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Objective: The production of reactive oxygen species is increased in diabetic patients, especially in those will poor glycemic control. We have investigated oxidative damage in type 2 diabetic patients using serum 8-hydroxyguanine (8-OHG) as a biomarker.Research Design and Methods: We studied 41 type 2 diabetic patients and compared them with 3 nondiabetic control subjects. Serum 8-OHG concentration was assayed using high-pressure liquid chromatography.Results: The type 2 diabetic patients had significantly higher concentrations of 8-OHG in their serum than the control subjects (5.03 +/- 0.69 vs. 0.96 +/- 0.15 pmol/ml P < 0.01). There was no association between the levels of 8-OHG and HbA1c. We also could not and any correlation between serum 8-OHG levels and age, duration of diabetes, serum lipids, or creatinine or albumin exeretion rate. Creatinine clearance showed marginal correlation with serum 8-OHG levels (P = 0.06). Among the diabetic patients, those with proliferative retinopathy had significantly higher 8-OHG levels than those with nonproliferative retinopathy or without retinopathy. Likewise, the serum 8-OHG levels in patients who had advanced nephropathy (azotemia) were higher than in patients with normoalbuminuria, microalbuminuria, or overt proteinuria.Conclusions: Our findings show that measuring serum 8-OHG is a novel convenient method for evaluating oxidative DNA damage. Diabetic patients, especially those with advanced microvascular complications, had significantly higher serum 8-OHG levels; this suggests that such changes may contribute to the development of microvascular complications of diabetes. [ABSTRACT FROM AUTHOR]

Infiltration of foreign materials into a fatigue crack has previously been shown to be able to retard the crack and extend fatigue life. Most of the related studies were empirical and phenomenological in nature. To aid engineering decisions, it would be advantageous if the possible outcome of a repair can be evaluated beforehand. To this end, a crack closure model taking into account the additional closure effect of the infiltrant has been developed and verified against experimental results. With this model, the sensitivity of the repair effect to various parameters such as mechanical properties of the infiltrant, depth of penetration and infiltration load level can be assessed. [ABSTRACT FROM AUTHOR]

We have previously indicated that human osteoblasts express a repertoire of cadherins and that perturbation of cadherin-mediated cell-cell interaction reduces bone morphogenetic protein 2 (BMP-2) stimulation of alkaline phosphatase activity. To test whether inhibition of cadherin function interferes with osteoblast function, we expressed a truncated N-cadherin mutant (NCaddeltaC) with dominant negative action in MC3T3-E1 osteoblastic cells. In stably transfected clones, calcium-dependent cell-cell adhesion was decreased by 50%. Analysis of matrix protein expression during a 4-week culture period revealed that bone sialoprotein, osteocalcin, and type I collagen were substantially inhibited with time in culture, whereas osteopontin transiently increased. Basal alkaline phosphatase activity declined in cells expressing NCaddeltaC, relative to control cells, after 3 weeks in culture, and their cell proliferation rate was reduced moderately (17%). Finally, 45Ca uptake, an index of matrix mineralization, was decreased by 35% in NCaddeltaC-expressing cells compared with control cultures after 4 weeks in medium containing ascorbic acid and beta-glycerophosphate. Similarly, BMP-2 stimulation of alkaline phosphatase activity and bone sialoprotein and osteopontin expression also were curtailed in NCaddeltaC cells. Therefore, expression of dominant negative cadherin results in decreased cell-cell adhesion associated with altered bone matrix protein expression and decreased matrix mineralization. Cadherin-mediated cell-cell adhesion is involved in regulating the function of bone-forming cells.

Non-redundant expressed sequence tags (ESTs) were generated from six different organs at various developmental stages of Chinese cabbage, Brassica rapa L. ssp. pekinensis. Of the 1,295 ESTs, 915 (71%) showed significantly high homology in nucleotide or deduced amino acid sequences with other sequences deposited in databases, while 380 did not show similarity to any sequences. Briefly, 598 ESTs matched with proteins of identified biological function, 177 with hypothetical proteins or non-annotated Arabidopsis genome sequences, and 140 with other ESTs. About 82% of the top-scored matching sequences were from Arabidopsis or Brassica, but overall 558 (43%) ESTs matched with Arabidopsis ESTs at the nucleotide sequence level. This observation strongly supports the idea that gene-expression profiles of Chinese cabbage differ from that of Arabidopsis, despite their genome structures being similar to each other. Moreover, sequence analyses of 21 Brassica ESTs revealed that their primary structure is different from those of corresponding annotated sequences of Arabidopsis genes. Our data suggest that direct prediction of Brassica gene expression pattern based on the information from Arabidopsis genome research has some limitations. Thus, information obtained from the Brassica EST study is useful not only for understanding of unique developmental processes of the plant, but also for the study of Arabidopsis genome structure.

Objectives: To compare the prevalence and metabolic profiles of glucose tolerance categories according to World Health Organization(WHO) and 1997 American Diabetes Association(ADA) fasting criteria for the diagnosis of diabetes mellitus and impaired glucose metabolism in the Korean population., Methods: 2251 subjects without previous history of diabetes, who participated in the Yonchon diabetes epidemiology survey in 1993, were classified according to both criteria. The prevalence of glucose tolerance categories and the agreement across all categories of glucose tolerance were calculated. Metabolic characteristics of different glucose tolerance categories were compared., Results: The prevalence of diabetes and impaired fasting glucose(IFG) according to ADA fasting criteria was similar to those of diabetes and impaired glucose tolerance(IGT) according to WHO criteria, respectively. However, 35.5% of the subjects who were diagnosed as diabetes by WHO criteria were reclassified as either IFG or normal fasting glucose (NFG), and 38.5% of diabetic patients according to ADA fasting criteria were IGT or normal glucose tolerance (NGT) by WHO criteria. Only 31.3% of IGT subjects remained as IFG and 62.1% were reclassified as NFG. Similarly, 69.4% of IFG subjects were NGT by WHO criteria. The agreement between the two criteria was poor (K = 0.31). Discordant diabetes groups had higher WHR, systolic and diastolic blood pressure, cholesterol and triglyceride levels than concordant non-diabetes group. Non-diabetes(WHO)/diabetes(ADA) group had higher WHR than diabetes (WHO)/non-diabetes(ADA) group. There were no differences in other metabolic characteristics between the two discordant diabetes groups. IGT/NFG and NGT/IFG group showed higher BMI, WHR, systolic and diastolic blood pressure, cholesterol and triglyceride levels than NGT/NFG group. Metabolic characteristics of IGT/NFG group were not different from those of NGT/IFG group except IGT/NFG subjects were older than NGT/IFG subjects., Conclusion: The agreement between WHO and ADA fasting criteria was poor. ADA fasting criteria can detect new diabetic patients and subjects with impaired glucose metabolism who are not classified as diabetes or IGT by WHO criteria. However, a substantial number of subjects, who may have increased cardiovascular risk and/or increased risk for the development of diabetes and its complication, will be missed when using ADA fasting criteria.

Controlled mechanical ventilation (CMV) with positive and expiratory pressure (PEEP) is often used to improve the pulmonary gas exchange in patients with acute respiratory distress syndrome. However, this ventilatory technique may induce hemodynamic and hormonal changes which may lead to vital organ dysfunction, such as oliguria. Low dose dopamine, acting as a dopaminergic receptor agonist, may improve vital organ perfusions, i.e. renal, mesenteric and coronary perfusions. The purpose of this current study was to evaluate the effects of low dose dopamine on renal function and hemodynamic change during controlled mechanical ventilation with PEEP. The study was performed on 10 patients treated with PEEP in the surgical intensive care unit. Starting with 0 cmH2O of PEEP and adding 4 cmH2O of PEEP at 4-hour intervals until it reached 12 cmH2O of PEEP, dopamine, 2 ug/kg/min, was selectively, administered, intravenously during the last two hours of each four hour intervals. Following each procedure, hemodynamic parameters, urine output, creatinine clearance and fractional excretion of sodium were measured. The cardiac index and mean arterial pressure had both decreased, but the mean pulmonary arterial pressure was increased at 12 cmH2O of PEEP compared with 0 cmH2O of PEEP in both groups with and without low dose dopamine. The main result of this study was that low dose dopamine attenuated the decrease of the cardiac index, urine output and creatinine clearance induced by mechanical ventilation with PEEP at 12 cmH2O.

Mitochondrial tRNA(Leu)(UUR) gene mutation is one of the candidates in the pathogenesis of NIDDM. Especially the 3243 (A-->G) mutation is associated with the maternally-inherited diabetes and deafness. To evaluate the prevalence and characteristics of the 3243 point mutation in Koreans, we screened 433 Korean diabetic patients (220 men and 213 women). Genomic DNA was extracted from peripheral white blood cells and PCR was carried out with mitochondrial DNA primers (3130-3149, 3558-3539) encompassing the 3243 position. After digestion with Apa-1, five subjects showed polymorphism suggesting 3243 point mutation but when we directly sequenced the amplified DNA with an automatic sequencer, only 2 of the 5 patients were shown to have 3243 (A-->G) mutation and the other 3 subjects had 3426 (A-->G) mutation rather than 3243 mutation. Two diabetic patients with 3243 mutation were lean (BMI = 14.4, 17.0 kg/m2), had relatively lower fasting C-peptide concentrations (0.9 ng/ml each), and required insulin for management. In contrast, those with 3426 point mutation were not lean (BMI = 22.6-28.0 kg/m2), had relatively higher C-peptide levels (3.9-5.4 ng/ml), and could be managed with oral hypoglycemic agents. None of the 5 patients had deafness. In conclusion, the prevalence of 3243 point mutation in Korean diabetic patients was approximately 0.5% and we found a new mutation mimicking 3243 mutation by PCR-RFLP (restriction fragment length polymorphism) pattern. We suggest that sequencing of the PCR product or designing smaller PCR fragment size to enhance the specificity may help to identify the exact location of the point mutation.

Although heparin is better known as an anticoagulant, it also has several anti-inflammatory effects. Heparin is known to inhibit neutrophil adhesion, chemotaxis and oxygen free radical production. In addition, heparin is also known to act as an oxygen radical scavenger. Our hypothesis was that heparin would attenuate renal ischemia reperfusion injury. In this study, we investigated whether heparin had a protective effect on renal ischemia reperfusion injury. Sheep (n = 12) were prepared for the chronic study with venous, arterial and urinary catheters inserted. In addition, pneumatic occluders and ultrasonic flow probes were placed on renal arteries. After a 5-day recovery period, the sheep were randomized to either a heparin treatment group (400 IU/kg i.v. bolus 10 minutes before renal artery occlusion, followed by a continuous effusion 25,000 IU in 250 ml of 0.9% NaCl at 10 ml/hr, n = 6) or a control group (n = 6), which received an equivalent volume of 0.9% NaCl. All the sheep then underwent 90 minutes of bilateral renal ischemia followed by 24 hours of reperfusion. Blood urea nitrogen (BUN), serum creatinine (Scr), and creatinine clearance (CrCl) were determined at various intervals during both the ischemic and reperfusion periods. Kidney tissue samples were obtained at autopsy for histologic examination. As a result, there were significant differences in the degree of inflammation (1.50 +/- 1.24 Vs 0.50 +/- 0.79, P < 0.05) between the control and heparin treatment groups, but not in the degree of injury (2.83 +/- 0.44 Vs 2.33 +/- 0.28). In this study, heparin significantly attenuated polymorphonuclear leukocytes (PMNs) infiltration within the interstitium, but it did not affect the degree of renal damage as measured by urinary chemistries or renal tubular damage as assessed by histopathologic evaluation.

Objectives: The prognosis of IDDM is mainly dependent on complicated diabetic nephropathy which is probably determined by both metabolic abnormalities and genetic predisposition. Angiotensin I converting enzyme (ACE) regulates systemic and renal circulations through angiotensin II formation and kinins metabolism. The insertion(i)/deletion(D) polymorphism in intron 16 of ACE gene is strongly associated with ACE levels, and subjects homozygote for deletion (genotype DD) have the highest plasma values. Recently, it was reported that I/D polymorphism of ACE gene is associated with diabetic nephropathy in Caucasian IDDM patients. We studied the relationship between the ACE gene polymorphism and diabetic nephropathy in Korean IDDM patients., Methods: The study population consisted of 59 IDDM patients (duration > 5 yrs) and 107 control subjects. IDDM subjects were divided into 2 groups according to the presence or absence of diabetic nephropathy (with nephropathy: n = 31, without nephropathy: n = 28). After extraction of genomic DNA from peripheral blood leukocytes, PCR was performed using the sense primer (5' -GCC CTG CAG GTG TCT GCA GC-3') and anti-sense primer (3'-TGC CCA TAA CAG TGC TTC ATA -5'), respectively. The PCR products were electrophoresed in 2% agarose gels, and DNA was visualized directly with ethidium bromide staining., Results: Frequencies for II, ID and DD genotypes were similar in IDDM subjects and controls (23: 19:17 vs 49:41:17, p = 0.142) and derived allele frequencies for I and D alleles were similar in both groups (0.551:0.449 vs 0.649:0.351, p = 0.098). The ACE genotype distributions were not different in diabetic subjects with or without nephropathy (12:9:10 vs 11:10:7, p = 0.78) and derived allele frequencies were also similar (0.532:0.468 vs 0.571:0.429, p = 0.81)., Conclusion: The I and D allele frequency in our controls was different compared to ACE allele frequencies of Caucasian populations, but very similar compared to those of Chinese or Japanese subjects. We found that I/D polymorphism of ACE gene is not implicated in the diabetic nephropathy of Korean IDDM patients and may be explained by ethnic differences.

The effects of ginseng total saponins (GTS) on L-glutamate-induced swelling of cultured astrocytes from rat brain were studied. Following exposure to 0.5 mM glutamate for 1 h, the intracellular water space (as measured by [3H]O-methyl-D-glucose uptake) of astrocytes increased three-fold with a morphological change: the disappearance of cellular processes. Simultaneous addition of GTS with glutamate reduced the astrocytic swelling in a dose-dependent manner. GTS at 0.5 mg/ml did not affect the viability of astrocytes for up to 18 h, which was determined by a colorimetric assay for cellular growth and survival. These data suggest that GTS prevents the cell swelling of astrocytes induced by glutamate.

Fifty-one patients required the implantation of a Cordis Omnis-Stanicor permanent pacemaker. His bundle electrograms studies, which included right atrial pacing and sinoatrial (SA) node postsuppression recovery times, were performed prior to the implantations. Pacing and sensing thresholds were obtained in all patients. Syncope or episodes of dizziness were the presenting symptoms in virtually every patient. Twenty-eight of the 51 patients had the sick sinus syndrome. Only nine patients were in complete heart block, and an additional nine were in second-degree heart block. The His bundle electrogram technique was not particularly helpful in selecting the potential pacemaker candidate. The symptomatic patient with second- or third-degree heart block requires a pacemaker. In the sick sinus syndrome, the His bundle electrogram was a disappointing tool in detecting abnormalities. In chronic bundle branch block, the His bundle electrogram appears to play a major role. A prolonged H-V interval in a symptomatic patient, in whom a specific noncardiac cause cannot be identified, signifies that a pacemaker is required.