Aqueous-based microencapsulation enhances virus-specific humoral immune responses in mice after parenteral inoculation

Vaccines are commonly administered by the parenteral route. Therefore, adjuvant strategies which include parenteral immunization may improve the efficacy of a number of current vaccines. The capacity of aqueous-based microencapsulation to enhance virus-specific IgG responses in mice inoculated intramuscularly with small quantities of antigen was evaluated. Mice were inoculated with either 10(4), 10(3), or 10(2) p.f.u. of microencapsulated rotavirus (bovine strain WC3), placebo microcapsules plus free virus, or virus alone. Mice were subsequently bled 1, 2, 4, 6, and 9 months after inoculation. Microencapsulation of rotavirus enhanced virus-specific humoral immune responses. In addition, virus-containing microcapsules composed of spermine-chondroitin sulfate induced levels of virus-specific antibodies greater than those found after inoculation with virus-containing microcapsules composed of spermine-alginate. Mechanisms by which microencapsulation may enhance virus-specific humoral immunity are discussed.     

Interstitial cells of the medulla and the renin-angiotensin system in disorders of water-salt homeostasis

Electron microscopic studies of the intersticial cells of the renal medullar layer and the count of lipid granules in them were conducted in two experimental states accompanied by a reduction of the circulating blood volume--72 hours of water-free diet and intravenous administration of Lazyx that possesses a potent natriuretic and diuretic effect. The concentration of renin and angiotensin was determined in the plasma of the same animals, using the radioimmunoassay technique, and the juxtaglomerular apparatus of the kidneys was examined. The study has demonstrated that the reduction of the circulating blood volume is accompanied, on the one hand, by a significant elevation of the plasma concentration of renin and angiotensin, and, on the other hand, by a reduction of the number of lipid granules in the intersticial cells that is interpreted by the authors as an index of an increased synthesis of renal prostaglandins. It has been concluded that a close functional interrelashionship exists between the two hormonal systems of the kidneys that regulate the water-electrolyte homeostasis, i.e. the renin-angiotensin system and the prostaglandins system.     

Pathomorphology of kidney lesions induced by non-steroidal anti-inflammatory drugs

Pathomorphological findings on nephrobiopsies from two groups of patients with NSAID-induced kidney lesions are provided. In the first group (9 patients) the disease developed in patients of different age after short-term use of NSAID and was clinically manifested by acute renal failure with extrarenal allergic symptoms (skin, rash, eosinophilia). Morphological features were acute tubulo-interstitial nephritis without glomerular lesions. In the second group (23 patients) the disease developed after longterm use of NSAID in older patients with a compromised renal blood circulation presenting clinically with nephrotic syndrome, and morphologically by acute tubulo-interstitial nephritis with minimal change (lipoid nephrosis).     

Studies on plasma lipid and phospholipid composition in pernicious anemia before and after specific treatment

Over a period of two years, 7 137 localisations of placenta were performed. In 67 patients on the first examination it was found that the lower margin of placenta reached the internal os of the uterus. All these patients were followed up by examinations every two or four weeks. In 63 of the 67 patients, placental migration was found involving a change in the level of the lower placental edge from the cervix towards the fundus. The change in this position varied from 3 to 9 cm. All four cases where the placenta extended from anterior to posterior wall ended as placenta praevia. Ultrasonic proof of placental migration shows the necessity for ultrasonic examination shortly before the birth, as only then is the final diagnosis of placenta praevia possible.     

Diagnostic significance of electrocortical responses to rhythmic and solitary photic stimuli in patients with hepato-portal encephalopathy]

In order to clarify some diagnostical criteria of latent hepato-portal encephalopathy in 57 patients with intrahepatic forms of portal hypertension the authors studied the character of driving response in photorhythmical stimulation. In 9 patients the development of evoked potentials depending upon the significance of the stimula was studied as well. The studies confirmed the prognostical significance of a slowing down the mean frequency of rhythms in the EEG in relation to the development of acute encephalopathy and a certain tendency to the shift in the spectrum of driving responses to low frequency and a worsening of driving responses in slowing down the medium rhythm frequency of EEG. In patients with changed resting activity in the Background EEG there was a drop in the amplitude of late components of evoked potentials.     

Ubiquitin‐Based Probes Prepared by Total Synthesis To Profile the Activity of Deubiquitinating Enzymes

Epitope‐tagged active‐site‐directed probes are widely used to visualize the activity of deubiquitinases (DUBs) in cell extracts, to investigate the specificity and potency of small‐molecule DUB inhibitors, and to isolate and identify DUBs by mass spectrometry. With DUBs arising as novel potential drug targets, probes are required that can be produced in sufficient amounts and to meet the specific needs of a given experiment. The established method for the generation of DUB probes makes use of labor‐intensive intein‐based methods that have inherent limitations concerning the incorporation of unnatural amino acids and the amount of material that can be obtained. Here, we describe the total chemical synthesis of active‐site‐directed probes and their application to activity‐based profiling and identification of functional DUBs. This synthetic methodology allowed the easy incorporation of desired tags for specific applications, for example, fluorescent reporters, handles for immunoprecipitation or affinity pull‐down, and cleavable linkers. Additionally, the synthetic method can be scaled up to provide significant amounts of probe. Fluorescent ubiquitin probes allowed faster, in‐gel detection of active DUBs, as compared to (immuno)blotting procedures. A biotinylated probe holding a photocleavable linker enabled the affinity pull‐down and subsequent mild, photorelease of DUBs. Also, DUB activity levels were monitored in response to overexpression or knockdown, and to inhibition by small molecules. Furthermore, fluorescent probes revealed differential DUB activity profiles in a panel of lung and prostate cancer cells.     

Inhibition of Bacterial Dihydrofolate Reductase by 6‐Alkyl‐2,4‐diaminopyrimidines

(±)‐6‐Alkyl‐2,4‐diaminopyrimidine‐based inhibitors of bacterial dihydrofolate reductase (DHFR) have been prepared and evaluated for biological potency against Bacillus anthracis and Staphylococcus aureus. Biological studies revealed attenuated activity relative to earlier structures lacking substitution at C6 of the diaminopyrimidine moiety, though minimum inhibitory concentration (MIC) values are in the 0.125–8 μg mL^?1 range for both organisms. This effect was rationalized from three‐ dimensional X‐ray structure studies that indicate the presence of a side pocket containing two water molecules adjacent to the main binding pocket. Because of the hydrophobic nature of the substitutions at C6, the main interactions are with protein residues Leu 20 and Leu 28. These interactions lead to a minor conformational change in the protein, which opens the pocket containing these water molecules such that it becomes continuous with the main binding pocket. These water molecules are reported to play a critical role in the catalytic reaction, highlighting a new area for inhibitor expansion within the limited architectural variation at the catalytic site of bacterial DHFR.     

Polymerization of filled propylene: A new principle for formation of conducting composites

A new approach to the formation of electrically conducting polymeric materials has been formulated. It is based on the phenomenon of pressure-induced injection of charge carriers from conducting particles into dielectric media. This process has been recently discovered by the authors. In practice, this approach can be accomplished by synthesizing macromolecules of proper dielectric next to the surface of a conducting filler. The experiments supporting the validity of the main assumptions are used to provide a background for the “polymerization filling” concept. The application of this principle makes it possible to obtain systems with larger specific conductivity than with the usual “blended” composites.