The Effect of Lockdown and Physical Activity on Glycemic Control in Italian Children and Young Patients With Type 1 Diabetes.

Aims: The purpose of the study was to evaluate the impact of the lockdown established by the Italian government to limit the spread of Coronavirus disease (COVID-19) on glycemic control in a large sample of patients with type 1 diabetes (T1D) based on age, type of insulin therapy, number of telemedicine visits and physical activity. Material and Methods: We retrospectively evaluated glycemic control in young T1D patients using the DexcomG6® system before the Italian lockdown (February 10-23, 2020-Time 0) and during lockdown (April 17-30, 2020-Time 1). Data on age, type of insulin therapy, number of telemedicine visits and physical activity of 202 patients with T1D and a median age of 18.2 years (range: 6-39) were collected. Results: Data showed a significant improvement of TIR from 54.58% at T0 to 59.09% at T1 (p ≤0.0001). Glycemic control improved significantly in patients ≥14 years old, showing the best outcome in the "university students and young adults" group (55.40% at T0 and 61.37% at T1, p ≤0.001). All patients reduced physical activity during lockdown; in the 56 patients of "intense physical activity" group both at T0 and T1 TIR increased from ±56.91 to 64.11% (p ≤0.0001). Conclusions: Overall, the lockdown led to an unexpected improvement in glycemic control of young patients with T1D. A healthier and stressless lifestyle changes in association with the maintenance of physical activity resulted in a significant age-proportional improvement in glycemic control.

Transformations of 3-hydroxy steroids with lewis and anhydrous protic acids: the case of pregn-4-en-3ß,17α,20ß-triol.

The acid-catalyzed dehydration is one of the most important processes, which transforms 3-hydroxy steroids into their corresponding unsaturated derivatives. This reaction is of great importance because it can produce molecules that play a key role in the understanding of the natural metabolism of steroids. Sterol dehydration is generally performed with aqueous acidic systems, and the treatment often affords low yields of the desired compounds and/or complex mixtures of by-products. In this paper, we report the results obtained from the study of the structural and stereochemical effects of the acid-induced reaction of pregn-4-en-3ß,17α,20ß-triol in anhydrous systems. In particular, the treatment of this trihydroxy steroid model with Lewis acids leads to the corresponding Δ(3,5) -steradiene as the only product and in very high yields. With Lewis acids, no modifications of the 1,2-diol function on the D-ring are observed, even when the reactions are performed at high temperatures. Protic acid catalysis in non-aqueous organic solvents causes the formation of an epimeric mixture of the corresponding Δ(3,5) -steradiene derivatives by a partial stereochemical inversion of the asymmetric C-17. The reactivity of the 17α,20ß-diolic residue is also evaluated by exposing pregn-4-en-3ß,17α,20ß-triol and the corresponding Δ(3,5) -steradiene to the prolonged action of anhydrous protic acid systems under thermal conditions.

Site-selective methylation of N(beta)-nosyl hydrazides of N-nosyl protected alpha-amino acids.

The methylation reaction of N(beta)-nosyl hydrazides of N-nosyl protected alpha-amino acids by using diazomethane shows a controlled regiochemical trend and makes it possible to obtain the corresponding products methylated at specific positions depending on the amount of diazomethane used. The observed selectivity is closely connected with the different acidity of sulfonyl hydrazide, sulfonamide, and acyl hydrazine protons present in the analyzed substrates. The reactivity order of these three diverse reactive sites is supported by theoretical calculations. The hydrazine derivatives considered in this work belong to a class of compounds with interesting biological activity and of great interest in organic synthesis.

An efficient preparation of N-methyl-alpha-amino acids from N-nosyl-alpha-amino acid phenacyl esters.

In this paper we describe a simple and efficient solution-phase synthesis of N-methyl-N-nosyl-alpha-amino acids and N-Fmoc-N-methyl-alpha-amino acids. This represents a very important application in peptide synthesis to obtain N-methylated peptides in both solution and solid phase. The developed methodology involves the use of N-nosyl-alpha-amino acids with the carboxyl function protected as a phenacyl ester and the methylating reagent diazomethane. An important aspect of this synthetic strategy is the possibility to selectively deprotect the carboxyl function or alternatively both amino and carboxyl moieties by using the same reagent with a different molar excess and under mild conditions. Furthermore, the adopted procedure keeps unchanged the acid-sensitive side chain protecting groups used in Fmoc-based synthetic strategies.

A new non-natural arginine-like amino acid derivative with a sulfamoyl group in the side-chain.

Sulfamoylation of the L-ornithine methyl ester side-chain generates a non-natural arginine isostere which can be coupled with N-Fmoc-L-proline to synthesize analogues which maintain the structural characteristics of the biologically important Pro-Arg dipeptide sequence. As a probe of its biological importance, the sulfamoylated amino acid derivative was also incorporated as P1 residue in tripeptide structures matching the C-terminal subsequence of fibrinogen. The reported results demonstrate that the functionalization of L-ornithine side-chain with a neutral sulfamoyl group can generate an arginine bioisostere which can be used for the synthesis of prototypes of a new class of human thrombin inhibitors.

A preparation of N-Fmoc-N-methyl-alpha-amino acids and N-nosyl-N-methyl-alpha-amino acids.

A convenient route for the synthesis of lipophilic N-Fmoc-N-methyl-alpha-amino acids and N-nosyl-N-methyl-alpha-amino acids, interesting building blocks to be used for the preparation of N-methylated peptides, is presented. Both nosyl- and Fmoc-protected monomers are accessible, so these compounds can be used in solution as well as in solid phase peptide synthesis. The methodology is based on the use of benzhydryl group to protect temporarily the carboxyl function of N-nosyl-alpha-amino acids and on the subsequent methylation of the N-nosyl-alpha-amino acid benzhydryl esters with diazomethane. The benzhydryl esters offer several beneficial features such as simple preparation, stability to methylation and selective deprotection under mild conditions. The overall procedure is highly efficient in that the adopted conditions keep the chiral integrity of amino acid precursors and the process does not require chromatographic purification of the methylated products.

Methylation of alpha-amino acids and derivatives using trimethylsilyldiazomethane.

A study of the methylation of N-nosyl-alpha-amino acids and derivatives with trimethylsilyldiazomethane is here reported. Trimethylsilyldiazomethane allows the chemo-specific methylation of the carboxyl function of N-nosyl-alpha-amino acids in high yields and purity. This method provides a practical route to N-methyl-alpha-amino acids avoiding the use of the more toxic and explosive diazomethane. This simple and safe methylation methodology of alpha-amino acids and derivatives is not limited to organic synthesis and involves the use of a commercially available reagent as well.

Comparison of the volatile constituents in cold-pressed bergamot oil and a volatile oil isolated by vacuum distillation.

The vacuum distillation of bergamot peels furnishes a high-quality essential oil that is totally bergapten-free. This oil was compared with that produced by distillation of cold-pressed oils and those commercially available. The oil obtained by vacuum distillation of the bergamot vegetable matrix shows a composition quite similar to that of the cold-pressed oil. It also displays qualitative characteristics that are superior with respect to those normally observed for essential oils isolated by distillation of cold-pressed oils. Oils isolated by the method presented here can constitute ideal candidates in producing foods, for example, Earl Grey tea, and cosmetic preparations.

N-methyl-N-nosyl-beta(3)-amino acids.

N-Methyl-beta(3)-amino acids are important building blocks in the synthesis of biologically active molecules. A very simple and efficient approach to transform natural alpha-amino acids into their corresponding N-methyl-beta(3)-amino acids is here presented. In the method, the key intermediates N-methyl-N-nosyl-alpha-aminoacyldiazomethanes are prepared in only one step, by a simple treatment of the corresponding N-nosyl-alpha-aminoacyl chlorides with diazomethane. The synthetic route takes advantage from the use of the nosyl group. This N-masking moiety activates the NH function, and the N-methylation can directly occur during the acylation step of diazomethane, rendering useless a second step that instead is shown to be necessary in all the classical procedures already reported for the preparation of N-methyl-beta(3)-amino acids. The Wolff rearrangement of N-methyl-N-nosyl-alpha-aminoacyldiazomethanes provides the corresponding N-methyl-N-nosyl-beta(3)-amino acids with total retention of the chiral configuration of the starting alpha-amino acids. No epimerization of the chiral carbon atom is observed also when N-methyl-N-nosyl-beta(3)-amino acids are transformed into chlorides and coupled with alpha-amino acid methyl esters to achieve model scaffolds for biologically important modified peptides.

Solid-phase synthesis of N-nosyl- and N-Fmoc-N-methyl-alpha-amino acids.

We report here a convenient and simple solid-phase synthesis of N-nosyl-N-methyl-alpha-amino acids and N-Fmoc-N-methyl-alpha-amino acids, important building blocks for the synthesis of conformationally restricted and protease-resistant natural peptides and peptide analogues. The methodology involves the use of 2-chlorotrityl chloride resin to temporarily protect the carboxylic group of alpha-amino acids and of diazomethane as the reagent to methylate the sulfonamidic function. The approach developed is particularly efficient also with alpha-amino acids bearing appropriately protected functionalized side chains.

D-homoannulation of 17alpha,21-dihydroxy-20-keto steroids (corticosteroids).

Synthetic corticosteroids are widely used as anti-inflammatory agents. Mechanisms of their degradation continue to be studied. D-ring homoannulation is a well-known metabolic pathway for steroids in vivo. The rearrangement with aluminium trichloride of the commercial anti-inflammatory drugs hydrocortisone, cortisone and dexamethasone is here presented. The structures of the corresponding 17a-keto-17-hydroxy-D-homosteroids are established by mono- and two-dimensional NMR analysis. Inversion of the alpha-configuration of C-16 is observed in the Lewis acid assisted D-homoannulation of dexamethasone.

Steroidal seven-membered A-ring epoxy lactones by oxidation of the corresponding Delta 4-3-ketosteroids.

Treatment of Delta 4-3-ketosteroids with m-chloroperbenzoic acid at 0 degrees C produced the corresponding steroidal seven-membered A-ring epoxy lactones. The adopted procedure allowed for efficient recovery and separation of the products with definite stereochemistry.

Determination by gas chromatography/mass spectrometry of p-phenylenediamine in hair dyes after conversion to an imine derivative.

In this paper we describe an analytical method for the determination of p-phenylenediamine (PPDA) in hair dyes. In the adopted methodology the analyte is transformed into the corresponding imine derivative by treatment with benzaldehyde, and then analyzed by gas chromatography (GC) combined to mass spectrometry (MS), operating in SIM conditions. The direct and simultaneous chemical derivatization of the two amino functions of the analyte with benzaldehyde enhances the instrumental responses enabling the use of a sensitive and accurate method. Concentrations of PPDA in a set of commercial hair coloring creams are determined making use of N-benzylidene-4-methylbenzene-amine as a very stable internal standard which is easily prepared by condensation of 4-methylbenzene-amine with benzaldehyde. The regression calibration curves for PPDA in hair dyes are linear within 0.1 +/- 25 mg/ml with 0.99 as a typical correlation coefficient.