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Drugs in Context 2023Tinea pedis is one of the most common superficial fungal infections of the skin, with various clinical manifestations. This review aims to familiarize physicians with... (Review)
Review
BACKGROUND
Tinea pedis is one of the most common superficial fungal infections of the skin, with various clinical manifestations. This review aims to familiarize physicians with the clinical features, diagnosis and management of tinea pedis.
METHODS
A search was conducted in April 2023 in PubMed Clinical Queries using the key terms 'tinea pedis' OR 'athlete's foot'. The search strategy included all clinical trials, observational studies and reviews published in English within the past 10 years.
RESULTS
Tinea pedis is most often caused by and . It is estimated that approximately 3% of the world population have tinea pedis. The prevalence is higher in adolescents and adults than in children. The peak age incidence is between 16 and 45 years of age. Tinea pedis is more common amongst males than females. Transmission amongst family members is the most common route, and transmission can also occur through indirect contact with contaminated belongings of the affected patient. Three main clinical forms of tinea pedis are recognized: interdigital, hyperkeratotic (moccasin-type) and vesiculobullous (inflammatory). The accuracy of clinical diagnosis of tinea pedis is low. A KOH wet-mount examination of skin scrapings of the active border of the lesion is recommended as a point-of-care testing. The diagnosis can be confirmed, if necessary, by fungal culture or culture-independent molecular tools of skin scrapings. Superficial or localized tinea pedis usually responds to topical antifungal therapy. Oral antifungal therapy should be reserved for severe disease, failed topical antifungal therapy, concomitant presence of onychomycosis or in immunocompromised patients.
CONCLUSION
Topical antifungal therapy (once to twice daily for 1-6 weeks) is the mainstay of treatment for superficial or localized tinea pedis. Examples of topical antifungal agents include allylamines (e.g. terbinafine), azoles (e.g. ketoconazole), benzylamine, ciclopirox, tolnaftate and amorolfine. Oral antifungal agents used for the treatment of tinea pedis include terbinafine, itraconazole and fluconazole. Combined therapy with topical and oral antifungals may increase the cure rate. The prognosis is good with appropriate antifungal treatment. Untreated, the lesions may persist and progress.
PubMed: 37415917
DOI: 10.7573/dic.2023-5-1 -
European Heart Journal Nov 2023Mavacamten is a first-in-class, targeted, cardiac-specific myosin inhibitor approved by the US Food and Drug Administration for the treatment of adults with symptomatic... (Review)
Review
Mavacamten is a first-in-class, targeted, cardiac-specific myosin inhibitor approved by the US Food and Drug Administration for the treatment of adults with symptomatic New York Heart Association Classes II and III obstructive hypertrophic cardiomyopathy (oHCM). Mavacamten was developed to target the hyper-contractile phenotype, which plays a critical role in the pathophysiology of the disease. In Phase 2 and 3 clinical trials, mavacamten was well tolerated, reduced left ventricular outflow tract gradients, improved exercise capacity and symptoms, and was associated with improvements in other clinically relevant parameters, such as patient-reported outcomes and circulating biomarkers. In addition, treatment with mavacamten was associated with evidence of favourable cardiac remodelling in multi-modality imaging studies. Mavacamten substantially reduced guideline eligibility for septal reduction therapy candidates with oHCM and drug-refractory symptoms. In this article, the available efficacy and safety data from completed and ongoing clinical studies of mavacamten in patients with symptomatic oHCM are reviewed. Longer term extension studies may help address questions related to the positioning of mavacamten in current oHCM management algorithms, interactions with background therapy, as well as the potential for disease modification beyond symptomatic relief of left ventricular outflow tract obstruction.
Topics: Adult; Humans; Benzylamines; Cardiomyopathy, Hypertrophic; Heart; United States; Uracil
PubMed: 37804245
DOI: 10.1093/eurheartj/ehad637 -
Molbank Jun 2023()-(+)-3,5-dinitro--(1-phenylethyl)benzothioamide is a potential chiral solvating agent (CSA) for the spectral resolution of enantiomers via H NMR spectroscopy. The...
()-(+)-3,5-dinitro--(1-phenylethyl)benzothioamide is a potential chiral solvating agent (CSA) for the spectral resolution of enantiomers via H NMR spectroscopy. The single enantiomer of was synthesized from commercially available ()-(+)-a-methylbenzylamine in two steps with 85% yield.
PubMed: 38274708
DOI: 10.3390/m1650 -
International Braz J Urol : Official... 2023
Topics: Male; Humans; Premature Ejaculation; Ejaculation; Benzylamines; Naphthalenes; Treatment Outcome
PubMed: 37267615
DOI: 10.1590/S1677-5538.IBJU.2023.9908 -
Science Advances Jul 2023Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder characterized by left ventricular hypertrophy, hyperdynamic contraction, and impaired relaxation of... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder characterized by left ventricular hypertrophy, hyperdynamic contraction, and impaired relaxation of the heart. These functional derangements arise directly from altered sarcomeric function due to either mutations in genes encoding sarcomere proteins, or other defects such as abnormal energetics. Current treatment options do not directly address this causal biology but focus on surgical and extra-sarcomeric (sarcolemmal) pharmacological symptomatic relief. Mavacamten (formerly known as MYK-461), is a small molecule designed to regulate cardiac function at the sarcomere level by selectively but reversibly inhibiting the enzymatic activity of myosin, the fundamental motor of the sarcomere. This review summarizes the mechanism and translational progress of mavacamten from proteins to patients, describing how the mechanism of action and pharmacological characteristics, involving both systolic and diastolic effects, can directly target pathophysiological derangements within the cardiac sarcomere to improve cardiac structure and function in HCM. Mavacamten was approved by the Food and Drug Administration in April 2022 for the treatment of obstructive HCM and now goes by the commercial name of Camzyos. Full information about the risks, limitations, and side effects can be found at www.accessdata.fda.gov/drugsatfda_docs/label/2022/214998s000lbl.pdf.
Topics: United States; Humans; Precision Medicine; Cardiomyopathy, Hypertrophic; Benzylamines; Myosins
PubMed: 37506209
DOI: 10.1126/sciadv.abo7622 -
Microbial Physiology 2024The denitrifying betaproteobacterium Aromatoleum aromaticum EbN1T is a facultative anaerobic degradation specialist and belongs to the environmental bacteria studied... (Review)
Review
The denitrifying betaproteobacterium Aromatoleum aromaticum EbN1T is a facultative anaerobic degradation specialist and belongs to the environmental bacteria studied best on the proteogenomic level. This review summarizes the current state of knowledge about the anaerobic and aerobic degradation (to CO2) of 47 organic growth substrates (23 aromatic, 21 aliphatic, and 3 amino acids) as well as the modes of respiratory energy conservation (denitrification vs. O2-respiration). The constructed catabolic network is comprised of 256 genes, which occupy ∼7.5% of the coding regions of the genome. In total, 219 encoded proteins have been identified by differential proteomics, yielding a proteome coverage of ∼74% of the network. Its degradation section is composed of 31 peripheral and 4 central pathways, with several peripheral modules (e.g., for 4-ethylphenol, 2-phenylethylamine, indoleacetate, and phenylpropanoids) discovered only after the complete genome [Arch Microbiol. 2005 Jan;183(1):27-36] and a first proteomic survey [Proteomics. 2007 Jun;7(13):2222-39] of A. aromaticum EbN1T were reported. The activation of recalcitrant aromatic compounds involves a suite of biochemically intriguing reactions ranging from C-H-bond activation (e.g., ethylbenzene dehydrogenase) via carboxylation (e.g., acetophenone carboxylase) to oxidative deamination (e.g., benzylamine), reductive dearomatization (benzoyl-CoA), and epoxide-forming oxygenases (e.g., phenylacetyl-CoA). The peripheral reaction sequences are substrate-specifically induced, mediated by specific transcriptional regulators with in vivo response thresholds in the nanomolar range. While lipophilic substrates (e.g., phenolics) enter the cells via passive diffusion, polar ones require active uptake that is driven by specific transporters. Next to the protein repertoire for canonical complexes I-III, denitrification, and O2-respiration (low- and high-affinity oxidases), the genome encodes an Ndh-II, a tetrathionate reductase, two ETF:quinone oxidoreductases, and two Rnf-type complexes, broadening the electron transfer flexibility of the strain. Taken together, the detailed catabolic network presented here forms a solid basis for future systems biology-level studies with A. aromaticum EbN1T.
Topics: Bacterial Proteins; Anaerobiosis; Metabolic Networks and Pathways; Aerobiosis; Proteome; Proteomics; Denitrification; Rhodocyclaceae
PubMed: 37816339
DOI: 10.1159/000534425 -
ACS Chemical Neuroscience Jan 2024Primary metabolites of mushroom tryptamines, psilocybin and baeocystin (i.e., psilocin and norpsilocin), exhibit potent agonist activity at the serotonin 2A receptor...
Primary metabolites of mushroom tryptamines, psilocybin and baeocystin (i.e., psilocin and norpsilocin), exhibit potent agonist activity at the serotonin 2A receptor (5-HT) but differ in their 5-HT-mediated effects . In particular, psilocin produces centrally mediated psychedelic effects , whereas norpsilocin, differing only by the loss of an -methyl group, is devoid of psychedelic-like effects. These observations suggest that the secondary methylamine group in norpsilocin impacts its central nervous system (CNS) bioavailability but not its receptor pharmacodynamics. To test this hypothesis, eight norpsilocin derivatives were synthesized with varied secondary alkyl-, allyl-, and benzylamine groups, primarily aiming to increase their lipophilicity and brain permeability. Structure-activity relationships for the norpsilocin analogues were evaluated using the mouse head-twitch response (HTR) as a proxy for CNS-mediated psychedelic-like effects. HTR studies revealed that extending the -methyl group of norpsilocin by a single methyl group, to give the corresponding secondary -ethyl analogue (4-HO-NET), was sufficient to produce psilocin-like activity (median effective dose or ED = 1.4 mg/kg). Notably, -allyl, -propyl, -isopropyl, and -benzyl derivatives also induced psilocin-like HTR activity (ED = 1.1-3.2 mg/kg), with variable maximum effects (26-77 total HTR events). By contrast, adding bulkier -butyl or cyclohexyl groups in the same position did not elicit psilocin-like HTRs. Pharmacological assessments of the tryptamine series demonstrated interactions with multiple serotonin receptor subtypes, including 5-HT, and other CNS signaling proteins (e.g., sigma receptors). Overall, our data highlight key structural requirements for CNS-mediated psychedelic-like effects of norpsilocin analogues.
Topics: Mice; Animals; Hallucinogens; Serotonin; Receptors, Serotonin; Brain; Receptor, Serotonin, 5-HT2A
PubMed: 38189238
DOI: 10.1021/acschemneuro.3c00610 -
PloS One 2023Dysphagia is a potentially fatal symptom of Parkinson's disease (PD) and is characterized by frequent silent aspiration, a risk factor for aspiration pneumonia. The...
Dysphagia is a potentially fatal symptom of Parkinson's disease (PD) and is characterized by frequent silent aspiration, a risk factor for aspiration pneumonia. The transdermal dopamine agonist rotigotine alleviates dysphagia in patients with PD and is more effective than oral levodopa, suggesting the importance of continuous dopaminergic stimulation (CDS) in swallowing. Safinamide is a monoamine oxidase B (MAOB) inhibitor that facilitates CDS. In this retrospective open-label evaluator-blinded research, swallowing functions in nine patients with PD were examined using a video fluoroscopic swallowing study (VFSS) before and after treatment with 50 mg of oral safinamide. The VFSS results showed that safinamide significantly improved some swallowing measures during oral and pharyngeal phases, including oral transit time and pharyngeal transit time, without worsening of any measures. Notably, improvements in lip closure, an oral phase component, seemed to be most attributable to improvements in oral phase scores. In conclusion, a medicine for CDS may effectively improve swallowing functions in patients with PD. This is the first study to show that the MAOB inhibitor safinamide partly but significantly improves swallowing function in patients with PD.
Topics: Humans; Parkinson Disease; Deglutition Disorders; Retrospective Studies; Levodopa; Benzylamines; Alanine; Monoamine Oxidase Inhibitors; Antiparkinson Agents
PubMed: 37228084
DOI: 10.1371/journal.pone.0286066 -
Journal of Neural Transmission (Vienna,... Jul 2023Fatigue is a common non-motor symptom in Parkinson's disease (PD). Among other pathophysiological mechanisms, neuroinflammation, a pathological PD hallmark associated...
Fatigue is a common non-motor symptom in Parkinson's disease (PD). Among other pathophysiological mechanisms, neuroinflammation, a pathological PD hallmark associated with changes in glutamatergic transmission in basal ganglia, has been proposed as a crucial factor closely related to fatigue. To test the hypothesis that safinamide could represent an effective treatment of fatigue in PD patients, given its dual mechanism of action (it selectively and reversibly inhibits MAOB and modulates glutamate release), we administered the validated versions of fatigue severity scale (FSS) and Parkinson fatigue scale-16 (PFS-16) to 39 fluctuating PD patients with fatigue before and after a 24-week treatment period with safinamide as add-on therapy. An assessment of secondary variables such as depression, quality of life (QoL), and motor and non-motor symptoms (NMS) was conducted. After 24 weeks of treatment with safinamide, both FSS (p < 0.001) and PF-S16 (p = 0.02) scores were significantly lower than at baseline. Moreover, 46.2% and 41% of patients scored below the cut-off for the presence of fatigue according to FSS and PFS-16, respectively (responders). At follow-up, a significant difference emerged between responders and non-responders in mood, QoL, and NMS. Fatigue improved in fluctuating PD, and more than 40% of patients were "fatigue-free" after a 6 month treatment with safinamide. Patients without fatigue at follow-up displayed significantly better scores in QoL domains, such as mobility or activities of daily living, although disease severity remained stable, supporting the hypothesis that fatigue could considerably affect QoL. Drugs that interact with multiple neurotransmission systems, such as safinamide, could be useful in reducing this symptom.
Topics: Humans; Parkinson Disease; Antiparkinson Agents; Quality of Life; Activities of Daily Living; Benzylamines
PubMed: 37210459
DOI: 10.1007/s00702-023-02654-1 -
Signal Transduction and Targeted Therapy Mar 2024Neurotransmitter-initiated signaling pathway were reported to play an important role in regulating the malignant phenotype of tumor cells. Cancer cells could exhibit a...
Neurotransmitter-initiated signaling pathway were reported to play an important role in regulating the malignant phenotype of tumor cells. Cancer cells could exhibit a "neural addiction" property and build up local nerve networks to achieve an enhanced neurotransmitter-initiated signaling through nerve growth factor-mediated axonogenesis. Targeting the dysregulated nervous systems might represent a novel strategy for cancer treatment. However, whether intrahepatic cholangiocarcinoma (ICC) could build its own nerve networks and the role of neurotransmitters in the progression ICC remains largely unknown. Immunofluorescence staining and Enzyme-linked immunosorbent assay suggested that ICC cells and the infiltrated nerves could generate a tumor microenvironment rich in acetylcholine that promotes ICC metastasis by inducing epithelial-mesenchymal transition (EMT). Acetylcholine promoted ICC metastasis through interacting with its receptor, alpha 5 nicotine acetylcholine receptor subunits (CHRNA5). Furthermore, acetylcholine/CHRNA5 axis activated GSK3β/β-catenin signaling pathway partially through the influx of Ca-mediated activation of Ca/calmodulin-dependent protein kinases (CAMKII). In addition, acetylcholine signaling activation also expanded nerve infiltration through increasing the expression of Brain-Derived Neurotrophic Factor (BDNF), which formed a feedforward acetylcholine-BDNF axis to promote ICC progression. KN93, a small-molecule inhibitor of CAMKII, significantly inhibited the migration and enhanced the sensitivity to gemcitabine of ICC cells. Above all, Acetylcholine/CHRNA5 axis increased the expression of β-catenin to promote the metastasis and resistance to gemcitabine of ICC via CAMKII/GSK3β signaling, and the CAMKII inhibitor KN93 may be an effective therapeutic strategy for combating ICC metastasis.
Topics: Humans; beta Catenin; Brain-Derived Neurotrophic Factor; Nicotine; Acetylcholine; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Gemcitabine; Glycogen Synthase Kinase 3 beta; Cell Line, Tumor; Cholangiocarcinoma; Bile Ducts, Intrahepatic; Bile Duct Neoplasms; Neurotransmitter Agents; Receptors, Cholinergic; Tumor Microenvironment; Benzenesulfonamides; Benzylamines
PubMed: 38453934
DOI: 10.1038/s41392-024-01761-z