endometrium‐like tissues within and outside of the pelvic cavity. Currently available drugs are only efficacious in treating endometriosis‐related pain, however it's not a targeted treatment. In this sense, the aim of this work is evaluate the effects of R‐954 (a bradykinin B1 receptor antagonist), in a murine model of endometriosis. Female Swiss Webster mice (25–30g, n=7) were anesthetized with intraperitoneal injection of ketamine/xylazine. The abdomen was opened to expose the uterus. One uterine horn was ligated at both the uterotubal junction and the cervical end, and the intermediate segment was removed and split longitudinally. Pieces with 5‐mm were sectioned. These explants were then anchored onto the peritoneum. After 35 days, the abdomen was opened to assess the viability of the endometrial explants. The animals were divided and treated with: R‐954 (2 and 5 mg/kg, s.c), progesterone (1 mg/kg, p.o) or vehicle, for 15 consecutive days. In every day mice were submitted to vaginal smear. At the last day the animals were euthanized and blood, peritoneal fluid and ectopic cyst were collected for quantification of pro‐inflammatory cytokines. The results are presented as mean±SD and statistical analysis were performed by ANOVA followed by Newman‐Keuls post‐test (*p<0.05). Protocols for animal use received number #DFBCICB015‐04/16 (COBEA/UFRJ/Brazil). In vehicle‐treated groups entire cycle remained for 15 days (proestrous, estrous, metaestrous and diestus phases). In progesterone‐treated group animais remained in estrus phase. Pretreatment with R‐954 did not affect changes the phases of estrous cycle. All doses of R‐954 reduced the levels of TNF‐α and IL‐6 in blood, peritoneal fluid and ectopic cyst. In ectopic cyst, levels of TNF‐α were reduced in 47.7% (6.3±1.6*pg/μg of protein) and 79% (2.5±1.4*pg/μg of protein), when compared to vehicle‐treated group (12.0±6.3 pg/μg of protein). IL‐6 levels were reduced in 77.7% (2.0±0.7*pg/μg) and 85.5% (1.3±0.9*pg/μg), when compared to vehicle‐treated group (9±4.2 pg/μg), to 2 and 5 mg/kg, respectively. In the blood, a similar pattern was observed, TNF‐α was reduced in 56.5% (320.0±136.9*pg/mL) and 58.4% (306.3±146.0*pg/mL) when compared to vehicle‐treated group (736.1±298.4 pg/mL) and IL‐6 was significantly reduced in 83.2% (41.8±30.7*pg/mL) and 84.8% (37.8±19.4*pg/mL) when compared to vehicle‐treated group (248.7±106.7 pg/mL), at doses 2 and 5 mg/kg, respectively. In the peritoneal fluid, the production of TNF‐α decreased in 67.6% (222.1±129.7*pg/mL) and 80.3% (134.7±39.5*pg/mL), when compared to vehicle‐treated group (686.8±167.7 pg/mL) and the IL‐6 was reduced in 75.5% (36.3±13* pg/mL) and 52.4% (70.1±44.1* pg/mL) when compared to vehicle‐treated group (146.8±53.3 pg/mL), to 2 and 5 mg/kg, respectively. Our results suggest that R‐954 doesn't have influence in estrous cycle and show significant anti‐inflammatory effects through reduction of production of cytokines. Support or Funding Information This study was financed in part by the CAPES/Finance Code 001, CNPq and FAPERJ. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".