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Medicines, Volume 10, Issue 7 (July 2023) – 7 articles

Cover Story (view full-size image): Many anti-cancer drugs cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. Since two 3-styrylchromone derivatives (A and B) showed much higher anti-cancer activity against human oral squamous cell carcinoma (OSCC) cell lines than hundreds of polyphenols and chromone-related compounds, their side effects were investigated. As compared with doxorubicin, 5-FU, cisplatin and docetaxel, A/B showed lower cytotoxicity against human gingival epithelial progenitor. Cytotoxicity against OSCC was detected at the concentrations that do not affect the viability of neuronal cells. The potential inhibition of estrogen-related receptor signaling pathways suggests possible applications to hormone-dependent cancer. View this paper
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11 pages, 579 KiB  
Article
Intermittent Proton Pump Inhibitor Therapy in Low-Risk Non-Variceal Upper Gastrointestinal Bleeding May Be Significantly Cost-Saving
by Yang Lei, Jennifer Halasz, Kerri L. Novak and Stephen E. Congly
Medicines 2023, 10(7), 44; https://doi.org/10.3390/medicines10070044 - 20 Jul 2023
Viewed by 1460
Abstract
Background: High-dose proton pump inhibitor (PPI) therapy, given either intermittently or continuously for non-variceal upper gastrointestinal bleeding (NV-UGIB), is efficacious. Using intermittent PPI for low-risk patients may be cost-saving. Our objective was to estimate the annual cost savings if all low-risk NV-UGIB patients [...] Read more.
Background: High-dose proton pump inhibitor (PPI) therapy, given either intermittently or continuously for non-variceal upper gastrointestinal bleeding (NV-UGIB), is efficacious. Using intermittent PPI for low-risk patients may be cost-saving. Our objective was to estimate the annual cost savings if all low-risk NV-UGIB patients received intermittent PPI therapy. Methods: Patients who presented to hospital in Calgary, Alberta, who received a PPI for NV-UGIB from July 2015 to March 2017 were identified using ICD-10 codes. Patients were stratified into no endoscopy, high-risk, and low-risk lesion groups and further subdivided into no PPI, oral PPI, intermittent intravenous (IV), and continuous IV subgroups. Average length of stay (LOS) in each subgroup and costs were calculated. Results: We identified 4141 patients with NV-UGIBs, (median age 61, 57.4% male). One-thousand two-hundred and thirty-one low-risk patients received continuous IV PPI, with an average LOS of 6.8 days (95% CI 6.2–7.3) versus 4.9 days (95% CI 3.9–5.9) for intermittent IV patients. If continuous IV PPI patients instead received intermittent IV PPI, 3852 patient days and CAD 11,714,390 (2017 CAD)/year could be saved. Conclusions: Using real-world administrative data, we demonstrate that a sizable portion of low-risk patients with NV-UGIB who were given continuous IV PPI if switched to intermittent IV therapy could generate significant potential cost savings. Full article
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14 pages, 4913 KiB  
Article
A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs
by Tomoyuki Abe, Hiroshi Sakagami, Shigeru Amano, Shin Uota, Kenjiro Bandow, Yoshihiro Uesawa, Shiori U, Hiroki Shibata, Yuri Takemura, Yu Kimura, Koichi Takao, Yoshiaki Sugita, Akira Sato, Sei-ichi Tanuma and Hiroshi Takeshima
Medicines 2023, 10(7), 43; https://doi.org/10.3390/medicines10070043 - 14 Jul 2023
Cited by 2 | Viewed by 1252
Abstract
Background. Many anti-cancer drugs used in clinical practice cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that two 3-styrylchromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (Compound A) and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one (Compound B), [...] Read more.
Background. Many anti-cancer drugs used in clinical practice cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that two 3-styrylchromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (Compound A) and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one (Compound B), showed the highest tumor-specificity against human oral squamous cell carcinoma (OSCC) cell lines among 291 related compounds. After confirming their superiority by comparing their tumor specificity with newly synthesized 65 derivatives, we investigated the neurotoxicity of these compounds in comparison with four popular anti-cancer drugs. Methods: Tumor-specificity (TSM, TSE, TSN) was evaluated as the ratio of mean CC50 for human normal oral mesenchymal (gingival fibroblast, pulp cell), oral epithelial cells (gingival epithelial progenitor), and neuronal cells (PC-12, SH-SY5Y, LY-PPB6, differentiated PC-12) to OSCC cells (Ca9-22, HSC-2), respectively. Results: Compounds A and B showed one order of magnitude higher TSM than newly synthesized derivatives, confirming its prominent tumor-specificity. Docetaxel showed one order of magnitude higher TSM, but two orders of magnitude lower TSE than Compounds A and B. Compounds A and B showed higher TSM, TSE, and TSN values than doxorubicin, 5-FU, and cisplatin, damaging OSCC cells at concentrations that do not affect the viability of normal epithelial and neuronal cells. QSAR prediction based on the Tox21 database suggested that Compounds A and B may inhibit the signaling pathway of estrogen-related receptors. Full article
(This article belongs to the Section New Drugs Exploration and Development)
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8 pages, 557 KiB  
Case Report
Longitudinal Changes in Motor Estimation Error and Motor Function in Patients with Parkinson’s Disease: A Case Report
by Katsuya Sakai, Tsubasa Kawasaki, Hiroya Kiminarita and Yumi Ikeda
Medicines 2023, 10(7), 42; https://doi.org/10.3390/medicines10070042 - 06 Jul 2023
Viewed by 1114
Abstract
Background and Objectives: This report described two cases with clear longitudinal changes in motor estimation error (difference between the motor imagery and motor execution) and their progression and motor and activities of daily living (ADL) function changes in patients with PD. Materials and [...] Read more.
Background and Objectives: This report described two cases with clear longitudinal changes in motor estimation error (difference between the motor imagery and motor execution) and their progression and motor and activities of daily living (ADL) function changes in patients with PD. Materials and Methods: Patient 1 was a 68-year-old man (Hoehn and Yahr [H and Y] stage: IV, diagnosed with PD for 11.8 years) and patient 2 was a 68-year-old woman (H and Y stage: II, diagnosed with PD for 9.6 years). Imagined two-step test (iTST), two-step test (TST), and PD-related assessments (Unified Parkinson’s Disease Rating Scale [UPDRS], and Freezing of Gait Questionnaire [FOGQ]) were assessed at baseline and after 6 months. Motor estimation error was calculated as the iTST distance minus TST distance. Results: In patient 1, motor estimation error was greater after 6 months (baseline: 5.7 [4.8%]/after 6 months: 25.7 cm [26.1%]). Moreover, UPDRS and FOGQ total scores deteriorated after 6 months (UPDRS total: 29/34 point, and FOGQ: 9/16 point). Conversely, in patient 2, motor estimation error did not change notably (−3.6 [7.6%]/−2.5 cm [7.0%]), while UPDRS and FOGQ total scores improved after 6 months (UPDRS total: 17/12 point, and FOGQ: 6/1 point). Conclusions: This report indicated that greater motor estimation error may be associated with declining motor and ADL function and disease progression in patients with PD. Full article
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8 pages, 525 KiB  
Article
Vitamin D Levels in Patients with Active and Remission Graves’ Disease
by Natapon Rattanamusik, Suriyon Uitrakul and Atchara Charoenpiriya
Medicines 2023, 10(7), 41; https://doi.org/10.3390/medicines10070041 - 06 Jul 2023
Viewed by 1294
Abstract
Background: The association between Graves’ disease (GD) and serum vitamin D levels has been studied for decades although the results were controversial. Moreover, the difference in vitamin D levels between the different stages of GD is not well studied. Therefore, this study aimed [...] Read more.
Background: The association between Graves’ disease (GD) and serum vitamin D levels has been studied for decades although the results were controversial. Moreover, the difference in vitamin D levels between the different stages of GD is not well studied. Therefore, this study aimed to compare the vitamin D levels between active and remission GD and to investigate the factors affecting vitamin D levels in GD patients. Methods: This cross-sectional study was performed between 1 January to 31 December 2021. The eligible patients were in either the active or remission stage of GD. The demographic and clinical data of the patients willing to participate in the study were collected, as well as their vitamin D levels. Comparisons of continuous parameters between the active and remission groups were performed using the Mann–Whitney U test, while categorical parameters were performed using the Chi-square test. Results: 75 patients were diagnosed with GD, with 54.7% in the active stage. The mean vitamin D level was lower in the active GD group than in the remission GD group (28.23 vs. 31.58 ng/mL, respectively, p-value 0.079). The prevalence of vitamin D deficiency (i.e., serum vitamin D level < 20 ng/mL) in the active GD group was 14.6%, and in the remission GD group was 0% (p-value 0.02). Moreover, there was a significant negative correlation between the serum vitamin D level and serum free T4 level (p-value 0.03). Conclusions: In spite of non-significance, patients with active GD had lower mean vitamin D levels compared to those with remission GD. The prevalence of vitamin D deficiency was significantly higher in the active GD patients. Additionally, a negative correlation between serum vitamin D levels and serum free T4 levels was observed in this study. Full article
(This article belongs to the Section Endocrinology and Metabolic Disorders)
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9 pages, 786 KiB  
Brief Report
Multichannel Recovery Potential with Activated Autologous Intraovarian Platelet-Rich Plasma and Its Derivatives
by E. Scott Sills and Samuel H. Wood
Medicines 2023, 10(7), 40; https://doi.org/10.3390/medicines10070040 - 03 Jul 2023
Viewed by 1340
Abstract
Platelet-rich plasma (PRP) is an ‘orthobiologic’ with recognized roles in plastic surgery, musculoskeletal disorders, dentistry, dermatology, and more recently, ‘ovarian rejuvenation’. Intraovarian PRP involves a complex secretome discharged after platelet activation, comprising multiple cytokine mediators delivered surgically to older or inactive ovarian tissue. [...] Read more.
Platelet-rich plasma (PRP) is an ‘orthobiologic’ with recognized roles in plastic surgery, musculoskeletal disorders, dentistry, dermatology, and more recently, ‘ovarian rejuvenation’. Intraovarian PRP involves a complex secretome discharged after platelet activation, comprising multiple cytokine mediators delivered surgically to older or inactive ovarian tissue. Loss of oocyte meiotic fidelity and impaired fertilization accompanying advanced maternal age are already managed by IVF, but only with eggs provided by younger donors. However, if the observed effect of rectifying embryo ploidy error can be proven beyond case reports and small series, activated PRP (or its condensed plasma cytokines) would deliver a welcome therapeutic disruption that is difficult to overstate. Because shortcomings in ovarian function are presently addressed mainly by pharmacological approaches (i.e., via recombinant gonadotropins, GnRH analogs, or luteal support), autologous PRP would represent an unusual departure from these interventions. Given the diversity of platelet cargo proteins, the target response of intraovarian PRP is probably not confined to oocytes or follicles. For example, PRP manipulates signal networks driving improved perfusion, HOX regulation, N-glycan post-translational modification, adjustment of voltage-gated ion channels, telomere stabilization, optimization of SIRT3, and ribosome and mitochondria recovery in older oocytes. While multichannel signals operating on various pathways are not unique to reproductive biology, in intraovarian PRP this feature has received little study and may help explain why its standardization has been difficult. Against this background, our report examines the research themes considered most likely to shape clinical practice. Full article
(This article belongs to the Section Stem Cell Investigation and Regenerative Medicine)
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12 pages, 873 KiB  
Article
Antimicrobial Prescribing Preparedness of Croatian Medical Students—Did It Change between 2015 and 2019?
by Dora Palčevski, Andrej Belančić, Ivan Mikuličić, Eduard Oštarijaš, Robert Likić, Oliver Dyar and Vera Vlahović-Palčevski
Medicines 2023, 10(7), 39; https://doi.org/10.3390/medicines10070039 - 29 Jun 2023
Cited by 1 | Viewed by 878
Abstract
Background: Antimicrobials are some of the most prescribed drugs by junior doctors, but studies suggest most medical graduates feel unprepared for their future prescribing tasks. The aim of the present study was to compare the self-reported preparedness to prudently prescribe antimicrobials of final-year [...] Read more.
Background: Antimicrobials are some of the most prescribed drugs by junior doctors, but studies suggest most medical graduates feel unprepared for their future prescribing tasks. The aim of the present study was to compare the self-reported preparedness to prudently prescribe antimicrobials of final-year medical students in Croatia in 2015 and 2019. Methods: The same self-reported web-based survey on the preparedness to prescribe antibiotics was used in both 2015 and 2019. All final-year students at all four medical schools in Croatia (Osijek, Rijeka, Split, and Zagreb) were invited to participate in both 2015 and 2019. Preparedness scores were divided into “topic preparedness scores” and “global preparedness scores”. Topic preparedness scores represented the percentage of students at a medical school who felt sufficiently prepared for each topic. They were first established at a medical school level and then at the national level. Global preparedness scores were determined for each student separately and then calculated at the medical school and national levels. Results: The country’s global preparedness score, representing the average proportion of topics in which students felt sufficiently prepared, was slightly higher in 2015 compared with the 2019 results (62.7% vs. 56.5%; p = 0.191). Croatian students reported higher preparedness in 2015 than in 2019 for 25 out of 27 topics included in the survey. The majority of students reported a need for more education on antibiotic use both in 2015 and 2019 (78.0% vs. 83.0%; p = 0.199). Conclusions: Despite increasing antimicrobial stewardship activities in various healthcare settings, medical students who are about to start prescribing antibiotics on their own do not feel sufficiently prepared to do so. Antimicrobial stewardship programs should be designed to incorporate undergraduate medical student education, for instance, as a specific, mandatory course or integrated into other courses, such as clinical pharmacology. Full article
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11 pages, 992 KiB  
Article
Health-Seeking Behavior Regarding Coughs in Urban Slums in Lagos, Nigeria
by Victor Abiola Adepoju, Olanrewaju Oladimeji and Olusola Daniel Sokoya
Medicines 2023, 10(7), 38; https://doi.org/10.3390/medicines10070038 - 26 Jun 2023
Viewed by 1003
Abstract
Background: TB is a major cause of morbidity and mortality, with slum residents being disproportionately affected. This study aimed to assess health-seeking behavior among adult residents of slum communities presenting with coughs in Lagos, Nigeria. Methods: A community-based, cross-sectional study was conducted across [...] Read more.
Background: TB is a major cause of morbidity and mortality, with slum residents being disproportionately affected. This study aimed to assess health-seeking behavior among adult residents of slum communities presenting with coughs in Lagos, Nigeria. Methods: A community-based, cross-sectional study was conducted across six urban slums in Nigeria as part of community outreaches to mark World TB Day. A structured, pretested questionnaire was used to capture relevant sociodemographic details and questions regarding symptoms of coughs and related symptoms as well as care-seeking behavior. Data were explored, analyzed, and presented using descriptive statistics. Results: A total of 632 respondents participated in this study. The majority were 25–34 years old (24.7%), male (65.8%), Christian (55.7%), married (73.7%), with secondary education (37.8%), with 3–4 persons per household (41%) and with 1–2 persons per room (44.5%). In total, 26.6% had had a cough for two weeks or more and were considered as presumptive TB patients. Overall, 37.2% of respondents with a cough visited patent proprietary medicine vendors (PPMVs) as the first port of call. Good health-seeking behavior was exhibited by only 36.2% of respondents. In total, 38.9% delayed seeking care from a health facility (government or private) more than one month after the onset of symptoms. None of the factors included in the multivariate analysis showed a significant association with good health-seeking behavior (i.e., visiting government or private hospitals/clinics). Conclusions: The poor health-seeking behavior, delay in seeking TB care and preference for PPMVs emphasizes the need for National tuberculosis programs (NTPs) to further engage these informal providers in TB prevention, diagnosis and treatment services in urban slum communities. Full article
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