Regen BioPharma (United States)

ObjectiveAs clinicians and patients await consensus on intraovarian platelet-rich plasma (PRP) treatment, this project evaluated contemporary research trends in the literature.MethodsA PubMed/NLM search aggregated all ovarian PRP-related publications (n=54) to evaluate their scope, abstract utility, submission-to-publication interval, journal selected, article processing charge (APC), free reader access to full-text manuscripts, number and nationality of authors, and inclusion of international collaborators. The NIH Clinical Trials database was also audited.ResultsPublished output on intraovarian PRP has increased consistently since 2016, especially among investigators in Greece, Iran, USA, and Turkey. Between 2013 and 2021, 42 articles met the relevancy criteria, of which 40.5% reported clinical studies, small series, or case reports, 33% described experimental animal models, and 23.8% were opinion/review papers. Only two works included a placebo control group. The submission-to-publication interval (mean±standard deviation) was 130±96 days, there were 5.9±3.2 authors per project, and journals invoiced US $1,642±1,466 (range, $0–$3,860) for APCs.ConclusionThere was no correlation between APC and time to publish (Pearson’s r=–0.01). content was inconsistent; sample size and patient age were often missing, yet free full-text “open access” was available for most publications (59.5%). The NIH Clinical Trials portal lists eight registered studies on “ovarian rejuvenation,” of which two are actively recruiting patients, while four have been terminated or have an uncertain status. Two studies have concluded, with results from one posted to the NIH website. PRP and its derivatives for ovarian treatment show early promise, but require further investigation. Research is accelerating and should be encouraged, particularly placebo-controlled randomized clinical trials.

Female age has been known to define reproductive outcome since antiquity; attempts to improve ovarian function may be considered against a sociocultural landscape that foreshadows current practice. Ancient writs heralded the unlikely event of an older woman conceiving as nothing less than miraculous. Always deeply personal and sometimes dynastically pivotal, the goal of achieving pregnancy often engaged elite healers or revered clerics for help. The sorrow of defeat became a potent motif of barrenness or miscarriage lamented in art, music, and literature. Less well known is that rejuvenation practices from the 1900s were not confined to gynecology, as older men also eagerly pursued methods to turn back their biological clock. This interest coalesced within the nascent field of endocrinology, then an emerging specialty. The modern era of molecular science is now offering proof-of-concept evidence to address the once intractable problem of low or absent ovarian reserve. Yet, ovarian rejuvenation by platelet-rich plasma (PRP) originates from a heritage shared with both hormone replacement therapy (HRT) and sex reassignment surgery. These therapeutic ancestors later developed into allied, but now distinct, clinical fields. Here, current iterations of intraovarian PRP are discussed with historical and cultural precursors centering on cell and tissue regenerative effects. Intraovarian PRP thus shows promise for women in menopause as an alternative to conventional HRT, and to those seeking pregnancy—either with advanced reproductive technologies or as unassisted conceptions.

It has been shown that the analgesic and cyclooxygenase inhibitor activity of ketorolac tromethamine (KT), which is marketed as the racemic mixture of (-)S and (+)R enantiomers, resides primarily with (-)S ketorolac and that the ulcerogenic activity of this agent also resides in (-)S ketorolac. Resolution of individual enantiomers for analysis in plasma samples has been accomplished by two methods: derivatization to form diastereomers that are separated by HPLC, or direct HPLC using a chiral phase column. When mice and rats were given oral solutions of (-)S and (+) KT, it was found that the kinetics and interconversion of the enantiomers were species and dose dependent. Interconversion was higher in mice than in rats; when (-)S KT was administered, 71% of the area under the concentration-time curve (AUC) was due to (+)R ketorolac in mice, compared with 12% in rats. More interconversion was observed at higher doses; the percent of AUC due to (-)S ketorolac when (+)R KT was administered increased from 12% to 25% in mice and from 2% to 8% in rats. In general, more interconversion occurred from (-)S to (+)R ketorolac in the animal studies. Human subjects were given single oral solution doses of racemic KT (30 mg), (-)S KT (15 mg), and (+)R KT (15 mg). The plasma concentrations of (-)S ketorolac were lower than (+)R ketorolac at all sample times after racemic KT (22% of the AUC was due to (-)S ketorolac). When (+)R KT was administered, (-)S ketorolac was not detectable and interconversion was essentially 0%. When (-)S KT was administered, significant levels of (+)R ketorolac were detectable and interconversion was 6.5%. After all doses, plasma half-life was shorter and clearance greater for (-)S ketorolac than for (+)R ketorolac. Thus, in humans very little or no interconversion of (+)R to (-)S was observed, and interconversion of (-)S to (+)R was minimal (6.5%). These data demonstrate that the kinetics and interconversion of the enantiomers of ketorolac is different in animals and humans as well as from most other NSAIDs. This may be due to more rapid excretion or metabolism of (-)S ketorolac and a different mechanism of interconversion.