Discovery of Alkyl Triphenylphosphonium Pinostrobin Derivatives as Potent Anti-Breast Cancer Agents.

Pinostrobin demonstrated anticancer properties, but its hydrophobic feature led to a reduction in bioavailability. The mitochondria-targeted approach successfully synthesized eight new alkyl triphenylphosphonium pinostrobin derivatives (1-8) with good yield in this study. Seven compounds (1-3, 5-8) showed greater cytotoxic potency against the human MCF-7 breast cancer cell line than pinostrobin. Molecular docking studies were performed with two important targets in hormone-dependent anticancer strategies, estrogen receptor α (ERα) ligand binding domains, 3ERT (antagonist recognition and antiproliferative function), and 1GWR (agonist recognition and pro-proliferative function). In addition, the MD simulation study of the two most potent compounds (2 and 3) complexed with both ERα forms suggested that compounds 2 and 3 could serve as favourable antagonists. Furthermore, the in silico ADMET prediction indicated that compounds 2 and 3 could be potential drug candidates.

Graphene Oxide-Reinforced Alginate Hydrogel for Controlled Release of Local Anesthetics: Synthesis, Characterization, and Release Studies.

In pain relief, lidocaine has gained more attention as a local anesthetic. However, there are several side effects that limit the use of local anesthetics. Therefore, it is hypothesized that a hydrogel system with facile design can be used for prolonged release of lidocaine. In this study, we developed a formulation comprises of sodium alginate (SA) and graphene oxide (GO) to prolong the release of lidocaine. The gelation was induced by physically crosslinking the alginate with Ca2+ ions. The formation of blank SA and GO-reinforced SA hydrogels was investigated with different concentration of Ca2+ ions. The controlled release of lidocaine hydrochloride (LH) on both hydrogel systems was studied in PBS solution. The GO-reinforced SA hydrogels exhibited more sustained release than SA hydrogels without GO. In vitro biocompatibility test in L929 fibroblast cells confirmed the non-toxic property of hydrogels. Furthermore, to prove the in-situ gelation and biodegradability of hydrogels the hydrogels were injected on mice model and confirmed the stable gel formation. The hydrogels implanted onto the subcutaneous tissue of hydrogels retained over one week. These results indicate that LH-loaded GO-reinforced SA hydrogel can be a potential biomaterial for controlled release of local anesthetics.

Unspecified opioids among opioid overdoses in Oslo, Norway.

OBJECTIVE: Since 2017, an increasing number of opioid overdoses in Oslo, Norway, has been categorized as involving unspecified opioids, as noted in the patient records by the doctor treating the patient. In this study we compare the characteristics of overdoses involving unspecified opioids, long-acting opioids, and heroin. Data on patients presenting with opioid overdose was retrospectively collected from 1 October 2013 to 31 December 2019 at the Oslo Accident and Emergency Outpatient Clinic. RESULTS: Among 2381 included cases, 459 (19.3%) involved unspecified opioids, 134 (5.6%) long-acting opioids, and 1788 (75.1%) heroin. Overdoses involving unspecified opioids needed longer observation, median 5 h 29 min vs. 4 h 54 min (long-acting opioids) and 4 h 49 min (heroin) (p < 0.001), and had a lower Glasgow coma scale score, median 10 vs. 13 in both the other groups (p < 0.001). Naloxone was given in 23.3% of cases involving unspecified opioids, vs. 12.7% involving long-acting opioids and 30.2% involving heroin (p < 0.001). A larger proportion of patients were transferred to hospital care when unspecified or long-acting opioids were involved compared to heroin, 16.3% and 18.7% respectively vs. 10.1% (p < 0.001). Our results indicate that the category "unspecified opioids" encompasses a substantial proportion of opioids acting longer than heroin.

Respiratory syncytial virus and human metapneumovirus after allogeneic hematopoietic stem cell transplantation: Impact of the immunodeficiency scoring index, viral load, and ribavirin treatment on the outcomes.

INTRODUCTION: Respiratory viral infections are a major cause of morbidity and mortality among stem cell transplant recipients. While there is a substantial amount of information on prognostic factors and response to ribavirin therapy is available for RSV infections, this information is largely lacking for hMPV. PATIENTS AND METHODS: In total, 71 patients were included in this study: 47 patients with RSV and 24 with hMPV. Forty-one patients presented as an upper respiratory tract infection (URTI) and 30 as a primary lower respiratory tract infection (LRTI). Patients were stratified as per ISI criteria into low-, moderate-, and high-risk groups. Twenty-two patients in the URTI cohort received treatment with ribavirin (mainly oral), and 19 patients received no antiviral therapy. The decision for antiviral treatment was at the discretion of the attending physician. All 30 patients with primary LRTI and 10 patients with secondary LRTI were treated with ribavirin, 95% with the intravenous formulation. 45% of these patients received additional treatment with intravenous immunoglobulins. The viral load was assessed indirectly by using the CT value of the RT-PCR. RESULTS: In the cohort, as whole 11.5% suffered a virus-associated death, 5% in the URTI group, and 20% in the LRTI group. Sixty-day mortality was significantly higher in the ISI high-risk group (log-rank P = .05). Mortality was independent of the type of virus (P = .817). Respiratory failure with an indication for mechanical ventilation developed in 11.5%, this risk was independent of the type of virus. Progression from URTI to LRTI was observed in 24% of cases with a significantly higher risk (75%) in the ISI high group (log-rank P = .001). In the ISI high-risk group, treatment with ribavirin significantly reduced the risk of progression (log-rank P < .001). Neither the type of virus nor the viral load in the nasopharyngeal swab impacted the risk of progression (P = .529 and P = .141, respectively). The detection of co-pathogens in the BAL fluid was borderline significant for mortality (P = .07). CONCLUSIONS: We could detect no differences between RSV and hMPV with respect to progression to LRTI, risk of respiratory failure or need for mechanical ventilation and virus-associated death. The ISI index is of predictive value in hMPV patients with a high ISI score and treatment with oral ribavirin has an equivalent protective effect in RSV and hMPV patients. Treatment of LRTI with intravenous ribavirin results in a similar outcome in RSV- and hMPV-infected patients. We could not detect any benefit of adjunctive treatment with immunoglobulins in both primary and secondary LRTI. No role of viral load as an independent prognostic marker could be detected either for progression to LRTI or death.