Vorinostat with Sustained Exposure and High Solubility in Poly(ethylene glycol)-b-poly(DL-lactic acid) Micelle Nanocarriers: Characterization and Effects on Pharmacokinetics in Rat Serum and Urine

The histone deacetylase inhibitor suberoylanilide hydroxamic acid, known as vorinostat, is a promising anti-cancer drug with a unique mode of action; however, it is plagued by low water solubility, low permeability, and suboptimal pharmacokinetics. In this study, poly(ethylene glycol)-b-poly(DL-lactic acid) (PEG-b-PLA) micelles of vorinostat were developed. Vorinostat’s pharmacokinetics in rats were investigated after intravenous (i.v.) (10 mg/kg) and oral (50 mg/kg) micellar administrations and compared to a conventional PEG400 solution and methylcellulose suspension. The micelles increased the aqueous solubility of vorinostat from 0.2 mg/ml to 8.15 ± 0.60 mg/ml and 10.24 ± 0.92 mg/ml at drug to nanocarrier ratios of 1:10 and 1:15, respectively. Micelles had nanoscopic mean diameters of 75.67 ± 7.57 nm and 87.33 ± 8.62 nm for 1:10 and 1:15 micelles, respectively, with drug loading capacities of 9.93 ± 0.21% and 6.91 ± 1.19 %, and encapsulation efficiencies of 42.74 ± 1.67% and 73.29 ± 4.78%, respectively. The micelles provided sustained exposure and improved pharmacokinetics characterized by a significant increase in serum half-life, area under curve, and mean residence time. The micelles reduced vorinostat clearance particularly after i.v. dosing. Thus, PEG-b-PLA micelles significantly improved the oral and intravenous pharmacokinetics and bioavailability of vorinostat, which warrants further investigation

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Microwave synthesis and fluorescence properties of homo- and heterodimeric monomethine cyanine dyes TOTO and their precursors

A series of monomeric and dimeric cyanine dyes belonging to the thiazole orange family have been prepared via an improved synthetic procedure, by the reaction of the monomethine dye containing an iodoalkyl group with tertiary diamine linkers under microwave irradiation. The effects of microwave power and irradiation time on yield were examined. The electronic absorption and steady-state fluorescence spectra of prepared dyes have been investigated. Fluorescence properties indicate significance in singlet oxygen sensitization and make the present compounds potential candidates in the area of photodynamic therapy

Technique and outcome of autotransplanting thyroid tissue after total thyroidectomy for simple multinodular goiters

Background/Objective: Limited animal and human studies have shown function, albeit inadequate, of implanted thyroid tissue in muscles. This work aimed to ascertain results in a larger number of patients, finding practical method for implantation, studying the effect of changing weight of implant and effect of passage of time on its function. Methods: Forty patients had total thyroidectomy for simple multinodular goiters. A piece of the excised gland was finely minced, mixed with saline as emulsion, and injected in thigh muscles. Twelve patients had 5-g implants, while 28 patients had 10-g implants. Four parameters were studied at 2 months, 6 months, and 12 months: technetium isotope uptake by the implant; thyroid stimulating hormone (TSH); free T3 (FT3); and free T4 (FT4). Results: All autotransplanted thyroid tissue survived and functioned. After 12 months, mean values (± standard deviation) of isotope uptake, TSH, FT3, and FT4 of the 5-g implants were 0.44 ± 0.16%, 27.74 ± 30.4 UI/mL, 3.07 ± 1.10 pg/mL, and 1.01 ± 0.3 ng/dL, repectively. Those for the 10 g implants were 0.71 ± 0.20%, 22.78 ± 19.7 UI/mL, 3.92 ± 1.2 pg/mL, and 1.05 ± 0.3 ng/dL, repectively. Ten-gram implants showed significantly higher isotope uptake than 5-g. TSH, FT3, and FT4 significantly improved over the period of 1 year. Conclusion: Injection of thyroid tissue suspension is a simple method for thyroid autotransplantation. TSH was elevated in the majority to maintain normal or near normal thyroid hormones. Ten-gram implants showed higher isotope uptake than 5-g, although this difference was not reflected by thyroid hormone profile. The implant seemed to function better with the passage of time from 2 months to 12 months

Formulation of lipid polymer hybrid nanoparticles of the phytochemical Fisetin and its in vivo assessment against severe acute pancreatitis

Abstract Fisetin (FST) is a naturally occurring flavonol that has recently emerged as a bioactive phytochemical with an impressive array of biological activities. To the author knowledge, boosting the activity of FST against severe acute pancreatitis (SAP) through a nanostructured delivery system (Nanophytomedicine) has not been achieved before. Thereupon, FST-loaded lipid polymer hybrid nanoparticles (FST-loaded LPHNPs) were prepared through conjoined ultrasonication and double emulsion (w/o/w) techniques. Comprehensive in vitro and in vivo evaluations were conducted. The optimized nanoparticle formula displayed a high entrapment efficiency % of 61.76 ± 1.254%, high loading capacity % of 32.18 ± 0.734, low particle size of 125.39 ± 0.924 nm, low particle size distribution of 0.357 ± 0.012, high zeta potential of + 30.16 ± 1.416 mV, and high mucoadhesive strength of 35.64 ± 0.548%. In addition, it exhibited a sustained in vitro release pattern of FST. In the in vivo study, oral pre-treatment of FST-loaded LPHNPs protected against l-arginine induced SAP and multiple organ injuries in rats compared to both FST alone and plain LPHNPs, as well as the untreated group, proven by both biochemical studies, that included both amylase and lipase activities, and histochemical studies of pancreas, liver, kidney and lungs. Therefore, the study could conclude the potential efficacy of the novel phytopharmaceutical delivery system of FST as a prophylactic regimen for SAP and consequently, associated multiple organ injuries

“Medical student syndrome”: a real disease or just a myth?—a cross-sectional study at Menoufia University, Egypt

Abstract Background A widely held belief is that “Medical student syndrome” is frequently experienced by young medical students, that is, they experience the symptoms of the diseases they are studying or fear of having such illness. A hypothesis is that because medical students constantly learn about life-threatening conditions and diseases, they experience persistent fear and stress regarding having a severe medical condition, an anxiety-related illness called nosophobia. Results Although medical students scored an average of 14.14 on a scale measuring potential nosophobia a, the difference between their scores and those of non-medical students, who scored an average of 0.11, is significantly higher (p 0.001). According to the presented analysis, non-medical and medical students exhibit distinct levels of nosophobia. The analysis of responses to hypochondriacal behaviors revealed that students from non-medical faculties scored an average of 1.43 points. By contrast, the average score for medical students was 7.87, which is significantly higher than that of the non-medical students (p 0.001). Conclusions Medical students are at higher risk for health anxiety and hypochondrial attitudes than non-medical students are

Boosting Polyamines to Enhance Shoot Regeneration in Potato (<i>Solanum tuberosum</i> L.) Using AgNO₃

Advancements in shoot regeneration systems support biotechnology-based tools used in the genetic improvement of plant crops. This study aims to enhance shoot regeneration in potatoes by boosting polyamine content by adding AgNO3 to the shoot regeneration medium (MS medium supplemented with 30 g L−1 sucrose, 100 mg L−1 myoinositol, and 2.25 BA mg L−1). Five concentrations of AgNO3 (2, 4, 6, 8, and 10 mg L−1) were used in addition to a control. The effect of AgNO3 on regeneration assumed a more or less concentration-dependent bell-shaped curve peaking at 4 mg L−1. Enhancements in shoot regeneration were attributed to the known role of AgNO3 as an ethylene action blocker in addition to improvements in polyamine accumulation without an increase in H2O2 content, lipid peroxidation, or DNA damage. The uncoupling of shoot regeneration and polyamine content recorded at high AgNO3 concentrations can be attributed to the consumption of polyamines to counteract the synchronized oxidative stress manifested by increases in H2O2 content, lipid peroxidation, and DNA damage

Boosting Polyamines to Enhance Shoot Regeneration in Potato (Solanum tuberosum L.) Using AgNO3

Advancements in shoot regeneration systems support biotechnology-based tools used in the genetic improvement of plant crops. This study aims to enhance shoot regeneration in potatoes by boosting polyamine content by adding AgNO3 to the shoot regeneration medium (MS medium supplemented with 30 g L&minus;1 sucrose, 100 mg L&minus;1 myoinositol, and 2.25 BA mg L&minus;1). Five concentrations of AgNO3 (2, 4, 6, 8, and 10 mg L&minus;1) were used in addition to a control. The effect of AgNO3 on regeneration assumed a more or less concentration-dependent bell-shaped curve peaking at 4 mg L&minus;1. Enhancements in shoot regeneration were attributed to the known role of AgNO3 as an ethylene action blocker in addition to improvements in polyamine accumulation without an increase in H2O2 content, lipid peroxidation, or DNA damage. The uncoupling of shoot regeneration and polyamine content recorded at high AgNO3 concentrations can be attributed to the consumption of polyamines to counteract the synchronized oxidative stress manifested by increases in H2O2 content, lipid peroxidation, and DNA damage

Somaclonal Variation for Genetic Improvement of Starch Accumulation in Potato (<i>Solanum tuberosum</i>) Tubers

Starch content is one of the major quality criteria targeted by potato breeding programs. Traditional potato breeding is a laborious duty due to the tetraploid nature and immense heterozygosity of potato genomes. In addition, screening for functional genetic variations in wild relatives is slow and strenuous. Moreover, genetic diversity, which is the raw material for breeding programs, is limited due to vegetative propagation used in the potato industry. Somaclonal variation provides a time-efficient tool to breeders for obtaining genetic variability, which is essential for breeding programs, at a reasonable cost and independent of sophisticated technology. The present investigation aimed to create potato somaclones with an improved potential for starch accumulation. Based on the weight and starch content of tubers, the somaclonal variant Ros 119, among 105 callus-sourced clones, recorded a higher tuberization potential than the parent cv Lady Rosetta in a field experiment. Although this somaclone was similar to the parent in the number of tubers produced, it exhibited tubers with 42 and 61% higher fresh and dry weights, respectively. Additionally, this clone recorded 10 and 75% increases in starch content based on the dry weight and average content per plant, respectively. The enhanced starch accumulation was associated with the upregulation of six starch-synthesis-related genes, namely, the AGPase, GBSS I, SBE I, SBE II, SS II and SS III genes. AGPase affords the glycosyl moieties required for the synthesis of amylose and amylopectin. GBSS is required for amylose elongation, while SBE I, SBE II, SS II and SS III are responsible for amylopectin