Use of dibunol in pharmacological correction of post-vagotomy hypoxia of digestive organs in rats

1, 7, 14, 30 and 60 days after bilateral sub-diaphragmatic truncal vagotomy tension of oxygen (pO2) in liver, stomach and small intestine (jejunum) was determined. It was demonstrated that vagotomy leads to a decrease of pO2 in all investigated organs 1 day after the operation (such changes were observed in sham-operated rats) and 30 days, in jejunum--after 7 days, in liver--after 14 days, in stomach--after 60 days. Dibunol introduction in vagotomized rats during 29 days (starting from the second day after operation) results in pO2 normalization in all investigated organs.     

Use of liposomes as carriers for radiation synovectomy

Using [^99mTc]pertechnetate as an aqueous space marker, the permeability of liposomes composed of seven different mixtures of distearoylphosphatidylcholine (DSPC) and sphingomyelin (SM) was determined. Liposomes containing 20–33% SM were the least permeable in the presence of rheumatoid synovial fluid. Following injection of ^99mTc-containing liposomes into the knee joints of rabbits, retention of ^99mTc in the knee was more than 200 times greater than following injection of nonencapsulated [^99mTc]pertechnetate. The knee clearance biologic half time of ^99mTe with DSPC/SM (4:1) liposomes was 64 h. Most of the activity that had leaked from the knee was not found in extra-articular tissues, suggesting rapid excretion. When DSPC/SM (4:1) liposomes were labeled with ¹¹¹In(oxine), a knee clearance biologic half time of greater than 1200 h was observed.     

Use of liposomes in transforming yeast cells

Summary Plasmid DNAs of YEp13 and pMA56 were encapsulated in liposomes. Cells ofSaccharomyces cerevisiae strain SHY3 were protoplasted. After fusing membranes of the liposomes and the protoplasts, transformation of the regenerated yeast cells with the plasmids has been confirmed.     

Pulmonary circulation in experimental pneumonia

The ultrasonic technique was used in acute experiments on open-chest cats under controlled lung ventilation to test the blood flow in damaged and undamaged lung lobes in experimental pneumonia. It was shown that the absolute values of the linear and volumetric blood flow rate in the lower artery of the damaged lobe were similar to those in the analogous undamaged lobe. The blood flow in the damaged focus seems limited, while the blood volume passed through the vessels of the undamaged lobe is normal. This opinion is confirmed by high blood flow values in the artery supplying the damaged lobe with blood, when compared to the data on the absence of marked arterial hypoxaemia.     

Use of hyperbaric oxygenation to correct an acute experimental respiratory insufficiency syndrome

The results of the experiments on 159 Wistar rats have shown that one two-hour session of hyperbaric oxygenation (HBO) under the pressure of 3 ata affects considerably the course of acute respiratory insufficiency syndrome: the mortality rate decreases markedly, the development of arterial hypoxemia and structural changes peculiar to the "wet" lung could be averted. The results of the investigations demonstrate the possibility of HBO application for the prophylaxis and treatment of the syndrome.     

Use of a new M-cholinolytic drug KG-62 for correction of the course of experimental stomach ulcer]

The preparation KG-62 related to iodomethylates of hydroxyalkyl phosphinic acids with muscarinolytic effect has been studied. The study provides data on the development of experimental gastric ulcer among rats after injections of the preparation. On the basis of morphologic, morphometric and biochemical data it has been stated that the preparation KG-62 in a 5 mg/kg dose has a more strong effect leading to quick gastric ulcer healing. It was supposed that not only suppressing action on hydrochloric acid and pepsinogen secretion lies in the mechanism of the effect but also the activation of physiologic regulation in intact tissue.     

New paths in the pathogenetic correction of hemic hypoxia]

It is stated that prophylactic administration of ional (dibunol) and taurine to rats exerts an antihypoxic effect in case of acute hemic hypoxia. It is expressed in a decrease of methemoglobin level in blood, increase of pO2, in the skeletal muscles, normalization of the structure of hematoparenchymatous barriers, prevention or decrease in a fall of the rate of oxygen consumption by tissues.     

Moderate intermittent hypoxia/hyperoxia: implication for correction of mitochondrial dysfunction

The purpose of this study was to appreciate the acute hypoxia-induced mitochondrial oxidative damage development and the role of adaptation to hypoxia/hyperoxia (H/H) in correction of mitochondrial dysfunction. It was demonstrated that long-term sessions of moderate H/H [5 cycles of 5 min hypoxia (10% O₂ in N₂) alternated with 5 min hyperoxia (30% O₂ in N₂) daily for two weeks]_attenuated basal and Fe²⁺/ascorbate-induced lipid peroxidation (LPO) as well as production of carbonyl proteins and H₂O₂ in liver mitochondria of rats exposed to acute severe hypoxia (7% O₂ in N₂, 60 min) in comparison with untreated animals. It was shown that H/H increases the activity of glutathione peroxidase (GPx), reduces hyperactivation of Mn-SOD, and decreases Cu,Zn-SOD activity as compared with untreated rats. It has been suggested that the induction of Mn-SOD protein expression and the coordinated action of Mn-SOD and GPx could be the mechanisms underlying protective effects of H/H, which promote the correction of the acute hypoxia-induced mitochondrial dysfunction. The increase in Mn-SOD protein synthesis without changes in Mn-SOD mRNA level under H/H pretreatment indicates that the Mn-SOD activity is most likely dependent on its posttranslational modification or on the redox state of liver mitochondria.     

Carrageenin-induced experimental pneumonia in rats.

The authors verified the possibility of modelling pneumonia by the intratracheal administration of carrageenin solution into the lungs of rats. The most satisfactory dose was found to be 0.5 ml 0.7% carrageenin solution administered at 40 degrees C. The disease, evaluated by the morphological and functional signs, culminated after two days. Both macroscopically and histologically the lungs displayed typical signs of catarrhal suppurative aspiration bronchopneumonia. Functionally, marked tachypnoea (mean 180 cycles/min as against 110 c/min in the conscious controls) and raised functional residual capacity were found. A drop in the respiration rate and in FRC after bilateral cervical vagotomy indicated that a reflex component participates in the origin of the above two signs.     

Use of the post-insertion method for the formation of ligand-coupled liposomes

A new technique is described for the formation of ligand-targeted liposomes that can be used with whole antibodies, antibody fragments, peptides or other ligands. The ligands are coupled to polyethylene glycol micelles and then transferred in a simple incubation step from the micelles into the outer monolayer of pre-formed, drug-loaded liposomes. This versatile method allows a combinatorial approach to the design of targeted liposomes that minimises manufacturing complexities, allowing a variety of ligands to be inserted into a variety of pre-formed liposomes containing a variety of drugs. This allows the ligand-targeted therapeutics to be tailored to the needs of individual patients.     

Targeting of piperine intercalated in mannose-coated liposomes in experimental leishmaniasis

The leishmanicidal property of piperine intercalated in liposomes and in mannose-coated liposomes was tested in experimental visceral leishmaniasis in hamsters. Mannose-coated liposomal piperine eliminated intracellular amastigotes of Leishmania donovani in splenic macrophages much more efficiently than did the liposomal piperine or free piperine. At a dose equivalent to 6 mg/kg body wt every 4th day for a total of 4 doses in 12 days, the mannose-coated liposomal piperine was found to reduce spleen parasite load to the extent of 90% in comparison to that achieved by liposomal piperine (77%) or free piperine (29%). Histological examination of spleen and liver function tests showed that the toxicity of piperine was reduced when mannosylated liposomal piperine was administered.     

Use of liposomes as drug delivery vehicles for treatment of melanoma

Melanoma is a progressive disease that claims many lives each year due to lack of therapeutics effective for the long‐term treatment of patients. Currently, the best treatment option is early detection followed by surgical removal. Better melanoma therapies that are effectively delivered to tumors with minimal toxicity for patients are urgently needed. Nanotechnologies provide one approach to encapsulate therapeutic agents leading to improvements in circulation time, enhanced tumor uptake, avoidance of the reticulo‐endothelial system, and minimization of toxicity. Liposomes in particular are a promising nanotechnology that can be used for more effective delivery of therapeutic agents to treat melanoma. Liposomes delivering chemotherapies, siRNA, asODNs, DNA, and radioactive particles are just some of the promising new nanotechnology based therapies under development for the treatment of melanoma that are discussed in this review.     

Incorporation of respiratory cytochromes in liposomes: an efficient strategy to study the respiratory chain

The electron transport system present in the photosynthetic apparatus and respiratory chain were evolutionary acquisitions that allowed the organisms to convert electromagnetic energy in chemical energy and thus improve the use of energy fuels. These systems acquired by prokaryotes were preserved in the highly complex organisms always with the participation of the cytochromes. Since the discovery of the cytochromes, and the isolation and association of these proteins to model membranes, the liposomes, have been used to investigative strategies to characterize the structure and function of these proteins. From these studies important findings have contributed to the comprehension of the energy transduction mechanisms and the role played by the nonredox subunits present in the protein complexes of the respiratory chain of eukaryotes.