Ribosomal protein S3 associates with the TFIIH complex and positively regulates nucleotide excision repair.

In mammalian cells, the bulky DNA adducts caused by ultraviolet radiation are mainly repaired via the nucleotide excision repair (NER) pathway; some defects in this pathway lead to a genetic disorder known as xeroderma pigmentosum (XP). Ribosomal protein S3 (rpS3), a constituent of the 40S ribosomal subunit, is a multi-functional protein with various extra-ribosomal functions, including a role in the cellular stress response and DNA repair-related activities. We report that rpS3 associates with transcription factor IIH (TFIIH) via an interaction with the xeroderma pigmentosum complementation group D (XPD) protein and complements its function in the NER pathway. For optimal repair of UV-induced duplex DNA lesions, the strong helicase activity of the TFIIH complex is required for unwinding damaged DNA around the lesion. Here, we show that XP-D cells overexpressing rpS3 showed markedly increased resistance to UV radiation through XPD and rpS3 interaction. Additionally, the knockdown of rpS3 caused reduced NER efficiency in HeLa cells and the overexpression of rpS3 partially restored helicase activity of the TFIIH complex of XP-D cells in vitro. We also present data suggesting that rpS3 is involved in post-excision processing in NER, assisting TFIIH in expediting the repair process by increasing its turnover rate when DNA is damaged. We propose that rpS3 is an accessory protein of the NER pathway and its recruitment to the repair machinery augments repair efficiency upon UV damage by enhancing XPD helicase function and increasing its turnover rate.

Higher risk of hepatocellular carcinoma in chronic hepatitis B vs chronic hepatitis C after achievement of virologic response.

It is unclear whether the achievement of virologic response modifies the risk of hepatocellular carcinoma (HCC) differently in chronic hepatitis B (CHB) and chronic hepatitis C (CHC). Our aim was to compare the risk of HCC between patients with CHB and CHC who achieved virological response. We analysed data from patients with CHB treated with entecavir (n=2000) or CHC treated with peg-interferon and ribavirin (n=733) at a tertiary hospital from 2004 to 2011. Virological response was defined as serum HBV DNA<15 IU/mL at 1 year of treatment for CHB or the achievement of sustained virologic response for CHC. Virological response was achieved in 1520 patients with CHB (76.0%) and 475 patients with CHC (64.8%). During the median follow-up period of 6 years, 228 patients with CHB (11.4%) and 59 patients with CHC (8.0%) developed HCC. Among patients with virological response, CHB was independently associated with a significantly higher incidence of HCC (hazard ratio, 2.17; 95% CI, 1.30-3.63; P=.003) than CHC. Among patients without virological response, there were no differences in HCC incidence between the two cohorts (P=.52). In patients with cirrhosis at baseline, the incidence of HCC did not differ between the two cohorts even after achieving virological response (P>.99). In conclusion, patients with CHB treated with entecavir were associated with a higher risk of HCC compared to patients with CHC treated with peg-interferon and ribavirin after achieving virological response. However, the risk of HCC did not differ between the two cohorts if the patients had cirrhosis at baseline, even if virological response was achieved.

Tongue-to-palate resistance training improves tongue strength and oropharyngeal swallowing function in subacute stroke survivors with dysphagia.

Tongue function can affect both the oral and pharyngeal stages of the swallowing process, and proper tongue strength is vital for safe oropharyngeal swallowing. This trial investigated the effect of tongue-to-palate resistance training (TPRT) on tongue strength and oropharyngeal swallowing function in stroke with dysphagia patients. This trial was performed using a 4-week, two-group, pre-post-design. Participants were allocated to the experimental group (n = 18) or the control group (n = 17). The experimental group performed TPRT for 4 weeks (5 days per week) and traditional dysphagia therapy, whereas the control group performed traditional dysphagia therapy on the same schedule. Tongue strength was measured using the Iowa Oral Performance Instrument. Swallowing function was measured using the videofluoroscopic dysphagia scale (VDS) and penetration-aspiration scale (PAS) based on a videofluoroscopic swallowing study. Experimental group showed more improved in the tongue strength (both anterior and posterior regions, P = 0·009, 0·015). In addition, the experimental group showed more improved scores on the oral and pharyngeal phase of VDS (P = 0·029, 0·007), but not on the PAS (P = 0·471), compared with the control group. This study demonstrated the effectiveness of TPRT in increasing tongue muscle strength and improving swallowing function in patients with post-stroke dysphagia. Therefore, we recommend TPRT as an easy and simple rehabilitation strategy for improving swallowing in patients with dysphagia.

Thread lifting: a minimally invasive surgical technique for long-standing facial paralysis.

BACKGROUND: Chronic facial paralysis induces degenerative facial muscle changes on the involved side, thus, making the individual seem as older than their actual age. Furthermore, contralateral facial hypertrophy aggravates facial asymmetry. A thread-lifting procedure has been used widely for correction of a drooping or wrinkled face due to the aging process. In addition, botulinum toxin injection can be used to reduce facial hypertrophy. The aim of study was to evaluate the effectiveness of thread lifting with botulinum toxin injection for chronic facial paralysis. METHODS: A total 34 of patients with chronic facial paralysis were enrolled from March to October 2014. Thread lifting for elevating loose facial muscles on the ipsilateral side and botulinum toxin A for controlling the facial muscle hypertrophy on the contralateral side were conducted. Facial function was evaluated using the Sunnybrook grading system and dynamic facial asymmetry ratios 1 year after treatment. RESULTS: All 34 patients displayed improved facial symmetry and showed improvement in Sunnybrook scores (37.4 vs. 83.3) and dynamic facial asymmetry ratios (0.58 vs 0.92). Of the 34 patients, 28 (82.4%) reported being satisfied with treatment. CONCLUSION: The application of subdermal suspension with a reabsorbable thread in conjunction with botulinum toxin A to optimize facial rejuvenation of the contralateral side constitutes an effective and safe procedure for face lifting and rejuvenation of a drooping face as a result of long-lasting facial paralysis.

Importance of charge fluctuations for the topological phase in SmB(6).

Typical Kondo insulators (KIs) can have a nontrivial Z_{2} topology because the energy gap opens at the Fermi energy (E_{F}) by a hybridization between odd- and even-parity bands. SmB_{6} deviates from such KI behavior, and it has been unclear how the insulating phase occurs. Here, we demonstrate that charge fluctuations are the origin of the topological insulating phase in SmB_{6}. Our angle-resolved photoemission spectroscopy results reveal that with decreasing temperature the bottom of the d-f hybridized band at the X[over ¯] point, which is predicted to have odd parity and is required for a topological phase, gradually shifts from below to above E_{F}. We conclude that SmB_{6} is a charge-fluctuating topological insulator.

Immunological impact of Taekwondo competitions.

Immunological changes in elite adolescent female athletes during Taekwondo competitions were investigated on-field. 6 female athletes (16.7 ± 0.8 year-old) volunteered and performed 5 bouts of demonstration Taekwondo competitions simulating real tournaments in intensity, duration, and break-time intervals on the same day. Blood samples were taken before, after the competitions and during the recovery, respectively. Immunological changes and oxidative stress in peripheral blood mononuclear cells were evaluated by flow-cytometry. During the competitions, exercise intensity was 92.2 ± 3.8% (86.1~95.7) of the maximal heart rate. Blood lactate increased immediately after the competitions (p=0.0165) and decreased to baseline during recovery. Intracellular reactive oxygen species (ROS) in the peripheral blood increased continuously during recovery (p<0.05, respectively). Natural killer cells increased immediately after the competitions (p=0.0006), and decreased during recovery. B and T cells increased immediately after the competitions and remained elevated throughout recovery (p<0.05, respectively). CD4/CD8 ratio after the competitions was decreased (p=0.0091) and returned to baseline during recovery. These results suggest that the immunological function of the elite female adolescent athletes could be attenuated after Taekwondo competitions. Further large-scaled Taekwondo studies on immunologic and apoptotic changes related to oxidative stress should be performed for improving and protecting the health of adolescent athletes.

RKKY ferromagnetism with Ising-like spin states in intercalated Fe(1/4)TaS2.

We investigated the magnetic nature of Fe(1/4)TaS2 using x-ray absorption spectroscopy, photoemission spectroscopy, and first principles band calculations. The results show a large unquenched orbital magnetic moment (∼1.0 µ(B)/Fe) at intercalated Fe sites, resulting in a gigantic magnetic anisotropy (H(A)≃60 T). The magnetic coupling is well understood in terms of the Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction, suggesting a novel RKKY ferromagnet with Ising-type spin states. We also found that this indirect exchange coupling between the neighboring Fe spins is ferromagnetic and maximized at the Fe-Fe distance of 2×2 superstructure.

Severe Periodontal Disease Increases Acute Myocardial Infarction and Stroke: A 10-Year Retrospective Follow-up Study.

This study aimed to evaluate the causal association of periodontal disease with acute myocardial infarction (AMI) and stroke, after controlling for various confounders among the Korean population. A retrospective cohort study using the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) was performed during 2002 to 2015 (baseline: 2002 to 2005; follow-up: 2006 to 2015) in the Republic of Korea. A total of 298,128 participants with no history of AMI or stroke were followed up for 10 y. AMI and stroke were defined by a diagnosis using the International Classification of Diseases, 10th Revision (ICD-10) guideline. Periodontal condition was classified into 3 groups (healthy, moderate periodontal disease, severe periodontal disease [SPD]) using the combination of ICD codes, treatment codes in the NHIS, and recommendation of periodontal treatment by the dentists in HEALS. Various confounders, such as sociodemographic, behavioral, systemic, and oral health factors, including hypercholesterolemia, were considered. Multivariable Cox regression analysis was applied to estimate adjusted incidence rate ratio (adjusted hazard ratio [aHR]) based on person-year of periodontal condition for AMI, stroke, and nonfatal major adverse cardiovascular events (MACEs) encompassing AMI or stroke controlling for various confounders. Stratified analyses according to age group, sex, and toothbrushing frequency were also performed. After controlling for various confounders, participants with SPD compared with non-SPD participants had a higher incidence by 11% for AMI (aHR, 1.11; 95% confidence interval [CI], 1.02-1.20), by 3.5% for stroke (aHR, 1.035; 95% CI, 1.01-1.07), and by 4.1% for MACEs (aHR, 1.04; 95% CI, 1.01-1.07). The association of SPD with AMI and MACE was highly modified in females and adults aged 40 to 59 y. In the total Korean population, SPD increased total AMI events by 4.3%, total stroke events by 1.4%, and the total MACEs by 1.6%. Our data confirmed that SPD was causally associated with the new events of AMI and stroke.

Peripherally acting CB1-receptor antagonist: the relative importance of central and peripheral CB1 receptors in adiposity control.

OBJECTIVE: To investigate whether drugs targeting peripheral cannabinoid-1 (CB1) receptor ameliorate adiposity comparable to central CB1-receptor antagonist or not. MEASUREMENTS: Receptor binding assay and functional assay in vitro. Pharmacokinetic parameters in mice, brain uptake clearance of compounds in rats and antagonism on the CB1-agonist-induced hypothermia in mice. Diet consumption, body weight changes, hepatic gene expression of sterol-regulatory element-binding protein-1 (SREBP-1) and plasma/tissue concentrations of compounds in HF diet-induced obese (HF-DIO) mice after acute and chronic treatment. RESULTS: Compound-1, an SR141716A derivative, is a peripheral CB1-receptor-selective antagonist that is 10 times less potent than SR141716A in in vitro evaluations. Although the plasma concentrations of Compound-1 are five times higher than those of SR141716A, its potency is still 10 times lower than that of SR141716A in reducing the consumption of normal or HF diet by mice. Through evaluations of brain uptake and the effect on CB1-agonist-induced hypothermia, it was verified that the blood-brain barrier (BBB) penetration of Compound-1 is much lower than that of SR141716A. In HF-DIO mice, chronic treatment by Compound-1 showed dose-dependent antiobesity activities, while its brain distribution was very low as compared with that of SR141716A. Compound-1's effective doses for antiobesity activity were just over 30 mg kg(-1). However, Compound-1 completely suppressed the elevated hepatic SREBP-1 expression even at 10 mg kg(-1). CONCLUSION: These results suggest that (1) central CB1 receptors mediate anorectic response of CB1-receptor antagonists and (2) peripheral modulations, including SREBP-1 expression, are not major mechanisms in the antiobesity effects of CB1-receptor antagonists.

A Case-Control Study of Fluoridation and Osteosarcoma.

Public health policy decisions in the United States have resulted in 62.4% of the population having access to fluoridated water. The purpose of this study was to examine the association between community water fluoridation and osteosarcoma. A secondary data analysis was performed with data collected from 2 separate but linked studies. Patients for phase 1 and phase 2 were selected from US hospitals via a matched case-control study design. For both phases, cases included patients diagnosed with osteosarcoma, and controls were patients diagnosed with other bone tumors or nonneoplastic conditions. In phase 1, cases (n = 209) and controls (n = 440) were patients of record in the participating orthopedic departments from 1989 to 1993. In phase 2, cases (n = 108) and controls (n = 296) were incident patients who were identified and treated by orthopedic physicians from 1994 to 2000. This analysis included all patients who met eligibility criteria on whom we had complete data on covariates, exposures, and outcome. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% CIs for the association of community water fluoridation with osteosarcoma. A modestly significant interaction existed between fluoridation living status and bottled water use (P = 0.047). The adjusted OR for osteosarcoma and ever having lived in a fluoridated area for nonbottled water drinkers was 0.51 (95% CI, 0.31 to 0.84; P = 0.008). In the same comparison, the adjusted OR for bottled water drinkers was 1.86 (95% CI, 0.54 to 6.41; P = 0.326). Findings from this study demonstrated that community water fluoridation is not associated with an increased risk for osteosarcoma.

Adenosine triphosphate-deficient erythrocytes of the egg-laying mammal, echidna (tachyglossus aculeatus).

The erythrocytes of the short-beaked echidna (Tachyglossus aculeatus), an egg-laying mammal, were examined for the presence of phosphorylated compounds. The erythrocytes contained only 0.03 +/- 0.01 micromoles of adenosine 5'-triphosphate per milliliter of cells. This amount is two orders of magnitude less than that in human cells. Although the echidna erythrocytes had an abundance of 2,3-diphosphoglycerate and other glycolytic intermediates, no other energy-rich pyridine and purine compounds were detected.

Association of Periodontitis with Oral Cancer: A Case-Control Study.

The association between oral squamous cell carcinoma (OSCC) and periodontitis in large hospital cases with cohort controls has yet to be evaluated. The aim of this study was to investigate the association of periodontitis with OSCC across tumor location and tumor-node-metastasis (TNM) stage among Koreans ( N = 424). OSCC cases ( n = 146) were recruited from Seoul National University Dental Hospital and matched by age, sex, and smoking to controls ( n = 278) from the Yangpyeong health and periodontal cohort in Korea. OSCC was diagnosed through biopsy and radiographs, including computed tomography and magnetic resonance imaging. Tumor location and TNM stage were classified after the surgery. Periodontitis was defined by alveolar bone loss with panoramic radiographs following the guidelines of the Fifth European Workshop in Periodontology. Alcohol intake, education, physical activity, obesity by body mass index, hypertension by blood pressure, diabetes by plasma glucose, and hypercholesterolemia by plasma cholesterol were considered as confounders. Information about age, sex, smoking, alcohol intake, education, and physical activity was obtained through interview; body mass index and blood pressure, through physical examination; and preoperative glucose and cholesterol, through laboratory tests. Bivariate analysis was applied with Fisher's exact chi-square test. Multivariable conditional logistic regression models were applied to evaluate the adjusted association of periodontitis with OSCC after controlling for confounders. Subgroup analyses were explored by OSCC and periodontitis. Participants with periodontitis were 3.7 times more likely to have OSCC (adjusted odds ratio [aOR] = 3.66, 95% CI = 1.46 to 9.23) than participants without periodontitis. The differences in periodontitis were not statistically significant across TNM stages of OSCC ( P > 0.05) and its location ( P > 0.05). The link was highlighted among males (aOR = 6.55), elders aged >60 y (aOR = 4.98), and those with more tooth loss (aOR = 9.99). Our data showed that periodontitis was independently associated with OSCC. Thus, the risk of OSCC could be modulated by reducing periodontitis.

Efficacy and prognosis of a short course of prednisolone therapy for pediatric epilepsy.

PURPOSE: To evaluate the efficacy and safety of adjunctive prednisolone therapy in children with cryptogenic epileptic encephalopathy, other than infantile spasms, and to determine its prognosis. METHODS: Prednisolone, 2mg/kg per day for 6 weeks, tapered for a further 2 weeks, was given in combination with previously prescribed antiepileptic drugs. A retrospective assessment of 41 children thus treated included measurements of seizure frequency, electroencephalographic findings, global assessments of cognitive function, and adverse drug events. Long-term patient prognoses over a mean follow-up period of 3 years and 5 months (range, 14-90 months) were also examined. RESULTS: Of 41 patients, 32 had Lennox-Gastaut syndrome, 4 had Doose syndrome, 1 had Otahara syndrome, 2 had Landau-Kleffner syndrome, and 2 had other unspecified generalized epilepsies. After prednisolone therapy, 73% (30/41) of patients showed a reduction in seizure frequency of >50%, and 59% (24/41) became seizure free. However, only seven patients (four with Lennox-Gastaut syndrome, two with Doose syndrome, and one with unspecified generalized epilepsy) who became seizure free remained free of seizures at the time of the final follow-up. Electroencephalographic findings and global assessments of cognitive function correlated well with seizure outcomes. No significant demographic factors influenced the efficacy of prednisolone or patient prognoses after prednisolone tapering. Most adverse events were transient, or were tolerated well with conservative management, with maintenance of the medication. CONCLUSION: Prednisolone therapy may be a safe and effective adjunct in patients with cryptogenic epileptic encephalopathies, but the high relapse rate is of concern.

Continual remodeling of postsynaptic density and its regulation by synaptic activity.

A postsynaptic density (PSD) protein, PSD-95, was tagged with green fluorescent protein (GFP-PSD-95) and expressed in cultured hippocampal neurons using recombinant adenoviruses. GFP-PSD-95 was selectively localized to excitatory postsynaptic sites. Time-lapse fluorescence imaging of hippocampal neurons revealed that >20% of GFP-PSD-95 clusters turned over within 24 hours. The appearance rate of clusters was higher than the disappearance rate, and this difference accounted for the gradual increase of the cluster density observed in culture. Dynamics of PSD-95 clusters were also inhibited by blockers of excitatory synaptic transmission. Continual PSD turnover and its regulation by synaptic activity may be important in activity-dependent remodeling of neuronal connections.

Tripartite structure of Saccharomyces cerevisiae Dna2 helicase/endonuclease.

In order to gain insights into the structural basis of the multifunctional Dna2 enzyme involved in Okazaki fragment processing, we performed biochemical, biophysical and genetic studies to dissect the domain structure of Dna2. Proteolytic digestion of Dna2 using subtilisin produced a 127 kDa polypeptide that lacked the 45 kDa N-terminal region of Dna2. Further digestion generated two subtilisin-resistant core fragments of approximately equal size, 58 and 60 kDa. Surprisingly, digestion resulted in a significant (3- to 8-fold) increase in both ATPase and endonuclease activities compared to the intact enzyme. However, cells with a mutant DNA2 allele lacking the corresponding N-terminal region were severely impaired in growth, being unable to grow at 37 degrees C, indicating that the N-terminal region contains a domain critical for a cellular function(s) of Dna2. Analyses of the hydrodynamic properties of and in vivo complex formation by wild-type and/or mutant Dna2 lacking the N-terminal 45 kDa domain revealed that Dna2 is active as the monomer and thus the defect in the mutant Dna2 protein is not due to its inability to multimerize. In addition, we found that the N-terminal 45 kDa domain interacts physically with a central region located between the two catalytic domains. Our results suggest that the N-terminal 45 kDa domain of Dna2 plays a critical role in regulation of the enzymatic activities of Dna2 by serving as a site for intra- and intermolecular interactions essential for optimal function of Dna2 in Okazaki fragment processing. The possible mode of regulation of Dna2 is discussed based upon our recent finding that replication protein A interacts functionally and physically with Dna2 during Okazaki fragment processing.

Vagus nerve stimulation in pediatric intractable epilepsy: a Korean bicentric study.

OBJECTIVE: To present our experience with vagus nerve stimulation (VNS) and to evaluate the long-term efficacy and safety of the procedure in pediatric intractable epilepsy. METHODS: This study included sixteen patients, who were implanted with a vagus nerve stimulator and could be followed up for at least more than 12 months in two epilepsy centers. Data including seizure frequency, EEG, quality of life measures and adverse events were prospectively filed over a 5-year period. RESULTS: VNS resulted in a > 50% reduction in seizure frequency in 50.0% (8/16) of children with 31.3% (5/16) of patients achieving a > 90% reduction. Additionally, enhancements in quality of life were as follows: memory in 50.0% (8/16), mood in 62.5% (10/16), behavior in 68.8% (11/16), alertness in 68.8% (11/16), achievement in 37.5% (6/16), and verbal skills in 43.8% (7/16) of the patients. Adverse events included hoarseness in two patients, dyspnea during sleep in two patients, and sialorrhea in one patient. However, these events were tolerable or could be controlled by the adjustment of output currents. In one patient, wound revision was required. CONCLUSION: Our data supports the role of VNS as an alternative therapy for pediatric intractable epilepsy.

Uroguanylin treatment suppresses polyp formation in the Apc(Min/+) mouse and induces apoptosis in human colon adenocarcinoma cells via cyclic GMP.

The enteric peptides, guanylin and uroguanylin, are local regulators of intestinal secretion by activation of receptor-guanylate cyclase (R-GC) signaling molecules that produce cyclic GMP (cGMP) and stimulate the cystic fibrosis transmembrane conductance regulator-dependent secretion of Cl- and HCO3-. Our experiments demonstrate that mRNA transcripts for guanylin and uroguanylin are markedly reduced in colon polyps and adenocarcinomas. In contrast, a specific uroguanylin-R-GC, R-GCC, is expressed in polyps and adenocarcinomas at levels comparable with normal colon mucosa. Activation of R-GCC by uroguanylin in vitro inhibits the proliferation of T84 colon cells and elicits profound apoptosis in human colon cancer cells, T84. Therefore, down-regulation of gene expression and loss of the peptides may interfere with renewal and/or removal of the epithelial cells resulting in the formation of polyps, which can progress to malignant cancers of the colon and rectum. Oral replacement therapy with human uroguanylin was used to evaluate its effects on the formation of intestinal polyps in the Min/+ mouse model for colorectal cancer. Uroguanylin significantly reduces the number of polyps found in the intestine of Min/+ mice by approximately 50% of control. Our findings suggest that uroguanylin and guanylin regulate the turnover of epithelial cells within the intestinal mucosa via activation of a cGMP signaling mechanism that elicits apoptosis of target enterocytes. The intestinal R-GC signaling molecules for guanylin regulatory peptides are promising targets for prevention and/or therapeutic treatment of intestinal polyps and cancers by oral administration of human uroguanylin.

Glucose-regulated stresses cause decreased expression of cyclin D1 and hypophosphorylation of retinoblastoma protein in human cancer cells.

Glucose-regulated stress response of cancer cells occurs during the growth of solid tumors and is induced in culture by treatments with various agents, including 2-deoxyglucose, glucosamine, and calcium ionophore A23187. We previously reported that the three stressors commonly induced cell-cycle arrest in the G1 phase and resistance to antitumor drugs in human cancer A2780 and HT-29 cells. In this study, we investigated the mechanisms of stress-induced G1 arrest by determining the expression of cell-cycle-regulating proteins. Among G1 cyclins and cyclin-dependent kinases (cdk) examined, the expression levels of cyclin D1 preferentially decreased in the stressed cells. A time-course study showed that the decrease in cyclin D1 coincided with the appearance of hypophosphorylated retinoblastoma protein (pRb), which is the growth suppressive form. These findings suggest that the stress-induced G1 arrest is mediated through the down-regulation of cyclin D1-associated kinases (cdk4/6), pRb kinases during G1 phase. This was also supported by decreased cdk4 expression in stressed HT-29 cells. In addition, p21WAF1, a cdk inhibitor, was induced in the stressed cells, particularly A23187-treated cells. A23187, compared with the other stressors, caused extreme pRb hypophosphorylation, suggesting that p21WAf1 is involved in the regulation of pRb phosphorylation in the stressed cells. Our present findings could explain a molecular-based mechanism of a growth-arrested quiescent state and also resistance to chemotherapy of solid tumor cells.

Cow red blood cells. III. Postnatal adaptation of energy metabolism in the calf red blood cells.

1. The change in energy metabolism of red blood cells from the newborn calf to adult cow was examined utilizing a number of metabolic substrates including glyceraldehyde, dihydroxyacetone, ribose, glucose, adenosine and inosine. 2. All of these substrates are utilizes by the newborn calf cells to a varying degree. With glyceraldehyde, dihydroxyacetone or glucose as a substrate, lactate is formed at a rate of 2-3 mumol/ml cells per h. As in other species, ribose utilization depends on substrate concentration, with an optimum of 3 mM ribose yielding lactate 1-1.5 mumol/ml cells per h in the calf cells. 3. In sharp contrast, adult cow red blood cells lost the bulk of the postnatal metabolic substrate affinities except for glyceraldehyde and glucose which are consumed at less than half of the rate at birth. 4. While the transition of the metabolic properties from the newborn to the adult state takes place within 2 to 3 months after birth, the red blood cells produced shortly after birth have already assumed the metabolic machinery characteristic to the adult cells. 5. Even though adenosine in itself is a poor substrate in producing lactate, a net synthesis of ATP from adenosine can take place in both calf and cow cells provided that an alternate carbon source such as glyceraldehyde, dihydroxyacetone or glucose is given. 6. Of the test substrates, glucose is the only substrate for the adult cow cells exhibiting a greater than 50% increase in utilization by exogenously added adenine. By contrast, the calf cell is affected to a much lesser extent. The possible in vivo regulatory metabolic role of certain purine and pyrimidine compounds unique to the adult stage of this species is discussed.

Is adenosine a second metabolic substrate for human red blood cells?

Adenosine is present in the micromolar range in human plasma. In this study, metabolism of adenosine, which was maintained between 0.62 +/- 0.03 and 2.92 +/- 0.43 microM by means of a continuous infusion using a Harvard infusion pump, was investigated in human red blood cells. It was found that lactate production increases linearly as the adenosine concentration was raised. Cells infused with an average adenosine concentration of 2 microM produced lactate comparable to that produced by 5 mM glucose. The extent to which ATP concentration is maintained by adenosine also depends on its concentration. After a 4 h infusion with an average adenosine concentration of 0.7 microM, ATP content amounts to 75% of the glucose control. Raising the adenosine infusion concentration to 1.5 microM results in a full maintenance of ATP levels and at concentrations higher than 1.5 microM, adenosine produces a net synthesis of ATP. A net synthesis of ATP also occurs with adenosine concentration below 1.5 microM, if supplemented with glucose. In contrast, inosine infusion provides only a partial support of ATP and fails to produce a net synthesis of ATP in the presence of glucose. In addition, the presence of purine nucleoside and glucose together influence the metabolism of each other, depending on inorganic phosphate content (Pi). At a Pi concentration of 1 mM, the glucose consumption rate is reduced by approx. 25% by purine nucleoside infusion and vice versa. In sharp contrast, glucose consumption at 16 mM Pi is potentiated by adenosine. These findings suggest that plasma adenosine contributes significantly to human red cell energetics, even though it is present at a concentration several orders of magnitude lower than glucose.