Redox and Nucleophilic Reactions of Naphthoquinones with Small Thiols and Their Effects on Oxidization of H2S to Inorganic and Organic Hydropolysulfides and Thiosulfate.

Naphthoquinone (1,4-NQ) and its derivatives (NQs, juglone, plumbagin, 2-methoxy-1,4-NQ, and menadione) have a variety of therapeutic applications, many of which are attributed to redox cycling and the production of reactive oxygen species (ROS). We previously demonstrated that NQs also oxidize hydrogen sulfide (H2S) to reactive sulfur species (RSS), potentially conveying identical benefits. Here we use RSS-specific fluorophores, mass spectroscopy, EPR and UV-Vis spectrometry, and oxygen-sensitive optodes to examine the effects of thiols and thiol-NQ adducts on H2S-NQ reactions. In the presence of glutathione (GSH) and cysteine (Cys), 1,4-NQ oxidizes H2S to both inorganic and organic hydroper-/hydropolysulfides (R2Sn, R=H, Cys, GSH; n = 2-4) and organic sulfoxides (GSnOH, n = 1, 2). These reactions reduce NQs and consume oxygen via a semiquinone intermediate. NQs are also reduced as they form adducts with GSH, Cys, protein thiols, and amines. Thiol, but not amine, adducts may increase or decrease H2S oxidation in reactions that are both NQ- and thiol-specific. Amine adducts also inhibit the formation of thiol adducts. These results suggest that NQs may react with endogenous thiols, including GSH, Cys, and protein Cys, and that these adducts may affect both thiol reactions as well as RSS production from H2S.

Naphthoquinones Oxidize H2S to Polysulfides and Thiosulfate, Implications for Therapeutic Applications.

1,4-Napththoquinones (NQs) are clinically relevant therapeutics that affect cell function through production of reactive oxygen species (ROS) and formation of adducts with regulatory protein thiols. Reactive sulfur species (RSS) are chemically and biologically similar to ROS and here we examine RSS production by NQ oxidation of hydrogen sulfide (H2S) using RSS-specific fluorophores, liquid chromatography-mass spectrometry, UV-Vis absorption spectrometry, oxygen-sensitive optodes, thiosulfate-specific nanoparticles, HPLC-monobromobimane derivatization, and ion chromatographic assays. We show that NQs, catalytically oxidize H2S to per- and polysulfides (H2Sn, n = 2−6), thiosulfate, sulfite and sulfate in reactions that consume oxygen and are accelerated by superoxide dismutase (SOD) and inhibited by catalase. The approximate efficacy of NQs (in decreasing order) is, 1,4-NQ ≈ juglone ≈ plumbagin > 2-methoxy-1,4-NQ ≈ menadione >> phylloquinone ≈ anthraquinone ≈ menaquinone ≈ lawsone. We propose that the most probable reactions are an initial two-electron oxidation of H2S to S0 and reduction of NQ to NQH2. S0 may react with H2S or elongate H2Sn in variety of reactions. Reoxidation of NQH2 likely involves a semiquinone radical (NQ·−) intermediate via several mechanisms involving oxygen and comproportionation to produce NQ and superoxide. Dismutation of the latter forms hydrogen peroxide which then further oxidizes RSS to sulfoxides. These findings provide the chemical background for novel sulfur-based approaches to naphthoquinone-directed therapies.

Functional and Radiological Improvement in a COVID-19 Pneumonia Patient Treated With Steroids.

Like its predecessors, coronavirus disease 2019 (COVID-19) can lead to long-term health-related consequences in a significant segment of the afflicted population. Although the medical community has developed multiple vaccines by now, COVID-19 has affected over 100 million individuals worldwide and will infect millions more before vaccines can be effectively distributed on a global scale. Additionally, it seems probable that another outbreak caused by a coronavirus may occur in the future, given that this is the third outbreak caused by a coronavirus in recent history. In light of this, the medical community must develop reliable methods of curtailing long-term sequelae of coronaviruses, and the use of corticosteroids in affected patients may be vital for this purpose. In this report, we present a case of progressive dyspnea caused by COVID-19 pneumonia; the patient was treated with a short course of oral corticosteroids, and subsequently showed marked improvement of the dyspnea with corresponding improvements on chest CT.

Concurrent Incidental Presentation of Primary Retroperitoneal Follicular Lymphoma With Acute Pancreatitis.

BACKGROUND: Follicular lymphomas are a common type of non-Hodgkin's lymphomas (NHL). Presentation varies widely from being asymptomatic to painless peripheral lymphadenopathy to classic B symptoms. We present an unusual case of follicular lymphoma where the patient initially presented with signs and symptoms of acute pancreatitis. The aim of this study is to recognize the challenges faced while diagnosing retroperitoneal NHL and the need for timely management of this disease. CASE REPORT: A 66-year-old Hispanic female with a medical history of treatment compliant asthma and hypertension presented to the ER with complaints of abdominal pain in the right upper quadrant with serum lipase >3000 U/L and elevated liver function tests (LFTs), aspartate aminotransferase (AST) 139 U/L, alanine aminotransferase (ALT) 65 U/L, alkaline phosphatase (ALP) 122 U/L. Abdominal ultrasound identified gall bladder wall thickening and dilation of biliary ducts. CT scan showed soft tissue mass in the retroperitoneum, measuring 9.3x4.8cm which wrapped around the aorta and pushed it off the spine. After two days of conservative management, her pain resolved and lipase levels normalized, she was discharged and scheduled for outpatient endoscopic ultrasound (EUS) with biopsy of the retroperitoneal mass. The next day, the patient presented to the ER with similar pain, and labs again showed elevated lipase, EUS, and fine needle biopsy of mass showed CD-10 positive B-cell lymphoma. The patient was discharged after the resolution of pain. A positron emission tomography (PET) scan four weeks after the initial CT scan showed an increase in tumor size without any metastatic lesions. While awaiting core biopsy, the patient presented to the ER for the third time with worsening abdominal pain, lipase >3000 IU/L, and ultrasound showing cholelithiasis with cholecystitis. The patient underwent laparoscopic cholecystectomy. Core needle biopsy of paraspinal lymph nodes showed grade 1-2 follicular lymphoma. Finally, the patient underwent six cycles of chemotherapy with Bendamustine and Rituximab and after the fourth cycle, a repeat CT scan showed resolution of adenopathy with minimal residual soft tissue attenuation in retroperitoneum. DISCUSSION: NHL rarely occurs in retroperitoneum and its diagnosis is challenging. Our patient presented with the primary and unique occurrence of follicular lymphoma in the retroperitoneum. She presented with symptoms of an acute abdomen with elevated lipase and LFTs. She underwent multiple hospitalization and cholecystectomy before the correct diagnosis was made and until she was treated for follicular lymphoma. CONCLUSION: This study emphasizes the importance of being vigilant when a patient presents with unusual presentations of a disease in order to diagnose and treat the condition early to decrease the risk of complications and to mitigate the risk of poor outcomes.

A Cross-Sectional Survey on Telemedicine Use for Doctor-Patient Communication.

Introduction Use of computers for doctor-patient communication is increasing. Considering effective doctor-patient communication is important for good health outcomes. This study helps to determine the level of acceptance of telemedicine in general public and factors associated with it. Methods: This survey with cross-sectional analysis comprised a brief survey with 15 questions. The survey was distributed in public places to determine the opinions of the general public. Results Randomly selected 125 participants completed the questionnaire. Synchronous telemedicine was favored by young people (82% in the 18-34 age group vs 37.5% of participants aged >55 years; p<0.01), those with a higher education level (46.7% of non-college-educated persons vs 80.6% of college-educated persons; p<0.01), and frequent computer users (67% who used a computer for less than two hours a month vs 86.5% of those who used a computer more than hours a month; p=0.03). Asynchronous communication, like sending health information to doctors via a safe portal was acknowledged mostly by people who had used patient portals in the past (84.1% vs 65.4%; p=0.02). Use of patient portals was less among older users and senior citizens (20.8% use in the age group >55 vs. 51.3% in the age group 35-53 years vs. 71% in age group 18-34 years). Receiving video education for specific health concerns was favored by those who used a computer frequently (94.6% who used a computer more than two hours a month vs 77% who used a computer less than two hours a month; p =0.02). Conclusion Telemedicine is generally favored, but physicians should be mindful about older people as they may not feel comfortable. Step by step guidance should be provided especially to senior citizens for telemedicine and portal use.

Tuberculosis in West Virginia: an island in an encroaching sea.

West Virginia, for the past one hundred fifty years has adapted to the changing character of tuberculosis. The historical factors that influenced the changes from isolation of infected patients to mainstream treatment of tuberculosis are chronicled in this report. West Virginia, with its organized public health system and favorable demographics has, since 1970, seen a steady decline of tuberculosis. This decline in incidence exceeded national projection goals for TB elimination. New tuberculosis threats from increased third world immigration and global epidemic pressures are challenges for tuberculous management in both the United States and West Virginia. This report concludes with organizational guides designed to meet the new potential tuberculosis threats.