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PubMed1978

Inosine: clinical results of ischaemic renal surgery.

Ten patients requiring ischaemic renal surgery for calculus or tumour were operated on with the kidney protected by perfusion with a room temperature solution of inosine. The warm ischaemic times ranged from 35 to 75 min (mean 57.1 min). Post-operative recovery was uneventful in all patients. No adverse cardiodynamic effects due to inosine were noted. There was only moderate transient depression in renal function as assessed by gamma camera renography and serum creatinine estimations. Three of the 10 patients have now been followed for over a year. The results with inosine perfusion are comparable to those obtained with hypothermic protection.

Adult↗
PubMed1999

Inosine supplementation has no effect on aerobic or anaerobic cycling performance.

The two basic aims of this study were to add to the limited literature concerning Inosine as an ergogenic aid, and to determine the effects of Inosine supplementation over a period of 5 and 10 days, at a dosage of 10,000 mg.d-1 on measures associated with aerobic and anaerobic performance. Seven trained, volunteer male subjects (body mass = 63.0 +/- 8.7 kg, VO2max = 67.9 +/- 3.3 ml.kg-1.min-1) participated in this study. The subjects completed three test sessions, each comprising three tests (5 x 6-s sprint, 30-s sprint, and 20-min time trial). Supplementation was carried out in a random, double-blind manner, and the test sessions were undertaken prior to (Baseline, B), on Day 6, and on Day 11. Blood was sampled prior to supplementation as well as on Days 6 and 11 and was analyzed for uric acid and 2,3 DPG. An analysis of the data indicated no performance benefit of supplementation and no improvement in 2,3 DPG concentration. Uric acid concentration increased significantly after both Days 6 and 11 (p < 0.03 and p < 0.004, respectively). It is concluded that Inosine has no ergogenic effects but may cause possible health problems if taken over long periods of time.

2,3-Diphosphoglycerate↗
PubMed1979

Inosine may be an endogenous ligand for benzodiazepine receptors on cultured spinal neurons.

Mouse spinal neurons grown in tissue culture were used to study the membrane effects of the benzodiazepine flurazepam and the naturally occurring purine nucleoside inosine, which competes for benzodiazepine receptor sites in the central nervous system. Application of inosine elicited two types of transmitter-like membrane effects: a rapidly desensitizing excitatory response and a nondesensitizing inhibitory response. Flurazepam produced a similar excitatory response which showed cross-desensitization with the purine excitation. Flurazepam also blocked the inhibitory inosine response. The results provide electrophysiological evidence that an endogenous purine can activate two different conductances on spinal neurons and that flurazepam can activate one of the conductances and antagonize the other.

Animals↗
PubMed1991

Use of inosine-containing oligonucleotide primers for enzymatic amplification of different alleles of the gene coding for heat-stable toxin type I of enterotoxigenic Escherichia coli.

A method which employs the polymerase chain reaction (PCR) to identify Escherichia coli strains containing the estA gene was developed. This gene codes for heat-stable enterotoxin type I. The use of an inosine-containing pair of amplification primers allowed the amplification of a specific 175-bp DNA fragment from several different estA alleles. The amplified fragments were identified and distinguished by allele-specific oligonucleotide hybridization and characterized by restriction endonuclease analysis. An extension of the classical two-primer PCR proved to be a very simple and rapid method to identify and characterize the estA alleles. Besides the inosine-containing pair of primers, which recognized all described alleles, additional oligonucleotides were used as primers. The sequence of each of these primers was allele specific, and each was amplification compatible with one of the inosine-containing primers. Thus, in one PCR the 175-bp fragment typical for all estA alleles and an allele-specific fragment of different size were produced. These fragments could be separated by agarose gel electrophoresis and were recognized by ethidium bromide staining. Twenty-seven E. coli strains were tested with this amplification system. The presence or lack of the genetic information for production of heat-stable enterotoxin type I was perfectly consistent with the ability of these strains to produce this enterotoxin, as determined by enzyme-linked immunosorbent assay.

Alleles↗
PubMed1981

Induction of Bacillus subtilis sporulation by nucleosides: inosine appears to be sporogen.

Inosine completely reversed the selective inhibition of sporulation in Bacillus subtilis 168 caused bym-aminobenzeneboronic acid; guanosine and adenosine, but not xanthosine, partially reversed inhibition, whereas pyrimidine nucleosides were slightly effective. In addition, 0.005 to 0.025 mM inosine caused a four- to fivefold stimulation of sporulation of B. subtilis grown in minimal salts medium. Ultraviolet and infrared spectra and other physical and chemical properties of inosine were markedly similar to those of "sporogen," a previously described endogenous sporogenesis factor present in sporulating Bacillus species.

Adenine↗
PubMed1984

Enhanced ATP and GTP synthesis from hypoxanthine or inosine after myocardial ischemia.

Increasing therapeutic use is made of purines for the treatment of ischemic heart disease, but little is known about regulatory mechanisms involved. Therefore we perfused isolated rat hearts with 0.02 mmol/l [8-14C]hypoxanthine or inosine. Under normoxic conditions about 1% is taken up by the heart and partially used for synthesis of ATP and GTP at a rate of 0.4 and 0.1 nmol X min-1 X g dry wt-1, respectively. After relatively mild ischemia (coronary flow reduction of 70% for 20 min), no increase in myocardial purine uptake is observed, but ATP and GTP synthesis rates are doubled (P less than 0.001). D-Ribose stimulates the hypoxanthine incorporation rate in normoxic perfused rat hearts to 1.1 and 0.5 nmol X min-1 X g dry wt-1 for ATP and GTP, respectively, which is further increased during postischemic perfusion. About 80% of the [8-14C]inosine or [8-14C]hypoxanthine passes through the heart unchanged, while 15% is converted to (hypo)xanthine and uric acid. We conclude from these experiments that inosine and hypoxanthine incorporation into ATP and GTP is at least partly regulated by the availability of 5-phosphoribosyl-1-pyrophosphate.

Adenosine Triphosphate↗
PubMed2004

Variation of the spore population of a natural source strain of Bacillus cereus in the presence of inosine.

The heat resistance of a wild strain of Bacillus cereus spores isolated from liquid egg was characterized, and the effect of the nutritional germinant inosine on the spore population was then studied, considering different factors such as germination temperature, inosine concentration, and age of spore culture. The heat resistance clearly indicates that these spores can survive mild heat treatments such as those used for cooked refrigerated food of extended durability or liquid egg, posing safety problems for these foods with temperature abuse. The germination study indicates that temperature, spore age, and the interaction between the two were the factors affecting the level of spores remaining after the germination process. No significant differences were found for the three inosine concentrations used in the study (1, 5, and 10 mM). The highest reduction in the spore concentration was reached at 30 degrees C after 120 min, although the reduction in the spore counts at germination temperatures of 4 and 8 degrees C was also considerable.

Bacillus cereus↗
PubMed1975

[Comparative study of adenosine and inosine as corrigents of ACD (Acid Citrate Dextrose) solution in preservation of human blood].

The examination was made on the effects of adenosine and inosine on glycolysis in ACD stored human red cells. Total glycolytic capacity was checked by the incorporation of inorganic phosphate into the acid soluble nucleoside phosphates of erythrocytes. Adenosine and inosine increase the glycolysis in ACD stored human red cells. This stimulation depends on the nucleoside concentration used up to the saturation level (2.0 muM of adenosine or inosine/ml). By the saturation level it was demonstrated that adenosine gives 30%higher stimulation than inosine. It may be concluded that by the same conditions adenosine may serve as a better corrigens for ACD stored human blood.

Adenosine↗
PubMed1975

Correlation between coronary venous inosine concentration and myocardial wall thickening during regional ischemia.

Correlations between local mechanical and metabolic events were studied during partial decrease in flow in the left anterior descending coronary artery in the open-chest pig. During ischemia, systolic ventricular wall thickening decreased. Concomitantly, the concentration of inosine, hypoxanthine, lactate, and potassium in the regional anterior coronary vein increased, whereas the concentration of these compounds in the femoral artery did not change. A negative correlation was observed between the venous inosine concentration and the decreased myocardial wall thickening during ischemia. This study indicates that the local venous inosine concentration is a sensitive indicator of regional myocardial ischemia in the pig.

Adenosine Diphosphate↗
PubMed1975

Prevention of chronic experimental heart insufficiency by inosine.

The administration of inosine dosed 25 mg/kg daily during 10 1/2 months prevented the development of excentric cardiac hypertrophy on the background of experimental aortic stenosis in rats, reduced the lowering of the working capacity of the animals, and partially inhibited the full development of functional and morphological myocardial changes, detected by electrocardiographic, vectorcardiographic, microscopic, and electronmicroscopic examinations. Differences were found in the relative weights of the heart, thymus, liver and other organs; these findings attested to an anabolic activity of inosine. The results obtained justify the application of inosine for the prevention of excentric hypertrophy and decompensation of the heart in cardiac failures varying in etiology; any efficient preventive measure is of importance, because the degree of excentric hypertrophy is a factor influencing the survival of the patients.

Adrenal Glands↗
PubMed1992

Comparison of L-5-hydroxytryptophan and L-5-hydroxytryptophan inosinate as agents for increasing brain serotonin formation in rats.

The effects of L-5-hydroxytryptophan (L-5HTP) and L-5HTP inosinate injection on brain 5-hydroxyindoles in rats were compared. L-5HTP and L-5HTP inosinate caused indistinguishable dose-dependent increases in 5HTP and 5HIAA (5-hydroxyindoleacetic acid) but not serotonin concentrations in whole brain at 1 hr in rats. Our results do not substantiate a previous claim that L-5HTP inosinate is superior to L-5HTP itself in increasing brain serotonin formation.

5-Hydroxytryptophan↗
PubMed2005

[Immunological and clinical study on therapeutic efficacy of inosine pranobex].

Many studies in vitro and in vivo have shown immunomodulating and antiviral activities of inosine pranobex. The object of this research was to examine the potential beneficial effects of inosine pranobex (Groprinosin) on immune system in children with cellular immunodeficiency as a prophylaxis of recurrent infections, mainly of viral origin. 50 mg/kg b.w/day of inosine pranobex in divided doses was given to the group of 30 children aged 3-15 years for 10 days in 3 following months. Clinical and immunological investigations were done before and after the treatment. Statistically significant rise of CD3T lymphocytes number (p = 0.02) and in this CD4T lymphocytes number (p = 0.02) as well as statistically significant improvement of their function (p = 0.005) evaluated with blastic transformation method were found. These laboratory findings were parallel to clinical benefits. Control study was performed in the group of children completed by randomization and treated in the same way with garlic (Alliofil).

Adjuvants, Immunologic↗
PubMed2006

[Effects of inosine injection in expression of myosin heavy chain in intrafusal and extrafusal myofibers in soleus muscle of tail-suspended rats].

AIM: To study the effects of inosine on myosin heavy chain (MHC) activity in rats soleus muscle after tail-suspension. METHODS: Weightlessness was simulated by tail-suspension of rats. Using immunohistochemistry technique, changes of expression of MHC in intrafusal and extrafusal fibers in soleus muscle were detected. RESULTS: Expression of fast MHC in intrafusal and extrafusal fibers in soleus muscle increased after 14 d of simulated weightlessness, whereas in tail-suspended rats given inosine, the expression of fast MHC was not detected. CONCLUSION: Inosine could counteract the changes in expression of MHC in intrafusal and extrafusal fibers of rats soleus under simulated weightless situation.

Animals↗
PubMed1990

Induction of millimolar amounts of 5-phosphoribosyl-1-pyrophosphate in human erythrocytes by incubation in inosine-pyruvate-phosphate medium. A 31P-NMR study.

Incubation of human erythrocytes in inosine (10 mM), pyruvate (10 mM), phosphate (50 mM) and NaCl (75 mM) (IPP-medium)1 at pH 6.6 leads to a ca. 1000 fold increase in the concentration of 5-phosphoribosyl-1-pyrophosphate (PRPP) as identified and measured by 31P-NMR spectroscopy. PRPP accumulation is pH-dependent with a maximum at extracellular pH 6.60 and the maximum value of 1.3-1.6 mmol/l RBC is reached within one hour at 37 degrees C. PRPP accumulated despite high concentrations of 2,3-diphosphoglycerate (2,3-DPG), an inhibitor of PRPP-synthetase. The concentration of PRPP attained correlated with the intracellular concentration of inorganic phosphate (P1). Substitution of either adenosine or adenosine plus inosine for inosine in the medium (APP or A+IPP media) did not lead to NMR detectable accumulation of PRPP, despite the same high concentrations of intracellular P1. The lack of accumulation of PRPP in adenosine containing media may be related to the higher concentrations of nucleoside diphosphates induced in these media. These results show that neither 2,3-DPG nor PRPP itself inhibit the synthesis of PRPP in the human erythrocyte under these circumstances.

Erythrocytes↗
PubMed1991

Synthesis of imidazo[4,5-e][1,4]diazepine and 3-substituted 3-deazapurine nucleosides from 1-substituted inosines.

New synthetic methods of imidazo[4,5-e][1,4]diazepine nucleosides 8-11 and 3-substituted 3-deazainosines 14 from inosine have been reported. Treatment of N1-substituted inosines 1-3 with aqueous NaOH gave 5-amino-4-(N-substituted carbamoyl)imidazole ribosides 5-7, followed by appropriate manipulations to afford ring-expanded guanosine, inosine, and xanthosine analogues. Additionally, the 5-amino group of 4-N-allylcarbamoyl derivative 12 was converted into corresponding 5-iodo nucleoside 13. We found that 13 was cyclized to form 3-deaza-3-methylinosine (14) in the presence of Pd catalysts.

Imidazoles↗
PubMed1990

Effects of inosine and adenine on nucleotide levels in the post-ischemic rat heart, perfused with and without pyruvate.

Reports on enhanced nucleotide regeneration by purines during reperfusion are conflicting. We have, therefore, evaluated the effects of inosine or adenine, administered after ischemia, on adenine nucleotide levels and function in isolated rat hearts. The hearts were perfused with a Tyrode solution, containing 10 mM D-glucose, with or without 5 mM pyruvate. After 15 minutes without flow, the hearts were reperfused for 45 minutes with 20 microM purine and 0.5 mM D-ribose. Adenine nucleotide levels tended to recover better in the purine-treated groups. The purines decreased the ATP/ADP ratio by 10-15% (p less than 0.05) if pyruvate was absent. The IMP level in the inosine/glucose group exceeded that in all other groups by a factor of two (p less than 0.001). Inosine increased the adenosine concentration in the effluent sixfold (p less than 0.005). The hypoxanthine concentration rose up to four times following adenine treatment (p less than 0.05). The administration of purine, with or without pyruvate, did not affect mechanical recovery, heart rate or coronary flow. We conclude that inosine and adenine failed to improve cardiac function and hardly affected nucleotide levels in the reperfused heart.

Adenine↗
PubMed1989

[The effect of allopurinol on the synthesis of adenine nucleotides and ribonucleic acid from inosine via a salvage pathway in the brain of rats].

The authors investigated in experiments on rats the action of allopurinol and isoproterenol on the metabolism of adenine nucleotides and the total fraction of ribonucleic acids in the brain, liver heart and kidneys. It was revealed that allopurinol enhances the synthesis of adenine nucleotides from administered inosine in the brain and liver of rats. In the heart and kidneys allopurinol did not affect the synthesis of these compounds. Isoproterenol has a more marked effect on the metabolism of adenine nucleotides in the heart only: it reduced the amount of adenine nucleotides and enhanced their synthesis from inosine. It is assumed that the protective effect of allopurinol on the restoration of the reduced amount of these substances in brain and liver after their ischaemization could take place also by their increased resynthetization from accumulated inosine.

Adenine Nucleotides↗
PubMed1989

Ribosome binding to inosine-substituted mRNAs in the absence of ATP and mRNA factors.

Incubating ribosomes and eukaryotic initiation factor eIF3 with an inosine-substituted mRNA (where the mRNA secondary structure is strongly reduced) in the absence of ATP and other protein synthesis factors produces a 40 S ribosome.mRNA complex. When Met-tRNAMeti and eIF2 are added, a 60 S ribosome subunit attaches forming an 80 S ribosome.mRNA complex. ATP and the three mRNA factors, eIF4B, cap-site factor, and eIF4A, strongly stimulate the attachment of the 60 S subunit. In the absence of Met-tRNAMeti, the 60-S subunit does not attach, and adding ATP and the mRNA factors inhibits the accumulation of 40 S ribosome.inosine mRNA complexes. These results indicate that a 40 S ribosome, probably in a complex with eIF3, has an intrinsic capacity to attach to mRNA. Further, they suggest that Met-tRNAMeti may interact in a subsequent step to stabilize the 40 S ribosome.mRNA complex and allow the attachment of a 60 S ribosome subunit. Although seen most clearly with the inosine-substituted mRNAs, the 40 S ribosome reaction is also obtained with "guanosine" mRNA. A 40 S ribosome attaches to guanosine mRNA without ATP and mRNA factors when an incubation mixture containing ribosomes, eIF3, and mRNA is fixed with glutaraldehyde. In addition, a 40 S ribosome.guanosine mRNA complex can be obtained without glutaraldehyde in incubations containing ATP and the three mRNA factors in the absence of Met-tRNAMeti. The latter reaction is limited because of the instability of the 40 S ribosome.mRNA complex in the absence of Met-tRNA. Nevertheless, its authenticity is indicated by its full dependence upon ATP and the three mRNA factors. The lack of factor requirement for the formation of 40 S ribosome complexes with inosine-substituted mRNAs indicates that ATP and the three mRNA factors function primarily to unwind the secondary structure of a guanosine mRNA. Data relevant to a role for ATP in facilitating ribosome migration on an mRNA are also discussed.

Adenosine Triphosphate↗