Kyosuke Nagura, Satoko Watanabe, Taro Watanabe
et al.
IntroductionOveractive bladder (OAB) drugs are widely prescribed, yet the occurrence of atrial fibrillation (AF) after treatment initiation remains poorly characterized.MethodsWe evaluated reports of AF associated with OAB medications using two spontaneous reporting systems (SRSs): the Japanese Adverse Drug Event Report (JADER) database and the U.S. FDA Adverse Event Reporting System (FAERS). We screened eight agents and assessed signals using three disproportionality metrics: the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN). For drugs showing signals in both databases, we conducted stratified analyses by sex, age, and number of concomitant medications, and evaluated time-to-onset (TTO) using Weibull modeling.ResultsConsistent AF signals were identified for solifenacin succinate and mirabegron, whereas other agents did not meet the prespecified criteria. Solifenacin met the criteria in women and older adults in both JADER and FAERS. Mirabegron met the criteria across multiple strata in both datasets, indicating cross-stratum reproducibility. TTO was right‐skewed, with most reports occurring within one year of initiation. Exploratory Weibull modeling, based on limited numbers of date‐complete reports, suggested a wear-out pattern for solifenacin in JADER and an early pattern in FAERS, while mirabegron showed a random pattern in JADER and an early pattern in FAERS. These failure‐type patterns should therefore be interpreted cautiously.DiscussionThese findings are hypothesis-generating, given the limitations of SRSs, such as underreporting, missing dates, and unknown exposure—and they reflect reporting patterns rather than causal risk. They outline strata and early treatment periods that may warrant clinical attention and help prioritize pharmacovigilance and targeted hypothesis‐driven evaluation in routine OAB care.
Julia Keller, Pascale Plaisancié, Edwin Fouché
et al.
Objective: Colorectal cancer is a major public health issue for which dietary factors such as red and processed meat consumption seem to play a prominent role. Heme iron, which is present in important concentration in those food products, was reported to play a role in colorectal cancer promotion in animal studies. However, its role in colorectal cancer initiation remains to be established. Methods: Male Fischer 344 rats were given experimental diets (control diet, ferric citrate-supplemented diet or hemin-supplemented diet) for 2 weeks before being initiated for colon cancer with azoxymethane. Rats were then fed a control diet for 8 weeks. Preneoplastic lesions, lipid peroxidation, genotoxicity and oxidative stress markers, together with gut microbiota, were analyzed. Results: Heme iron, given in the rat diet for only 2 weeks before the colorectal cancer initiating event, increased two types of preneoplastic lesions in the rat colon, namely aberrant crypt foci and mucin-depleted foci, when compared to a control diet containing the same amount of iron in a non-heminic form. This heme iron concentration in the diet, representative of human consumption, induced at the same time a huge increase in luminal lipid peroxidation, a significant increase in RNA/DNA oxidative damage and an increase in the expression of antioxidant defenses in colon mucosa, accompanied by epithelial cell proliferation together with a reduction in colon mucus cells, and a gut dysbiosis. Conclusion: These results, obtained in an animal model, suggest that iron, only in its heminic form, has a co-initiating effect on colorectal carcinogenesis.
BackgroundDrug repurposing has emerged as a promising approach for discovering novel anticancer therapeutics. In this study, we systematically investigated the antitumor potential of fedratinib, a JAK2 inhibitor approved for myelofibrosis, against esophageal squamous cell carcinoma (ESCC) using integrated in vitro, in vivo, and patient-derived organoid (PDO) models. We further explored its underlying mechanisms of action.MethodsESCC cell lines (Eca109 and KYSE150) were treated with fedratinib to evaluate its effects on proliferation, migration, apoptosis, and cell cycle distribution. Molecular changes were examined using RT-qPCR and Western blot analyses. Antitumor efficacy was further validated in subcutaneous xenograft models and ESCC PDOs. Mechanistic investigations included STAT3 overexpression and functional rescue experiments.ResultsFedratinib significantly inhibited ESCC cell proliferation and migration and induced cell cycle arrest at the G2/M phase while promoting apoptosis in vitro. It also suppressed tumor growth in xenograft models and showed consistent efficacy in PDOs. Mechanistically, fedratinib inhibited the activation of the JAK2/STAT3 signaling pathway and downregulated the expression of vimentin, survivin, and cyclin D1. Overexpression of STAT3 reversed these molecular alterations and diminished the functional effects of fedratinib. Similarly, ectopic expression of survivin, vimentin, or cyclin D1 partially rescued the phenotypic changes induced by fedratinib.ConclusionFedratinib exerts antitumor effects against ESCC in vitro, in vivo, and in patient-derived organoid models by suppressing the JAK2–STAT3 signaling axis and its downstream effectors, vimentin, survivin, and cyclin D1.
Abstract Background Fatigue is a common complication of stroke that has a significant impact on quality of life. The biological mechanisms that underly post-stroke fatigue are currently unclear, however, reactivation of latent viruses and their impact on systemic immune function have been increasingly reported in other conditions where fatigue is a predominant symptom. Epstein-Barr virus (EBV) in particular has been associated with fatigue, including in long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome, but has not yet been explored within the context of stroke. Aims We performed an exploratory analysis to determine if there is evidence of a relationship between EBV reactivation and post-stroke fatigue. Methods In a chronic ischemic stroke cohort (> 5 months post-stroke), we assayed circulating EBV by qPCR and measured the titres of anti-EBV antibodies by ELISA in patients with high fatigue (FACIT-F < 40) and low fatigue (FACIT-F > 41). Statistical analysis between two-groups were performed by t-test when normally distributed according to the Shapiro-Wilk test, by Mann-Whitney test when the data was not normally distributed, and by Fisher’s exact test for categorical data. Results We observed a similar incidence of viral reactivation between people with low versus high levels of post-stroke fatigue (5 of 22 participants (24%) versus 6 of 22 participants (27%)). Although the amount of circulating EBV was similar, we observed an altered circulating anti-EBV antibody profile in participants with high fatigue, with reduced IgM against the Viral Capsid Antigen (2.244 ± 0.926 vs. 3.334 ± 2.68; P = 0.031). Total IgM levels were not different between groups indicating this effect was specific to anti-EBV antibodies (3.23 × 105 ± 4.44 × 104 high fatigue versus 4.60 × 105 ± 9.28 × 104 low fatigue; P = 0.288). Conclusions These data indicate that EBV is not more prone to reactivation during chronic stroke recovery in those with post-stroke fatigue. However, the dysregulated antibody response to EBV may be suggestive of viral reactivation at an earlier stage after stroke.
The consumption of seafood is crucial for food security, but poor hygiene along the food production chain can result in low microbiological quality, posing significant risks for public health and seafood quality. Thus, this study aimed to assess the microbiological quality and antimicrobial sensitivity of <i>E. coli</i> from 69 samples of illegally marketed shrimp and mussels in the Vitória Region, Brazil. These foods exhibited poor microbiological quality due to high counts of mesophilic, psychrotrophic, and enterobacteria microorganisms. While this issue is widespread in this area, shrimp samples displayed higher microbial counts compared to mussels, and fresh mussels had elevated counts of enterobacteria compared to frozen ones. Among the 10 <i>E. coli</i> isolates, none carried the genes <i>blaCTX-M-1</i>, <i>blaCTX-M-2</i>, <i>blaCTX-M-3</i>, <i>blaCTX-M-15</i>, <i>mcr-1</i>, <i>mcr-2</i>, <i>mcr-3</i>, <i>mcr-4</i>, and <i>tet</i>, associated with antibiotic resistance. Phenotypical resistance to tetracycline and fosfomycin was not observed in any isolate, while only 20% demonstrated resistance to ciprofloxacin. Regarding ampicillin and amoxicillin with clavulanic acid, 60% of isolates were resistant, 10% showed intermediate susceptibility, and 30% were sensitive. One isolate was considered simultaneously resistant to β-lactams and quinolones, and none were conserved as ESBL producers. These findings highlight the inherent risks to local public health that arise from consuming improperly prepared seafood in this area.
Rutger Osterthun, Katharina Sunnerhagen, Henk J. Stam
et al.
Objective: As Physical and Rehabilitation Medicine physicians are experts in functional prognoses of disabling health conditions, the aim of this study was to gain insight into their involvement in end-of-life decisions in patients with neurological or terminal diseases in European countries.
Design: Exploratory cross-sectional survey.
Subjects: Delegates of the Union of European Medical Specialists, Physical and Rehabilitation Medicine Section.
Methods: In July 2020, a self-constructed survey was sent to 82 delegates from 38 European countries, who were asked to answer from the point of view of their country. Topics included the legal status of end-of-life decisions and the involvement of Physical and
Rehabilitation Medicine physicians in these decisions.
Results: Between July 2020 and December 2020, 32 delegates from 28 countries completed the survey (response rate country level of 74%). If legal frameworks allow for these specific end-of-life decisions, involvement of Physical and Rehabilitation Medicine physicians was reported in 2 of 3 countries in euthanasia cases, 10 of 17 countries in non-treatment decision cases, and 13 of 16 countries in cases of intensified symptom management by the administration of drugs using potentially life-shortening doses.
Conclusion: Estimated involvement of Physical and Rehabilitation Medicine physicians in end-of-life decisions varied between European countries, even when legal frameworks allow for these decisions.
LAY ABSTRACT
End-of-life considerations may arise after severe disabling health conditions and lead to end-of-life decisions. As Physical and Rehabilitation Medicine physicians are experts in functional prognosis for patients with these health conditions, their expertise could be of value to consider in these decisions. Legal frameworks and attitudes towards end-of-life decisions differ between European countries. However, there is a lack of information on the involvement of Physical and Rehabilitation Medicine physicians in these decisions. Therefore, delegates of Physical and Rehabilitation Medicine physicians in European countries were surveyed on the legal status of end-of-life decisions and the involvement of Physical and Rehabilitation Medicine physicians. The responses of delegates from 28 countries suggested differences in involvement of Physical and Rehabilitation Medicine physicians in end-of-life decisions between European countries, even between countries with a legal status of these end-of-life decisions. In the light of the ageing population and a general tendency toward more liberal attitudes concerning end-of-life decisions in Europe, these findings could be of interest in order to optimize end-of-life care in the coming years.
Joseph A Boscarino,1 Richard E Adams,2 Thomas G Urosevich,3 Stuart N Hoffman,4 H Lester Kirchner,1 Xin Chu,5 Weixing Shi,5 Joseph J Boscarino,6 Ryan J Dugan,1 Carrie A Withey,1 Charles R Figley7 1Department Population Health Sciences, Geisinger Clinic, Danville, PA, 17822, USA; 2Department Sociology, Kent State University, Kent, OH, 44242, USA; 3Ophthalmology Service, Geisinger Clinic, Mount Pocono, PA, 18344, USA; 4Department Sleep Medicine, Geisinger Clinic, Danville, PA, 17822, USA; 5Obesity Institute, Geisinger Clinic, Danville, PA, 17822, USA; 6Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, STC 7, Tampa, FL, 33606, USA; 7School of Social Work, Tulane University, New Orleans, LA, 70112, USACorrespondence: Joseph A BoscarinoDepartment Population Health Sciences, Geisinger Clinic, 100 N. Academy Ave., 44-00, Danville, PA, 17822, USATel +1 570-214-9825Email joseph.boscarino@gmail.comIntroduction: Since veteran suicide is a concern and our knowledge of predictive factors is still limited, our objective was to assess risk factors for suicide, including genetic factors, among deployed veterans.Methods: For this study, we surveyed 1730 veterans who were outpatients in a multi-hospital system in Pennsylvania. Altogether, 1041 veterans (60%) provided a DNA sample. The genetic risk variants investigated were within loci previously associated with PTSD and substance misuse, including CRHR1, CHRNA5, RORA, and FKBP5 genetic variations, which were used to calculate a polygenic risk score (range=0– 8, mean=3.6, SD=1.4).Results: Most veterans (56.2%) were deployed to Vietnam while significant numbers were deployed to Iraq, Afghanistan, and other post-Vietnam conflicts. Overall, 95.1% of the veterans were male, their mean age was 56.2 (SD=12), and 95.6% were Caucasian. Among the veterans, 24% had high combat exposure. The prevalence of lifetime suicidal thoughts was 11.3%. Additionally, 5.7% ever developed a suicide plan or attempted suicide in their lifetimes. Among those with a history of a lifetime suicide attempt or suicide plan, the PTSD genetic risk score was significantly higher (OR=3.96 vs 3.55, p=0.033), but for suicidal thoughts, this association was not significant (p=0.717). In multivariable analysis (MVA) logistic regression, significant predictors of attempting suicide or having a suicide plan were history of depression (OR=5.04, p< 0.001), PTSD genetic risk score (OR=1.25, p=0.036), history of childhood abuse/neglect (OR=2.24, p=0.009), and lifetime marijuana use (OR= 1.56, p=0.020). Conversely, rural residence was protective for suicide risk (OR=0.49; p=0.031). For suicidal thoughts, in the MVA genetic risk score was not significant (p=0.697), but history of child abuse/neglect (p< 0.001), history of depression (p> 0.001), low psychological resilience (p=0.004), and lifetime marijuana use (p=0.022) were significant.Discussion: In this study, we identified genetic risk variants and other predictors for suicide among veterans that may have implications for future screening and clinical care. Further research is advised.Keywords: veterans, warzone deployment, suicide, genetic factors, patient screening, precision medicine
Jose Angel García-Merino, Beatriz de Lucas, Karen Herrera-Rocha
et al.
The potential role of cocoa supplementation in an exercise context remains unclear. We describe the effects of flavanol-rich cocoa supplementation during training on exercise performance and mitochondrial biogenesis. Forty-two male endurance athletes at the beginning of the training season received either 5 g of cocoa (425 mg of flavanols) or maltodextrin (control) daily for 10 weeks. Two different doses of cocoa (equivalent to 5 g and 15 g per day of cocoa for a 70 kg person) were tested in a mouse exercise training study. In the athletes, while both groups had improved exercise performance, the maximal aerobic speed increased only in the control group. A mitochondrial DNA analysis revealed that the control group responded to training by increasing the mitochondrial load whereas the cocoa group showed no increase. Oxidative stress was lower in the cocoa group than in the control group, together with lower interleukin-6 levels. In the muscle of mice receiving cocoa, we corroborated an inhibition of mitochondrial biogenesis, which might be mediated by the decrease in the expression of nuclear factor erythroid-2-related factor 2. Our study shows that supplementation with flavanol-rich cocoa during the training period inhibits mitochondrial biogenesis adaptation through the inhibition of reactive oxygen species generation without impacting exercise performance.
Andre Luis Dias Araujo Mazzari, Mariella Guimarães Lacerda, Flora Aparecida Milton
et al.
Many medicinal plants species from European -such as Artemisia absinthium, Equisetum arvense, Lamium album, Malva sylvestris, Morus nigra, Passiflora incarnata, Frangula purshiana, and Salix alba- as well as Latin American traditions -such as Libidibia ferrea, Bidens pilosa, Casearia sylvestris, Costus spicatus, Monteverdia ilicifolia, Persea americana, Schinus terebinthifolia, Solidago chilensis, Syzygium cumini, Handroanthus impetiginosus, and Vernonanthura phosphorica- are shortlisted by the Brazilian National Health System for future clinical use. However, they lack many data on their action upon some key ADME targets. In this study, we assess non-toxic concentrations (up to100 μg/ml) of their infusions for in vitro ability to modulate CYP3A4 mRNA gene expression and intracellular glutathione levels in HepG2 cells, as well as P-glycoprotein (P-gp) activity in vincristine-resistant Caco-2 cells (Caco-2 VCR). We further investigated the activation of human pregnane X receptor (hPXR) in transiently co-transfected HeLa cells and the inhibition of Gamma-glutamyl transferase (GGT) in HepG2 cells. Our results demonstrate L. ferrea, C. sylvestris, M. ilicifolia, P. americana, S. terebinthifolia, S. cumini, V. phosphorica, E. arvense, P. incarnata, F. purshiana, and S. alba can significantly increase CYP3A4 mRNA gene expression in HepG2 cells. Only F. purshiana shown to do so likely via hPXR activation. P-gp activity was affected by L. ferrea, F. purshiana, S. terebinthifolia, and S. cumini. Total intracellular glutathione levels were significantly depleted by exposure to all extracts except S. alba and S. cumini This was accompanied by a lower GGT activity in the case of C. spicatus, P. americana, S. alba, and S. terebinthifolia, whilst L. ferrea, P. incarnata and F. purshiana increased it. Surprisingly, S. cumini aqueous extract drastically decreased GGT activity (−48%, p < 0.01). In conclusion, this preclinical study shows that the administration of some of these herbal medicines causes in vitro disturbances to key drug metabolism mechanisms. We recommend active pharmacovigilance for Libidibia ferrea (Mart.) L. P. Queiroz, Frangula purshiana Cooper, Schinus terebinthifolia Raddi, and Salix alba L. which were able to alter all targets in our preclinical study.
The menopause-related decline in estrogen levels leads to an array of genital, sexual, and urinary symptoms collectively known as genitourinary syndrome of menopause. The constellation of symptoms associated with vulvar and vaginal atrophy (VVA) can have a profoundly detrimental effect on a woman’s sexual function, relationships, and quality of life. Ospemifene is a selective estrogen receptor modulator indicated for treatment of moderate-to-severe symptomatic VVA in postmenopausal women who are not candidates for local vaginal estrogen therapy or have contraindications for estrogen products. Ospemifene is administered orally, thus avoiding the inconveniences of local therapy, and can be used in women with VVA and a history of breast cancer after completing all (including adjuvant) breast cancer treatment. As well as restoring vaginal health in symptomatic VVA, ospemifene may have collateral benefits of importance to postmenopausal women. In this Special Issue entitled “Treatment of Vulvar and Vaginal Atrophy: Clinical Experience with Ospemifene,” illustrative case studies examine the experiences of women with VVA during treatment with ospemifene. Specific topics include the effects of ospemifene on bone markers; its use in breast cancer survivors and in women with dyslipidemia, urinary incontinence, or VVA-related sexual dysfunction; and its concomitant use with laser therapy.
S. H. Ubohov, V. V. Trokhymchuk, G. V. Zagoriy
et al.
One of the most promising ways to increase the efficiency of pharmaceutical enterprises in the field of quality assurance of medicines is the introduction of integrated quality systems (IQS).
The aim of the work is to study of the state of readiness of pharmaceutical institutions (pharmaceutical warehouses, pharmacies) and hospital pharmaceutical services of Ukraine for the implementation of integrated quality systems.
The materials of the research are: scientific publications; regulatory legal acts of the Ministry of Health of Ukraine; public reporting information of the State Service of Ukraine on Medicines and Drug Control; information posted on professional specialized websites and official websites of pharmaceutical enterprises, hospitals, health departments of local government; information obtained in the process of direct observation and questionnaire survey. Research methods are: systematic review, generalization, observation, questionnaire survey, mathematical-statistical, graphical modeling.
The paper analyzes the availability of certificates of conformity to the requirements of good distribution practice (GDP) in wholesale pharmaceutical enterprises of Ukraine. The geography of the location of certified pharmaceutical warehouses in different regions of Ukraine is considered. In the context of the prospect of formation of IQS, the experience of a wholesale pharmaceutical company with respect to environmental, hygiene and safety and social responsibility is demonstrated. Based on the study of public information, the state of implementation of certified quality management systems (QMS) based on the standard ISO 9001 in pharmacies and hospitals of Ukraine is considered. The expediency of the development of the pharmaceutical IQS as an integral part of the overall QMS of the hospital is shown. Through the questionnaire survey of pharmacists, the state of readiness of Ukrainian pharmacies for the implementation of IQS based on the requirements of good practices and international standards in the field of quality, ecology, health and safety and social responsibility was explored. The state of implementation of good pharmaceutical practice (GPP), the requirements of the ISO 9001 standard, the risk management process for medicines quality, corrective and preventive actions has been studied in pharmacies. Positive tendencies and problems in the context of the readiness of pharmacies of Ukraine for the implementation of IQS have been established. Priority steps for improving the state of readiness of Ukrainian pharmacies for the implementation of IQS are identified.
The research results confirm that over the last years the pharmaceutical sector of Ukraine has made significant progress towards increasing the readiness of pharmaceutical institutions for the implementation of integrated quality systems.
Therapeutics. Pharmacology, Pharmacy and materia medica
Ruijian Li,1–3,* Sumei Cui,1–3,* Youshun Xu,4 Junhui Xing,5 Li Xue,1–3 Yuguo Chen1–3 1Department of Emergency, Qilu Hospital, Shandong University, Jinan, China; 2Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Qilu Hospital, Shandong University, Jinan, China; 3Key Laboratory of Cardiovascular Remodeling & Function Research, Chinese Ministry of Education & Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China; 4Qilu Medical College of Shandong University, Jinan, China; 5Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China *These authors contributed equally to this work Background: The incidence of recurrent cardiovascular events from the progression of nontarget lesions (NTLs) is high for percutaneous coronary intervention-treated patients. However, the underlying mechanisms have not been thoroughly elucidated. Methods: In this study, ten atherosclerotic rabbits with multiple plaques in the upper and lower segments of abdominal aorta (group A) were randomly divided into two subgroups: group A1 underwent intravascular ultrasound examination and stent implantation in the lower segments of the abdominal aorta (n=5), whereas group A2 was without stenting (n=5). Group B was a control group without balloon injury. The serum levels of high-sensitivity CRP, interleukin-6 (IL-6), oxidized low-density lipoprotein, and CD36 were assessed via ELISA at five time points between the 10th and 18th weeks. The upper abdominal aorta was examined via the immunohistochemical stain and Western blotting of matrix metallopeptidase 9 (MMP-9), CD36, IL-6, and tumor necrosis factor α. Results: As a result, we found that stent implantation aggravated serum levels of CD36, oxidative stress, and inflammatory cytokines. Meanwhile, the upper abdominal arterial plaque burden significantly increased after stenting by intravascular ultrasound. Immunohistochemistry and Western blotting showed that the local NTLs’ matrix metallopeptidase 9, CD36, IL-6, and tumor necrosis factor α expressions in group A1 were significantly higher than those in groups A2 and B (P<0.05–0.01). More importantly, a strong correlation was identified between CD36 expression and NTLs’ plaque burden before the rabbits were killed. Conclusion: Taken together, stent implantation accelerated inflammation, induced oxidative stress, and increased the NTLs’ progression, which were associated with the upregulated CD36 expression. Keywords: inflammation, oxidative stress, CD36, atherosclerosis, stent
Context: The genus Premna (Lamiaceae), distributed throughout tropical and subtropical Asia, Africa, Australia and the Pacific Islands, is used in folk medicine primarily to treat inflammation, immune-related diseases, stomach disorders, wound healing, and skin diseases. Objectives: This review exhaustively gathers available information on ethnopharmacological uses, phytochemistry, and bioactivity studies on more than 20 species of Premna and critically analyzes the reports to provide the perspectives and directions for future research for the plants as potential source of drug leads and pharmaceutical agents. Methods: A literature search was performed on Premna species based on books of herbal medicine, major scientific databases including Chemical Abstract, Pubmed, SciFinder, Springerlink, Science Direct, Scopus, the Web of Science, Google Scholar, and ethnobotanical databases. Results: More than 250 compounds have been isolated and identified from Premna species, comprising of diterpenoids, iridoid glycosides, and flavonoids as the most common secondary metabolites, followed by sesquiterpenes, lignans, phenylethanoids, megastigmanes, glyceroglycolipids, and ceramides. Many in vitro and in vivo studies have been conducted to evaluate the biological and pharmacological properties of the extracts, and isolated compounds of Premna species with antimicrobial, antioxidant, anti-inflammatory, immunomodulatory, antihyperglycaemia, and cytotoxic activities. Conclusion: The bioactive compounds responsible for the bioactivities of most plants have not been well identified as the reported in vivo pharmacological studies were mostly carried out on the crude extracts. The isolated bioactive components should also be further subjected to more preclinical studies and elaborate toxicity study before clinical trials can be pursued.
Atanu Singha Roy, Amit Kumar Dinda, Nitin Kumar Pandey
et al.
The interaction of baicalein with bovine serum albumin (BSA) was investigated with the help of spectroscopic and molecular docking studies. The binding affinity of baicalein towards BSA was estimated to be in order of 105 M−1 from fluorescence quenching studies. Negative ΔH° (−5.66±0.14 kJ/mol) and positive (ΔS°) (+79.96±0.65 J/mol K) indicate the presence of electrostatic interactions along with the hydrophobic forces that result in a positive ΔS°. The hydrophobic association of baicalein with BSA diminishes in the presence of sodium dodecyl sulfate (SDS) due to probable hydrophobic association of baicalein with SDS, resulting in a negative ΔS° (−40.65±0.87 J/mol K). Matrix-assisted laser desorption ionization/time of flight (MALDI--TOF) experiments indicate a 1:1 complexation between baicalein and BSA. The unfolding and refolding phenomena of BSA were investigated in the absence and presence of baicalein using steady-state and fluorescence lifetime measurements. It was observed that the presence of urea ruptured the non-covalent interaction between baicalein and BSA. The presence of metal ions (Ag+, Mg2+, Ni2+, Mn2+, Co2+and Zn2+) increased the binding affinity of ligand towards BSA. The changes in conformational aspects of BSA after ligand binding were also investigated using circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopic techniques. Site selectivity studies following molecular docking analyses indicated the binding of baicalein to site 1 (subdomain IIA) of BSA.
Paulina Fuentes-León, Natalia Jara-Poblete, Pía Bastías-Sánchez
et al.
ABSTRACT The use of hot pack is a common superficial thermotherapy strategy and one of its benefits is the increase of muscle flexibility. However, there is a lack of information about the effects of the heat pack alone, without being used in association with other therapeutic interventions, in the flexibility of the lumbar region. The aim of this study was to compare the effects generated by the application of three different pack on the flexibility of the lower backs of healthy students. Three sessions of 15 minutes of superficial heat through a hot pack (moist heat pack-MHP, seed pack-SP or gel pack-GP) were applied to the lower back. Pack and lower back temperatures and erythema were registered every 5 minutes. A Schober test was performed before the first session and after the third session. After 15 minutes of treatment, pack temperature was higher in the SP group. At the same time, lumbar temperature was lower in the GP group. The heat treatment also increased erythema in the lower back for all three groups. There was a significant increase in intragroup flexibility as assessed by the Schober Test for all groups. There are significant differences in the effect generated between the three types of pack on the flexibility of the lower back. The MHP was able to transfer more heat to the lumbar area and provided a more pronounced increase in the flexibility of lower back tissues.
Xiao Zhou, Ji Liu Department of Anesthesia, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China Abstract: This study developed a revised high-performance liquid chromatography fluorescence method to determine plasma tramadol concentration, and thereby to examine the bioequivalence of two tramadol formulations among healthy male Chinese volunteers. The study used a double-blind, randomized, 2×2 crossover-design principle. Calculated pharmacokinetic parameters for both formulations were consistent with previous reports. According to the observation of vital signs and laboratory measurement, no subjects had any adverse reactions. The geometric mean ratios (90% confidence interval) of the test drug/reference drug for tramadol were 100.2% (95.3%–103.4%) for the area under the plasma concentration–time curve (AUC) from time zero to the last measurable concentration, 99.6% (94.2%–102.7%) for the AUC from administration to infinite time, and 100.8% (93.1%–106.4%) for maximum concentration. For the 90% confidence intervals of the test/reference AUC ratio and maximum concentration ratio of tramadol, both were in the acceptance range for bioequivalence. According to the two preparations by pharmacokinetic parameter statistics, the half-life, mean residence time, and clearance values showed no significant statistical differences. Therefore, the conclusion of this study was that the two tramadol formulations (tablets and capsules) were bioequivalent. Keywords: tramadol hydrochloride, in vitro release, pharmacokinetic, bioequivalence, fluorescence detector
Lesetja J Legoabe,1 Anél Petzer,1 Jacobus P Petzer1,21Centre of Excellence for Pharmaceutical Sciences, 2Department of Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom, South AfricaAbstract: Based on a previous report that substituted 2-acetylphenols may be promising leads for the design of novel monoamine oxidase (MAO) inhibitors, a series of C5-substituted 2-acetylphenol analogs (15) and related compounds (two) were synthesized and evaluated as inhibitors of human MAO-A and MAO-B. Generally, the study compounds exhibited inhibitory activities against both MAO-A and MAO-B, with selectivity for the B isoform. Among the compounds evaluated, seven compounds exhibited IC50 values <0.01 µM for MAO-B inhibition, with the most selective compound being 17,000-fold selective for MAO-B over the MAO-A isoform. Analyses of the structure–activity relationships for MAO inhibition show that substitution on the C5 position of the 2-acetylphenol moiety is a requirement for MAO-B inhibition, and the benzyloxy substituent is particularly favorable in this regard. This study concludes that C5-substituted 2-acetylphenol analogs are potent and selective MAO-B inhibitors, appropriate for the design of therapies for neurodegenerative disorders such as Parkinson’s disease.Keywords: monoamine oxidase, MAO, inhibition, 2-acetylphenol, structure–activity relationship
Objectives: The purpose of this study is to report a case of a plexiform neurofibroma (PNF) in the pelvic region treated with sweet bee venom (SBV) and mountain ginseng pharmacopuncture (MGP).
Methods: A 16-year-old girl was diagnosed as having PNFs, neurofibromatosis type 1, 10 years ago and she had surgery three times to remove the benign tumors, but the growth of the PNFs continued. She has been treated in our clinic with SBV and MGP two times per month from March 2010 to April 2014. SBV was injected intra-subcutaneously at the borders of the PNFs in the pelvic region, and MGP was administrated intravenously each treatment time.
Results: The growths of the PNFs occurred rapidly and continued steadily before treatment. Since March 2010, she has been treated in our clinic, and the growths of the PNFs have almost stopped; further-more, the discomfort of hip joint pain has been reduced, and her general condition has improved.
Conclusion: We cautiously conclude that SBV and MGP treatment has some effects that suppress the growth and the spread of the PNFs in this patient.