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Pneumocystis carinii
Published in Peter D. Walzer, Robert M. Genta, Parasitic Infections in the Compromised Host, 2020
Peter D. Walzer, C. Kurtis Kim, Melanie T. Cushion
There is accumulating evidence that DFMO represents a new type of therapeutic approach to P. carinii pneumonia (147,473,474). This drug inhibits ornithine decarboxylase, a necessary step in the synthesis of polyamines, which play an important role in the replication of eukaryotic cells. While DFMO has inhibitory effects on a variety of protozoans, its main clinical use has been in the treatment of African trypanosomiasis. The use of DFMO in the treatment of P. carinii pneumonia has mainly been on a compassionate basis in patients who have failed or have experienced serious adverse reactions to TMP-SMX or pentamidine. The clinical experience with DFMO in more than 100 patients with pneumocystosis has been briefly summarized in a recent symposium (147). Of 53 persons who received the drug for more than 2 weeks, 70% achieved a good clinical response; 12 of these responders had begun therapy on ventilator support. DFMO was usually well tolerated, with adverse reactions (e.g., thrombocytopenia, leukopenia, high-frequency hearing loss, patchy alopecia, diarhhea) being reversible upon reduction in dose or cessation of therapy.
The Role of Relaxin in Uterine Function
Published in Gabor Huszar, The Physiology and Biochemistry of the Uterus in Pregnancy and Labor, 2020
Relaxin has been shown to increase uterine ornithine decarboxylase activity in mouse uterus.74 This effect does not appear to require E priming, since it was observed in uteri from ovariectomized mice. Ornithine decarboxylase activity is increased by cAMP, which may relate to the effect of relaxin. Ornithine decarboxylase regulates polyamine synthesis, and polyamines are thought to play a role in cell division and the stabilization of polysomes. Whether these changes relate to the trophic actions of relaxin remains to be determined.
Polycystic ovary syndrome and hyperandrogenism in adolescents
Published in Joseph S. Sanfilippo, Eduardo Lara-Torre, Veronica Gomez-Lobo, Sanfilippo's Textbook of Pediatric and Adolescent GynecologySecond Edition, 2019
Andrea E. Bonny, Asma Javed Chattha
A cosmetic hair removal process can offer more immediate results for patients without need for prescription. Electrolysis and laser hair removal therapies are becoming increasingly popular and affordable. Eflornithine is a prescription topical cream effective for removal of unwanted facial hair in females.66 It inhibits the enzyme ornithine decarboxylase at the hair follicle, reducing the rate of hair growth. Eflornithine combined with laser therapy resulted in more rapid reduction in facial hair as compared to laser treatment alone.119,120 Drawbacks include need for indefinite use to maintain efficacy and lack of coverage by most insurance plans in the United States.
Evaluation of androgen-dependent skin findings of polycystic ovary syndrome (PCOS)
Published in Gynecological Endocrinology, 2022
Gokhan Artar, Betul Tas, Gokce Turan, Hasan Huseyin Uckan
In the physiology of HR, the stimulation of hair growth from the follicle depends not only on the circulating androgen concentration but also on the peripheral metabolism of androgens and the end-organ sensitivity of circulating androgens [13, 14]. Local factors are also effective in this mechanism. Such as l-ornithine decarboxylase enzyme activity is an important contributor to hair follicle development as a local factor that catalayses the synthesis of polyamines implicated in cell migration, androgen receptor concentration, and 17-β hydroxysteroid dehydrogenase and 5 alpha reductase activities [15]. For this reason, the severity of HR may not correlate well with androgen levels because the androgen-dependent hair follicle response to androgen excess differs at significant levels in women. The laboratory results of women with HR might also change for this reason.
Polyamine biomarkers as indicators of human disease
Published in Biomarkers, 2021
Mohsin Amin, Shiying Tang, Liliana Shalamanova, Rebecca L. Taylor, Stephen Wylie, Badr M. Abdullah, Kathryn A. Whitehead
The use of polyamines in the detection of cancer has been studied throughout the literature since it has been suggested that their role in the pathogenesis of cancers such as prostate, colon and pancreatic, is apparent (Soda 2011, Nowotarski et al.2013, Damiani and Wallace 2018). The first reported role of polyamines in cancer was documented by Russell and Snyder (1968), whereby the increased levels of ornithine decarboxylase (ODC), a biosynthetic polyamine enzyme, was identified in various pathological cancers, such as liver and breast cancer (Russell and Snyder 1968, Deng et al.2008). When suppressed, the activity of ODC, the rate-limiting enzyme for mammalian polyamine biosynthesis, showed inhibition of colon carcinogenesis in cancer rodent models. Such a finding may suggest that the reduction in polyamine biosynthesis demonstrated a positive correlation in reducing the rates of colon cancer in rodents (Erdman et al.1999).
Evolving treatments in high-risk neuroblastoma
Published in Expert Opinion on Orphan Drugs, 2020
Abhinav Kumar, John P J Rocke, B Nirmal Kumar
MYCN amplification has become synonymous with high-risk neuroblastoma formation but was often considered undruggable. Therefore, newer approaches are looking to target regulators of MYCN transcription. Ornithine Decarboxylase (ODC) is an enzyme involved in the biosynthesis of polyamines that supports N-MYC proteins, with the inhibition of this downstream regulator possibly slowing the growth of neuroblastomas [63]. Difluoromethylornithine (DFMO) is an irreversible inhibitor of ODC and has shown to have low toxicity in humans, with certified medical use for conditions such as trypanosomiasis [64]. Whilst DMFO targeting ODC is a possible treatment for MYCN-amplified neuroblastomas, elevated ODC is also seen in non-MYCN amplified neuroblastomas indicating that increased ODC expression is critical in all rapidly dividing tumor cells [65]. In an pre-clinical study of DMFO efficacy, the drug not only inhibited tumor growth in MYCN-amplified mice leading to prolonged survival, but also showed efficacy as an adjuvant to conventional chemotherapy [66]. In a phase 1 trial, DMFO showed no significant toxicities with or without etoposide (a chemotherapeutic agent) in patients with relapsed neuroblastoma [67]. Additionally, this study further emphasized the importance of ODC as an indicator of poor prognosis in neuroblastoma patients. A phase 2 trial is underway to assess oral DMFO as a maintenance therapy in high-risk cases [NCT02395666]. Whilst relatively un-tested for neuroblastoma, a well-tolerated and widely applicable drug such as DMFO could be very useful.