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BACKGROUND: Oral 5-aminolevulinic acid for transurethral resection of bladder tumor reduces bladder cancer recurrence compared with standard white-light transurethral resection of bladder tumor. However, data regarding risks of adverse events with this drug are unclear. The aim of the present study was to identify risk factors associated with oral 5-aminolevulinic acid induced adverse events in photodynamic diagnosis-transurethral resection of bladder tumor. METHODS: We studied 104 cases of 5-aminolevulinic acid-photodynamic diagnosis-transurethral resection of bladder tumor from October 2021 to April 2023, administering 20 mg/kg 5-aminolevulinic acid orally at least 2 hours pre-surgery. Four major adverse events associated with 5-aminolevulinic acid were selected to identify risk factors for their occurrence, including perioperative hypotension, nausea and/or vomiting, photosensitivity, and liver dysfunction. Univariate and multivariate analyses were conducted to identify the risk factors of those adverse events. RESULTS: Perioperative hypotension (11.5%), nausea and/or vomiting (37.5%) photosensitivity (31.7%), and liver dysfunction (51.9%) were observed. Multivariate analyses revealed that spinal anesthesia was associated with hypotension (p=0.02), whereas advanced age (p<0.01) and higher body mass index (p<0.01) were associated with nausea and/or vomiting. Also, male sex (p<0.01) and longer operative time (p=0.01) were associated with photosensitivity, and renin-angiotensin system inhibitors use was associated with postoperative liver dysfunction (p<0.01). CONCLUSIONS: For elderly male obese patients taking renin-angiotensin system inhibitors, particular attention is needed during the perioperative period of photodynamic diagnosis-transurethral resection of bladder tumor under spinal anesthesia due to the higher risk of onset of the adverse events involved in oral administration of 5-aminolevulinic acid.
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OBJECTIVES: Desmopressin is widely used for nocturia in patients with nocturnal polyuria. We investigated the continuation rate and adherence for desmopressin in patients with overactive bladder and nocturia using a claims database and evaluated factors that improved adherence. METHODS: Patients with nocturia in a Japanese claims database who started desmopressin between September 2019 and July 2021 were evaluated. Drug persistence was assessed using the Kaplan-Meier method for initial prescription of desmopressin. The proportion of days covered (PDC) was also evaluated among patients with prescription persistence. Multivariate analysis was performed using logistic regression analysis to identify factors predicting adherence to desmopressin. RESULTS: The study included 72,888 patients entered into Japan Medical Data Center (JMDC) database between September 2019 and July 2021. For the 236 patients prescribed desmopressin formulations, mean prescription duration was 114 days. Among the total cases, 90 (38.1%) cases were prescribed only once, mean PDC was 0.60, and the number of high-adherence patients (PDC ≥ 0.80) was 108 (45.8%). Desmopressin prescription doses were fixed in 216 patients and adjusted in 20 patients. Multivariate analysis identified prescription dose adjustment for desmopressin as significantly associated with high PDC. CONCLUSION: Desmopressin showed a 38% dropout rate after the first dose. However, high medication continuation and high medication adherence rates (PDC) could be maintained with prescription adjustments. Careful patient monitoring and appropriate adjustment of the desmopressin dosage appear to be important factors in improving nocturia.
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The yield of a chemical reaction is obtained by solving its rate equation. This study introduces an approach for differentiating yields by utilizing the parameters of the rate equation, which is expressed as a first-order linear differential equation. The yield derivative for a specific pair of reactants and products is derived by mathematically expressing the rate constant matrix contraction method, which is a simple kinetic analysis method. The parameters of the rate equation are the Gibbs energies of the intermediates and transition states in the reaction path network used to formulate the rate equation. Thus, our approach for differentiating the yield allows a numerical evaluation of the contribution of energy variation to the yield for each intermediate and transition state in the reaction path network. In other words, a comparison of these values automatically extracts the factors affecting the yield from a complicated reaction path network consisting of numerous reaction paths and intermediates. This study verifies the behavior of the proposed approach through numerical experiments on the reaction path networks of a model system and the Rh-catalyzed hydroformylation reaction. Moreover, the possibility of using this approach for designing ligands in organometallic catalysts is discussed.
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Nanocarbons incorporating non-hexagonal aromatic rings - such as five-, seven-, and eight-membered rings - have various intriguing physical properties such as curved structures, unique one-dimensional packing, and promising magnetic, optical, and conductivity properties. Herein, we report an efficient synthetic approach to polycyclic aromatics containing seven-membered rings via a palladium-catalyzed intramolecular Ar-H/Ar-Br coupling. In addition to all-hydrocarbon scaffolds, heteroatom-embedded heptagon-containing polyarenes can be efficiently constructed with this method. Rhodium- and palladium-catalyzed sequential six- and seven-membered ring formations also afford complex heptagon-containing molecular nanocarbons from readily available arylacetylenes and biphenyl boronic acids. Detailed mechanistic analysis by DFT calculations showed the feasibility of seven-membered ring formation by a concerted metalation-deprotonation mechanism. This reaction can serve as a template for the synthesis of a wide range of seven-membered ring-containing molecular nanocarbons.
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Ligand screening is a crucial step in the development of transition metal catalysis, as it involves identifying the optimal ligand for a particular reaction from a large pool of candidate molecules. Conventionally, this process is performed through an experimental trial-and-error, which can be time-consuming and resource-intensive in many cases. One of the ideal strategies for streamlining this process is a transition state theory (TST)-based approach, which aims to design optimal catalysts that results in the best energy profile for the desired reaction. However, the implementation of TST-based ligand screening remains challenging mainly due to the large number of potential ligands that need to be individually evaluated through quantum chemical calculations. In this study, we experimentally demonstrated a practical TST-based ligand screening in accordance with our virtual ligand-assisted (VLA) screening strategy. As a case study, the electronic anc steric features of phosphine ligands that maximize chemoselectivity in the Suzuki-Miyaura cross-coupling (SMC) reaction of p-chlorophenyl triflate were determined through quantum chemical calculations using virtual ligands, and several phosphine ligands were suggested to exhibit high chemoselectivity. Based on this suggestion, we successfully found that tri(1-adamantyl)phosphine and tri(neopentyl)phosphine show high to excellent selectivity for the C-Cl bond activation. This case study suggests that the VLA screening strategy could be a useful tool for ligand screening.
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BACKGROUND/AIM: Nocturia is defined as the symptom that an individual has to disrupt their sleep at night, for one or several times, in order to void. Nocturia is a bothersome event that markedly reduces a patient's quality of life. The aim of the study was to elucidate which drugs, prescribed to reduce nocturia, show real-world efficacy in patients with bladder storage symptoms. PATIENTS AND METHODS: One hundred consecutive patients who visited the Fukuoka University Medical Center were evaluated between May and July 2022. Anticholinergic drugs, ß3 adrenoceptor agonists, α1 blockers, desmopressin, and other medicines were prescribed for relieving nocturia. Desmopressin was used as second-line treatment of nocturia only in males with nocturnal polyuria. The association between each drug and actual decrease in nocturia was investigated using multivariate analysis. RESULTS: The number of nocturia episodes was reduced in patients using anticholinergic drugs, ß3 adrenoceptor agonists, and desmopressin (-1.4±0.9, -1.3±0.9, -2.0 ±0.8 episodes/night, respectively). Multivariate analysis for the entire cohort showed that anticholinergic drugs and ß3 adrenoceptor agonists were associated with significantly decreased nocturia episodes (p=0.01 and p=0.04, respectively). In males, only desmopressin was associated with a significant decrease in nocturia (p=0.03), and combination therapy significantly decreased the number of nocturia episodes compared to monotherapy (p=0.001). CONCLUSION: In a real-world clinical setting, anticholinergic drugs and ß3 adrenoceptor agonists were similarly effective in reducing nocturia. Administration of desmopressin combined with anticholinergic drugs and/or ß3 adrenoceptor agonists is the most effective method for reducing nocturia in male patients with both storage symptoms and nocturnal polyuria.
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Noctúria , Bexiga Urinária , Humanos , Masculino , Antidiuréticos/uso terapêutico , Antidiuréticos/efeitos adversos , Antagonistas Colinérgicos/uso terapêutico , Antagonistas Colinérgicos/farmacologia , Desamino Arginina Vasopressina/uso terapêutico , Noctúria/tratamento farmacológico , Poliúria/induzido quimicamente , Poliúria/complicações , Poliúria/tratamento farmacológico , Qualidade de Vida , Receptores Adrenérgicos/uso terapêutico , Bexiga Urinária/patologiaRESUMO
Among a large variety of organic semiconducting materials, rubrene (5,6,11,12-tetraphenyltetracene) represents one of the most prominent molecular entities mainly because of its unusually high carrier mobility. Toward finding superior rubrene-based organic semiconductors, several synthetic strategies for related molecules have been established. However, despite its outstanding properties and significant attention in the field of materials science, late-stage functionalizations of rubrene remains undeveloped, thereby limiting the accessible chemical space of rubrene-based materials. Herein, we report on a late-stage π-extension of rubrene by dearomative annulative π-extension (DAPEX), leading to the generation of rubrene derivatives having an extended acene core. The Diels-Alder reaction of rubrene with 4-methyl-1,2,4-triazoline-3,5-dione occurred to give 1:1 and 1:2 cycloadducts which further underwent iron-catalyzed annulative diarylation. The thus-formed 1:1 and 1:2 adducts were subjected to radical-mediated oxidation and thermal cycloreversion to furnish one-side and two-side π-extended rubrenes, respectively. These π-extended rubrenes displayed a marked red shift in absorption and emission spectra, clearly showing that the acene π-system of rubrene was extended not only structurally but also electronically. The X-ray crystallographic analysis uncovered interesting packing modes of these π-extended rubrenes. Particularly, two-side π-extended rubrene adopts a brick-wall packing structure with largely overlapping two-dimensional face-to-face π-π interactions. Finally, organic field-effect transistor devices using two-side π-extended rubrene were fabricated, and their carrier mobilities were measured. The observed maximum hole mobility of 1.49 × 10-3 cm2V-1 s-1, which is a comparable value to that of the thin-film transistor using rubrene, clearly shows the potential utility of two-side π-extended rubrene in organic electronics.
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BACKGROUND/AIM: This study aimed to determine whether psychological stress associated with the COVID-19 pandemic might exacerbate lower urinary tract symptoms (LUTS) and decrease lower urinary tract function in outpatients with LUTS. PATIENTS AND METHODS: We evaluated 104 patients who visited our hospital during the first wave of the COVID-19 pandemic. Psychological stress was evaluated by the Stress Response Scale-18 (SRS-18). Subjects were divided into aggravation and non-aggravation of psychological stress groups according to the SRS-18. LUTS was evaluated according to the International Prostate Symptom Score (IPSS). Lower urinary tract function was evaluated as the post-void residual urine volume (PVR). Comparisons of scores and changes in scores of each parameter before versus during/after the first wave of the COVID-19 pandemic were performed between the two groups. RESULTS: Forty-two patients were included in each group. We observed no significant differences in the comparison of scores at each time point and in changes in total IPSS score, voiding symptom subscores and PVR between the two groups. Although no significant differences in storage symptom subscores were observed between the two groups, changes in storage symptom subscores increased significantly during the first wave of the pandemic in the aggravation of psychological stress group (p=0.02). However, no significant increase was observed after the first wave. CONCLUSION: Psychological stress during the COVID-19 pandemic might transiently aggravate storage symptoms in patients with LUTS. Physicians should be aware of the possibility of transient worsening of LUTS during future pandemics, and transiently additional medication might be effective in such patients.
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COVID-19 , Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Masculino , Humanos , Hiperplasia Prostática/tratamento farmacológico , Pandemias , COVID-19/complicações , COVID-19/epidemiologia , Sintomas do Trato Urinário Inferior/epidemiologia , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/diagnóstico , Estresse PsicológicoRESUMO
Nanographenes and polycyclic aromatic hydrocarbons (PAHs) are among the most important classes of compounds, with potential applications in nearly all areas of science and technology. While the theoretically possible number of nanographene structures is extraordinary, most of these molecules remain synthetically out of reach due to a lack of programmable and diversity-oriented synthetic methods, and their potentially huge structure-property diversity has not been fully exploited. Herein we report a diversity-oriented, growth-from-template synthesis of nanographenes enabled by iterative annulative π-extension (APEX) reactions from small PAH starting materials. The developed dearomative annulative π-extension (DAPEX) reaction enables π-elongation at the less-reactive M-regions of PAHs, and is successfully combined with complementary APEX reactions that occur at K- and bay-regions to access a variety of previously untapped nanographenes.
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A nerve-sparing procedure during robot-assisted radical prostatectomy has been considered one of the most important techniques for preserving postoperative genitourinary function. The reason is that adequate nerve-sparing procedures could preserve both erectile function and lower urinary tract function after surgery. When a nerve-sparing procedure is carried out, the cavernous nerves themselves cannot be visualized, despite the magnified viewing field during robot-assisted radical prostatectomy. Thus, nerve-sparing procedures have been considered challenging operations, even now. However, because not all surgeons have carried out a sufficient number of nerve-sparing procedures, the development of new nerve-sparing procedures or new methods for mapping the cavernous nerves is required. Recently, various new operative techniques, for example, Retzius-sparing robot-assisted radical prostatectomy, transvesical robot-assisted radical prostatectomy and retrograde release of neurovascular bundle technique during robot-assisted radical prostatectomy, have been developed. In addition, new surgical devices, for example, biological/bioengineering solutions for cavernous nerve protection and devices for identifying the cavernous nerves during radical prostatectomy, have developed to preserve the cavernous nerves. In contrast, limitations or problems in preserving cavernous nerves and postoperative erectile function have become apparent. In particular, the recovery rate of erectile function, the positive surgical margin rate at the site of nerve-sparing and the indications for nerve sparing have become obvious with the accumulation of much evidence. Furthermore, predictive factors for postoperative erectile function after nerve-sparing procedures have also been clarified. In this article, the importance of a comprehensive approach for early recovery of erectile function in the robot-assisted radical prostatectomy era is discussed.
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Disfunção Erétil , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Disfunção Erétil/etiologia , Disfunção Erétil/prevenção & controle , Humanos , Masculino , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/efeitos adversosRESUMO
Nitrogen-containing polycyclic aromatic compounds (N-PACs) are an important class of compounds in materials science. Reported here is a new aza-annulative π-extension (aza-APEX) reaction that allows rapid access to a range of N-PACs in 11-84 % yields from readily available unfunctionalized aromatics and imidoyl chlorides. In the presence of silver hexafluorophosphate, arenes and imidoyl chlorides couple in a regioselective fashion. The follow-up oxidative treatment with p-chloranil affords structurally diverse N-PACs, which are very difficult to synthesize. DFT calculations reveal that the aza-APEX reaction proceeds through the formal [4+2] cycloaddition of an arene and an in situ generated diarylnitrilium salt, with sequential aromatizations having relatively low activation energies. Transformation of N-PACs into nitrogen-doped nanographenes and their photophysical properties are also described.
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A palladium-catalyzed one-step annulative π-extension (APEX) reaction of indoles and pyrroles that allows rapid access to nitrogen-containing polycyclic aromatic compounds is described. In the presence of palladium pivalate and silver carbonate, diverse indoles or pyrroles coupled with diiodobiaryls in a double direct C-H arylation manner to be transformed into the corresponding π-extended compounds in a single step. The newly developed catalytic system enables the use of various pyrroles and indoles as templates with a series of diiodobiaryls to provide structurally complicated and largely π-extended nitrogen-containing polycyclic aromatic compounds that are otherwise difficult to synthesize.
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Efficient and rapid access to nanographenes and π-extended fused heteroaromatics is important in materials science. Herein, we report a palladium-catalyzed efficient one-step annulative π-extension (APEX) reaction of polycyclic aromatic hydrocarbons (PAHs) and heteroaromatics, producing various π-extended aromatics. In the presence of a cationic Pd complex, triflic acid, silver pivalate, and diiodobiaryls, diverse unfunctionalized PAHs and heteroaromatics were directly transformed into larger PAHs, nanographenes, and π-extended fused heteroaromatics in a single step. In the reactions that afford [5]helicene substructures, simultaneous dehydrogenative ring closures occur at the fjord regions to form unprecedented larger nanographenes. This successive APEX reaction is notable as it stiches five aryl-aryl bonds by C-H functionalization in a single operation. Moreover, the unique molecular structures, crystal-packing structures, photophysical properties, and frontier molecular orbitals of the thus-formed nanographenes were elucidated.
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Annulative π-extension (APEX) reactions of heteroarenes are described herein. A catalytic system comprising a cationic palladium species and o-chloranil using dimethyldibenzosiloles as π-extending agents enabled the extension of the π-system of benzo[b]thiophenes. π-Extended dibenzofurans and carbazoles could also be obtained from benzofuran and N-tosylindole, respectively, with dimethyldibenzogermole as a germanium-based π-extending agent. Mechanistic investigations indicated two possible reaction pathways involving carbopalladation-based double C-H arylation of benzothiophene or formal cycloaddition/oxidation cascades.
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Reliable and short synthetic routes to polycyclic aromatic hydrocarbons and nanographenes are important in materials science. Herein, we report an efficient one-step annulative π-extension reaction of alkynes that provides access to diarylphenanthrenes and related nanographene precursors. In the presence of a cationic palladium/o-chloranil catalyst system and dibenzosiloles or dibenzogermoles as π-extending agents, a variety of diarylacetylenes are transformed successfully into 9,10-diarylphenanthrenes in a single step with good functional-group tolerance. Furthermore, double π-extension reactions of 1,4-bis(phenylethynyl)benzene and diphenyl-1,3-butadiyne are demonstrated, affording oligoarylene products, which show potential for application in the synthesis of larger polycyclic aromatic hydrocarbons and nanographenes.