Stable Gastric Pentadecapeptide BPC 157 Heals Established Vesicovaginal Fistula and Counteracts Stone Formation in Rats

Round 1

Reviewer 1 Report

The manuscript is well written, and the research well-conducted.

The research problem is relevant and insightful, the rational for studying the problem was well stated.

There is an adequate introductory or background, there is recognition of gaps in knowledge and in the literature, and the relevance of the significance of other current research on the subject was highlighted. The authors adequately summarized the relevant literature and the references were relevant to the paper.

The research questions were well-stated, the interpretation of study findings was appropriate, the discussion well-conducted.

there was an appropriate use and interpretation of statistics and the statistical and qualitative data presentation was clear enough.
The results could be potentially reproducible

Author Response

We fully appreciate the reviewer's point.

Reviewer 2 Report

I think this manuscript is well done and the presentation of the research is satisfying, complete and detailed. 

Many cases of vesico-vaginal fistulas are the consequence of surgery and often ischemia and necrosis induced by the instruments are concomitant with the fistula.

In many cases surgery is needed to remove pathological tissue. Can BPC 157 administered in association with fistula surgery ?

Please if possible add a comment regarding potential clinical application with somewhat date on costs

If available, any comment comparing this approach with already existing similar treatments?

Author Response

Reviewer 2

I think this manuscript is well done and the presentation of the research is satisfying, complete and detailed. 

Many cases of vesico-vaginal fistulas are the consequence of surgery and often ischemia and necrosis induced by the instruments are concomitant with the fistula.

In many cases surgery is needed to remove pathological tissue. Can BPC 157 administered in association with fistula surgery ?

Please if possible add a comment regarding potential clinical application with somewhat date on costs

If available, any comment comparing this approach with already existing similar treatments?

Ad Reviewer 2. We fully appreciate the reviewer's point. The significance of the BPC 157 effects appointed by the reviewer, we attemt to resolve in the following notations:

Considering If available, any comment comparing this approach with already existing similar treatments?, see Paragraph 2, Introduction

Of note, as an especial point,  the proposed BPC 157 effectiveness in the resistant vesicovaginal fistulas goes with its wound healing potential, recently reviewed (i.e., skin, muscle, tendon, ligament, bone; ulcers in the entire gastrointestinal tract; corneal ulcer; lethal dose (LD1) is not achieved) [4,17], and molecular pathways implicated in the healing [18-27], in the fistulas curing in particular [3]. Thereby, there is the assumption that the healing of the various wounds is equally essential for both gastrointestinal fistulas and urogenital fistulas healing [3,4]. Documented consistent healing of the various gastrointestinal fistulas, external (esophagocutaneous, gastrocutaneous, duodenocutaneous, and colocutaneous) [5-8]  and internal (colovesical, rectovaginal) [9,10], was ascribed to its original healing capacity as a peptide native and stable in human gastric juice, and its possible role as novel mediator of Robert’s cytoprotection maintaining gastrointestinal mucosal integrity [3], as it is effective in the whole gastrointestinal tract and used in ulcerative colitis clinical trials [1-4]. Taking fistulas as a pathological connection, and BPC 157 to reestablish original organ function [3],  this particular rescue is verified with the beneficial effects in the rats with the various gastrointestinal anastomoses (i.e., esophagogastric [28], jejunoileal [29,30], colo-colonic [31], ileoileal [32], esophagojejunal [33], esophagoduodenal [34], and gastrojejunal [35]) as well as vessel [36] and nerve [37] anastomoses.

This paragraph would summarize the essential background of BPC 157 application in the fistula healing. In this, the emphasize „as an especial point“ – suggests that according best of our knowledge, there is no „already existing similar treatments“.

Considering In many cases surgery is needed to remove pathological tissue. Can BPC 157 administered in association with fistula surgery ? Please if possible add a comment regarding potential clinical application with somewhat date on costs

see last paragraph, Discussion:

Thus, BPC 157 and resolved vesicovaginal fistula issue, together elaborated in this study, along with the other fistulas’ healing [5-10], would certainly pointed out BPC 157 as the especial agent for fistula healing. In general, the development of these fistulas models resulted from efforts to improve on agent’s healing spectrum of healing action and stay ahead of the spread of failed healing in fistulas course [3].  For the vesicovaginal fistulas, in particular,  BPC 157’s easy drug regimen, parenterally or per-orally, with suited drug costs, and thereby also improved vesicovaginal fistula surgery, would contribute to the additional resolving research, including clinical studies.

In this paragraph we attempt to summarize the essential advanges of BPC 157 application in the fistula healing. Providing that costs points can be hardly discussed in the scientific paper in many details particularly regarding the drug availability, we hope that the final statement (For the vesicovaginal fistulas, in particular,  BPC 157’s easy drug regimen, parenterally or per-orally, with suited drug costs, and thereby also improved vesicovaginal fistula surgery, would contribute to the additional resolving research, including clinical studies.)could provide adequate clue.