The characteristics of nucleobase transport and metabolism by the perfused sheep choroid plexus.

The uptake of nucleobases was investigated across the basolateral membrane of the sheep choroid plexus perfused in situ. The maximal uptake (U(max)) for hypoxanthine and adenine, was 35.51+/-1.50% and 30.71+/-0.49% and for guanine, thymine and uracil was 12.00+/-0.53%, 13.07+/-0.48% and 12.30+/-0.55%, respectively with a negligible backflux, except for that of thymine (35.11+/-5.37% of the U(max)). HPLC analysis revealed that the purine nucleobase hypoxanthine and the pyrimidine nucleobase thymine can pass intact through the choroid plexus and enter the cerebrospinal fluid CSF so the lack of backflux for hypoxanthine was not a result of metabolic trapping in the cell. Competition studies revealed that hypoxanthine, adenine and thymine shared the same transport system, while guanine and uracil were transported by a separate mechanism and that nucleosides can partially share the same transporter. HPLC analysis of sheep CSF collected in vivo revealed only two nucleobases were present adenine and hypoxanthine; with an R(CSF/Plasma) 0.19+/-0.02 and 3.43+/-0.20, respectively. Xanthine and urate, the final products of purine catabolism, could not be detected in the CSF even in trace amounts. These results suggest that the activity of xanthine oxidase in the brain of the sheep is very low so the metabolic degradation of purines is carried out only as far as hypoxanthine which then accumulates in the CSF. In conclusion, the presence of saturable transport systems for nucleobases at the basolateral membrane of the choroidal epithelium was demonstrated, which could be important for the distribution of the salvageable nucleobases, adenine and hypoxanthine in the central nervous system.

[The supply of blood, albumin and infusion solutions during war]. / Snabdevanje krvlju, albuminom i infuzijskim rastvorima u ratu.

Use of blood, albumin and infusion solutions is one of the essential measures in management of war casualties which significantly contributes to the decline in mortality rate of war injured. Human blood and albumin represents the critical national resources which, beside the other, are characterised by limitation of sources and manace of enemy's combat operations. However, because blood and albumin would not be available in sufficient quantities, it is necessary to provide solutions for infusion, since the infusion is the obligatory component of modern management of injured in war and peace. For this reason each injured should be provided 0.35 l of blood, 0.25 l of 5% albumin solution, 0.5 l of 6% clinical dextrane solution and one litre of crystalloid solutions. The availability of these quantities is directly proportional with the effectiveness of the systems for provision of blood, albumin and infusion solutions. The success of the systems depend on realisation of the definite prerequisites, especially of mass and well-organised blood donor service, qualified blood collecting personnel and modern equipment including mobile laboratories for production of solutions for infusion.

HI-6 in man: efficacy of the oxime in poisoning by organophosphorus insecticides.

The efficacy of the oxime HI-6 was studied as a treatment for organophosphorus poisoning. HI-6 was given four times daily as a single intramuscular injection of 500 mg accompanied by atropine and diazepam therapy. Oxime treatment was started on admission and continued for a minimum of 48 h and a maximum of 7 d. HI-6 rapidly reactivated human blood acetylcholinesterase inhibited by dimethoxy organophosphorus compounds, while the dimethoxy-inhibited enzyme was mainly resistant to the treatment by HI-6. Although both HI-6 and pralidoxime chloride reactivated the red blood cell cholinesterase in quinalphos-poisoned subjects, the return of enzyme activities was more rapid following the use of HI-6. The general improvement of poisoned patients, which was sometimes more rapid than the rise of acetylcholinesterase activity, pointed to direct pharmacological effects of HI-6. No undesirable side-effects were noted in patients when HI-6 plasma concentrations were maintained at levels far above the 'therapeutic' concentration for up to 7 d.

[The effect of the oxime HI-6 on miosis induced by topical administration of sarin and VX in the rabbit eye]. / Delovanje oksima HI-6 na miozu oka kunica, izazvanu lokalnom primenom sarina i VX-a.

Effect of oxime HI-6 to rabbit miosis induced by the topical sarin and VX administration is presented. It has been found that effects of both toxins are better antagonized by parenteral than by topical HI-6 administration. The sarin antagonizing effect was found more effective. It has been also confirmed that there was no significant difference concerning the oxime HI-6 effect when topically administered either as 2.5% hypertonic or isotonic solution. Opposite to PAM-2, HI-6 effect was better in parenteral and topical administration of isotonic solutions, and less effective in local administration of hypertonic solutions.

The protective effect of different drugs in rats poisoned by sulfur and nitrogen mustards.

Based on the recent pathognomic accomplishment in the mechanisms of toxic actions, the favorable degree of protection was achieved by several drugs in acute poisoning of rats with sulfur and nitrogen mustards. It has been established that dexamethasone, promethazine, vitamin E, heparin, and sodium thiosulfate (a) prolonged the survival time in animals poisoned by 3 LD50s of toxic agents, (b) diminished the lethalty (with the protective indices ranging from 1.5 to 2.7), (c) antagonized the decrease of body weight, and (d) lessened the degree of pathological organ changes. The simultaneous administration of two or three of the drugs mentioned, of which sodium thiosulfate as chemical inactivator of the toxic agents was basic and consonant component, led to the further increase in effectiveness. It is concluded that satisfactory results obtained in this study speak in favor of the basic pathological effects of mustard gases, as well as possible causes and their possible ways of action as postulated by Dannenberg (1983).

HI-6 in man: blood levels, urinary excretion, and tolerance after intramuscular administration of the oxime to healthy volunteers.

After intramuscular administration of graded doses of HI-6 (62.5, 125, 250, and 500 mg) to 22 healthy men, it has been established that therapeutic concentrations of the oxime in plasma, arbitrarily taken as 4 micrograms/ml, were achieved by doses of 250 and 500 mg in about 5 min, and maintained from 2 to 3 hr. The two lowest doses have not been satisfactory in this respect. Of the total doses injected, from 56.3 to 62% of HI-6 was excreted into urine unchanged during the first 6 hr. No side-effects were reported by the subjects, nor revealed by clinical or laboratory tests during the study. Exceptional tolerance of HI-6 in man found in this study, along with its high efficiency proven in experimental poisoning by sarin, VX, and soman, make it the most promising oxime aimed at the treatment of human poisoning by known chemical warfare nerve agents.