A systematic study of the aggregation behavior of alkyltriphenylphosphonium bromides (TPPB-n; n=8, 10, 12, 14, 16, 18; here n is the number of carbon atoms in alkyl groups) in aqueous solutions has been carried out and compared with trimethyl ammonium bromides (TMAB-n). Critical micelle concentrations (cmcs) of TPPB-n and TMAB-n decrease with the number of carbon atoms with the slope parameter of ca.0.3. The low cmcs and effective solubilization power toward Orange OT indicate high micellization capacity of phosphonium surfactants. The low counterion binding parameter β is revealed for TPPB-10 and TPPB-12, while high counterion binding of ⩾80% is observed for high TPPB-n homologs. Values of the surface potential ψ calculated on the basis of pK(a) shifts of p-nitrophenols is similar for both series and monotonously increase with alkyl chain length. Several points indicate non-monotonic changes within TPPB-n series. There are peculiarities of the tensiometry and solubilization plots for high homologs and above mentioned increases in counterion binding on transiting from low to high molecular weight surfactants. Differences in aggregation behavior between TPPB and TMAB series and between low and high homologs can be due to the specific structural character of the TPP(+) cation, which is supported by X-ray data.

A new macrocyclic bolaamphiphile with thiocytosine fragments in the molecule (B1) has been synthesized and advanced as perspective platform for the design of soft supramolecular systems. Strong concentration-dependent structural behavior is observed in the water-DMF (20% vol) solution of B1 as revealed by methods of tensiometry, conductometry, dynamic light scattering, and atomic force microscopy. Two breakpoints are observed in the surface tension isotherms. The first one, around 0.002 M, is identified as a critical micelle concentration (cmc), whereas the second critical concentration of 0.01 M is a turning point between the two models of the association involved. Large aggregates of ca. 200 nm are mostly formed beyond the cmc, whereas small micelle-like aggregates exist above 0.01 M. The growth of aggregates between these critical points occurs, resulting in a gel-like behavior. An unusual decrease in the solution pH with concentration takes place, which is assumed to originate from the steric hindrance around the B1 head groups. Because of controllable structural behavior, B1 is assumed to be a candidate for the development of biomimetic catalysts, nanocontainers, drug and gene carriers, etc.

New amphiphilic pyrimidinic (AP) compounds with two ammonium head groups and different kinds of counterions, inorganic bromide anions (APB) and hydrophobic tosylate anions (APT) were synthesized. Self-organization in these systems has been studied by methods of tensiometry, conductometry, potentiometry and NMR spectroscopy. The critical micelle concentrations (cmc's) of bola-type surfactants are only a little lower than those of cetyltrimethylammonium (CTA) analogues. For both pairs APB/CTAB and APT/CTAT the counterion binding is stronger for the conventional cationic surfactants as compared to 'bola' pyrimidinic surfactants. Unlike the CTAT micelles no sharp micellar growth occurs with the APT concentration. The geometry of AP compounds is assumed to be mainly responsible for the above finding. A branched molecular architecture prevents a close packing of the monomers in the bulk solution and at the interface producing a steric hindrance around the head groups.

A complex study of the functional state of the sympathoadrenal system and adrenal cortex in 10-15-year-old children of both sexes was carried out using the indices of daily excretion of adrenaline, noradrenaline, 17-ketosteroids, and 17-hydroxycorticosteroids. A synchronism in the functional activity of the mediator component of the sympathoadrenal system as well as of the androgenic and glucocorticoid functions of the adrenal cortex was observed with age and during pubertal development of children. At the same time, heterochronic maturation was observed in the sex groups: in girls at the age of 10 and 12 years and in boys at the age of 14-15 years. The changes of different direction and intensity in the excretion of the studied hormones and hormonal metabolites were observed in the sex and age groups. A sharp increase in the daily excretion of glucocorticoid metabolites accompanied by a considerable decrease in the age index of noradrenaline secretion was observed in 14- and 15-year-old boys from beginning to end of school year; in addition, an increase in the daily excretion of sex hormones was observed at the age of 15 years. In girls, these indices varied within the age range, which points to a more sophisticated neuroendocrine control of physiological functions in girls during puberty.

Background: Modern premixed insulins offer a flexible approach to the initiation of insulin therapy in patients with poorly controlled type 2 diabetes. A disadvantage of twice-daily regimens of biphasic insulin aspart 30 (BIAsp 30) is that lunchtime control (when no insulin is administered) can be suboptimal. Therefore, it is possible that administering BIAsp 30 thrice daily might further optimize glycemic control and offer an option for patients in whom metformin (MET) is contraindicated. Objective: This study evaluated the efficacy and safety profiles of 2 different regimens of BIAsp 30 compared with a regimen consisting of oral antidiabetic drugs (OADs) alone. Methods: In this multicenter, randomized, open-label, parallel-group trial, insulin-naive patients with poorly controlled type 2 diabetes (baseline glycosylated hemoglobin [HbA(1c)>/=8.0%) who were taking OADs (a sulfonylurea or meglitinide with/without MET or MET only) were randomized to receive BIAsp 30 TID, BIAsp 30 BID + MET, or continuation of their current OAD therapy for 16 weeks. The primary end point was HbA(1c) at the end of the study. Secondary end points included reductions in HbA(1c), mean blood glucose (BG), prandial increment, mean 7-point self-monitored BG profile, weight changes, tolerability (hypoglycemia, adverse events), and satisfaction/quality of life (derived from 2 questionnaires completed at weeks 0, 8, and 16). Results: The study enrolled 308 insulin-naive patients with type 2 diabetes (78.9% female; mean age, 58.3 years; body mass index, 29.4 kg/m(2); HbA(1c), 10.3%). Both BIAsp 30 TID and BIAsp 30 BID + MET were associated with significantly greater mean (SD) reductions in HbA(1c) relative to OADs alone (absolute percent reduction: 2.9%[1.5%], 3.0%[1.6%], and 2.1%[1.4%], respectively; P < 0.001, both insulin groups vs OAD group) and improved post-prandial glucose control (reduction in mean post-prandial glucose:-6.32 [4.07],-6.44 [4.70], and -3.59 [4.22] mmol/L; P < 0.001, both insulin groups vs OAD group). The mean decrease in the prandial increment was -1.26 mmol/L for BIAsp 30 TID,-2.15 mmol/L for BIAsp 30 BID + MET, and -0.44 mmol/L for OAD. The differences in reduction in the prandial increment were statistically significant for BIAsp 30 TID versus OAD (P = 0.047), BIAsp 30 BID + MET versus OAD (P < 0.001), and BIAsp 30 TID versus BIAsp 30 BID + MET (P = 0.042). Mean body weight increased significantly from baseline with both BIAsp 30 TID and BIAsp 30 BID + MET (+1.71 and +1.50 kg, respectively; both, P < 0.001), and decreased significantly in the OAD group (-0.75 kg; P = 0.003). There were no major hypoglycemic events, and most hypoglycemic events were recorded as symptoms only (144/158 [91.1%]). There were no significant differences in the mean frequency of overall hypoglycemic episodes between BIAsp 30 TID and BIAsp 30 BID + MET (0.73 and 0.69 episodes per patient-year, respectively). Conclusions: In these patients with type 2 diabetes that was poorly controlled by OADs, BIAsp 30 TID and BIAsp 30 BID plus MET were associated with significantly greater reductions in HbA(1c) and postprandial BG compared with OADs alone. The insulin regimens were associated with significantly more weight gain than OADs alone. There were no differences in rates of hypoglycemia between the insulin regimens.

New amphiphilic pyrimidinic macrocycles (APMs) with two (APM-1) and three (APM-2) decyl tails have been synthesized by quaternization of the bridged N. Complex examination of the APM-based systems with the help of tensiometry, conductometry, dynamic light scattering, and UV and NMR spectroscopy provides evidence for their aggregation. Calculations based on surface tension isotherms and on packing parameter considerations make it possible to assume a lamellar packing of macrocycles when aggregating. Marked differences in the aggregation behavior of APM-1 and APM-2 have been found. The additives of polyethylenimine (PEI) exert little influence on the critical micelle concentration (cmc) of APM-1, while in the APM-2/PEI systems there occurs a pronounced decrease in the cmc and also a ca. 2-fold decrease in the surface area per molecule. The APM-based assemblies are explored as nanoreactors for the hydrolysis of O-alkyl O-p-nitrophenyl (chloromethyl)phosphonates (alkyl = ethyl, hexyl). The kinetic study reveals a minor rate effect of the APM-1-based systems. In the APM-2-based systems an acceleration of the hydrolysis of both phosphonates occurs as compared to the uncatalyzed process. Within the APM-2 --> APM-2/PEI --> APM-2/PEI/La(III) series, due to the cooperative contributions of the supramolecular, polymer, and homogeneous catalysis, an increase in the catalytic effect is observed from 30 times to 3 orders of magnitude as compared to that of the basic hydrolysis of the substrates.

Effective nanoreactors based on polyethyleneimines (PEIs) for the hydrolytic cleavage of O-alkyl O-p-nitrophenyl chloromethylphosphonates (alkyl = ethyl, hexyl) and di(p-nitrophenyl)phosphate were developed in conformity with the idea of modeling the polyfunctional catalytic mechanism of enzymes. A step-by-step modification of the single PEI solution by additives with their own catalytic activities (sodium dodecyl sulfate and lanthanum salt) gave rise to a marked improvement in the reaction efficiency. A 104-106-fold acceleration of the reaction compared to the aqueous basic hydrolysis of the substrates was achieved in the sodium dodecyl sulfate-polyethyleneimine-La(III) ternary system. This system can be considered to be metallomicelles immobilized on a hydrophilic polymer matrix. When the PEI immobilized on silica gel was used as a catalyst, the full completion of the reaction was achieved for 100 min under mild conditions, while the half-life of the reaction in a comparable homogeneous regime exceeds 100 h.