Volatile molecules for COVID-19: A possible pharmacological strategy?

COVID-19 is a novel coronavirus disease with a higher incidence of bilateral pneumonia and pleural effusion. The high pulmonary tropism and contagiousness of the virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have stimulated new approaches to combat its widespread diffusion. In developing new pharmacological strategies, the chemical characteristic of volatility can add therapeutic value to the hypothetical drug candidate. Volatile molecules are characterized by a high vapor pressure and are consequently easily exhaled by the lungs after ingestion. This feature could be exploited from a pharmacological point of view, reaching the site of action in an uncommon way but allowing for drug delivery. In this way, a hypothetical molecule for COVID-19 should have a balance between its lung exhalation characteristics and both antiviral and anti-inflammatory pharmacological action. Here, the feasibility, advantages, and disadvantages of a therapy based on oral administration of possible volatile drugs for COVID-19 will be discussed. Both aerosolized antiviral therapy and oral intake of volatile molecules are briefly reviewed, and an evaluation of 1,8-cineole is provided in view of a possible clinical use and also for asymptomatic COVID-19.     

Baicalin-loaded PEGylated lipid nanoparticles: characterization,pharmacokinetics, and protective effects on acute myocardial ischemia in rats

Context: Baicalin has many pharmacological activities, including protective function against myocardial ischemia by antioxidant effects and free radical scavenging activity. However, its rapid elimination half-life in plasma and poor water solubility limits its clinical efficacy.

Objective: Novel baicalin-loaded PEGylated nanostructured lipid carriers (BN-PEG-NLC) were developed to improve bioavailability of BN, to prolong retention time in vivo and to enhance its protective effect.

Methods: In this study, BN-PEG-NLC were prepared by the emulsion-evaporation and low temperature-solidification method using a mixture of glycerol monostearate and polyethylene glycol monostearate as solid lipids, and oleic acid as the liquid lipid. The physicochemical properties of NLC were characterized. The pharmacokinetic and pharmacodynamic behaviors of BN-PEG-NLC or BN-NLC were evaluated in acute MI rats.

Results and discussion: The particle size, zeta potential, and entrapment efficiency for BN-PEG-NLC were observed as 83.9?nm, ?32.1?mV, and 83.5%, respectively. The release profiles of BN from both BN-PEG-NLC and BN-NLC were fitted to the Ritger–Peppas modal, which presented burst release initially and prolonged release afterwards. Pharmacokinetics results indicated that BN-PEG-NLC exhibited a 7.2-fold increase in AUC in comparison to BN solution, while a 3-fold increase in comparison to BN-NLC. Biodistribution results revealed that BN-PEG-NLC exhibited higher heart drug concentration compared with BN-NLC as well as BN solution. In the present study, BN-PEG-NLC significantly ameliorated infarct size.

Conclusion: The results of the present study imply that PEG-NLC could be the biocompatible carriers for heart-targeted drug delivery to improve myocardial ischemia.     

羟基磷灰石义眼台作为药物缓释载体减轻术后反应的临床观察

目的评价羟基磷灰石（HA）义眼台作为药物缓释载体减轻眼球摘除义眼台植入术后反应的效果。方法植入HA义眼台前，用地塞米松5mg，庆大霉素8万u，透明质酸酶1500U混合液浸泡HA义眼台15—20min后植入，手术步骤按常规。结果观察术后1周反应情况，52例中51例（98．07％）无疼痛或仅有轻度疼痛；44例（84．62％）结膜无水肿；36例（69．23％）无恶心；16例（30．77％）轻中度恶心；48例（92．31％）无呕吐。与对照组（43例）比较，术后疼痛、结膜水肿、恶心呕吐均较轻，其差别均有统计学意义（P〈0．001）。结论HA义眼台作为药物缓释载体植入眼球肌膜囊内能有效地控制术后反应，减轻患者痛苦。     

Urine as an alternative to urethral swabs for the diagnosis of Chlamydia trachomatis in infertile males

Swabbing the urethrae of men has been the traditional approach for collecting specimens for detection of Chlamydia trachomatis . Recently, however, urine testing using enzyme immunoassay has yielded promising results. A total of 105 patients attending the Andrology Clinic at Ga Rankuwa Hospital, Medunsa were included in the study. These patients were asymptomatic and had no urethral discharge. Three endo-urethral swabs and first-catch urine were collected fiom each patient. The urethral swabs were used for enzyme immunoassay (EIA) (IDEIA 111), tissue culture and direct immonufluorescent antibody (DFA) test (IMAGEN) to detect C. trachomatis . In addition about 15–30 ml of first-catch urine, or urine collected at least 2h after the previous micturition, was collected for each patient for EIA testing. Fifteen (14.3%) of 105 patients were positive on urethral swab EIA, in comparison with the DFA test in which 14 (13.3%) were positive. Eight (7.8%) were positive in tissue culture. Urine EIA was positive in 17 (16.2%) patients, of whom five (4.8%) were positive in urine EIA only. All EIA positive urines were confirmed by DFA. We recommend that first-catch urine or urine collected at least 2h after the previous micturition in infertile males may be considered a suitable alternative to urethral swab for chlamydial diagnosis because it is noninvasive and nontraumatic.     

以胆酸为载体的肝靶向疗法

通过肝靶向给药技术将化学治疗药物选择性地投放于肝脏,能够减轻或避免其全身的毒副作用.胆酸是唯一的口服有效的小分子肝靶向载体,以胆酸为载体的肝靶向疗法为肝病及肝脏代谢性疾病提供了新的疗法.如胆酸-一氧化氮供体靶向偶合物能够选择性地将一氧化氮投放于肝脏,产生治疗肝硬化的作用;胆酸-脂肪酸靶向偶合物能够选择性地调节肝脏的脂代谢,具有治疗胆结石、脂肪肝和动脉粥样硬化的作用;胆酸-米非司酮偶合物能够选择性地作用于肝脏,产生特异性的降糖作用,而没有全身副作用.     

Antibody dynamics to SARS-CoV-2 in asymptomatic COVID-19 infections

Background

The missing asymptomatic COVID-19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the humoral immunity in asymptomatic carriers will provide scientific knowledge for developing serological tests, improving early identification, and implementing more rational control strategies against the pandemic.

Measure

Utilizing both NAT and commercial kits for serum IgM and IgG antibodies, we extensively screened 11 766 epidemiologically suspected individuals on enrollment and 63 asymptomatic individuals were detected and recruited. Sixty-three healthy individuals and 51 mild patients without any preexisting conditions were set as controls. Serum IgM and IgG profiles were further probed using a SARS-CoV-2 proteome microarray, and neutralizing antibody was detected by a pseudotyped virus neutralization assay system. The dynamics of antibodies were analyzed with exposure time or symptoms onset.

Results

A combination test of NAT and serological testing for IgM antibody discovered 55.5% of the total of 63 asymptomatic infections, which significantly raises the detection sensitivity when compared with the NAT alone (19%). Serum proteome microarray analysis demonstrated that asymptomatics mainly produced IgM and IgG antibodies against S1 and N proteins out of 20 proteins of SARS-CoV-2. Different from strong and persistent N-specific antibodies, S1-specific IgM responses, which evolved in asymptomatic individuals as early as the seventh day after exposure, peaked on days from 17 days to 25 days, and then disappeared in two months, might be used as an early diagnostic biomarker. 11.8% (6/51) mild patients and 38.1% (24/63) asymptomatic individuals did not produce neutralizing antibody. In particular, neutralizing antibody in asymptomatics gradually vanished in two months.

Conclusion

Our findings might have important implications for the definition of asymptomatic COVID-19 infections, diagnosis, serological survey, public health, and immunization strategies.

     

The hyperpolarisation-activated current,I f,is not required for pacemaking in single cells from the rabbit atrioventricular node

Using electrophysiological and radiotracer studies in parallel, we have investigated the characteristics of the endogenous Na⁺-dependent amino acid transporter (system B^0,+) in Xenopus oocytes with regard to ion dependence, voltage dependence and transport stoichiometry. In voltage-clamped oocytes (–60 mV) superfusion with saturating concentrations of amino acids (1 mM) in 100 mM NaCl resulted in reversible, inward currents (mean±SEM): alanine, 1.83±0.09 nA (n=21); arginine, 2.54±0.18 nA (n=17); glutamine, 1.73±0.10 nA (n=19). Only arginine evoked a current in choline medium (0.50±0.13 nA, n=10), whereas Cl^– replacement had no effect on evoked currents. The glutamine-evoked current was saturable (I _max=1.73 nA, glutamine K _m=0.12 mM) and linearly dependent upon voltage between –90 and –30 mV. Using direct and indirect (activation) methods, we found that transport can proceed with Na⁺/amino acid coupling stoichiometry of either 11 or 21, but coupling was the same for each amino acid tested (alanine, arginine and glutamine) within a batch of oocytes (i.e. from a single toad). Despite the net single positive charge on arginine, the magnitude of the net transmembrane charge movement during Na⁺-coupled arginine transport was identical to that for the zwitterionic neutral amino acids glutamine and alanine; this may be explained by a concomitant stimulation of K⁺ efflux during arginine transport with a putative coupling of 1 K⁺1 arginine.     

抗骨肉瘤药物纳米载体的研究进展

骨肉痛是最常见的恶性骨肿瘤,病死率较高。而生物医用纳米材料是纳米材料和生物材料交叉的一个全新领域,在生物医学上有着十分诱人的、广泛的应用前景。本文对纳米无机生物材料、纳米高分子生物材料、纳米复合生物材料作为抗骨肉瘤药物载体的研究进展作了较全面的综述。     

Comparison of full length sequences of hepatitis B virus isolates in hepatocellular carcinoma patients and asymptomatic carriers of Korea

Relatively few genomic sequences of Korean hepatitis B virus (HBV) isolates are available. Moreover, no comparative study has been made between the full-length genomes of Korean HBV isolates and clinical status. To evaluate mutations in HBV isolates obtained from chronically infected HBV patients in terms of clinical significance, we determined the genomic sequences of HBV isolates obtained from three hepatocellular carcinoma (HCC) patients (He52, He53, and He82) and from three asymptomatic carriers (He74, He100, and He127). A comparison of sequence variations showed that the HBV isolates from the three HCC patients showed higher frequencies of mutation than the isolates from the three asymptomatic carriers. Three characteristic mutation patterns were identified in the HBV isolates from the HCC patients, which distinguished the HBV isolates from the asymptomatic carriers. First, HBV isolates from the three HCC patients both had double mutations in a core promoter (T1762/A1764) and a precore mutation (A1896). Second, although these isolates belonged to genotype C, 11 amino acids deletions in the preS1 region, specific for HBV genotype D, were detected in the isolates of two HCC patients (He52 and He82). Third, mutations (I127T/N, K130M, and V131I) at three codons in the carboxy functional region of X protein were observed in isolates from all three HCC patients. Additionally, phylogenetic analysis based on the entire HBV sequences showed that all six isolates belonged to genotype C2, as do other Korean strains.