Use of protein electrophoresis in the diagnosis of cerebrospinal fluid rhinorrhoea.

The diagnosis of CSF rhinorrhoea on clinical grounds alone can be difficult. We describe how the use of non-invasive electrophoretic analysis of nasal secretions for tau protein (asialotransferrin) helped in the management of cases where the existence of a CSF leak was in doubt. Patients were thus saved unnecessary invasive investigations or surgery. A modification of the method of analysis, which improves diagnostic accuracy, is described.     

宁国贝母生物碱的分离和结构鉴定

从贝母新种——宁国贝母(Fritillaria ningguoensis S. C. Chen et S. F. Yin)鳞茎中分离出五个生物碱,其中碱V是一种新的生物碱,命名为宁贝新(ningpeisine),根据理化常数和光谱解析以及衍生物制备,测定其结构为N-methyl-3β-hydroxy-5α-veratranine-6-one。其余四种生物碱鉴定为浙贝甲素(peimine,verticine,Ⅰ),浙贝乙素(peiminine,verticinone,Ⅱ),异浙贝甲素(isoverticine,Ⅲ)和贝母辛(peimisine,Ⅳ)。     

Immunoelectrophoretic Characterization of Insulin Monomers and Polymers

Insulin monomers and polymers were analysed by quantitative immunoelectrophoretic procedures. The Zn-insulin hexamer dissociated reversibly by dialysis against the Zn-free electrophoresis buffer. The Zn-insulin polymers showed precipitin reactions of partial identity. Monomeric salt-free insulin migrated as soluble immune complexes in the antiserum gel. The insulin monomer did not absorb the precipitating antibodies against the Zn-insulin polymers. Thus the polymer structure creates antigenic epitopes absent from the insulin monomer. As insulin is probably released from the β cells in the relatively stable form of Zn-insulin hexamers, selective monomer assays might underestimate the total content of immunoreactive insulin in the biological fluids. Electroimmunoassay of Zn-insulin immunoreactive antigens in human urine defines a normal reference range of 10–25 ng/ml.     

Growth in Rabbits during Alternate-Day Cortisone Injections: Near Normal Growth on Days without Cortisone

ABSTRACT. Longitudinal bone growth in rabbits during treatment with hydrocortisone was measured by means of Roentgen Stereophotogrammetric Analysis, RSA. This method allows accurate measurement of the distance between metallic markers inserted into long bones. Hydrocortisone was given in i.m. injections as single doses and as repeated doses, daily or every other day. Single injections of hydrocortisone resulted in three types of growth effect, depending on dosage. Low dosage (less than 4 mg/kg b.w.) produced no blunting of growth. Intermediate dosage (4–32 mg/kg b.w.) retarded growth during the first but not the second day after the injection. The effect of high dosage (64–128 mg/kg b.w.) lasted for two days. During daily treatment (4 and 16 mg/kg b.w.), growth decreased to a constant level. During alternate-day steroid injections with a double dose every other day, growth almost normalized during the steroid-free days. Average growth was significantly greater during alternate-day injections than during daily injections. It is concluded that alternate-day treatment has no unfavorable effect on growth so long as the interval between injections exceeds the duration of the growth effect of each single dose.     

Cross-linked polymeric nanogel formulations of 5'-triphosphates of nucleoside analogues: role of the cellular membrane in drug release

Activation of cytotoxic nucleoside analogues in vivo depends primarily on their cell-specific phosphorylation. Anticancer chemotherapy using nucleoside analogues may be significantly enhanced by intracellular administration of active phosphorylated drugs. However, the cellular transport of anionic compounds is very ineffective and restricted by many drug efflux transporters. Recently developed cationic nanogel carriers can encapsulate large amounts of nucleoside 5'-triphosphates that form polyionic complexes with protonated amino groups on the polyethylenimine backbone of the nanogels. In this paper, the 5'-triphosphate of an antiviral nucleoside analogue, 3'-azido-2',3'-dideoxythymidine (AZT), was efficiently synthesized and its complexes with nanogels were obtained and evaluated as potential cytotoxic drug formulations for treatment of human breast carcinoma cells. A selective phosphorylating reagent, tris-imidazolylphosphate, was used to convert AZT into the nucleoside analogue 5'-triphosphate using a one-pot procedure. The corresponding 3'-azido-2',3'-dideoxythymidine 5'-triphosphate (AZTTP) was isolated with high yield (75%). Nanogels encapsulated up to 30% of AZTTP by weight by mixing solutions of the carrier and the drug. The AZTTP/nanogel formulation showed enhanced cytotoxicity in two breast cancer cell lines, MCF-7 and MDA-MB-231, demonstrating IC50 values 130-200 times lower than those values for AZT alone. The exact mechanism of drug release from nanogels remains unclear. One mechanism could involve interaction with negatively charged counterions. A high affinity of nanogels to isolated cellular membranes has been observed, especially for nanogels made of amphiphilic block copolymer, Pluronic P85. Cellular trafficking of nanogel particles, contrasted by polyethylenimine-coordinated copper(II) ions, was studied by transmission electron microscopy (TEM), which revealed membranotropic properties of nanogels. A substantial release of encapsulated drug was observed following interactions of drug-loaded nanogels with cellular membranes. A drug release mechanism triggered by interaction of the drug-loaded nanogels with phospholipid bilayer is proposed. The results illustrate therapeutic potential of the phosphorylated nucleoside analogues formulated in nanosized cross-linked polymeric carriers for cancer chemotherapy.