Flavocoxid is as effective as naproxen for managing the signs and symptoms of osteoarthritis of the knee in humans: a short-term randomized,double-blind pilot study

Flavocoxid (Limbrel), a proprietary mixture of flavonoid molecules (baicalin and catechin), was tested against a traditional nonsteroidal anti-inflammatory drug, naproxen, for the management of the signs and symptoms of moderate osteoarthritis (OA) in humans. Discomfort and global disease activity were used as the primary end points, and safety assessments were also taken for both treatments as a secondary endpoint. In this double-blind study, 103 subjects were randomly assigned to receive either flavocoxid [500 mg twice daily (BID)] or naproxen (500 mg BID) in a 1-month onset of action trial. Outcome measures included the short Western Ontario and McMaster University Osteoarthritis Index, subject Visual Analogue Scale for discomfort and global response, and investigator Visual Analogue Scale for global response and fecal occult blood. Both flavocoxid and naproxen showed significant reduction in the signs and symptoms of knee OA (P ≤ .001). There were no statistically detectable differences between the flavocoxid and naproxen groups with respect to any of the outcome variables. Similarly, there were no statistically detectable differences between the groups with respect to any adverse event, although there was a trend toward a higher incidence of edema and nonspecific musculoskeletal discomfort in the naproxen group. In this short-term pilot study, flavocoxid was as effective as naproxen in controlling the signs and symptoms of OA of the knee and would present a safe and effective option for those individuals on traditional nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors. A low incidence of adverse events was reported for both groups.     

Dopamine transporter mutant animals: a translational perspective

The dopamine transporter (DAT) plays an important homeostatic role in the control of both the extracellular and intraneuronal concentrations of dopamine, thereby providing effective control over activity of dopaminergic transmission. Since brain dopamine is known to be involved in numerous neuropsychiatric disorders, investigations using mice with genetically altered DAT function and thus intensity of dopamine-mediated signaling have provided numerous insights into the pathology of these disorders and novel pathological mechanisms that could be targeted to provide new therapeutic approaches for these disorders. In this brief overview, we discuss recent investigations involving animals with genetically altered DAT function, particularly focusing on translational studies providing new insights into pathology and pharmacology of dopamine-related disorders. Perspective applications of these and newly developed models of DAT dysfunction are also discussed.     

Vertical Transmission of SARS-CoV-2 in Second Trimester Associated with Severe Neonatal Pathology

The effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in women on the gestation course and the health of the fetus, particularly in the first and second trimesters, remain very poorly explored. This report describes a case in which the normal development of pregnancy was complicated immediately after the patient had experienced Coronavirus disease 2019 (COVID-19) at the 21st week of gestation. Specific conditions included critical blood flow in the fetal umbilical artery, fetal growth restriction (1st percentile), right ventricular hypertrophy, hydropericardium, echo-characteristics of hypoxic-ischemic brain injury (leukomalacia in periventricular area) and intraventricular hemorrhage at the 25th week of gestation. Premature male neonate delivered at the 26th week of gestation died after 1 day 18 h due to asystole. The results of independent polymerase chain reaction (PCR), mass spectrometry and immunohistochemistry analyses of placenta tissue, umbilical cord blood and child blood jointly indicated vertical transmission of SARS–CoV-2 from mother to the fetus, which we conclude to be the major cause for the development of maternal vascular malperfusion in the studied case.     

Supramolecular D⋯A-layered structures based on germanium complexes with 2,3-dihydroxynaphthalene and N,N′-bidentate ligands

The concept of using redox-active ligands, which has become extremely widespread in organometallic chemistry, is often considered from ‘their effect on the metal center properties’ point of view and ‘how to modify the ligands’. In this paper, we present the reverse side of this effective approach – a dramatic change of redox properties of ligands under the influence of a redox-inert metal. Germanium derivatives based on 2,3-dihydroxynaphthalene (1) and N,N′-bidentate ligands, namely 2,2′-bipyridine (2) and 1,10-phenanthroline (3), were obtained and characterized by CV, UV-vis spectroscopy, DFT calculations and in the case of 3 X-ray diffraction. It was shown that the HOMO of the complexes is almost completely located on the naphthalene fragment while the LUMO is on the N,N-ligands. At the same time, there are no boundary molecular orbitals on the germanium atom, but it forms the axial part of the molecule holding two opposite motifs together. Moreover, it sharply affects the level of HOMO and LUMO. Derivatives 2 and 3 are more easily oxidized compared to 2,3-dihydroxynaphthalene by 0.31–0.34 V (7–8 kcal mol⁻¹) and are more easily reduced compared to N,N-donors by 1.08–1.15 V (25–26.5 kcal mol⁻¹). All this together makes it possible to form a system with a narrow HOMO/LUMO gap (∼2 eV). The crystal structure of 3 consists of alternating monomolecular easily oxidizing and easily reducing layers formed due to intermolecular interactions, in particular π-stacking. In addition, in contrast to 1 that starts to decompose noticeably at the temperatures from 200 °C, 2 and 3 have an extremely high thermal stability. They remain stable with no signs of decomposition and melting up to 400 °С. We believe that this approach to the formation of the supramolecular structure may present prospects for obtaining new functional materials.

The concept of using redox-active ligands is often considered from ‘their effect on the metal center properties’ point of view. We present the reverse side of this approach – change of redox properties of ligands under the influence of metal.     

Degradation kinetic study of ZIF-8 microcrystals with and without the presence of lactic acid

The zeolitic imidazolate framework ZIF-8 (Zn(mim)₂, mim = 2-methylimidazolate) has recently been proposed as a drug delivery platform for anticancer therapy based on its capability of decomposing in acidic media. The concept presumes a targeted release of encapsulated drug molecules in the vicinity of tumor tissues that typically produce secretions with elevated acidity. Due to challenges of in vivo and in vitro examination, many studies have addressed the kinetics of ZIF-8 decomposition and subsequent drug release in phosphate buffered saline (PBS) with adjusted acidity. However, the presence of hydrogen phosphate anions [HPO₄]²⁻ in PBS may also affect the stability of ZIF-8. As yet, no separate analysis has been performed comparing the dissolving capabilities of PBS and various acidification agents used for regulating pH. Here, we provide a systematic study addressing the effects of phosphate anions with and without lactic acid on the degradation rate of ZIF-8 microcrystals. Lactic acid has been chosen as an experimental acidification agent, since it is particularly secreted by tumor cells. Interestingly, the effect of a lactic acid solution with pH 5.0 on ZIF-8 degradation is shown to be weaker compared to a PBS solution with pH 7.4. However, as an additive, lactic acid is able to enhance the decomposition efficacy of other solutions by 10 to 40 percent at the initial stage, depending on the presence of other ions. Additionally, we report mild toxicity of ZIF-8 and its decomposition products, as examined on HDF and A549 cell lines.

ZIF-8 microcrystals demonstrate different degradation kinetics in water, PBS (pH 7.4), and PBS with lactic acid (pH 5.0).     

Efficient physics-based tracking of heart surface motion for beating heart surgery robotic systems

Purpose  

Tracking of beating heart motion in a robotic surgery system is required for complex cardiovascular interventions.