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PubMedDate not supplied

Nucleoside-nucleotide mixture increases peripheral neutrophils in cyclophosphamide-induced neutropenic mice.

The importance of nucleotides and nucleosides in human nutrition has now become an area of intensive research and clinical interest. To determine any potential benefits of administering a nucleoside-nucleotide mixture (NNM) to cyclophosphamide (CPA)-induced neutropenic mice, we randomly assigned 20 BALB/c mice to two groups and fed them a nucleic-acid-free 20%-casein diet for 20 days. The mice were intraperitoneally administered NNM or saline daily from the onset of the experiment. On the 10th day of this treatment, the mice were intraperitoneally injected with CPA. Blood was collected retro-orbitally and differential counts of leucocytes were done on blood smears by counting microscopically on day 0 (before) and 1, 3, 5, 7, and 10 days after CPA injection. By the 7th and 10th days after CPA injection, respectively, the peripheral neutrophil number in the saline group was significantly lower compared with the neutrophil number in the NNM group (p < 0.05). Also in the NNM group, more clusters of matured neutrophils were observed compared with the saline group. These results suggest that NNM may stimulate the proliferation, differentiation, and maturation of neutrophils, and that NNM alone or in combination with other pharmacologic agents may be an important therapeutic agent in patients after chemotherapy, immunosuppressive therapy, and organ transplant.

Animals↗
PubMed1997

The well-balanced nucleoside-nucleotide mixture "OG-VI" for special medical purposes.

Nucleotides and nucleosides are essential components in all cells. However, nucleotides have not been supplied in parenteral nutrition regimens. We developed a well-balanced nucleoside-nucleotide mixture "OG-VI" and examined its effect in animals under some stressed conditions. OG-VI was composed of 30 mmol/l of inosine, 30 mmol/l of guanosine monophosphate, 30 mmol/l of cytidine, 22.5 mmol/l of uridine and 7.4 mmol/l of thymidine. The whole body protein turnover increased significantly in rats receiving total parenteral nutrition (TPN) with OG-VI solution after 70% hepatectomy, compared with rats receiving normal TPN without OG-VI (122.1 +/- 20.9 mgN.kg-1.h-1 vs. 97.4 +/- 10.1 mgN.kg-1.h-1, P < 0.01, n = 10). OG-VI significantly enhanced protein synthesis while it did not decrease protein breakdown. The effect of OG-VI on myocardium after hypoxic challenge was also examined in rats. The creatine phosphate (PCr)/inorganic phosphate (Pi) was decreased in normal rat myocardium after hypoxic challenge. However, in the rats administered OG-VI, PCr/Pi was maintained at baseline level and did not decrease after hypoxia. There was no significant change in the level of adenosine triphosphate (ATP) between before and after hypoxic challenge in myocardium of the rats administered OG-VI. In the rats receiving normal saline, instead of OG-VI, the ATP level decreased significantly after hypoxic challenge (4132 +/- 276 nmol/g tissue, n = 3, vs. 3439 +/- 465 nmol/g tissue, n = 5, P < 0.05). These data suggested that the well-balanced nucleoside-nucleotide mixture, OG-VI improved nitrogen metabolism and might stimulate synthesis of high-energy phosphate in recovery after severe surgical stress.

Animals↗
PubMed1993

Protection of BALB/c mice against methicillin-resistant Staphylococcus aureus infection by intraperitoneal administration of nucleoside-nucleotide mixture.

The effect of intraperitoneally administered nucleic acid components (nucleoside-nucleotide mixture) on the recovery from methicillin-resistant Staphylococcus aureus (MRSA) strain 8985N infection was studied in mice. Two experiments were conducted in which BALB/c mice were fed a nucleotide-free 20% casein diet for 30 days. On the 10th day, the mice were inoculated intravenously with viable MRSA organisms. The mice were intraperitoneally administered nucleoside-nucleotide mixture or saline (control) daily from the onset of the experiment (experiment 1) or from the day of inoculation (experiment 2). The survival rate in the nucleoside-nucleotide group in experiment 1 (70%) was significantly higher than that in the saline group (20%) (p < 0.05). In experiment 2, the survival rate in the nucleoside-nucleotide group (55%) tended to be higher than that in the saline group (36%) without statistically significant difference; furthermore, in the surviving mice, the viable MRSA organisms recovered from the spleen and the kidney were fewer in the former group than in the latter group (p < 0.05). The studies showed that the intraperitoneal administration either before or after the MRSA challenge of the nucleoside-nucleotide mixture was effective for the recovery of the mice from the infection.

Animals↗
PubMed1996

Comparative effects of dietary nucleoside-nucleotide mixture and its components on endotoxin induced bacterial translocation and small intestinal injury in protein deficient mice.

BACKGROUND: Nucleoside-nucleotide mixture has been shown to improve gut morphology and reduce the incidence of bacterial translocation in protein deficient mice. AIMS: To compare the reparative effect of nucleoside-nucleotide mixture and their individual components on maintenance of gut integrity and bacterial translocation based on their differential metabolism and utilisation. METHODS: ICR (CD-1) mice were randomised into eight groups of 10 animals each and fed 20% casein diet (control), protein free diet, or protein free diet supplemented with 3 M cytidine, uridine, thymidine, inosine, guanosine monophosphate, or nucleoside-nucleotide mixture for four weeks. On the fourth week, each mouse was injected lipopolysaccharide intraperitoneally (50 micrograms/500 microliters) and the incidence of bacterial translocation, caecal bacterial populations, and the ileal histology, noted 48 hours later. RESULTS: The death rate in the control group was 40% compared with 10% in the nucleoside-nucleotide mixture and 20% each in the individual components groups, respectively. Bacterial translocation to the mesenteric lymph node did occur in 100% of the surviving mice fed the control diet in comparison with 44% (nucleoside-nucleotide), 50% (cytidine), 75% (thymidine), 75% (uridine), 63% (inosine), and 63% (guanosine monophosphate). Histologically, the damage to the gut was more distinct in the protein free diet group. Villous height, crypt depth, and wall thickness in the nucleoside-nucleotide mixture group mean (SEM) (5.01 (0.34); 0.87 (0.14); 0.33 (0.10)), were respectively, higher compared with the protein free diet (3.34 (0.34); 0.61 (0.03); 0.18 (0.04)) group. In the cytidine group, crypt depth (0.86) (0.08)), and wall thickness (0.30 (0.002)) were higher. The same measurements in the components groups tended to be higher than the protein free diet group. Caecal bacterial populations were, however, similar in all groups. CONCLUSIONS: These results suggest that dietary nucleosides and nucleotides are essential nutrients for intestinal repair; nucleotides or cytidine provide a better response.

Animals↗
PubMed1998

Nucleoside-nucleotide mixture increases bone marrow cell number and small intestinal RNA content in protein-deficient mice after an acute bacterial infection.

The aim of this study was to determine if intraperitoneal administration of a nucleoside-nucleotide mixture would affect small intestinal morphology, bone marrow cell number, and DNA content in protein-deficient mice subjected to acute bacterial infection. Mice were randomized into two groups and orally fed protein-free diet or nucleotide-free 20% casein diet for 10 d. The mice in each group were divided into two subgroups and intraperitoneally administered 0.35 mL saline or nucleoside-nucleotide mixture (17.5 mL/kg body weight) for 10 d. On day 10, one subgroup from each major dietary group was either inoculated intravenously with methicillin-resistant Staphylococcus aureus or saline. Three days later, small intestinal morphology, bone marrow cell number, and DNA content were evaluated in infected and noninfected mice. Protein-deficiency in association with infection significantly (P < 0.05) reduced body weight, small intestinal weight, crypt depth, villous height, and wall thickness. All dietary groups exhibited similar small intestinal DNA and protein contents (protein:DNA ratio, RNA:DNA ratio) at 3 d postinfection. However, small intestinal RNA content in the infected protein-free dietary group administered nucleoside-nucleotide mixture was higher (P < 0.05) and tended to be higher relative to the infected nucleotide-free 20% casein group administered nucleoside-nucleotide mixture compared with the rest of the groups. In the infected protein-free dietary group administered nucleoside-nucleotide mixture, bone marrow cell number and bone marrow DNA content were higher (P < 0.05) relative to the infected protein-free dietary group, nucleotide-free 20% casein diet administered saline, or nucleoside-nucleotide mixture, respectively. We conclude that intraperitoneal administration of nucleoside-nucleotide mixture may stimulate bone marrow cell proliferation, DNA content, and small intestinal RNA content during periods of relative deficiency such as protein-deficiency in combination with infection.

Animals↗
PubMed1997

Nucleoside-nucleotide-free diet suppresses cytokine production and contact sensitivity responses in rats with trinitrobenzene sulphonic acid-induced colitis.

We examined the effects of dietary nucleoside-nucleotide mixture on synthesis of inflammatory cytokines, interleukin-8 and tumor necrosis factor-alpha, in sensitized and nonsensitized colitic rats. Sensitized and nonsensitized colitic rats that were fed a nucleoside-nucleotide mixture had greater colonic weight and macroscopic and microscopic damage scores than nucleoside-nucleotide-free sensitized and nonsensitized colitic rats. Increased colonic tumor necrosis factor-alpha and interleukin-8 concentrations were associated with increased colonic inflammation and ulceration in the nucleoside-nucleotide mixture-fed group. There was also increased ear thickness in the nucleoside-nucleotide mixture-fed sensitized and nonsensitized colitic rats, which correlated highly with increased tumor necrosis factor-alpha and interleukin-8 levels in the ear lobes. Nucleoside-nucleotide-free diets may suppress cytokine secretion, thereby reducing colonic damage and contact sensitivity responses in colitic rats.

Animals↗
PubMedDate not supplied

The effects of oral RNA and intraperitoneal nucleoside-nucleotide administration on methicillin-resistant Staphylococcus aureus infection in mice.

The effects of oral RNA and intraperitoneal nucleoside-nucleotide mixture administration on methicillin-resistant Staphylococcus aureus (MRSA) strain 8985N infection were studied in mice. BALB/c mice were fed a nucleic acid-free diet or nucleic acid-free diet supplemented with 0.5% or 2.5% ribonucleic acid (RNA) for 30 days. Nucleoside-nucleotide mixture or saline (control) was intraperitoneally administered daily to these rats except for the 2.5% RNA group, which received saline only. On the 10th day of this treatment, the mice were inoculated intravenously with the viable MRSA organisms. Susceptibility to the MRSA was determined by animal survival and recovery of the MRSA from the organs. The survival rates in the three groups that were administered saline were 29%, 35%, and 40% for nucleic acid-free diet, 0.5% RNA, and 2.5% RNA groups, respectively, whereas in the two groups that received the nucleoside-nucleotide mixture the rates were 69% for the nucleic acid-free diet group and 55% for 0.5% RNA group. The susceptibility of the mice to the MRSA challenge was not affected by dietary RNA, which indicates the ineffectiveness of oral RNA. The combined survival rate in the two nucleoside-nucleotide groups (64%) was statistically different (p < .01) from that in the three saline groups (34%). There was a greater reduction in viable organism recovery in the kidney and spleen of the surviving mice that had been administered the nucleoside-nucleotide mixture than in those administered saline.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMedDate not supplied

Nucleoside-nucleotide mixture and its components and response to methicillin-resistant Staphylococcus aureus infection in mice.

The effects of a nucleoside-nucleotide mixture and its individual components on response to methicillin-resistant Staphylococcus aureus (MRSA) strain 8985N were studied in mice. BALB/c mice were fed a nucleic-acid-free 20% casein diet and intraperitoneally administered a nucleoside-nucleotide mixture, its individual components (inosine, GMP2Na, uridine, thymidine, cytidine), or saline for 30 days. On the 10th day of this treatment, the mice were inoculated intravenously with the viable MRSA organisms. By the 20th day after inoculation, mice in the saline group showed 33% survival, whereas mice in the nucleoside-nucleotide mixture group showed 75% survival. The survival rates in the inosine (62%), GMP2Na (57%), uridine (54%), cytidine (50%), and thymidine (46%) groups were not significantly different. The survival rates of the individual-component groups tended to be higher than that of the saline group, but this was not statistically different. Furthermore, there was a greater reduction in viable organism recovery in the spleen and kidney of the surviving mice in the component groups than in the saline group. However, the survival rates in the individual-component groups did not exceed that of the nucleoside-nucleotide mixture group. This study suggests that intraperitoneal administration of a nucleoside-nucleotide mixture appears to be important in producing a high survival rate after challenge with MRSA. The effect cannot be achieved with the specific components of the mixture administered individually.

Animals↗
PubMed1997

Modulation of age-related changes in immune functions of protein-deficient senescence-accelerated mice by dietary nucleoside-nucleotide mixture supplementation.

In the present study we examined the immune-enhancing effect of a nucleoside-nucleotide mixture on the non-specific T-cell immune functions of senescence-accelerated mice (SAM) fed on a low-protein diet. The immune functions studied were in vitro thymic and splenic cell lymphoproliferative responses to phytohaemagglutinin, lipopolysaccharide and concanavalin A and their production of interleukin-2 (IL-2) and interferon-gamma (INF-gamma) in response to mitogen stimulation. SAMP8 mice aged 3 and 6 months were used. In each age group, mice were fed on diets containing either 50 g casein/kg, 50 g casein/kg supplemented with 5 g nucleoside-nucleotide mixture/kg or 200 g casein/kg for 3 weeks. The supplemented 3- and 6-month-old mice had higher (P < 0.05) thymic and splenic cell counts compared with the low-protein group. In both age groups of mice, concanavalin A induced higher (P < 0.05) total thymic and splenic lymphoproliferative responses for the nucleoside-nucleotide mixture-supplemented group compared with the 50 g casein/kg dietary groups. Thymic and splenic production of IL-2 was higher for the 3-month-old mice in both the supplemented and the 200 g casein/kg dietary groups. INF-gamma production in the supplemented 3-month-old group and the 6-month-old 200 g casein/kg dietary group was higher (P < 0.05) compared with the other groups. Overall the supplemented 3-month-old mice exhibited both higher lymphoproliferative responses and production of cytokines compared with the supplemented 6-month-old mice. The results indicate that early nucleoside-nucleotide mixture supplementation may enhance the immune response in protein-deprived SAMP8 mice.

Aging↗
PubMed1992

Effect of intraperitoneally administered nucleoside-nucleotide on the recovery from methicillin-resistant Staphylococcus aureus strain 8985N infection in mice.

The effect of intraperitoneally administered nucleoside-nucleotide on the recovery from methicillin-resistant Staphylococcus aureus (MRSA) strain 8985N infection was studied in mice. Mice fed nucleic acid-free 20% casein diet were administered intraperitoneally with a nucleoside-nucleotide mixture or with saline (control group) daily for 30 days. On the tenth day on this treatment, mice were challenged with the bacteria. The survival rates were 25% and 72% for the control and nucleoside-nucleotide groups, respectively. The recovery of the survived mice from the infection was confirmed by the increment of body weight and the reduction of the bacteria in the organs. The results show the effectiveness of the intraperitoneal administration of the nucleoside-nucleotide mixture for the recovery from the MRSA strain 8985N infection in mice.

Animals↗
PubMed1996

Effect of a parenteral nucleoside-nucleotide mixture on hepatic metabolism in partially hepatectomized cirrhotic rats.

After hepatectomy, purine and pyrimidine metabolism is a key process in synthesis of DNA and RNA and in energy metabolism. To supply nucleosides for salvage synthesis, nucleoside-nucleotide mixture solutions have been developed, and they have been found to improve protein metabolism and hepatic regeneration after partial hepatectomy in normal rats. However, the effect of the solution in cirrhotic liver, common in patients with hepatocellular carcinoma, has not been reported. The aim of this study was to evaluate the metabolic effect of the nucleoside-nucleotide mixture on cirrhotic rats after partial hepatectomy. Seventy percent partial hepatectomy was performed in thioacetamide-administered cirrhotic rats. The fractional protein synthetic rate, nitrogen balance, hepatic content of nucleic acid, and blood chemistry after the administration of the nucleoside-nucleotide mixture solution (OG-VI) with total parenteral nutrition was evaluated at 7 d after partial hepatectomy. OG-VI increased hepatic RNA level and hepatic fractional protein synthetic rate (p < 0.05). It is concluded that the nucleoside-nucleotide mixture solution is an effective nutritional supplement to the metabolism of cirrhotic rats after partial hepatectomy.

Animals↗
PubMed1980

Current state of the art in the HPLC analyses of free nucleotides, nucleosides, and bases in biological fluids.

Because of the use of HPLC for the determination of free nucleotides, nucleosides, and bases in samples of biological origin, investigations that were very difficult or impossible to perform only a decade ago are now possible. Microparticulate, totally porous, chhemically bonded particles appear to be the column packings that will be used routinely in the future because analyses are achieved with high sensitivity, selectivity, efficiency, and speed. These packings are stable, the results are reproducible, and the data are quantitative. In addition, the reversed-phase mode of HPLC offers improvements over the ion-exchange mode for the analysis of nucleosides, bases, and other UV-absorbing compounds which are not ionic. However, the ion-exchange mode may be used as a complementary method for very polar or ionic compounds which are eluted too rapidly with reversed phase. A sample can be chromatographed with each mode and a profile--a complete picture of nucleotide, nucleoside, and base levels in the sample--obtained. Alternatively, ion pairing can be used with the reversed-phase mode; thus both the ionic and lipophilic compounds can be determined in one separation.

Chromatography, High Pressure Liquid↗