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JAMA Dermatology Jan 2020Contact dermatitis in the anogenital area is associated with sleep disturbance and dyspareunia and can profoundly affect quality of life. The literature on anogenital...
IMPORTANCE
Contact dermatitis in the anogenital area is associated with sleep disturbance and dyspareunia and can profoundly affect quality of life. The literature on anogenital contact dermatitis and culprit allergens is limited. The last large-scale study on common, relevant allergens in patients with anogenital dermatitis was published in 2008.
OBJECTIVES
To characterize patients with anogenital dermatitis referred for patch testing by the North American Contact Dermatitis Group, to identify common allergens, and to explore sex-associated differences between anogenital dermatitis and allergens.
DESIGN, SETTING, AND PARTICIPANTS
A retrospective, cross-sectional analysis was conducted of the North American Contact Dermatitis Group database among 28 481 patients who underwent patch testing from January 1, 2005, to December 31, 2016, at outpatient referral clinics in the United States and Canada.
EXPOSURE
Patch testing for allergens.
MAIN OUTCOMES AND MEASURES
Currently relevant allergic patch test reactions in patients with anogenital dermatitis.
RESULTS
Of 28 481 patients tested during the study period, 832 patients (336 men and 496 women; mean [SD] age, 50.1 [26.5] years) had anogenital involvement and 449 patients (177 men and 272 women; mean [SD] age, 49.6 [17.4] years) had anogenital dermatitis only. Compared with those without anogenital involvement, there were significantly more male patients in the group with anogenital dermatitis (177 [39.4%] vs 8857 of 27 649 [32.0%]; relative risk, 1.37; 95% CI, 1.14-1.66; P < .001). In the group with anogenital involvement, female patients were significantly less likely than male patients to have allergic contact dermatitis as a final diagnosis (130 [47.8%] vs 107 [60.5%]; relative risk, 0.78; 95% CI, 0.64-0.94; P = .01), whereas a final diagnosis of other dermatoses (eg, lichen planus, lichen sclerosus, or lichen simplex chronicus) was more frequent for female patients than for male patients (67 [24.6%] vs 28 [15.8%]; relative risk, 1.54; 95% CI, 1.02-2.31; P = .03). Of the 449 patients in the group with anogenital involvement only, 227 (50.6%) had 1 or more relevant reaction with patch testing. Allergens that were statistically significantly more common in patients with anogenital involvement compared with those without anogenital involvement included medicaments such as dibucaine (10 of 250 patients tested [4.0%] vs 32 of 17 494 patients tested [0.2%]; relative risk, 22.74; 95% CI, 11.05-46.78; P < .001) and preservatives such as methylchloroisothiazolinone and methylisothiazolinone (30 of 449 patients tested [6.7%] vs 1143 of 27 599 patients tested [4.1%]; relative risk, 1.61; 95% CI, 1.14-2.41; P = .008). A total of 152 patients met the definition for anogenital allergic contact dermatitis, which is defined as anogenital involvement only, allergic contact dermatitis as the only diagnosis, and 1 or more positive reaction of current clinical relevance.
CONCLUSIONS AND RELEVANCE
For patients with anogenital involvement only who were referred for patch testing, male patients were more likely to have allergic contact dermatitis, whereas female patients were more likely to have other dermatoses. Common allergens or sources consisted of those likely to contact the anogenital area. For individuals with anogenital involvement suspected of having allergic contact dermatitis, reactions to preservatives, fragrances, medications (particularly topical anesthetics), and topical corticosteroids should be tested.
Topics: Administration, Cutaneous; Adult; Aged; Allergens; Anesthetics; Anus Diseases; Cosmetics; Cross-Sectional Studies; Dermatitis, Allergic Contact; Female; Genital Diseases, Female; Genital Diseases, Male; Glucocorticoids; Humans; Male; Middle Aged; North America; Patch Tests; Quality of Life; Retrospective Studies; Young Adult
PubMed: 31774454
DOI: 10.1001/jamadermatol.2019.3844 -
Frontiers in Microbiology 2022Human enterovirus infections are mostly asymptomatic and occasionally could be severe and life-threatening. The conserved non-structural 2C from enteroviruses protein is...
Human enterovirus infections are mostly asymptomatic and occasionally could be severe and life-threatening. The conserved non-structural 2C from enteroviruses protein is a promising target in antiviral therapies against human enteroviruses. Understanding of 2C-drug interactions is crucial for developing the potential antiviral agents. While functions of enterovirus 2C proteins have been widely studied, three-dimensional structure information of 2C is limited. In this study, the structures of 2C proteins from 20 enteroviruses were simulated and reconstructed using programs. Subsequent docking studies of the known 22 antiviral inhibitors for 2C proteins were performed to uncover the inhibitor-binding characteristics of 2C. Among the potential inhibitors, the compound hydantoin exhibited the highest broad-spectrum antiviral activities with binding to 2C protein. The anti-enteroviral activity of GuaHCL, compound 19b, R523062, compound 12a, compound 12b, quinoline analogs 12a, compound 19d, N-benzyladenosine, dibucaine derivatives 6i, TBZE-029, fluoxetine analogs 2b, dibucaine, 2-(α-hydroxybenzyl)-benzimidazole (HBB), metrifudil, pirlindole, MRL-1237, quinoline analogs 10a, zuclopenthixol, fluoxetine, fluoxetine HCl, and quinoline analogs 12c showed a trend of gradual decrease. In addition, the free energy with 22 compounds binding to EV 2C ranged from -0.35 to -88.18 kcal/mol. Our studies will provide important information for the development of pan-enterovirus antiviral agents based on 2C.
PubMed: 35572704
DOI: 10.3389/fmicb.2022.856574 -
Journal of Clinical Biochemistry and... Jul 2023This study aimed to illustrate the dose-response relationships of the direct scavenging activity of amide-based local anesthetics against multiple free radicals . We...
This study aimed to illustrate the dose-response relationships of the direct scavenging activity of amide-based local anesthetics against multiple free radicals . We have demonstrated that amide-type local anesthetics selectively and directly scavenge some free radicals. Three kinds of free radicals were eliminated by all the four local anesthetics examined. Mepivacaine, lidocaine, bupivacaine, and dibucaine scavenged hydroxyl radicals in dose-dependent manners. Ascorbyl free radicals were also scavenged in dose-dependent manners, and lastly singlet oxygen was scavenged in dose-dependent manners. Three other free radicals were not scavenged by all of the four local anesthetics; -butoxyl radical was scavenged by all the anesthetics examined but dibucaine, nitric oxide by mepivacaine but not by the other three, and tyrosyl radical by mepivacaine and lidocaine but not by the other two. Some free radicals (superoxide anion, -butyl peroxyl radical, DPPH) were not scavenged by any of the four local anesthetics. The local anesthetics were also shown to inhibit lipid peroxidation by TBARS assay. These results suggest that local anesthetics have antioxidant properties through their free radical scavenging activities.
PubMed: 37534092
DOI: 10.3164/jcbn.22-131 -
Science Advances Jan 2022Enteroviruses are globally prevalent human pathogens responsible for many diseases. The nonstructural protein 2C is a AAA+ helicase and plays a key role in enterovirus...
Enteroviruses are globally prevalent human pathogens responsible for many diseases. The nonstructural protein 2C is a AAA+ helicase and plays a key role in enterovirus replication. Drug repurposing screens identified 2C-targeting compounds such as fluoxetine and dibucaine, but how they inhibit 2C is unknown. Here, we present a crystal structure of the soluble and monomeric fragment of coxsackievirus B3 2C protein in complex with ()-fluoxetine (SFX), revealing an allosteric binding site. To study the functional consequences of SFX binding, we engineered an adenosine triphosphatase (ATPase)–competent, hexameric 2C protein. Using this system, we show that SFX, dibucaine, HBB [2-(α-hydroxybenzyl)-benzimidazole], and guanidine hydrochloride inhibit 2C ATPase activity. Moreover, cryo–electron microscopy analysis demonstrated that SFX and dibucaine lock 2C in a defined hexameric state, rationalizing their mode of inhibition. Collectively, these results provide important insights into 2C inhibition and a robust engineering strategy for structural, functional, and drug-screening analysis of 2C proteins.
PubMed: 34985963
DOI: 10.1126/sciadv.abj7615 -
Molecular Pharmaceutics Jun 2023In this study, we investigated the effects of drugs on membrane function in which lipid peroxidation was inhibited by the antioxidant Trolox (TRO) in liposomes...
In this study, we investigated the effects of drugs on membrane function in which lipid peroxidation was inhibited by the antioxidant Trolox (TRO) in liposomes containing egg yolk lecithin. Local anesthetics (LAs), such as lidocaine (LID) and dibucaine (DIB), were used as model drugs. The effect of LAs on the inhibitory activity of TRO was evaluated by calculating the p from the inhibition constant calculated by curve fitting. p indicates the strength of TRO membrane protective function. p indicates the strength of LA activity. LAs inhibited lipid peroxidation in a dose-dependent manner and decreased p. The effect of DIB on p was 1.9 times more than that of LID. This result indicated that LA may improve the fluidity of the membrane, which may facilitate the migration of TRO from the membrane to the liquid phase. As a result, TRO is less likely to suppress lipid peroxidation within the lipid membrane, possibly resulting in a decrease in p. The effect of TRO on p was found to be similar in both, indicating that it did not depend on the type of the model drug. These results suggest that our developed procedure successfully quantified the effects of LAs on lipid membrane functions. We were able to obtain the characteristics of model drugs independent of TRO by simultaneously measuring and analyzing the lipid peroxidation inhibitory activities of TRO and model drugs in liposomes.
Topics: Anesthetics, Local; Liposomes; Lipid Peroxidation; Antioxidants; Dibucaine; Lidocaine; Lipids
PubMed: 37104048
DOI: 10.1021/acs.molpharmaceut.2c01053 -
Acta Anaesthesiologica Scandinavica Feb 2021Variants of butyrylcholinesterase are frequently associated with prolonged response to suxamethonium or mivacurium. Butyrylcholinesterase (BChE) can be characterized by...
INTRODUCTION
Variants of butyrylcholinesterase are frequently associated with prolonged response to suxamethonium or mivacurium. Butyrylcholinesterase (BChE) can be characterized by phenotyping and determination of genotype. Inappropriate timing of blood sampling might interfere with phenotyping methods. However, guidelines regarding delay between exposure to anaesthesia and testing are not clearly defined. In this study, the BChE activity and phenotype in an early (T1) and late (T2) phase were compared and the phenotype/genotype correlation was assessed.
METHODS
Patients with a prolonged paralysis after mivacurium or suxamethonium were selected after ethical committee approval and written consent. BChE activity was based on butyrylthiocholine hydrolysis rate and phenotyping on differential inhibition of BChE activity with dibucaine and fluoride. DNA sequencing allowed genotypic characterization.
RESULTS
We included the results of 20 patients with prolonged neuromuscular block (NMB) induced by mivacurium or suxamethonium. In these patients, BChE activity was different at T1 and T2 (2120 [1506-2733] U L and 4055 [2810-5301] U L , respectively; P = 0.0014; values are mean [95% CI]). When phenotyping was possible, phenotyping at T1 and T2 yielded identical results. Phenotyping failed to identify one new variant (p.Tyr146Cys) and the K variant in 14 of 16 patients.
CONCLUSION
Anaesthesia interfered with BChE activity, but not with phenotyping. Phenotyping can be performed on blood drawn during or immediately after recovery of mivacurium or suxamethonium to screen for clinically relevant variants of BChE. However, accurate diagnosis of BChE deficiency needs further confirmation by determination of genotype.
Topics: Apnea; Butyrylcholinesterase; Humans; Mivacurium; Neuromuscular Blockade; Succinylcholine
PubMed: 33010031
DOI: 10.1111/aas.13718 -
Journal of Pharmacy & Bioallied Sciences Jun 2021To compare and analyze the clinical adequacy of two topical anesthetic gels, Precaine (8% lidocaine + 0.8% dibucaine) and Precaine B (20% benzocaine) in children before...
AIM
To compare and analyze the clinical adequacy of two topical anesthetic gels, Precaine (8% lidocaine + 0.8% dibucaine) and Precaine B (20% benzocaine) in children before intraoral local anesthetic injections.
MATERIALS AND METHODS
This clinical study included thirty children who needed an inferior alveolar nerve block. They were divided into three groups: Group A: Precaine topical gel group, Group B: Precaine B topical gel Group, Group C: no anesthetic topical gel group (control group). These two effective topical gels were applied before giving intraoral local anesthesia, and afterward, the child's pain response was surveyed utilizing the Wong-Baker Faces Pain Rating Scale. The scores obtained were subjected to statistical analysis.
RESULTS
Intergroup comparison showed a significant mean difference between the control group and Precaine group ( > 0.05) as well as Precaine B group ( > 0.05). However, there is no significant difference obtained between Group A and Group B ( < 0.05).
CONCLUSION
It is psychologically and clinically beneficial to apply a topical anesthetic agent before injecting any intraoral anesthesia. In this study, both anesthetic gels showed a nonsignificant difference in reducing inferior alveolar injection pain, but Precaine B shows more promising results than Precaine.
PubMed: 34447172
DOI: 10.4103/jpbs.JPBS_772_20 -
Revista Brasileira de Ginecologia E... May 2021The diagnosis of genital ulcers remains a challenge in clinical practice. Lipschütz ulcer is a non-sexually transmitted rare and, probably, underdiagnosed condition,...
The diagnosis of genital ulcers remains a challenge in clinical practice. Lipschütz ulcer is a non-sexually transmitted rare and, probably, underdiagnosed condition, characterized by the sudden onset of vulvar edema along with painful necrotic ulcerations. Despite its unknown incidence, this seems to be an uncommon entity, with sparse cases reported in the literature. We report the case of an 11-year-old girl who presented at the emergency department with vulvar ulcers. She denied any sexual intercourse. The investigation excluded sexually transmitted infections, so, knowledge of different etiologies of non-venereal ulcers became essential. The differential diagnoses are extensive and include inflammatory processes, drug reactions, trauma, and malignant tumors. Lipschütz ulcer is a diagnosis of exclusion. With the presentation of this case report, the authors aim to describe the etiology, clinical course, and outcomes of this rare disease, to allow differential diagnosis of genital ulceration.
Topics: Administration, Topical; Anti-Infective Agents, Local; Child; Diagnosis, Differential; Dibucaine; Epstein-Barr Virus Infections; Female; Humans; Rare Diseases; Treatment Outcome; Ulcer; Vulvar Diseases
PubMed: 34077985
DOI: 10.1055/s-0041-1729147 -
Molecules (Basel, Switzerland) Aug 2022In this work, magnetic tetraethylenepentamine (TEPA)-modified carboxyl-carbon nanotubes were synthesized, characterized, and used as adsorbents to conduct magnetic...
In this work, magnetic tetraethylenepentamine (TEPA)-modified carboxyl-carbon nanotubes were synthesized, characterized, and used as adsorbents to conduct magnetic solid-phase extraction (MSPE) for the preconcentration of seven local anesthetic drugs (procaine, lidocaine, mepivacaine, oxybuprocaine, bupivacaine, tetracaine, and cinchocaine) from human plasma. The separation and determination of analytes were performed on high-performance liquid chromatography with UV detection. Several factors affected the extraction efficiency, such as the amount of adsorbents used, extraction time, sample pH, and optimization of elution conditions. Under optimal conditions, satisfactory linear relationships were obtained in the range of 0.02-5.00 mg/L, with the limits of detection (LOD) ranging from 0.003 mg/L to 0.008 mg/L. The recoveries of analytes for spiked human plasma were in the range of 82.0-108%. Moreover, the precision with intra-day and inter-day RSD values were obtained in the range of 1.5-7.7% and 1.5-8.3%. The results indicated that this method could determine the concentration of seven local anesthetic drugs in human plasma with high precision and repeatability and provide support for the clinical monitoring of the concentration of local anesthetic drugs in human plasma.
Topics: Anesthetics, Local; Chromatography, High Pressure Liquid; Humans; Magnetic Phenomena; Nanotubes, Carbon; Solid Phase Extraction
PubMed: 36080279
DOI: 10.3390/molecules27175509 -
The Journal of Biological Chemistry 2021The mitochondrial calcium uniporter (MCU) and cyclophilin D (CyD) are key players in induction of the permeability transition pore (PTP), which leads to mitochondrial...
The mitochondrial calcium uniporter (MCU) and cyclophilin D (CyD) are key players in induction of the permeability transition pore (PTP), which leads to mitochondrial depolarization and swelling, the major signs of Ca-induced mitochondrial damage. Mitochondrial depolarization inhibits ATP production, whereas swelling results in the release of mitochondrial pro-apoptotic proteins. The extent to which simultaneous deletion of MCU and CyD inhibits PTP induction and prevents damage of brain mitochondria is not clear. Here, we investigated the effects of MCU and CyD deletion on the propensity for PTP induction using mitochondria isolated from the brains of MCU-KO, CyD-KO, and newly created MCU/CyD-double knockout (DKO) mice. Neither deletion of MCU nor of CyD affected respiration or membrane potential in mitochondria isolated from the brains of these mice. Mitochondria from MCU-KO and MCU/CyD-DKO mice displayed reduced Ca uptake and diminished extent of PTP induction. The Ca uptake by mitochondria from CyD-KO mice was increased compared with mitochondria from WT mice. Deletion of CyD prevented mitochondrial swelling and resulted in transient depolarization in response to Ca, but it did not prevent Ca-induced delayed mitochondrial depolarization. Mitochondria from MCU/CyD-DKO mice did not swell in response to Ca, but they did exhibit mild sustained depolarization. Dibucaine, an inhibitor of the Ca-activated mitochondrial phospholipase A2, attenuated and bovine serum albumin completely eliminated the sustained depolarization. This suggests the involvement of phospholipase A2 and free fatty acids. Thus, in addition to induction of the classical PTP, alternative deleterious mechanisms may contribute to mitochondrial damage following exposure to elevated Ca.
Topics: Animals; Brain; Calcium; Calcium Channels; Peptidyl-Prolyl Isomerase F; Gene Knockout Techniques; Mice; Mice, Knockout; Mitochondria; Mitochondrial Proteins
PubMed: 33864812
DOI: 10.1016/j.jbc.2021.100669