COVID-19 and the heart: An update for clinicians

SARS-CoV-2, the cause of the COVID-19 pandemic has significantly impacted cardiovascular healthcare. Patients with pre-existing cardiovascular disease are at higher risk of morbidity and mortality. The virus may affect the heart directly and indirectly with clinical syndromes of acute myocardial injury, myocarditis, acute coronary syndromes, heart failure, arrhythmias, and venous thromboembolism. Some therapeutics under investigation for COVID-19 may also have adverse cardiac effects. The involvement of the RAAS system in viral entry makes it pertinent to consider the effects of medications that modulate the system. Comprehensive knowledge of peculiar cardiovascular manifestations of COVID-19 and the role of RAAS in the prognosis of COVID-19 disease is needed for optimal patient management.     

Hippocampal brain‐derived neurotrophic factor mediates recovery from chronic stress‐induced spatial reference memory deficits

Chronic restraint stress impairs hippocampal‐mediated spatial learning and memory, which improves following a post‐stress recovery period. Here, we investigated whether brain‐derived neurotrophic factor (BDNF), a protein important for hippocampal function, would alter the recovery from chronic stress‐induced spatial memory deficits. Adult male Sprague‐Dawley rats were infused into the dorsal hippocampal cornu ammonis (CA)3 region with an adeno‐associated viral vector containing the sequence for a short hairpin RNA (shRNA) directed against BDNF or a scrambled sequence (Scr). Rats were then chronically restrained (wire mesh, 6 h/day for 21 days) and assessed for spatial learning and memory using a radial arm water maze (RAWM) either immediately after stressor cessation (Str‐Imm) or following a 21‐day post‐stress recovery period (Str‐Rec). All groups learned the RAWM task similarly, but differed on the memory retention trials. Rats in the Str‐Imm group, regardless of adeno‐associated viral contents, committed more errors in the spatial reference memory domain on the single retention trial during day 3 than did the non‐stressed controls. Importantly, the typical improvement in spatial memory following the recovery from chronic stress was blocked with the shRNA against BDNF, as Str‐Rec‐shRNA performed worse on the RAWM compared with the non‐stressed controls or Str‐Rec‐Scr. The stress effects were specific for the reference memory domain, but knockdown of hippocampal BDNF in unstressed controls briefly disrupted spatial working memory as measured by repeated entry errors on day 2 of training. These results demonstrated that hippocampal BDNF was necessary for the recovery from stress‐induced hippocampal‐dependent spatial memory deficits in the reference memory domain.     

Innervation of the brain,intracerebral Schwann cells and intracerebral and intraventricular schwannomas

The cerebral vasculature and the choroid plexus are innervated by peripheral nerves. The anatomy of the vascular supply to the brain and its related perivascular nerves is reviewed. Intracerebral and intraventricular schwannomas most likely come from neoplastic transformation of Schwann cells investing the perivascular nerves and nerves within the choroid plexus.     

Pharmacokinetics of levosulpiride after single and multiple intramuscular administrations in healthy Chinese volunteers

The main purpose of this study was to evaluate the pharmacokinetics of levosulpiride in humans after single and multiple intramuscular injections. Six males and six females received single dose of either 25 mg or 50 mg levosulpiride, or multiple doses of 25 mg every 12 h for 5 consecutive days. In the single 25 mg study, the mean peak plasma concentration (C_max) was 441 ng/mL, the mean area under the concentration–time curve from 0 to 36 h (AUC_0–36) was 1724 ng h/mL, and the mean elimination half-life (t_1/2) was 7.0 h. In the single 50 mg study, the mean C_max was 823 ng/mL, the mean AUC_0–36 was 3748 ng·h/mL, and the mean t_1/2 was 6.8 h. After multiple doses of 25 mg levosulpiride, the average plasma concentration (C_av) was 136 ng/mL, the fluctuation index (DF) was 3.60, and the accumulation ratio (R) was 1.2. Levosulpiride injections appeared to be well tolerated by the subjects, and can be used for successive administration.KEY WORDS: Levosulpiride, Pharmacokinetics, Intramuscular administration, Safety and tolerability     

Next‐generation sequencing for the diagnosis of MYH9‐RD: Predicting pathogenic variants

The heterogeneous manifestations of MYH9‐related disorder (MYH9‐RD), characterized by macrothrombocytopenia, Döhle‐like inclusion bodies in leukocytes, bleeding of variable severity with, in some cases, ear, eye, kidney, and liver involvement, make the diagnosis for these patients still challenging in clinical practice. We collected phenotypic data and analyzed the genetic variants in more than 3,000 patients with a bleeding or platelet disorder. Patients were enrolled in the BRIDGE‐BPD and ThromboGenomics Projects and their samples processed by high throughput sequencing (HTS). We identified 50 patients with a rare variant in MYH9. All patients had macrothrombocytes and all except two had thrombocytopenia. Some degree of bleeding diathesis was reported in 41 of the 50 patients. Eleven patients presented hearing impairment, three renal failure and two elevated liver enzymes. Among the 28 rare variants identified in MYH9, 12 were novel. HTS was instrumental in diagnosing 23 patients (46%). Our results confirm the clinical heterogeneity of MYH9‐RD and show that, in the presence of an unclassified platelet disorder with macrothrombocytes, MYH9‐RD should always be considered. A HTS‐based strategy is a reliable method to reach a conclusive diagnosis of MYH9‐RD in clinical practice.     

Enzyme-catalyzed synthesis of poly(1,6-hexanediyl maleate-co-fumarate) in organic medium. Study of macrolactone formation in relation to the composition of the initial monomer mixture

The lipase-catalyzed synthesis of poly(1,6-hexanediyl maleate-co-fumarate) from 1,6-hexanediol, dimethyl maleate and dimethyl fumarate is described. No secondary reaction involving the double bounds takes place, so that the copolyester composition can be well defined by adjusting the mole fraction of the dimethyl esters in the initial monomer mixture. The average molar masses of the non-fractionated copolyesters depend on the mole fraction of the dimethyl maleate and are correlated with the amount of macrocycles formed. The possibility that the reaction system obeys a ring-linear chain equilibrium is discussed. Linear polyester chains and macrolactones are characterized by ¹H NMR spectroscopy, steric exclusion chromatography and tonometry. A comparison is made with the homopolyester syntheses which were described in previous works.