Identification of Diverse Adenosine-to-Inosine RNA Editing Subtypes in Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: RNA editing generates protein diversity by altering RNA sequences in coding regions without changing the overall DNA sequence. Adenosine-to-inosine (A-to-I) RNA editing events have recently been reported in some types of cancer, but they are rare in human colorectal cancer (CRC). Therefore, this study was conducted to identify diverse RNA editing in CRC. MATERIALS AND METHODS: We compared transcriptome data of 39 CRC samples and paired adjacent tissues from The Cancer Genome Atlas database to identify RNA editing patterns in CRC, focusing on canonical A-to-I RNA edits in coding sequence regions. We investigated nonsynonymous RNA editing patterns by comparing tumor and normal tissue transcriptome data. RESULTS: The number of RNA edits varied from 12 to 42 per sample. We also observed that hypoand hyper-RNA editing patterns were distinguishable within the samples. We found 10 recurrent nonsynonymous RNA editing candidates in nine genes (PDLIM, NEIL1, SRP9, GLI1, APMAP, IGFBP7, ZNF358, COPA, and ZNF587B) and validated some by Sanger sequencing and the inosine chemical erasing assay. We further showed that editing at these positions was performed by the adenosine deaminase acting on RNA 1 enzyme. Most of these genes are hypoedited in CRC, but editing of GLI1 was increased in cancer tissues compared with normal tissues. CONCLUSION: Our results show that nonsynonymous RNA editing patterns can be used to identify CRC patients and could serve as novel biomarkers for CRC.

Assistência fisioterapêutica na atenção primária à saúde infantil: uma revisão das experiências / Physical therapy in pediatric primary care: a review of experiences

OBJETIVO: Revisar as experiências de atenção fisioterapêutica dirigidas à população pediátrica descritas na literatura e analisar a produção de conhecimento sobre fisioterapia no contexto da atenção primária à saúde infantil (APSI). MÉTODOS: Foi realizada uma revisão sistemática conforme PRISMA, com busca nas seguintes bases de dados: MEDLINE, LILACS, SciELO, PubMed, Scopus, Cochrane; banco de teses da CAPES; e System for Information on Grey Literature in Europe (SIGLE). Foram utilizados os descritores "atenção primária à saúde", "fisioterapia", "lactente ou criança" e seus correspondentes na língua inglesa e espanhola, sem restrição de ano de publicação. RESULTADOS: Analisamos 13 artigos de seis países, reunidos em três eixos temáticos: dilemas profissionais (três artigos), competências e habilidades específicas para a APSI (sete artigos) e relatos de prática (quatro artigos). Os dilemas profissionais mencionados foram a ampliação do papel do fisioterapeuta para incluir ambientes comunitários, compartilhando a tomada de decisão com as famílias, e o trabalho em colaboração com outros serviços de saúde para identificar as necessidades da criança. As competências e habilidades citadas foram a identificação de sintomas clínicos e socioculturais para além das condições musculoesqueléticas, o diagnóstico fisioterapêutico precoce, a prevenção contra o uso excessivo de medicamentos e a capacidade de trabalhar em equipe. Os relatos de prática discorreram sobre estimulação em crianças com quadros neurológicos, tratamento respiratório e grupos com mães de crianças com esses acometimentos. CONCLUSÕES: O baixo número de estudos sugere desconhecimento quanto ao modo como a fisioterapia se insere na APSI e, provavelmente, quanto às habilidades profissionais necessárias nesse ambiente. Assim, são necessários mais estudos para fornecer dados sobre a área e um esforço de qualificação continuada por parte dos fisioterapeutas.

OBJECTIVE: To review pediatric physical therapy experiences described in the literature and to analyze the production of knowledge on physical therapy in the context of pediatric primary health care (PPHC). METHODS: A systematic review was conducted according to the PRISMA criteria. The following databases were searched: MEDLINE, LILACS, SciELO, PubMed, Scopus and Cochrane; Brazilian Ministry of Health's CAPES doctoral dissertations database; and System for Information on Grey Literature in Europe (SIGLE). The following search terms were used: ["primary health care" and ("physical therapy" or "physiotherapy") and ("child" or "infant")] and equivalent terms in Portuguese and Spanish, with no restriction on publication year. RESULTS: Thirteen articles from six countries were analyzed and grouped into three main themes: professional dilemmas (three articles), specific competencies and skills required in a PPHC setting (seven articles), and practice reports (four articles). Professional dilemmas involved expanding the role of physical therapists to encompass community environments and sharing the decision-making process with the family, as well as collaborative work with other health services to identify the needs of children. The competencies and skills mentioned in the literature related to the identification of clinical and sociocultural symptoms that go beyond musculoskeletal conditions, the establishment of early physical therapy diagnoses, prevention of overmedication, and the ability to work as team players. Practice reports addressed stimulation in children with neurological diseases, respiratory treatment, and establishing groups with mothers of children with these conditions. CONCLUSIONS: The small number of studies identified in this review suggests that there is little knowledge regarding the roles of physical therapists in PPHC and possibly regarding the professional abilities required in this setting. Therefore, further studies are required to provide data on the field, along with a continuing education effort on the part of physical therapists.

Gene expression changes of regucalcin and prohibitin in cirrhotic rat liver and the related effects of compound glutathione inosine injection intervention / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study expression of regucalcin (RGN) and prohibitin (PHB) genes in cirrhotic rat liver and to investigate the related effects of compound glutathione inosine injection (CGII) intervention.</p><p><b>METHODS</b>Forty male Wistar rats were randomly divided into a control group (n=12) and a model group (n=28).The model was established by injecting sterile porcine serum (0.5 mL) into the rat abdominal cavity, twice weekly for 8 consecutive weeks; the control group rats were treated with physiological saline injection (0.5 mL) into the abdominal cavity with the same frequency and time span. During the modeling period, four rats from the model group were randomly selected at different time points to examine changes in liver pathology. Upon pathology confirmation of liver cirrhosis, the porcine serum injection was terminated. The remaining 24 rats in the model group were randomly divided into a fibrosis group and a CGII treatment group.The CGII group received CGII (intramuscular injection of 0.018 mL 100g-1 body weight) once a day for 6 continuous weeks; the fibrosis rats were treated with the same dosage of physiological saline with the same frequency and time span.Liver tissue morphology was examined by both hematoxylin-eosin and Masson's staining. RGN and PHB expression at the mRNA and protein levels in liver tissues were detected by real time RT-PCR and immunohistochemical staining, respectively.</p><p><b>RESULTS</b>Both the mRNA and protein expression levels of RGN and PHB were significantly lower in the liver tissues of the fibrosis group than in the control group.CGII intervention led to significant alleviation of the liver fibrosis severity; moreover, the mRNA and protein expression levels of RGN and PHB were significantly higher than those in the fibrosis group.</p><p><b>CONCLUSION</b>Down-regulation of regucalcin and prohibitin gene expression might contribute to the pathogenesis of liver cirrhosis.</p>

Antiarrhythmic and arrhythmogenic action of inosine in experimental ventricular tachyarrhythmias / Efectos antiarrítmicos y arritmogénicos de la inosina en taquiarritmias ventriculares experimentales

OBJECTIVE: To study the possible action of inosine on experimental ventricular tachyarrhythmias. MATERIAL AND METHODS: We used 92 mongrel dogs weighing 13 kg-17 kg, anesthetized with 30 mg/kg sodium pentobarbital applied intravenously. Myocardial lesions were induced by injecting 1 ml-1.5 ml of 70% phenol in the free wall of the left ventricle. In 36 dogs, the ventricular arrhythmia (VT) was induced 30 min later with aconitine crystals inserted into the periphery of the damaged area; in 16, VT was due only to myocardial damage and in the other 13 VT was spontaneously originated. Twenty-nine animals constituted the control group; no inosine was administered to them. The possible effects of inosine were studied in 63 animals. Leads II, aVR or aVL, right and Left unipolar intraventricular leads and that on the wall of the superior vena cava were recorded under control conditions, once the myocardial damage had been induced, during the ventricular tachycardia, and following the injection of inosine. Of the 63 inosine-treated animals; in 34, VT was due to aconitine; in 16, it was produced only by the myocardial damage and, in 13, VT was presented spontaneously. RESULTS: Sinus rhythm was not reestablished in the animals of the control group. Inosine reestablished the sinus rhythm in 26 of 34 dogs (76%) that received phenol and aconitine, in 13 of the 16 (81%) presenting only the myocardial damage, and in 6 of the 13 (46%) with spontaneous ventricular tachycardia. In some experiments, inosine induced supraventricular tachycardias, ventricular-atrial blocks, and ventricular pre-excitation phenomena. CONCLUSIONS: In this experimental series, inosine showed antiarrhythmic and arrhythmogenic effects, similar to those of adenosine from which it derives.

An enzyme electrode biosensor for inosine determination / 生物工程学报

An enzyme electrode biosensor was used for the amperometric determination of inosine in its tablets by co-immobilizing nucleoside phosporylase and xanthine oxidase on a hydrogen peroxide electrode. As a fundamental electrode the hydrogen peroxide electrode has an advantage of stability in analysis compared with the 02 electrode. The enzyme electrode showed a linear response to inosine in the range of 1-268 mg/L with a response of 60 seconds under a sample injection volume of 25 microL. Based on the enzyme electrode, inosine solutions were determined with an average recover rate of 100.8% and a relative standard deviation (RSD) of les than 0.14% in 20 assays. The lifetime of the enzyme electrode was relative long and could be used continuously at 25 degrees C for 25 days. These results demonstrated that the enzyme electrode biosensor could be used to determine inosine and its derivatives specifically, rapidly, conveniently and economically.

Changes in Serum Adenosine Deaminase Activity during Normal Pregnancy

Adenosine deaminase (ADA), an enzyme essential for the differentiation of lymphoid cells, has been used for monitoring diseases with altered immunity. The purpose of this study was to investigate the changes in serum ADA activity throughout normal pregnancy. We measured the catalytic values of serum ADA from 202 normal pregnant women using a commercial kit. Subjects were divided into four groups according to the gestational age in weeks (Gwks) (Group I: 5-9 Gwks [n=58]; Group II: 15-20 Gwks [n= 63]; Group III: 24-30 Gwks [n=34]; Group IV: 30-39 Gwks [n=47]). The serum ADA levels for the Groups I, II, III, and IV were as follows: 20.1+/-6.9 IU/L, 20.0+/-7.6 IU/L, 37.9+/-19.9 IU/L, and 24.5+/-8.6 IU/L, respectively. The serum ADA activity of group III was significantly higher than the other groups (p<0.05). However, there was no significant correlation between the Gwks and the serum ADA activity. Furthermore, other parameters, such as maternal age (p=0.29), gestational age at delivery (p=0.07), delivery mode (p=0.39), and birth weight (p=0.59) had no correlation with ADA activity. Reference values of serum ADA in normal pregnancy may provide important database for making clinical decisions in pregnancies complicated by conditions where cellular immunity has been altered.

Effects of Inosine Monophosphate Dehydrogenase Inhibition on Platelet-derived Growth Factor- Induced Fibronectin Secretion and Cellular Reactive Oxygen Species in Mouse Mesangial Cells / 대한이식학회지

PURPOSE: Mesangial cell extracellular matrix (ECM) synthesis plays an important role in various renal diseases. Mycophenolic acid (MPA), which is an inhibitor of inosine monophosphate dehydrogenase (IMPDH), inhibits mesangial cell proliferation and ECM synthesis. However, the exact mechanism of MPA has not been clearly elucidated in mesangial cells. To examine the relative importance of IMPDH on the inhibitory action of MPA, we compared the effects of MPA or IMPDH2 siRNA on platelet-derived growth factor (PDGF)-induced fibronectin secretion and cellular reactive oxygen species (ROS) in mouse mesangial cells (MMC). METHODS: MMC were stimulated with PDGF 10 ng/ml with or without MPA 0.1~10micrometer, IMPDH2 siRNA 10~50 nM, or N-acetylcystein (NAC). IMPDH2 siRNA was transiently transfected by lipofectamine for 24 hours. MPA 0.1~10micrometer, ribavirin 10~100micrometer, and NAC 5 mM were administered 1 hour before the stimulation. Cell viability was measured by methylthiazoletetrazolium (MTT) assay, fibronectin secretion by Western blot analysis, and dichlorofluorescein (DCF)-sensitive cellular ROS by flow cytometry. RESULTS: PDGF 10 ng/ml effectively increased fibronectin secretion and cellular ROS in MMC. MPA and NAC at concentration without affecting basal level of fibronectin and cellular ROS ameliorated PDGF-induced fibronectin secretion and cellular ROS. However, IMPDH2 siRNA only partially reduced PDGF- induced fibronectin secretion and cellular ROS in MMC. CONCLUSION: These results suggest that MPA may inhibit PDGF-induced fibronectin secretion partly through IMPDH2 or cellular ROS in MMC, and there may be other mechanisms on the inhibitory action of MPA in mesenchymal cells.

Clinical study on Ganbi decoction in treating antituberculotic agent-caused liver injury / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effect and mechanism of Ganbi decoction (GBD) in treating patients with antituberculotic agent caused liver injury (ATB-LI).</p><p><b>METHODS</b>One hundred and twenty-eight patients with ATB-LI were randomly assigned to the treated group (n = 66) and the control group (n = 62) with the envelop method. Meanwhile, 60 healthy persons were selected as the healthy control group. The treated group was treated by GBD one dose every day with the constituents modified depending on patients' symptoms, and the control group was treated with glucuronolactone tablets and inosine injection. One week was taken as one treatment course. The changes of clinical syndromes, physical signs, T-lymphycyte sub-groups and serum level of nitric oxide (NO) were observed before and after treatment and the recovery time of liver function was recorded. The outcome was compared with that in the healthy control group.</p><p><b>RESULTS</b>In the treated group, 28 patients (42.4%) were cured, 30 (45.5%) improved and 8 (12.1%) ineffectively cured, the total effective rate being 87.9% (58/66). In the control group, 17 patients (27.4%) were cured, 24 (38.7%) improved, and 21 (33.9%) ineffectively cured, the total effective rate being 66.1% (41/62). The total effective rate in the treated group was significantly higher than that in the control group (P < 0.05). Liver function was improved in both groups, recovery time in the treated group was 12.0 +/- 7.0 days, which was significantly shorter than that in the control group (16.0 +/- 8.0 days), showing significant difference between the two groups (P < 0.05). The levels of CD3, CD4 and CD8 were significantly higher and level of NO significantly lower in the two groups of patients than those in the healthy control group (P < 0.05), but these parameters were improved more significantly in the treated group after treatment, when compared with those before treatment or with those in the control group, all showing significant difference (P < 0.05).</p><p><b>CONCLUSION</b>GBD could prevent ATB-LI, and its mechanism could be by way of reducing NO production induced by endotoxin of macrophage and stimulating the proliferation of T-lymphycyte to elevate immunity.</p>

Effects of inosine on neuronal apoptosis and the expression of cytochrome C mRNA following hypoxic-ischemic brain damage in neonatal rats / 中国当代儿科杂志

<p><b>OBJECTIVE</b>It has been reported that neuronal apoptosis plays a critical role in pathology of hypoxic-ischemic encephalopathy (HIE). Cytochrome C (CytC) is an important apoptotic protease activating factor. Inosine might have a neuroprotective effect against cerebral ischemia reperfusion injury by inhibiting the neuronal apoptosis and the expression of CytC mRNA in adult rats. This study examined the effects of inosine on neuronal apoptosis and CytC mRNA expression following hypoxic-ischemic brain damage (HIBD) in order to investigate the neuroprotectivity of inosine against cerebral ischemia injury in neonatal rats and the possible mechanism.</p><p><b>METHODS</b>A total of 140 healthy 7-day-old Sprague-Dawley rat pups were randomly assigned into Control (n=40), HIBD (n=50) and Inosine treatment groups (n=50). HIBD rat models were established by ligating the left common carotid artery, followed by 8% O2 hypoxia exposure for 2 hrs in the HIBD and Inosine treatment groups. The Control group was not subjected to hypoxia-ischemia (HI). The Inosine treatment and the HIBD groups were randomly divided into 5 sub-groups sacrificed at 6 and 12 hrs, and 1, 3 and 7 days post- HI (n=10 each). The Control group rats were sacrificed at the corresponding time points (n=8 each). Inosine was administered to the Inosine treatment group by intraperitoneal injection immediately after HIBD at the dosage of 100 mg/kg twice daily for 7 days. TUNEL staining and in situ hybridization method was used to detect neuronal apoptosis and CytC mRNA expression respectively.</p><p><b>RESULTS</b>Few apoptotic cells and CytC mRNA positive cells were found in brain tissues of the Control group. In the HIBD group, the number of apoptotic cells and the CytC mRNA expression in the cortical and hippocampal gyrum CA1 areas increased 6 hrs after HI, peaking at 1 day after HI and then decreased gradually. Until the 7th day, the number of apoptotic cells and the CytC mRNA expression in the cortical and hippocampal gyrum CA1 areas in the HIBD group remained significantly higher than in the Control group. Inosine treatment decreased the apoptotic cells and the CytC mRNA expression in both areas from 6 hrs to 7 days after HI compared with the HIBD group. The linear correlation analysis demonstrated that the number of apoptotic cells was positively correlated to the CytC mRNA expression in neonatal rats with HIBD (r=0.88, P < 0.01) .</p><p><b>CONCLUSIONS</b>Inosine can reduce the number of apoptotic cells and down-regulate the expression of CytC mRNA following HIBD in neonatal rats. The decreased number of apoptotic cells was positively correlated to the decreased CytC mRNA expression after inosine treatment, suggesting that inosine offered neuroprotectivity against HIBD possibly through inhibiting the CytC mRNA expression and resulting in a decrease of cell apoptosis.</p>

Quantitative analysis of the nucleosides in Cordyceps sinensis with capillary zone electrophoresis / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a quantitative analysis method for analyzing the nucleosides in Cordyceps sinensis with capillary electrophoresis, and compare the difference between natural and the cultured C. mycelia.</p><p><b>METHOD</b>Capillary zone electrophoresis method was employed to quantitate the adenosine, uridine, guanosine and inosine in C. sinensis, with 0.25 mg x L(-1) boric acid-sodium hydroxide buffer, pH 9.5. The working voltage was 20 kV, the temperature was 25 degrees C, and the detection wavelength was 260 nm.</p><p><b>RESULT</b>With the capillary zone electrophoresis method, the average recovery of the above 4 nucleosides was 98.9%, 95.1%, 97.8% and 98.8% respectively, with the RSD 0.4%, 1.7%, 1.3% and 5.0%. There was no adenosine in natural C. sinensis and no inosine in the cultured C. mycelia detected.</p><p><b>CONCLUSION</b>This method can be used to determine the adenosine, uridine, guanosine and inosine in C. sinensis. The nucleosides in C. sinensis produced from Qinghai province and cultured C. mycelia are obviously different.</p>

Studies on the germination of Bacillus anthracoides spores induced by nutrient germinant / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the germination effects of Bacillus anthracoides spores germinant to nutrient germinant.</p><p><b>METHODS</b>Heat factors and nutrient germinant were used to stimulate the Bacillus anthracoides spores and to germinate. Ultraviolet spectrophotometer was used to measured the A value of spore solution in the wavelength of 600 nm. Accrding to the A value, the germination rates in different condition. Transmission electron microscope was used to observe the ultrastructure changes of spores.</p><p><b>RESULTS</b>The rate of germination effects were 68.0% under 6 mmol/L inosine at 37 degrees C, pH 7.9; 74.5% under 70 mmol/L L-alanine at 30 degrees C, pH 8.9; and 85.6% under 6 mmol/L inosine and 70 mmol/L L-alanine at 37 degrees C, pH 8.2. Under transmission electron microscope, the germinated spores' coat and cortex were brokendown and degraded with its core completely exposed.</p><p><b>CONCLUSION</b>Under suitable environment, the nutrient germinant with inosine and L-alanine might be helpful for germinating the bacillus anthracoides spores.</p>

Structure identification of jujuboside E / 药学学报

<p><b>AIM</b>To study the chemical constituents of the seeds of Ziziphus jujuba Mill var. spinosa (Bunge) Hu ex. H.F. Chou.</p><p><b>METHODS</b>To separate the constituents by using various kinds of chromatography methods and identify their structures on the basis of spectral analysis.</p><p><b>RESULTS</b>Seven compounds were isolated. Their structures were established as jujuboside E (1), jujuboside B (2), jujuboside A (3), betulic acid (4), stearic acid (5), sucrose (6) and inosine (7).</p><p><b>CONCLUSION</b>Compound 1 is a new compound named jujuboside E. Compounds 5, 6, 7 were isolated for the first time from this plant.</p>

Distinctive compound in Rhizome of Pinellia ternata / 中国中药杂志

<p><b>OBJECTIVE</b>To look for and determine the distinctive compound in Pinellia ternata.</p><p><b>METHOD</b>With TLC, HPLC, the distinctive compound was found and obtained by using the method of HPLC preparation. Its structure was elucidated by spectral analysis and physico-chemical properties.</p><p><b>RESULT</b>The compound was identified as inosine.</p><p><b>CONCLUSION</b>Inosine is the distinctive compound in Rhizome of P. ternata, and it was isolated from Banxia for the first time.</p>

Wobble base-pairing in codon-anticodon interactions: a theoretical modelling study.

The Crick wobble hypothesis attributes the phenomenon of codon degeneracy to a certain impreciseness of pairing between the third base of the codon and the first base of the anticodon. This theoretical study investigates the pairing properties of some wobble bases, including both, observed and unobserved pairs. Some wobble base-pairs are predicted to follow the Watson-Crick pairs in configuration and pairing facility, while others deviate from this norm. The observed U:V pair is unique in that a pairing configuration may be suggested for it wherein the hydrogen-bonding involves the exocyclic 5-carboxymethoxy group of V. By comparing the theoretical data on the configurations of these pairs with the evidence for their existence/non-existence in nature, some guidelines emerge for differentiating between observed and unobserved base pairs on the basis of the pairing configuration.

A resposta imuno-inflamatória na leishmaniose tegumentar humana / The immune-inflammatory response in human cutaneous leishmaniasis

Na LTA é reconhecido um espectro de manifestações clínico-munológicas que varia da forma cutânea localizada (LCL) e mucocutânea (LCM), à difusa (LCD). A forma de apresentação clínica é influenciada pela resposta do hospedeiro. A maioria dos pacientes infectados com L. braziliensis desenvolve LCL, uma resposta imuno é montada contra o parasito. Poucos pacientes infectados por L. braziliensis apresentam LCM que é vista como o p!Jlo hiperresponsivo da doença. Raramente, se observa a forma anérgica, LCD, que no Brasil é causada por L. amazonensis. O objetivo deste trabalho foi caracterizar in situ o perfil fenotípico das células do infiltrado inflamatório mononuclear e as citocinas, TNF-a, TGF-B, IFN-y e a enzima iNOS, na tentativa de estabelecer correlações com os váriados aspectos morfológicos da L TA. Foram estudados 43 pacientes, 35 com LCL, 5 com LCM e 3 com LCD. As biópsias de pele e mucosa foram submetidas a estudo histológico e imunohistoquímico pela técnica de imunoperoxidase indireta. As três formas clínicas da L TA mostraram diferenças na composição celular do infiltrado inflamatório. Na LCL os macrófagos foram mais numerosos que T CD4+ e T CD8+, sendo os T CD8+ menos numerosos. Linfócitos T CD8+ foram mais numerosos nas lesões com tempo de evolução maior que 10 semanas ou naquelas que mostraram necrose em granulomas. Na LCM observou se uma equivalência numérica entre estes três fenótipos. Na LCD macrófagos representaram 89% das células do infiltrado inflamatório. Os linfócitos TCD4+ e T CD8+ foram numericamente iguais ou equivalentes. IFN-y foi observado em raras células na LCL e LCM e esteve ausente na LCD. TNF-a foi observado em células mononucleares em torno de vasos, circundando áreas de necrose e apoptose e em células epitelióides de granuloma. TNF-a associado a membrana foi observado em células mononuleares em torno de vasos...

Modulation of Mitochondrial Uptake of Adenosine by Nitrobenzylthionosine

In this study the uptake and metabolism of adenosine by mitochondria has been investigated. Incubation of CEM cells mitochondria preparation with [3H]-adenosine showed substantial uptake and metabolism of adenosine. Adenosine was both anabolized to AMP, ADP and ATP, and also catabolized to inosine. The highest concentration of metabolites in extracted mitochondria was due to AMP. The mitochondria preparation did not show any 5'-nucleotidase activity and this will exclude any possibility of the production of adenosine from AMP in the preparation. Coincubation of [3H]-adenosine with mitochondria in the presence of 2 [micro] M of a known potent nucleoside transporter inhibitor, nitrobenzylthioinosine [NBMPR], substantially reduced the mitochondria content of adenosine and its metabolites. The results of this study showed that adenosine was uptaken by the mitochondria preparation. Metabolism of adenosine after incubation with CEM mitochondria provided further evidence for mitochondrial uptake and metabolism of this nucleoside

Clinical Utility of Adenosine Deaminase Isoenzyme Determinations in Leukemia / 대한임상병리학회지

BACKGROUND: Adenosine deaminase (ADA), an enzyme involved in purine metabolism, catalyzes the hydrolytic deamination of adenosine or 2-deoxyadenosine to inosine or 2-deoxyinosine. Human ADA consists of three molecular forms: ADA1, ADA1+CP, and ADA2. The two ADA isoenzymes represent two different gene products and have different tissue distributions, and their concentrations in serum appear to reflect different pathological conditions or physiological responses. Elevation of serum ADA activity has been described especially in leukemia and lymphoma. The purpose of this study was to evaluate the clinical utility of ADA isoenzyme determination in the diagnosis of leukemia. METHODS: We studied the activity of serum ADA and its isoenzyme in 44 leukemic patients. The study population consisted of 17 patients with acute lymphoblastic leukemia (ALL), 23 with acute myeloid leukemia (AML), and 4 with chronic myelogenous leukemia (CML). ADA isoenzyme was measured by erythro-9- (2-hydroxy-3-nonyl) adenine [EHNA] inhibitory assay using the Hitachi 7170 autoanalyzer. RESULTS: The rates of abnormally high total ADA activity were 100% for ALL, 60.8% for AML, and 50% for CML. In isoenzyme pattern, there was a clear difference between ALL and AML. High level of ADA1 activity was found in patients with ALL (P <0.01). The ADA1/ADA2 ratio was significantly higher (P <0.001) in ALL than AML. There was a correlation between ADA1 and absolute number of peripheral blasts in AML (r=0.840). CONCLUSIONS: It is concluded that the measurement of ADA isoenzyme may be a useful biochemical marker for leukemic diagnosis.

Efeitos do alopurinol sobre as alteraçöes morfológicas produzidas pela isquemia testicular temporária em ratos / Reperfusion injury with allopurinol after short term testicular ischemia in rats

O objetivo do presente estudo foi avaliar, em ratos, se o alopurinol é capaz de proteger o testículo contra os efeitos da isquemia com duraçäo de uma hora, seguida de reperfusäo. Dezoito ratos adultos, Wistar-EPM1, com peso variando entre 300 e 340g, foram divididos em três grupos: controle (G1), isquemia (G2) e isquemia com alopurinol (G3) com seis animais cada. Após anestesia com pentobarbital sódico intraperitoneal (30mg/Kg), o testículo esquerdo era exteriorizado e mantido imerso em soluçäo salina (0,9 por cento) à temperatura ambiente durante uma hora. Nos grupos G2 e G3 o pedículo era clampeado durante o experimento (1h). No grupo G3 cada animal recebeu 50 mg/Kg de alopurinol V.O. nos dois dias anteriores e duas horas antes da isquemia. Após 60 dias os animais foram anestesiados, sacrificados e os testículos removidos, pesados e preparados para exame histopatológico (HE). As lâminas foram analisadas de acordo com a classificaçäo de Cosentino. Observou-se diminuiçäo significante do peso do testículo esquerdo nos grupos G2 e G3 (p<0,05) e o escore histopatológico mostrou grau importante de sofrimento testicular esquerdo nos grupos G2 e G3 (p<0,05). Concluiu-se que o alopurinol näo foi capaz de proteger o testículo do rato contra os efeitos do fenômeno de isquemia/reperfusäo