Quantal Two-Centre Coulomb Problem treated by means of the Phase-Integral Method II. Quantization Conditions in the Symmetric Case Expressed in Terms of Complete Elliptic Integrals. Numerical Illustration

The contour integrals, occurring in the arbitrary-order phase-integral quantization conditions given in a previous paper, are in the first- and third-order approximations expressed in terms of complete elliptic integrals in the case that the charges of the Coulomb centres are equal. The evaluation of the integrals is facilitated by the knowledge of quasiclassical dynamics. The resulting quantization conditions involving complete elliptic integrals are solved numerically to obtain the energy eigenvalues and the separation constants of the $1s\sigma$ and $2p\sigma$ states of the hydrogen molecule ion for various values of the internuclear distance. The accuracy of the formulas obtained is illustrated by comparison with available numerically exact results.Comment: 19 pages, RevTeX 4, 4 EPS figures, submitted to J. Math. Phy

Metabolic and kidney disorders correlate with high atazanavir concentrations in HIV-infected patients : is it time to revise atazanavir dosages?

Introduction: Ritonavir-boosted atazanavir (ATV/r) is a relatively well tolerated antiretroviral drug. However, side effects including hyperbilirubinemia, dyslipidemia, nephrolithiasis and cholelithiasis have been reported in the medium and long term. Unboosted ATV may be selected for some patients because it has fewer gastrointestinal adverse effects, less hyperbilirubinemia and less impact on lipid profiles. Methods: We investigated the distribution of ATV plasma trough concentrations according to drug dosage and the potential relationship between ATV plasma trough concentrations and drug-related adverse events in a consecutive series of 240 HIV-infected patients treated with ATV/r 300/100 mg (68%) or ATV 400 mg (32%). Results: 43.9% of patients treated with ATV/r 300/100 mg had ATV concentrations exceeding the upper therapeutic threshold. A significant and direct association has been observed between the severity of hyperbilirubinemia and ATV plasma trough concentrations (ATV concentrations: 271 [77-555], 548 [206-902], 793 [440-1164], 768 [494-1527] and 1491 [1122-1798] ng/mL in patients with grade 0, 1, 2, 3 and 4 hyperbilirubinemia, respectively). In an exploratory analysis we found that patients with dyslipidemia or nephrolitiasis had ATV concentrations significantly higher (582 [266-1148], and 1098 [631-1238] ng/mL, respectively) (p<0.001), as compared with patients with no ATV-related complications (218 [77-541] ng/mL). Conclusions: A significant proportion of patients treated with the conventional dosage of ATV (300/100) had plasma concentrations exceeding the upper therapeutic threshold. These patients that are at high risk to experience ATV-related complications may benefit from TDM-driven adjustments in ATV dosage with potential advantages in terms of costs and toxicity

Dynamics of Prolyl hydroxylases levels during disease progression in experimental colitis

Hypoxia inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitors are shown to be protective in several models of inflammatory bowel disease (IBD). However, these non-selective inhibitors are known to inhibit all the three isoforms of PHD, i.e. PHD-1, PHD-2 and PHD-3. In the present report, we investigated the associated changes in levels of PHDs during the development and recovery of chemically induced colitis in mice. The results indicated that in the experimental model of murine colitis, levels of both, PHD-1 and PHD-2 were found to be increased with the progression of the disease; however, the level of PHD-3 remained the same in group of healthy controls and mice with colitis. Thus, the findings advocated that inhibitors, which inhibited all three isoforms of PHD could not be ideal therapeutics for IBD since PHD-3 is required for normal gut function. Hence, this necessitates the development of new compounds capable of selectively inhibiting PHD-1 and PHD-2 for effective treatment of IBD

Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer Via Downregulation of Nuclear p65 and HIF-1 alpha

Piceatannol (PIC) is known to have anticancer activity, which has been attributed to its ability to block the proliferation of cancer cells via suppression of the NF-kB signaling pathway. However, its effect on hypoxia-inducible factor (HIF) is not well known in cancer. In this study, PIC was loaded into bovine serum albumin (BSA) by desolvation method as PIC-BSA nanoparticles (NPs). These PIC-BSA nanoparticles were assessed for in vitro cytotoxicity, migration, invasion, and colony formation studies and levels of p65 and HIF-1α. Our results indicate that PIC-BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1α in colon cancer cells as compared to free PIC. We also observed a significant reduction in inflammation induced by chemical colitis in mice by PIC-BSA NPs. Furthermore, a significant reduction in tumor size and number of colon tumors was also observed in the murine model of colitis-associated colorectal cancer, when treated with PIC-BSA NPs as compared to free PIC. The overall results indicate that PIC, when formulated as PIC-BSA NPs, enhances its therpautice potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possiable human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients

Correction: Aljabali, A.A.A.; et al. Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer via down Regulation of Nuclear p65 and HIF-1α. Cancers 2020, 12, 113

The authors wish to make the following corrections to this paper [...]

The viral capsid as novel nanomaterials for drug delivery

The purpose of this review is to highlight recent scientific developments and provide an overview of virus self-assembly and viral particle dynamics. Viruses are organized supramolecular structures with distinct yet related features and functions. Plant viruses are extensively used in biotechnology, and virus-like particulate matter is generated by genetic modification. Both provide a material-based means for selective distribution and delivery of drug molecules. Through surface engineering of their capsids, virus-derived nanomaterials facilitate various potential applications for selective drug delivery. Viruses have significant implications in chemotherapy, gene transfer, vaccine production, immunotherapy and molecular imaging

Is it time to revise antiretrovirals dosing? : a pharmacokinetic viewpoint

We document our experience with therapeutic drug monitoring (TDM) of antiretroviral agents (1807 determinations) carried out as day-by-day clinical practice for the optimization of drug dosing in HIV-infected patients. A significant proportion of patients had lopinavir, atazanavir and nevirapine trough concentrations exceeding the upper therapeutic threshold. Further studies are needed to identify good candidates/drugs for TDM, eventually allowing the selection of patients who may benefit from TDM-driven adjustments in antiretrovirals dosage