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Objective: The prevalence of antimicrobial resistance in Helicobacter pylori (HP) infection has increased globally. This study aimed to compare the efficacy of Biling Weitong granules (BLWTG) combined with quadruple therapy in patients with refractory HP infection who had previously failed eradication therapy. Methods: This single-center prospective study enrolled patients with two or more consecutive failed HP treatments. A total of 122 patients with previously failed HP treatment from our hospital were recruited as participants and randomly (1:1) allocated to two eradication groups: patients treated with bismuth-containing quadruple therapy (esomeprazole 40 mg, amoxicillin 1.0 g, bismuth potassium citrate 220 mg, and clarithromycin 500 mg, twice daily [EACB group]) for 14 days. And those treated with BLWTG (5 g three times daily) combined with the EACB group for 14 days (BLWTG+EACB group). The therapeutic effects of the two treatment programs were comprehensively evaluated. Results: The study group had a significantly higher improvement rate in symptoms (dull stomach pain, nausea, gastric distension, loss of appetite, and belching) compared to the control group (P < .05). Eight weeks after drug withdrawal, the eradication rates in the control and study groups were 49.18% and 73.77%, respectively. The levels of interleukin-6, C-reactive protein, and tumor necrosis factor-α were significantly lower in both groups after treatment but were significantly lower in the study group than in the control group (P < .05). Conclusions: The combination of BLWTG and standard four-drug therapy had a high eradication rate and low recurrence rate in patients with refractory HP infection. Additionally, this combined therapy could regulate inflammatory reactions and reduce drug-related adverse reactions.
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Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/etiología , Bismuto/farmacología , Bismuto/uso terapéutico , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Estudios Prospectivos , Quimioterapia Combinada , Resultado del Tratamiento , Amoxicilina/uso terapéutico , Amoxicilina/farmacologíaRESUMEN
This paper aims to study the difference in the intestinal absorption kinetics of main active components of Sini decoction and its separated recipes and explain the scientificity and rationality of the compatibility of Sini Decoction. A in situ intestinal perfusion rat model was established to evaluate the differences in the absorption of benzoylmesaconine, benzoylaconine, benzoylhypacoitine, mesaconitine, hypaconitine, glycyrrhizic acid, liquiritin and 6-gingerol from Sini Decoction and its separated recipes in the duodenum, jejunum and ileum by high performance liquid chromatography(HPLC). The results indicated that the Sini Decoction group was superior to the Aconiti Lateralis Radix Praeparata group in terms of absorption degree and rate for aconitum alkaloids. The absorption of benzoylmesaconine and hypaconitine in the duodenum, jejunum and ileum was faster and stronger in the Sini Decoction group(P<0.05). The absorption degree of glycyrrhizic acid in the duodenum was significantly higher in the Sini Decoction group than in the Glycyrrhizae Radix et Rhizoma group and the Glycyrrhizae Radix et Rhizoma-Zingiberis Rhizoma group(P<0.05). The absorption rate and degree of 6-gingerol in the ileum in the Sini Decoction group were significantly higher than those in the Zingiberis Rhizoma group(P<0.05). In short, Zingiberis Rhizoma and Glycyrrhizae Radix et Rhizoma can promote the absorption of aconitum alkaloids in different intestinal segments, which reflects the scientific composition of Sini Decoction.
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Aconitum , Alcaloides , Medicamentos Herbarios Chinos , Aconitina/análogos & derivados , Animales , Catecoles , Alcoholes Grasos , Ácido Glicirrínico , Absorción Intestinal , Cinética , RatasRESUMEN
The changes of serum cyclophilin A (CyPA), its receptor CD147 and the downstream signaling pathway during the process of cardiac hypertrophy remain unknown. The present study aims to investigate the relationships between CyPA-CD147-ERK1/2-cyclin D2 signaling pathway and the development of cardiac hypertrophy. Left ventricular hypertrophy was prepared by 2-kidney, 2-clip in Sprague-Dawley rats and observed for 1 week, 4 and 8 weeks. Left ventricular hypertrophy was evaluated by ratio of left ventricular heart weight to body weight (LVW/BW) and cardiomyocyte cross sectional area (CSA). CyPA levels in serum were determined with a rat CyPA ELISA kit. Expressions of CyPA, CD147, phospho-ERK1/2 and cyclin D2 in left ventricular myocytes were determined by Western blot and immunostaining. Compared with sham groups, systolic blood pressure reached hypertensive levels at 4 weeks in 2K2C groups. LVW/BW and CSA in 2K2C groups were significantly increased at 4 and 8 weeks after clipping. ELISA results indicated a prominent increase in serum CyPA level associated with the degree of left ventricular hypertrophy. Western blot revealed that the expressions of CyPA, CD147, phospho-ERK1/2 and cyclin D2 in left ventricular tissues were also remarkably increased as the cardiac hypertrophy developed. The results of the present study demonstrates that serum CyPA and CyPA-CD147-ERK1/2-cyclin D2 signaling pathway in ventricular tissues are time-dependently upregulated and activated with the process of left ventricular hypertrophy. These data suggest that CyPA-CD147 signaling cascade might play a role in the pathogenesis of left ventricular hypertrophy, and CyPA might be a prognosticator of the degree of left ventricular hypertrophy.
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Hipertrofia Ventricular Izquierda/metabolismo , Transducción de Señal , Animales , Basigina/metabolismo , Presión Sanguínea , Ciclina D2 , Ciclofilina A/metabolismo , Hipertensión , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Miocitos Cardíacos , Ratas , Ratas Sprague-Dawley , Regulación hacia ArribaRESUMEN
The pseudorabies virus (PRV) early protein EP0 is a homologue of the herpes simplex virus 1 (HSV-1) immediate-early protein ICP0, which is a multifunctional protein and important for HSV-1 infection. However, the exact function of EP0 is not clear. In this study, using polymerase chain reaction, a 1,104 base-pair sequence of the EP0 gene was amplified from the PRV Becker strain genome and identification of the EP0gene was confirmed by further cloning and sequencing. Bioinformatics analysis indicated that the PRV EP0 gene encoded a putative polypeptide with 367 amino acids. The encoded protein, designated as EP0 contained a conserved RING-finger superfamily domain and was found to be closely related with the herpes virus RING-finger superfamily and was highly conserved among the counterparts encoded by RING-finger genes. Multiple nucleic acid sequence and amino-acid sequence alignments suggested that PRV EP0 showed a relatively higher similarity with EP0-like proteins of genus Varicellovirus than with those of other genera of Alphaherpesvirinae. In addition, phylogenetic analysis showed that PRV EP0 had a close evolutionary relationship with members of genus Varicellovirus, especially bovine herpesvirus 1 (BoHV-1) and BoHV-5. Antigen prediction indicated that several potential B-cell epitopes were located in EP0. Also, subcellular localization analysis demonstrated that EP0 was predominantly localized in the nucleus, suggesting that it might function as a nuclear-targeted protein.
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Herpesvirus Suido 1/genética , Proteínas Virales/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Bovinos , Clonación Molecular , Biología Computacional , ADN Viral/genética , Datos de Secuencia Molecular , Filogenia , Reacción en Cadena de la Polimerasa , Estructura Secundaria de Proteína , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico , Proteínas Virales/químicaRESUMEN
BACKGROUND: Cronkhite-Canada syndrome (CCS) is a rare disease of unknown etiology. The optimal treatment for CCS remains unknown. Treatment with corticosteroids is considered the mainstay treatment because of its high efficacy, but the therapeutic strategy for steroid-resistant CCS is not yet established. CASE SUMMARY: This is the case of an 81-year-old woman who was diagnosed with CCS. Given her severe diarrhea, nausea, vomiting, and hypoproteinemia, hormone therapy (40 mg/d) was administered, and the symptoms improved within 1 wk. After 3 mo, the patient had no obvious symptoms. The polyps were significantly reduced on review gastroscopy and colonoscopy, thus hormone reduction gradually began. The hormone level was maintained at 10 mg/d after 6 mo. Despite the age of the patient and the side effects of hormones, the patient had no obvious discomfort. However, hormone drugs were discontinued, and mesalazine was administered orally at 3 g/d. The patient's symptoms continued to improve after a follow-up of 5 years. CONCLUSION: Corticosteroids and mesalazine are potential treatment options for CCS.
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RAB3B is essential for the transportation and secretion within cells. Its increased expression is linked to the development and progression of various malignancies. However, understanding of RAB3B's involvement in carcinogenesis is mostly limited to specific cancer subtypes. Hence, exploring RAB3B's regulatory roles and molecular mechanisms through comprehensive cancer datasets might offer innovative approaches for managing clinical cancer. To examine the potential involvement of RAB3B in the development of cancer, we analyzed data from various sources including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), cBioPortal, HPA, UALCAN, and tissue microarray (TAM). Using bioinformatics techniques, we examined the correlation between RAB3B expression and prognosis, tumor heterogeneity, methylation modifications, and immune microenvironment across different cancer types. Our findings indicate that elevated RAB3B expression can independently predict prognosis in many tumors and has moderate accuracy for diagnosing most cancers. In most cancer types, we identified RAB3B mutations that showed a significant correlation with tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and microsatellite instability (MSI). Abnormal DNA methylation patterns were also observed in most cancers compared to normal tissues. Additionally, we found significant correlations between RAB3B expression, immune cell infiltration, and immune scores across various cancers. Through pan-cancer analysis, we observed significant differences in RAB3B expression levels between tumors and normal tissues, making it a potential primary factor for cancer diagnosis and prognosis. The IHC results revealed that the expression of RAB3B in six types of tumors was consistent with the results of the pan-cancer analysis of the database. Furthermore, RAB3B showed potential associations with tumor heterogeneity and immunity. Thus, RAB3B can be utilized as an auxiliary diagnostic marker for early tumor detection and a prognostic biomarker for various tumor types.
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Biomarcadores de Tumor , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Neoplasias , Microambiente Tumoral , Proteínas de Unión al GTP rab3 , Humanos , Biomarcadores de Tumor/genética , Biología Computacional/métodos , Mutación , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/diagnóstico , Neoplasias/patología , Pronóstico , Proteínas de Unión al GTP rab3/genética , Proteínas de Unión al GTP rab3/metabolismo , Microambiente Tumoral/inmunología , Microambiente Tumoral/genéticaRESUMEN
Intestinal perforation (IP) is a rare complication of systemic lupus erythematosus (SLE), and the timely diagnosis and treatment of IP are necessary to prevent death. In this study, the clinical features of IP in SLE were described in an attempt to enhance its understanding to reduce mortality. The clinical data of IP in SLE from 1984 to 2022 were retrospectively collected. A total of 18 patients were enrolled, and data on clinical symptoms, preoperative evaluation, surgical procedures, and postoperative outcomes were collected and retrospectively analyzed. The analysis included 15 females and 3 males, with a mean age of 49.2 years. Fifteen patients (83.3%) had a history of the disease for >5 years, and the SLE disease activity index score of 1 (5.6%) patient was <5 points and that of 17 (94.4%) patients was >10 points. A total of 9 (50%), 5 (27.7%), 3 (16.7%), and 1 (5.6%) patient had lesions in the rectum, colon, ileum, and both ileum and appendix, respectively. The cause of perforation in 12 (66.7%) patients was lupus mesenteric vasculitis and in 3 (16.7%) patients was chronic inflammation. Seven (38.9%) patients had other immune system diseases. All patients were treated with steroids and surgical treatment. However, 5 patients died after surgery. A disease duration of >5 years, SLE disease activity index score of >10, nonstandard use of steroids, and concomitant presence of other immune system diseases are the possible risk factors of IP in SLE. The most common site of perforation was the rectum, which was caused by lupus mesenteric vasculitis. The results suggest that the key to successfully manage such cases is early diagnosis, aggressive resuscitation, antibiotics, steroid therapy, and prompt surgical intervention.
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Perforación Intestinal , Lupus Eritematoso Sistémico , Vasculitis , Masculino , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Perforación Intestinal/cirugía , Perforación Intestinal/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Factores de Riesgo , Vasculitis/diagnósticoRESUMEN
BACKGROUND: Esophageal granular cell tumor (eGCT) is a relatively rare, usually benign neoplasm of the neuroectoderm. It is derived from Schwann cells. Clinical symptoms of this disease are non-specific. However, the most common presenting symptom is dysphagia, which is mostly misdiagnosed as esophageal polyps under gastroscopy, yet it has a 2% chance of forming cancers. We report the case of a 52-year-old woman with solitary eGCT, then analysed retrospectivelyanalyze the clinical features and elucidate on the reduction of misdiagnosis and missed diagnosis. CASE SUMMARY: A 52-year-old woman was diagnosed with "esophageal granulossoma" after esophagoscopy, which was mistaken for eGCT. CONCLUSION: eGCT diagnosis depends on characteristic pathomorphologies and detection of the S-100 protein. Endoscopic mucosal resection is the preferred therapeutic method.
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BACKGROUND: Intraneural ganglion cysts of the ulnar nerve at the wrist are rare and poorly understood. We report a case of an intraneural ganglion cyst at the level of the wrist.Case presentation: A 48-year-old man presented with the complaints of weakness for 6 months and serious aggravation for 1 month in his right hand. After examinations, including ultrasound, the patient was diagnosed with an intraneural ganglion cyst. Intraoperatively, with exposure of the ulnar nerve, we found that the intraneural ganglion cyst was at the level of Guyon's canal and extended approximately 6 cm proximally. Postoperatively, sensation of the fingers was normal, but atrophy of his muscles and limited straightening of his ring and little fingers were similar to those preoperatively. CONCLUSIONS: Diagnosis of an intraneural cyst before surgery is mostly based on ultrasound and magnetic resonance imaging. Transection of the articular branch is an important measure to prevent recurrence of this cyst. If the ulnar nerve is compressed and causes symptoms, nerve decompression, including removal/aspiration of the cyst, and sometimes external neurolysis of the nerve, are necessary to relieve the symptoms and allow regeneration of the nerve. However, these should be performed without damaging the nerve fascicles.
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Ganglión , Ganglión/diagnóstico por imagen , Ganglión/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Nervio Cubital , Muñeca/diagnóstico por imagen , Muñeca/cirugía , Articulación de la MuñecaRESUMEN
OBJECTIVE: To evaluate the effectiveness and safety of allogeneic tendons for functional reconstruction of severe hand injuries. METHODS: From August 2007 to July 2014, we performed functional reconstruction with tendon allografts for severe hand injuries affecting two or more tendons. At the final follow-up, we assessed total active motion (TAM); pincer pinch strength; grip strength; Disabilities of the Arm, Shoulder, and Hand (DASH) score; degree of satisfaction; and adhesion. We measured the white blood cell count, C-reactive protein concentration, erythrocyte sedimentation rate, total T-cell count, and CD4+T/CD8+T ratio to evaluate the immune response and check for infection. RESULTS: Ten patients received 26 allogeneic tendons to reconstruct hand function. The average follow-up period was 50.0 months (range, 24-82 months). The TAM was 126.4° (12°-253°), pincer pinch strength was 0.83 kg (0-4.5 kg), and grip strength was 13.69 kg (4-41.5 kg). The DASH score was 14.25 (3.3-30.8), and seven and three patients were satisfied and partially satisfied, respectively. One patient developed tendon adhesion. All immune and infectious parameters were within the reference range. CONCLUSION: Functional reconstruction using allogeneic tendons for severe hand injuries with multiple tendon defects was effective and safe; however, more research is needed.
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Traumatismos de la Mano , Trasplante de Células Madre Hematopoyéticas , Mano , Traumatismos de la Mano/cirugía , Fuerza de la Mano , Humanos , Rango del Movimiento Articular , Estudios Retrospectivos , Tendones/cirugíaRESUMEN
AIM: To determine the association between retinal vasculature changes and stroke. METHODS: MEDLINE and EMBASE were searched for relevant human studies to September 2015 that investigated the association between retinal vasculature changes and the prevalence or incidence of stroke; the studies were independently examined for their qualities. Data on clinical characteristics and calculated summary odds ratios (ORs) were extracted for associations between retinal microvascular abnormalities and stroke, including stroke subtypes where possible, and adjusted for key variables. RESULTS: Nine cases were included in the study comprising 20 659 patients, 1178 of whom were stroke patients. The retinal microvascular morphological markers used were hemorrhage, microaneurysm, vessel caliber, arteriovenous nicking, and fractal dimension. OR of retinal arteriole narrowing and retinal arteriovenous nicking and stroke was 1.42 and 1.91, respectively, indicating that a small-caliber retinal arteriole and retinal arteriovenous nicking were associated with stroke. OR of retinal hemorrhage and retinal microaneurysm and stroke was 3.21 and 3.83, respectively, indicating that retinal microvascular lesions were highly associated with stroke. Results also showed that retinal fractal dimension reduction was associated with stroke (OR: 2.28 for arteriole network, OR: 1.80 for venular network). CONCLUSION: Retinal vasculature changes have a specific relationship to stroke, which is promising evidence for the prediction of stroke using computerized retinal vessel analysis.
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Reactive oxygen speciesinduced cyclophilin A (CyPA) release from vascular smooth muscle cells (VSMCs) may be inhibited by simvastatin in vitro. The present study aimed to further examine the effect of simvastatin on serum CyPA levels and the basigin (CD147)extracellular signalregulated kinase (ERK) 1/2cyclin pathway during thoracic aorta remodeling. The mechanisms through which simvastatin may inhibit CyPA secretion from VSMCs were further investigated. Serum CyPA levels and the expression kinetics of CyPAassociated signaling pathways were examined following simvastatin treatment in rat thoracic aortas during hypertension. Cell lysates were prepared from middle layer of thoracic aortas at 1, 4, 8 and 12 weeks subsequent to surgery. ELISA analysis revealed that serum CyPA levels were gradually increased with the progression of thoracic aorta remodeling. Western blotting demonstrated that the expression of CD147, phosphorylatedERK1/2, cyclin D1, cyclin A, and cyclin E were increased with the progression of thoracic aorta remodeling. Simvastatin administration for 4, 8 and 12 weeks diminished all these changes, as observed in the hypertensive group. VSMCs from simvastatintreated rats secreted a decreased amount of CyPA compared with VSMCs from hypertensive rats. In addition, pretreatment with geranylgeraniol partly reversed the inhibitory effect of simvastatin on LY83583induced CyPA secretion in cultured VSMCs, whereas GGTI298 and KD025 [a selective Rhoassociated protein kinase 2 (ROCK2) inhibitor] mimicked the inhibitory effect of simvastatin. The present study demonstrated that simvastatin alleviated thoracic aorta remodeling by reducing CyPA secretion and expression of the CD147ERK1/2cyclin signaling pathway. In addition, the results of the present study demonstrated that the RhoROCK2 pathway mediated CyPA secretion from VSMCs.
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Aorta Torácica/metabolismo , Aorta Torácica/patología , Ciclofilina A/metabolismo , Transducción de Señal/efectos de los fármacos , Simvastatina/farmacología , Remodelación Vascular/efectos de los fármacos , Quinasas Asociadas a rho/metabolismo , Animales , Basigina/metabolismo , Biomarcadores , Biopsia , Ciclinas/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , RatasRESUMEN
AIMS: To evaluate the efficacy, tolerability, and safety of long-acting versus standard non-ergot dopamine agonists (NEDAs) in Parkinson's disease (PD), we performed a meta-analysis of randomized controlled trials (RCTs). MATERIALS AND METHODS: The PubMed, EMBASE, Cochrane Library databases, and Web of Knowledge were searched up to November 20th 2013. The pooled weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs) were calculated. RESULTS: Eight large-scale RCTs, involving 2402 patients, were included in this meta-analysis. Compared with the standard NEDAs, long-acting NEDAs exhibited similar improvements in Unified Parkinson's Disease Rating Scale activities of daily living (ADL) score (WMD 0.09, 95% CI -0.33 to 0.50), motor score (WMD -0.35, 95% CI -1.60 to 0.90), and "off" time (WMD 0.18, 95% CI -0.14 to 0.50). No differences were found in overall withdrawals (RR 1.11, 95% CI 0.94 to 1.32), withdrawals due to adverse events (RR 1.19, 95% CI 0.91 to 1.56), or the ten commonly reported adverse events between the two formulations. CONCLUSIONS: Our meta-analysis showed long-acting NEDAs were noninferior to standard NEDAs in efficacy, tolerability, and safety in the treatment of PD.
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Antiparkinsonianos/uso terapéutico , Agonistas de Dopamina/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Antiparkinsonianos/efectos adversos , Agonistas de Dopamina/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pacientes Desistentes del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: Delayed diagnosis of scabies can cause an institutional outbreak, which causes considerably economic burden to control. This study was to find the risk factors for delayed diagnosis of scabies in hospitalized patients from long-term care facilities. METHODS: We conducted a retrospective analysis of the hospitalized patients from long-term care facilities, diagnosed to have scabies between January 2006 and December 2008. A stepwise logistic regression analysis was performed to determine the risk factors for delayed diagnosis of scabies. RESULTS: A total of 706 episodes with scabies were identified retrospectively in 399 hospitalized patients from long-term care facilities. Of these, 44 episodes were considered as delayed diagnosis of scabies. These patients were more associated with chronic usage of steroid (73% vs. 10%, P < 0.001) and had longer duration of hospitalization than the others (30 vs. 13 days, P < 0.001). After logistic regression, steroid therapy was the risk factor of delayed diagnosis of scabies (odds ratio: 23.493). CONCLUSIONS: In the patients from long-term care facilities, clinical physicians should pay more attention to those with chronic usage of steroid to avoid delayed diagnosis of scabies. KEYWORDS: Scabies; Delayed diagnosis; Risk factor; Long-term care facility.
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The purpose of this study was to examine the differences in the induction of DNA damage and cytotoxic effects by quinonoid derivatives of naphthalene in calf thymus DNA (ct-DNA) and in human T47D breast cancer cells. Results indicated that copper(II) and NADPH were essential for causing oxidant-mediated aldehydic DNA lesions (ADLs), including abasic sites and aldehydic base/sugar lesions, in ct-DNA exposed to 1,2-naphthalenediol (NCAT), 1,4-naphthalenediol (NHQ), 1,2-naphthoquinone (1,2-NQ), and 1,4-naphthoquinone (1,4-NQ). The ADLs induced by naphthalene quinonoids in ct-DNA decrease in the rank order NCAT congruent with 1,2-NQ > NHQ >> 1,4-NQ. Results from the analyses in cells indicated that after 1.5-5 h of exposure all naphthalene quinonoids induced a cytotoxic response in T47D cells at concentrations 10-100 microM or above, where NHQ and 1,4-NQ were approximately 5-10 times more efficient than NCAT and 1,2-NQ in the induction of cell death. In addition, NHQ, 1,2-NQ, and 1,4-NQ were not able to produce measurable levels of ADLs in cells at concentrations up to 1.25 mM, whereas NCAT (0.75-1.25 mM) induced a significant increase in the number of ADLs in T47D cells after 1.5 h of exposure when compared to control. The specific type of ADLs induced by NCAT is resistant to cellular excision repair pathway. Results from the measurements of reactive oxygen species (ROS) indicated that all naphthalene quinonoids induced increases in ROS formation in T47D cells. The induction of ROS formation in cells by naphthalene quinonoids decreases in the rank order 1,4-NQ congruent with 1,2-NQ > NHQ > NCAT. Overall, results from our investigation suggest that naphthalene quinonoids cause cell death at concentrations well below the concentrations at which they induce the formation of ADLs, perhaps by altering intracellular redox status.