New Palladacycle-Derived Acylhydrazones as Pre-catalysts in Mirozoki-Heck Coupling and Oxyarylations.

New acylhydrazone-based palladacycles are prepared and evaluated as pre-catalysts in Mirozoki-Heck and oxyarylation reactions.

[Prevention of gastrointestinal bleeding in patients with advanced burns]. / Profilaktika zheludochno-kishechnykh krovotechenii u patsientov s obshirnymi termicheskimi ozhogami.

AIM: To reduce the incidence of gastrointestinal bleeding in patients with advanced burns by developing a prophylactic algorithm. MATERIAL AND METHODS: The study consisted of retrospective group of 488 patients with thermal burns grade II-III over 20% of body surface area and prospective group of 135 patients with a similar thermal trauma. Standard clinical and laboratory examination was applied. Instrumental survey included fibrogastroduodenoscopy, endoscopic pH-metry and invasive volumetric monitoring (PICCO plus). Statistical processing was carried out with Microsoft Office Excel 2007 and IBM SPSS 20.0. RESULTS: New algorithm significantly decreased incidence of gastrointestinal bleeding (p<0.001) and mortality rate (p=0.006) in patients with advanced burns.

Laboratory-Scale Membrane Reactor for the Generation of Anhydrous Diazomethane.

A configurationally simple and robust semibatch apparatus for the in situ on-demand generation of anhydrous solutions of diazomethane (CH2N2) avoiding distillation methods is presented. Diazomethane is produced by base-mediated decomposition of commercially available Diazald within a semipermeable Teflon AF-2400 tubing and subsequently selectively separated from the tubing into a solvent- and substrate-filled flask (tube-in-flask reactor). Reactions with CH2N2 can therefore be performed directly in the flask without dangerous and labor-intensive purification operations or exposure of the operator to CH2N2. The reactor has been employed for the methylation of carboxylic acids, the synthesis of α-chloro ketones and pyrazoles, and palladium-catalyzed cyclopropanation reactions on laboratory scale. The implementation of in-line FTIR technology allowed monitoring of the CH2N2 generation and its consumption. In addition, larger scales (1.8 g diazomethane per hour) could be obtained via parallelization (numbering up) by simply wrapping several membrane tubings into the flask.

Three-step synthesis of (±)-preussin from decanal.

A straightforward and stereoselective synthesis of the alkaloid preussin is described starting from decanal and diethyl 3-diazo-2-oxopropylphosphonate. The key steps are an aza-Michael reaction from an α,ß-unsaturated diazoketone followed by a highly stereoselective Cu-catalyzed ylide formation and then a [1,2]-Stevens rearrangement. This strategy is feasible for extension to preussin analogues, demonstrating its utility for the rapid construction of all-cis-substituted pyrrolidines.

Continuous flow synthesis of α-halo ketones: essential building blocks of antiretroviral agents.

The development of a continuous flow process for the multistep synthesis of α-halo ketones starting from N-protected amino acids is described. The obtained α-halo ketones are chiral building blocks for the synthesis of HIV protease inhibitors, such as atazanavir and darunavir. The synthesis starts with the formation of a mixed anhydride in a first tubular reactor. The anhydride is subsequently combined with anhydrous diazomethane in a tube-in-tube reactor. The tube-in-tube reactor consists of an inner tube, made from a gas-permeable, hydrophobic material, enclosed in a thick-walled, impermeable outer tube. Diazomethane is generated in the inner tube in an aqueous medium, and anhydrous diazomethane subsequently diffuses through the permeable membrane into the outer chamber. The α-diazo ketone is produced from the mixed anhydride and diazomethane in the outer chamber, and the resulting diazo ketone is finally converted to the halo ketone with anhydrous ethereal hydrogen halide. This method eliminates the need to store, transport, or handle diazomethane and produces α-halo ketone building blocks in a multistep system without racemization in excellent yields. A fully continuous process allowed the synthesis of 1.84 g of α-chloro ketone from the respective N-protected amino acid within ~4.5 h (87% yield).

An overlooked relationship in recovery from substance use disorders: Associations between body mass index and negative emotional states.

Recovery from substance use disorders (SUD) is multifactorial. Being overweight could negatively impact physiological and psychological health-related parameters. Using model selection, we examined associations between body mass index (BMI) and negative emotional states (NES; e.g., stress, anxiety, depression) in 54 men with SUD and under treatment in five different therapeutic recovery centers. We found that BMI was positively associated with stress (p < .001), anxiety (p < .001), and depression (p = .002). Therefore, our findings suggest that decreasing the accumulation of body fat might contribute to improving mental health in individuals with SUD during recovery.

[Risk factors of gastroduodenal bleeding in patients with severe burns].

An experience of treatment of 133 patients with severe bums was analyzed. Bleedings from the upper parts of the gastrointestinal tract were diagnosed in 16 patients in different terms since their admission to the hospital. At the moment of carrying out of the endoscopic research all bleedings were considered as taking place. Statistically significant risk factors of the development of gastroduodenal bleedings were considered to be an alcoholic intoxication at the moment of injury and insufficient fluid therapy during the pre-admission stage and young age of the patients. The antisecretory therapy showed that the detection of risk factors in question should be regarded as an indication to the reinforced regime of preventive measures for gastroduodenal injuries.

Alkylation of 6-thiopurine derivatives by the Mitsunobu reaction.

Alkylation of thiopurine derivatives with alcohols by the Mitsunobu reaction are reported in moderated to good yields. The method was applied in synthesis of number of thiopurine and thiopurine ribosides derivatives.

Preclinical development of kinetin as a safe error-prone SARS-CoV-2 antiviral able to attenuate virus-induced inflammation.

Orally available antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary because of the continuous circulation of new variants that challenge immunized individuals. Because severe COVID-19 is a virus-triggered immune and inflammatory dysfunction, molecules endowed with both antiviral and anti-inflammatory activity are highly desirable. We identified here that kinetin (MB-905) inhibits the in vitro replication of SARS-CoV-2 in human hepatic and pulmonary cell lines. On infected monocytes, MB-905 reduced virus replication, IL-6 and TNFα levels. MB-905 is converted into its triphosphate nucleotide to inhibit viral RNA synthesis and induce error-prone virus replication. Coinhibition of SARS-CoV-2 exonuclease, a proofreading enzyme that corrects erroneously incorporated nucleotides during viral RNA replication, potentiated the inhibitory effect of MB-905. MB-905 shows good oral absorption, its metabolites are stable, achieving long-lasting plasma and lung concentrations, and this drug is not mutagenic nor cardiotoxic in acute and chronic treatments. SARS-CoV-2-infected hACE-mice and hamsters treated with MB-905 show decreased viral replication, lung necrosis, hemorrhage and inflammation. Because kinetin is clinically investigated for a rare genetic disease at regimens beyond the predicted concentrations of antiviral/anti-inflammatory inhibition, our investigation suggests the opportunity for the rapid clinical development of a new antiviral substance for the treatment of COVID-19.

α,ß-Unsaturated diazoketones as platforms in the asymmetric synthesis of hydroxylated alkaloids. Total synthesis of 1-deoxy-8,8a-diepicastanospermine and 1,6-dideoxyepicastanospermine and formal synthesis of pumiliotoxin 251D.

A versatile and concise approach for the stereoselective synthesis of mono-, di-, and trihydroxylated indolizidines is presented in four to six steps from Cbz-prolinal and a diazophosphonate. The key steps involved a Wolff rearrangement, followed by a stereoselective dihydroxylation/epoxidation reaction, from an α,ß-unsaturated diazoketone. The strategy also permits extension to the synthesis of many natural hydroxylated indolizidine alkaloids as demonstrated in the formal synthesis of pumiliotoxin 251D.

Preparation of α,ß-unsaturated diazoketones employing a Horner-Wadsworth-Emmons reagent.

A new method for the preparation of α,ß-unsaturated diazoketones from aldehydes and a Horner-Wadsworth-Emmons reagent is reported. The method was applied to the short synthesis of two substituted pyrrolidines.

Does being overweight play a role in the reduced inhibitory control of patients receiving treatment for substance use disorder?

BACKGROUND: Impaired inhibitory control is present in individuals with substance use disorder (SUD) and in those with obesity. However, the question as to whether patients with SUD who are either overweight or obese have impaired inhibitory control, relative to patients with SUD and normal weight, remains unanswered. METHODS: Sixty-two adult men (mean age: 31.17±8.79) under treatment for SUD performed a general and drug-specific inhibitory control test (GoNogo). Participants were divided in two groups based on their BMI. Patients with a BMI higher or equal than ≥25 kg/m² were in the overweight and obese group (OB), and patients with a BMI lower than 25 kg/m² were in the normal weight group (NW). Analyses of covariance (ANCOVA) were performed to explore differences in drug-specific and general commission errors, as well as reaction time for go trials during both drug-specific and general inhibition tasks. Models were adjusted for anxiety, depression, age, and duration of drug use. RESULTS: No differences were found for commission errors in both tasks. With regards to reaction time, no differences were found for the general inhibitory control paradigm, whereas the OB group demonstrated slower reaction time during the drug specific paradigm, relative to the NW group (p=0.03, f2 = 0.09; OB: 520.65±71.39 ms vs. NW: 486.07±51.75 ms). CONCLUSION: Our findings suggest that those undergoing treatment for SUD and are either overweight or obese present impaired inhibitory control when facing drug cues. Future research should explore the effects of physical activity, nutritional counseling, and food monitoring on inhibitory control outcomes in SUD rehabilitation.

[Hemodynamic effects of intravenous injections of amiodarone chlorhydrate in normal subjects and coronary patients]. / Effets hémodynamiques de l'injection intra-veineuse de chlorhydrate d'amiodarone chez le sujet normal et le coronarien

A study has been made of the haemodynamic affects of a single intravenous injection of amiodarone chorhydrate (5 mg/kg); the injection was given at rest to six normal subjects and six patients with coronary insufficiency due to atherosclerosis. The effects of the drug are most marked at the fifteenth minute after injection, and are: slowing of the heart rate; lessened cardiac output and left ventricular effort; a significant increase in mean pulmonary arterial pressure and diastolic pressure; slight variations in flow in the coronary sinus, with an increase in the ratio of coronary sinus flow to cardiac output. Amiodarone chlorhydrate appears to exert a favourable action upon the heart because, while it maintains myocardial perfusion, it tends to diminish the myocardial oxygen requirement by decreasing the rate of contraction and the contractility of the myocardium.

SmI2-mediated couplings of α-amino acid derivatives. Formal synthesis of (-)-pumiliotoxin 251D and (±)-epiquinamide.

The coupling between cyclic and acyclic α-amino acid derivatives and methyl acrylate, mediated by samarium diiodide, is described. The method constitutes a powerful tool to construct indolizidine, quinolizidine, and piperidine systems in a straightforward two-step fashion. The formal synthesis of (-)-pumiliotoxin 251D and (±)-epiquinamide is achieved after two or three steps from these amino acid derivatives.

Relato de um caso de reação à vacina oral contra a poliomielite tratado com homeopatia / Report of a case of reaction to oral polio vaccine treated with homeopathy

Este estudo relata um caso de paresia flácida assimétrica após administração da vacina oral contra poliomielite, com acometimento do membro inferior esquerdo. A primeira dose de medicamento homeopático foi prescrita no 20º dia após o início dos sintomas. Evoluiu com desaparecimento da paresia e normalização do padrão de marcha nos 40 dias subsequentes. Pode-se considerar a homeopatia como escolha terapêutica em casos de paresias agudas. (AU)

We report a case of asymmetric flaccid paresis which developed following intake of oral polio vaccine affecting the left lower limb. Homeopathic treatment was started 20 days after the onset of symptoms. Paresis disappeared and the gait pattern became normal along the following 40 days. Homeopathy might be considered for treatment of acute paresis. (AU)