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Skin Therapy Letter Sep 2021Hair removal practices have evolved from adhering to social, cultural, and religious traditions to meeting aesthetic standards. Hair removal methods can be divided into... (Review)
Review
Hair removal practices have evolved from adhering to social, cultural, and religious traditions to meeting aesthetic standards. Hair removal methods can be divided into two categories: 1) depilation, which involves removing the hair shaft and includes shaving and chemical depilatories, and 2) epilation, which involves removing the hair shaft, follicle, and bulb, and includes plucking, threading, waxing, sugaring, lasers, intense pulsed light system, electrolysis, and photodynamic therapy. Furthermore, an eflornithine hydrochloride 13.9% cream (Vaniqa®, neither an epilatory or depilatory technique), has been US FDA- and Health Canada-approved to slow the rate of facial hair growth and to be used in combination with other hair removal methods. All methods are temporary except for electrolysis, and each technique has advantages and disadvantages in terms of efficacy and adverse events. Importantly, most studies examining the efficacy of hair removal techniques are limited to darker hair and fairer skin, and further research is required especially for those with light-colored hair.
Topics: Eflornithine; Face; Hair Removal; Humans; Lasers; Photochemotherapy
PubMed: 34524781
DOI: No ID Found -
Taiwanese Journal of Obstetrics &... Jan 2022Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women is characterized by polycystic ovaries, chronic anovulation and hyperandrogenism. The treatment... (Review)
Review
Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women is characterized by polycystic ovaries, chronic anovulation and hyperandrogenism. The treatment in PCOS is mainly symptomatic and involves lifestyle interventions and medications such as Metformin, Oral contraceptives and Antiandrogens. However, the management of PCOS is challenging and current interventions are not able to deal with outcomes of this syndrome. This review encompasses latest pharmacotherapeutic and non-pharmacotherapeutic interventions currently in use to tackle various symptomatic contentions in PCOS. Our focus has been mainly on novel therapeutic modalities for treatment/management of PCOS, like use of newer insulin sensitizers viz., Inositols, Glucagon-like peptide-1(GLP-1) agonists, Dipeptidyl pepdidase-4 (DPP-4) inhibitors, and sodium-glucose transport protein 2 (SGLT2) inhibitors. Also, evidence suggesting the use of vitamin D, statins, and Letrozole as emerging therapies in PCOS have been summarized in this review. Additionally, novel cosmetic techniques like electrolysis, laser and use of topically applied eflornithine to tackle the most distressing feature of facial hirsutism associated with PCOS, non-pharmacological therapy like acupuncture and the role of herbal medicine in PCOS management have also been discussed.
Topics: Acupuncture; Anovulation; Eflornithine; Female; Herbal Medicine; Hirsutism; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperandrogenism; Hypoglycemic Agents; Laser Therapy; Letrozole; Metformin; Polycystic Ovary Syndrome; Vitamin D
PubMed: 35181044
DOI: 10.1016/j.tjog.2021.11.009 -
Developmental Medicine and Child... Apr 2024Bachmann-Bupp syndrome (BABS) is a neurodevelopmental disorder characterized by developmental delay, hypotonia, and varying forms of non-congenital alopecia. The... (Review)
Review
Bachmann-Bupp syndrome (BABS) is a neurodevelopmental disorder characterized by developmental delay, hypotonia, and varying forms of non-congenital alopecia. The condition is caused by 3'-end mutations of the ornithine decarboxylase 1 (ODC1) gene, which produce carboxy (C)-terminally truncated variants of ODC, a pyridoxal 5'-phosphate-dependent enzyme. C-terminal truncation of ODC prevents its ubiquitin-independent proteasomal degradation and leads to cellular accumulation of ODC enzyme that remains catalytically active. ODC is the first rate-limiting enzyme that converts ornithine to putrescine in the polyamine pathway. Polyamines (putrescine, spermidine, spermine) are aliphatic molecules found in all forms of life and are important during embryogenesis, organogenesis, and tumorigenesis. BABS is an ultra-rare condition with few reported cases, but it serves as a convincing example for drug repurposing therapy. α-Difluoromethylornithine (DFMO, also known as eflornithine) is an ODC inhibitor with a strong safety profile in pediatric use for neuroblastoma and other cancers as well as West African sleeping sickness (trypanosomiasis). Patients with BABS have been treated with DFMO and have shown improvement in hair growth, muscle tone, and development.
Topics: Humans; Child; Putrescine; Spermidine; Polyamines; Spermine; Eflornithine
PubMed: 37469105
DOI: 10.1111/dmcn.15687 -
Journal of Clinical Oncology : Official... Jan 2024Long-term survival in high-risk neuroblastoma (HRNB) is approximately 50%, with mortality primarily driven by relapse. Eflornithine (DFMO) to reduce risk of relapse...
PURPOSE
Long-term survival in high-risk neuroblastoma (HRNB) is approximately 50%, with mortality primarily driven by relapse. Eflornithine (DFMO) to reduce risk of relapse after completion of immunotherapy was investigated previously in a single-arm, phase II study (NMTRC003B; ClinicalTrials.gov identifier: NCT02395666) that suggested improved event-free survival (EFS) and overall survival (OS) compared with historical rates in a phase III trial (Children Oncology Group ANBL0032; ClinicalTrials.gov identifier: NCT00026312). Using patient-level data from ANBL0032 as an external control, we present new analyses to further evaluate DFMO as HRNB postimmunotherapy maintenance.
PATIENTS AND METHODS
NMTRC003B (2012-2016) enrolled patients with HRNB (N = 141) after standard up-front or refractory/relapse treatment who received up to 2 years of continuous treatment with oral DFMO (750 ± 250 mg/m twice a day). ANBL0032 (2001-2015) enrolled patients with HRNB postconsolidation, 1,328 of whom were assigned to dinutuximab (ch.14.18) treatment. Selection rules identified 92 NMTRC003B patients who participated in (n = 87) or received up-front treatment consistent with (n = 5) ANBL0032 (the DFMO/treated group) and 852 patients from ANBL0032 who could have been eligible for NMTRC003B after immunotherapy, but did not enroll (the NO-DFMO/control group). The median follow-up time for DFMO/treated patients was 6.1 years (IQR, 5.2-7.2) versus 5.0 years (IQR, 3.5-7.0) for NO-DFMO/control patients. Kaplan-Meier and Cox regression compared EFS and OS for overall groups, 3:1 (NO-DFMO:DFMO) propensity score-matched cohorts balanced on 11 baseline demographic and disease characteristics with exact matching on , and additional sensitivity analyses.
RESULTS
DFMO after completion of immunotherapy was associated with improved EFS (hazard ratio [HR], 0.50 [95% CI, 0.29 to 0.84]; = .008) and OS (HR, 0.38 [95% CI, 0.19 to 0.76]; = .007). The results were confirmed with propensity score-matched cohorts and sensitivity analyses.
CONCLUSION
The externally controlled analyses presented show a relapse risk reduction in patients with HRNB treated with postimmunotherapy DFMO.
Topics: Child; Humans; Eflornithine; Propensity Score; Neoplasm Recurrence, Local; Neuroblastoma; Recurrence; Disease-Free Survival
PubMed: 37883734
DOI: 10.1200/JCO.22.02875 -
PloS One 2020The plenteous resistance to and undesirable consequences of the existing antipiroplasmic therapies have emphasized the urgent need for new chemotherapeutics and drug...
BACKGROUND
The plenteous resistance to and undesirable consequences of the existing antipiroplasmic therapies have emphasized the urgent need for new chemotherapeutics and drug targets for both prophylaxis and chemotherapy. Hydroxyurea (HYD) is an antineoplastic agent with antitrypanosomal activity. Eflornithine (α-difluoro-methyl ornithine, DFMO) is the best choice therapy for the treatment of late-stage Gambian human African trypanosomiasis.
METHODS
In this study, the inhibitory and combination efficacy of HYD and DFMO with existing babesicidal drugs (diminazene aceturate (DA), atovaquone (ATV), and clofazimine (CLF)) deoxyribonucleotide in vitro against the multiplication of Babesia and Theileria. As well as, their chemotherapeutic effects were assessed on B. microti strain that infects rodents. The Cell Counting Kits-8 (CCK-8) test was used to examine their cytotoxicity on human foreskin fibroblast (HFF), mouse embryonic fibroblast (NIH/3T3), and Madin-Darby bovine kidney (MDBK) cells.
FINDINGS
HYD and DFMO suppressed the multiplication of all tested species (B. bigemina, B. bovis, B. caballi, B. divergens, and T. equi) in a dose-related manner. HFF, NIH/3T3, or MDBK cell viability was not influenced by DFMO at 1000 μM, while HYD affected the MDBK cell viability at EC50 value of 887.5±14.4 μM. The in vitro combination treatments of DFMO and HYD with CLF, DA, and ATV exhibited synergistic and additive efficacy toward all tested species. The in vivo experiment revealed that HYD and DFMO oral administration at 100 and 50 mg/kg inhibited B. microti multiplication in mice by 60.1% and 78.2%, respectively. HYD-DA and DFMO-DA combined treatments showed higher chemotherapeutic efficacy than their monotherapies.
CONCLUSION
These results indicate the prospects of HYD and DFMO as drug candidates for piroplasmosis treatment, when combined mainly with DA, ATV, and CLF. Therefore, further studies are needed to combine HYD or DFMO with either ATV or CLF and examine their impact on B. microti infection in mice.
Topics: Animals; Antineoplastic Agents; Antiprotozoal Agents; Atovaquone; Babesia; Cell Survival; Clofazimine; Diminazene; Dogs; Eflornithine; Foreskin; Humans; Hydroxyurea; Male; Mice; NIH 3T3 Cells; Theileria
PubMed: 32053698
DOI: 10.1371/journal.pone.0228996 -
PLoS Neglected Tropical Diseases Jul 2021The polyamine synthesis inhibitor eflornithine is a recommended treatment for the neglected tropical disease Gambian human African trypanosomiasis in late stage. This...
The polyamine synthesis inhibitor eflornithine is a recommended treatment for the neglected tropical disease Gambian human African trypanosomiasis in late stage. This parasitic disease, transmitted by the tsetse fly, is lethal unless treated. Eflornithine is administered by repeated intravenous infusions as a racemic mixture of L-eflornithine and D-eflornithine. The study compared the in vitro antitrypanosomal activity of the two enantiomers with the racemic mixture against three Trypanosoma brucei gambiense strains. Antitrypanosomal in vitro activity at varying drug concentrations was analysed by non-linear mixed effects modelling. For all three strains, L-eflornithine was more potent than D-eflornithine. Estimated 50% inhibitory concentrations of the three strains combined were 9.1 μM (95% confidence interval [8.1; 10]), 5.5 μM [4.5; 6.6], and 50 μM [42; 57] for racemic eflornithine, L-eflornithine and D-eflornithine, respectively. The higher in vitro potency of L-eflornithine warrants further studies to assess its potential for improving the treatment of late-stage Gambian human African trypanosomiasis.
Topics: Eflornithine; Humans; Trypanocidal Agents; Trypanosoma brucei gambiense
PubMed: 34252098
DOI: 10.1371/journal.pntd.0009583 -
Skin Therapy LetterTwenty-two percent of women in North America have unwanted facial hair, which can cause embarrassment and result in a significant emotional burden. Treatment options... (Review)
Review
Twenty-two percent of women in North America have unwanted facial hair, which can cause embarrassment and result in a significant emotional burden. Treatment options include plucking, waxing (including the sugar forms), depilatories, bleaching, shaving, electrolysis, laser, intense pulsed light (IPL), and eflornithine 13.9% cream (Vaniqa, Barrier Therapeutics in Canada and Shire Pharmaceuticals elsewhere). Eflornithine 13.9% cream is a topical treatment that does not remove the hairs, but acts to reduce the rate of growth and appears to be effective for unwanted facial hair on the mustache and chin area. Eflornithine 13.9% cream can be used in combination with other treatments such as lasers and IPL to give the patient the best chance for successful hair removal.
Topics: Administration, Topical; Eflornithine; Enzyme Inhibitors; Face; Female; Hair Removal; Hirsutism; Humans; Polycystic Ovary Syndrome
PubMed: 16408139
DOI: No ID Found -
The Cochrane Database of Systematic... Jun 2013Human African trypanosomiasis, or sleeping sickness, is a painful and protracted disease affecting people in the poorest parts of Africa and is fatal without treatment.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Human African trypanosomiasis, or sleeping sickness, is a painful and protracted disease affecting people in the poorest parts of Africa and is fatal without treatment. Few drugs are currently available for second-stage sleeping sickness, with considerable adverse events and variable efficacy.
OBJECTIVES
To evaluate the effectiveness and safety of drugs for treating second-stage human African trypanosomiasis.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register (January 2013), CENTRAL (The Cochrane Library Issue 12 2012) , MEDLINE (1966 to January 2013), EMBASE (1974 to January 2013), LILACS (1982 to January 2013 ), BIOSIS (1926-January 2013), mRCT (January 2013) and reference lists. We contacted researchers working in the field and organizations.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials including adults and children with second-stage HAT, treated with anti-trypanosomal drugs.
DATA COLLECTION AND ANALYSIS
Two authors (VL and AK) extracted data and assessed methodological quality; a third author (JS) acted as an arbitrator. Included trials only reported dichotomous outcomes, and we present these as risk ratio (RR) with 95% confidence intervals (CI).
MAIN RESULTS
Nine trials with 2577 participants, all with Trypansoma brucei gambiense HAT, were included. Seven trials tested currently available drugs: melarsoprol, eflornithine, nifurtimox, alone or in combination; one trial tested pentamidine, and one trial assessed the addition of prednisolone to melarsoprol. The frequency of death and number of adverse events were similar between patients treated with fixed 10-day regimens of melarsoprol or 26-days regimens. Melarsoprol monotherapy gave fewer relapses than pentamidine or nifurtimox, but resulted in more adverse events.Later trials evaluate nifurtimox combined with eflornithine (NECT), showing this gives few relapses and is well tolerated. It also has practical advantages in reducing the frequency and number of eflornithine slow infusions to twice a day, thus easing the burden on health personnel and patients.
AUTHORS' CONCLUSIONS
Choice of therapy for second stage Gambiense HAT will continue to be determined by what is locally available, but eflornithine and NECT are likely to replace melarsoprol, with careful parasite resistance monitoring. We need research on reducing adverse effects of currently used drugs, testing different regimens, and experimental and clinical studies of new compounds, effective for both stages of the disease.
Topics: Animals; Antiprotozoal Agents; Drug Therapy, Combination; Eflornithine; Humans; Melarsoprol; Nifurtimox; Pentamidine; Prednisolone; Randomized Controlled Trials as Topic; Recurrence; Trypanosoma brucei gambiense; Trypanosomiasis, African
PubMed: 23807762
DOI: 10.1002/14651858.CD006201.pub3 -
CNS Oncology Apr 2018This review covers the literature between 1989 and 2007 on studies relevant to the neuro-oncology usage of eflornithine (α-difluoromethylornithine), an oral agent that... (Review)
Review
This review covers the literature between 1989 and 2007 on studies relevant to the neuro-oncology usage of eflornithine (α-difluoromethylornithine), an oral agent that irreversibly inhibits the enzyme ornithine decarboxylase. It covers the use of eflornithine, alone or in combination, to treat high-grade gliomas. In addition, we provide an update on overall survival from The University of Texas MD Anderson Cancer Center Community Clinical Oncology Program and Clinical Trials Data Office that demonstrates a meaningful benefit in overall survival for eflornithine as a single agent and in combination with nitrosourea-based therapies for anaplastic gliomas. We also provide a framework for understanding the basis and study design of the ongoing pivotal, registrational Phase III multicenter trial for recurrent/progressive anaplastic astrocytoma.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Clinical Trials as Topic; Eflornithine; Glioma; Humans
PubMed: 29378419
DOI: 10.2217/cns-2017-0031 -
Cancer Medicine May 2024Most high-risk neuroblastoma patients who relapse succumb to disease despite the existing therapy. We recently reported increased event-free and overall survival in...
BACKGROUND
Most high-risk neuroblastoma patients who relapse succumb to disease despite the existing therapy. We recently reported increased event-free and overall survival in neuroblastoma patients receiving difluoromethylornithine (DFMO) during maintenance therapy. The effect of DFMO on cellular processes associated with neuroblastoma tumorigenesis needs further elucidation. Previous studies have shown cytotoxicity with IC50 values >5-15 mM, these doses are physiologically unattainable in patients, prompting further mechanistic studies at therapeutic doses.
METHODS
We characterized the effect of DFMO on cell viability, cell cycle, apoptosis, neurosphere formation, and protein expression in vitro using five established neuroblastoma cell lines (BE2C, CHLA-90, SHSY5Y, SMS-KCNR, and NGP) at clinically relevant doses of 0, 50, 100, 500, 1000, and 2500 μM. Limiting Dilution studies of tumor formation in murine models were performed. Statistical analysis was done using GraphPad and the level of significance set at p = 0.05.
RESULTS
There was not a significant loss of cell viability or gain of apoptotic activity in the in vitro assays (p > 0.05). DFMO treatment initiated G1 to S phase cell cycle arrest. There was a dose-dependent decrease in frequency and size of neurospheres and a dose-dependent increase in beta-galactosidase activity in all cell lines. Tumor formation was decreased in xenografts both with DFMO-pretreated cells and in mice treated with DFMO.
CONCLUSION
DFMO treatment is cytostatic at physiologically relevant doses and inhibits tumor initiation and progression in mice. This study suggests that DFMO, inhibits neuroblastoma by targeting cellular processes integral to neuroblastoma tumorigenesis at clinically relevant doses.
Topics: Neuroblastoma; Humans; Animals; Cell Line, Tumor; Mice; Apoptosis; Eflornithine; Xenograft Model Antitumor Assays; Cell Survival; Carcinogenesis; Cell Cycle; Cell Proliferation; Antineoplastic Agents; Female
PubMed: 38686627
DOI: 10.1002/cam4.7207