Peptide targeting and delivery across the blood-brain barrier utilizing synthetic triglyceride esters: design, synthesis, and bioactivity

As an approach to the development of therapeutically useful peptide pharmaceuticals that can penetrate the blood-brain barrier, we have designed and demonstrated the application of a carrier-targeting system. We have developed a prodrug design strategy that is designed to utilize membrane-bound enzymes whereby release of a bioactive peptide from a highly lipophilic triglyceride peptide-carrier is achieved in situ, thus attaining high localized concentrations of the bioactive peptide. Following localization of such a system, normal peptidase and lipase action is utilized to release the active peptide (deltorphin II) intact and in high concentration. At present, the exact mechanisms are unclear, but the observed results in which analgesia is observed following peripheral administration suggest that the active peptide is able to cross the blood-brain barrier and sustain prolonged periods of analgesia as determined by antinociception tests by release of the bioactive peptide. In vitro tests of binding and bioactivity by the peptide conjugate show essentially no potency in either target or control analogues, but potent antinociceptive effects are observed following peripheral administration.     

High levels of interleukin-6 are associated with low tumor burden and low growth fraction in multiple myeloma

Interleukin-6 (IL-6) is a multifunctional cytokine postulated to play a central role as a growth factor for multiple myeloma (MM). We evaluated the spontaneous secretion of IL-6 in supernatants of Ficoll-Hypaque--enriched bone marrow (BM) cultures from 35 patients with MM. The levels of IL-6 were correlated with biological and clinical characteristics of the disease. High levels of IL-6 production defined a subgroup of patients with low tumor burden as determined by lower serum beta 2-microglobulin (B2M) (P = .02) and lower percentage of myeloma cells infiltrating the bone marrow (P = .003), higher synthetic rates of monoclonal protein (P = .006), and low proliferative compartments as measured by the percentage of Ki-67--positive myeloma cells. Patients with high proliferative fractions (Ki-67--positive myeloma cells > 20%) had significantly lower levels of IL-6 when compared with patients with low proliferative fractions (P = .005). Our findings do not support IL-6 as a major growth factor for MM, but demonstrate an association of high levels of IL-6 secretion with low tumor cell burden and low proliferative fraction.     

The renal effects of melatonin in intact and epiphysectomized rats

Epiphysectomy in adult pubescent Wistar rats causes polyuria and Na uresis at the expense of the increased rate of the glomerular filtration and sodium filtration charge. Melatonin in a dose of 4.31 mkM/100 g of the body weight increased the glomerular filtration of both sodium and water and stimulated the sodium tubular transport in rats with intact epiphysis and did not normalize changes of the nephron excretory activity after epiphysectomy.     

Signal equalization in digital magnetic recording

The signal applied to the head in the writing process undergoes changes and distortions of various sources. Equalization must be applied to the read signal to help restore the input waveshape. The object is to improve timing accuracy which ultimately allows the use of increased bit density. An equalization method is presented in which amplitude and phase are controlled separately. The phase equalizer is adjustable, compensating for waveshape asymmetry. The networks are extremely simple and not sensitive to component tolerances. In continuous waveshape codes, such as phase recording or double frequency recording, the system is capable of compensating for considerable variations in the spacial parameters of recording. The equalization can also be used in nonreturn to zero (NRZ) code, where the ability to restore symmetry can be used to great advantage in eliminating errors.     

Percutaneous absorption of 1,3-bis (2-chloroethyl)-I-nitrosourea (BCNU, carmustine) in mycosis fungoides

The total percutaneous absorption of 1,3-bis(2-chloroethyl)-I-nitrosourea (BCNU, carmustine) in 5 patients with mycosis fungoides, based on the 5 day urinary excretion of 14C-labelled BCNU, ranged from 5 to 28%. Absorption through diseased skin was greater than through uninvolved skin.     

A comparison of clinical results in brain scanning using germanium semiconductor detectors and sodium iodide detectors

A comparison is presented of the image quality obtained with a 70 mm Ge(Li) detector scanner and with routine techniques based on NaI (Tl) detectors. One hundred and sixty-five pairs of brain scans have been examined for which the patients have been scanned with both Ge(Li) and NaI (Tl) detectors. It is concluded that no major difficulties exist in introducing Ge(Li) scanners and that while a comparison of scans from different instruments is difficult there is evidence that improved diagnostic information may be obtained from scanners with Ge(Li) detectors.     

Electrochemical behavior of cerium ion in molten LiCI-KCI

The electrode process of cerium(Ⅲ) on the Mo electrode in eutectic LiCl-KCl melt was investigated by electrochemical transient techniques in the temperature range of 673-783 K,respectively.These results unanimously indicated that the reduction process of cerium(Ⅲ) to cerium metal was a single step exchanging three electrons which was controlled by diffusion of cerium(Ⅲ).Diffusion coefficients(D Ce(Ⅲ)) in eutectic LiCl-KCl melt were determined by cyclic voltammetry,chronopotentiometry and square wave voltammetry.An empirical diffusion coefficient function depending on temperature was proposed:lnD Ce(Ⅲ) =-2.129-5704/T.The formal potentials(Eθ’ Ce(Ⅲ)/Ce(0) versus Ag/AgCl reference electrode) at different temperatures were obtained from chronopotentiometry,which were-2.10 V(673 K) and-2.07 V(733 K),respectively.     

U形件模具表面摩擦对回弹影响的数值模拟

通过对U形件模具表面进行激光复合造型处理,有效的控制模具表面各区域的摩擦系数,从而改善了板料的回弹,同时提高了模具的寿命.利用ABAQUS10.0有限元模拟软件对U形件进行数值模拟,在模具表面各区域设置不同的摩擦系数,揭示了各区域摩擦系数对U形件回弹的影响规律.结果表明:增加凹模圆角、法兰区与板料之间的摩擦,减小凸模圆...     

A Probable Flavoring Principle in Vegetable-Protein Hydrolysates

SUMMARY— The characteristic seasoning flavor of hydrolyzed vegetable proteins has previously been attributed to α-ketobutyric acid formed from threonine under the conditions of acid-hydrolysis. However, pure α-ketobutyric acid is virtually odorless and tasteless, and it develops the characteristic flavor only upon ageing. The true flavoring principle is probably α-hydroxy-β-methyl-Δ.^α,β-γ-hexenolactone, which is formed from the acid by dimerization, lactonization, and decarboxylation. This conversion occurs spontaneously, but is greatly accelerated under acidic conditions.