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Identification and characterization of a second chromophore of DNA photolyase from Thermus thermophilus HB27.

Cyclobutane pyrimidine dimer (CPD) photolyases use light to repair CPDs. For efficient light absorption, CPD photolyases use a second chromophore. We purified Thermus thermophilus CPD photolyase with its second chromophore. UV-visible absorption spectra, reverse-phase HPLC, and NMR analyses of the chromophores revealed that the second chromophore of the enzyme is flavin mononucleotide (FMN). To clarify the role of FMN in the CPD repair reaction, the enzyme without FMN (Enz-FMN(-) and that with a stoichiometric amount of FMN (Enz-FMN(+)) were both successfully obtained. The CPD repair activity of Enz-FMN(+) was higher than that of Enz-FMN(-), and the CPD repair activity ratio of Enz-FMN(+) and Enz-FMN(-) was dependent on the wavelength of light. These results suggest that FMN increases the light absorption efficiency of the enzyme. NMR analyses of Enz-FMN(+) and Enz-FMN(-) revealed that the binding mode of FMN is similar to that of 7,8-didemethyl-8-hydroxy-5-deazariboflavin in Anacystis nidulans CPD photolyase, and thus a direct electron transfer between FMN and CPD is not likely to occur. Based on these results, we concluded that FMN acts as a highly efficient light harvester that gathers light and transfers the energy to FAD.

Cellulose↗

Similarities and differences between cyclobutane pyrimidine dimer photolyase and (6-4) photolyase as revealed by resonance Raman spectroscopy: Electron transfer from the FAD cofactor to ultraviolet-damaged DNA.

The cyclobutane pyrimidine dimer (CPD) and (6-4) photoproduct, two major types of DNA damage caused by UV light, are repaired under illumination with near UV-visible light by CPD and (6-4) photolyases, respectively. To understand the mechanism of DNA repair, we examined the resonance Raman spectra of complexes between damaged DNA and the neutral semiquinoid and oxidized forms of (6-4) and CPD photolyases. The marker band for a neutral semiquinoid flavin and band I of the oxidized flavin, which are derived from the vibrations of the benzene ring of FAD, were shifted to lower frequencies upon binding of damaged DNA by CPD photolyase but not by (6-4) photolyase, indicating that CPD interacts with the benzene ring of FAD directly but that the (6-4) photoproduct does not. Bands II and VII of the oxidized flavin and the 1398/1391 cm(-1) bands of the neutral semiquinoid flavin, which may reflect the bending of U-shaped FAD, were altered upon substrate binding, suggesting that CPD and the (6-4) photoproduct interact with the adenine ring of FAD. When substrate was bound, there was an upshifted 1528 cm(-1) band of the neutral semiquinoid flavin in CPD photolyase, indicating a weakened hydrogen bond at N5-H of FAD, and band X seemed to be downshifted in (6-4) photolyase, indicating a weakened hydrogen bond at N3-H of FAD. These Raman spectra led us to conclude that the two photolyases have different electron transfer mechanisms as well as different hydrogen bonding environments, which account for the higher redox potential of CPD photolyase.

Arabidopsis↗

A new predictor of cephalopelvic disproportion?

Cephalopelvic disproportion (CPD) is a recognised obstetric problem with potential risk to both mother and infant. Identification of those mothers at risk of CPD is difficult and has concentrated in the past on such measurements as maternal shoe size and height. Our objective in this study was to examine new anthropomorphic parameters as indicators of CPD. This was a case controlled study of sixty consecutive women, and their partners, who had caesarean section performed for CPD and 60 case matched controls. Measurements included maternal and paternal head circumference, height, shoe-size, body mass index (BMI), infant weight and head circumference. Parity, gestation at delivery, and mode of onset of labour were recorded. Data were analysed using Stata Release 6. Prognostic factors were tested for association with CPD using conditional logic regression. The most important anthropomorphic risk factors for CPD were maternal head circumference in relation of height (P < 0.001), and paternal head to height ratio (P = 0.017). Head to height ratio is taken as the head circumference in centimeters divided by the height in metres. Body mass index was higher in CPD cases (maternal case mean = 27.1, control mean = 25.5; paternal case mean = 27.2, control mean = 26.2). Infant head circumference was not a predictor. Primiparity was an important independent predictor (P<0.001), regardless of the mode of onset of labour. Maternal or paternal shoe-size, induction of labour and gestation at delivery were not predictors. The risk profile for CPD which emerges is one of a tall father where both mother and father have large head-to-height ratios.

Adult↗

Polytetrafluoroethylene versus polypropylene sutures for Essed-Schroeder tunical plication.

PURPOSE: Essed-Schroeder plication is an established operative technique to correct congenital and acquired penile deviation. However, a third of all patients complain about discomfort from the suture material used. We prospectively evaluated patient satisfaction and quality of life after modified Essed-Schroeder plication by comparing 2 suture materials. MATERIALS AND METHODS: Between 1998 and 2001, 88 patients underwent surgical correction of penile deviation at our hospital. Mean patient age was 40 years (range 18 to 71) and mean followup was 30 months. Preoperatively penile curvature was greater than 20 degrees in all patients. A standardized questionnaire was sent to all patients. A total of 55 patients, including 30 with Peyronie's disease (PD) and 25 with congenital penile deviation (CPD), were available for evaluation and had complete followup. RESULTS: In 25 of these patients (12 with PD and 13 with CPD) nonabsorbable polypropylene (PP) sutures were used for plication, whereas in the other 30 (18 with PD and 12 with CPD) nonabsorbable polytetrafluoroethylene (PT) sutures were used. In the PP group 22 of the 25 patients (88%) could notice the sutures (11 with PD and 11 with CPD), 10 had discomfort (6 with PD and 4 with CPD) and 3 had pain during penile erection (2 with PD and 1 with CPD). In the PT group 15 of the 30 patients (50%) could notice the sutures (10 with PD and 5 with CPD), 3 had discomfort (1 with PD and 2 with CPD) and 1 with PD had painful erections. Three patients had recurrent deviation, of whom 2 and 1 underwent plication with PP and PT, respectively. CONCLUSIONS: These results indicate the PT is the more superior suture material with regard to postoperative patient discomfort after Essed-Schroeder correction of penile deviation. Nonabsorbable PT sutures do not impair the efficacy of the modified Essed-Schroeder plication technique and the success rate is not related to the underlying pathological condition.

Adolescent↗

A clinical trial of red-cell concentrate prepared from blood collected in half-strength citrate anticoagulant.

Earlier studies have indicated that plasma from blood donations drawn into half-strength citrate anticoagulant (0.5 CPD-A2) may give improved yields of factor VIII:C after fractionation. It has also been shown previously that cellular components from blood donations drawn into 0.5 CPD-A2 have satisfactory in-vitro and in-vivo properties. The present study examines the clinical use of red cell concentrate (RCC) from 0.5 CPD-A2 blood donations. Forty-nine patients who were undergoing elective orthopaedic surgery and who required blood transfusion received 0.5 CPD-A2 RCC. A transfused control group of 107 patients received standard CPD-A1 RCC for their transfusion requirements. Patients in the two transfused groups had similar haemoglobin responses to transfusion. All patients experienced a moderate pyrexia following the operation. Both study groups showed similar responses to serum lactate dehydrogenase levels in the 2 weeks following surgery, and in postoperative peripheral blood platelet counts. Serious postoperative complications arose in both groups. In the 0.5 CPD-A2 group two patients had pulmonary emboli (one fatal) and one patient had a non-fatal myocardial infarction. Three patients had pulmonary emboli in the CPD-A1 transfused group. These incidences of major adverse events were within the expected range of these complications in patients who were undergoing major joint replacement surgery and did not differ significantly between the study groups. This study indicates that red cell concentrate prepared in half-strength citrate anticoagulant is comparable to that prepared in CPD-A1 for patients undergoing orthopaedic surgery.

Adenine↗

Continuing professional development--global perspectives: synopsis of a workshop held during the International Association of Dental Research meeting in Gothenburg, Sweden, 2003. Part 1: access, funding and participation patterns.

There appears to have been little previous research interest in continuing professional development (CPD) of dentists and the oral health team. This paper presents data and information on the following aspects of CPD in 17 countries in Asia, Australasia, Europe and North America: availability of different types of CPD, its providers, data on uptake of CPD courses and activities, and funding of CPD. The results indicate that lectures and hands-on skills courses were held in all 17 countries but the use of the Internet to deliver CPD was by no means universal. CPD was funded from a variety of sources including universities, governments and commercial companies. However, the only universal source of funding for CPD was dentists themselves. Data on participation were available from only three countries. Research issues based on these results will be listed in a second paper.

Asia↗

Crystal doping aided by rapid expansion of supercritical solutions.

The purpose of this study was to test the utility of rapid expansion of supercritical solution (RESS) based cocrystallizations in inducing polymorph conversion and crystal disruption of chlorpropamide (CPD). CPD crystals were recrystallized by the RESS process utilizing supercritical carbon dioxide as the solvent. The supercritical region investigated for solute extraction ranged from 45 to 100 degrees C and 2000 to 8000 psi. While pure solute recrystallization formed stage I of these studies, stage II involved recrystallization of CPD in the presence of urea (model impurity). The composition, morphology, and crystallinity of the particles thus produced were characterized utilizing techniques such as microscopy, thermal analysis, x-ray powder diffractometry, and high-performance liquid chromatography. Also, comparative evaluation between RESS and evaporative crystallization from liquid solvents was performed. RESS recrystallizations of commercially available CPD (form A) resulted in polymorph conversion to metastable forms C and V, depending on the temperature and pressure of the recrystallizing solvent. Cocrystallization studies revealed the formation of eutectic mixtures and solid solutions of CPD + urea. Formation of the solid solutions resulted in the crystal disruption of CPD and subsequent amorphous conversion at urea levels higher than 40% wt/wt. Consistent with these results were the reductions in melting point (up to 9 degrees C) and in the DeltaH(f) values of CPD (up to 50%). Scanning electron microscopy revealed a particle size reduction of up to an order of magnitude upon RESS processing. Unlike RESS, recrystallizations from liquid organic solvents lacked the ability to affect polymorphic conversions. Also, the incorporation of urea into the lattice of CPD was found to be inadequate. In providing the ability to control both the particle and crystal morphologies of active pharmaceutical ingredients, RESS proved potentially advantageous to crystal engineering. Rapid crystallization kinetics were found vital in making RESS-based doping superior to conventional solvent-based cocrystallizations.

Calorimetry, Differential Scanning↗

[Intraocular lenses with blue light filter].

PURPOSE: To evaluate if a SN60AT < > IOL (Alcon) with IMPRUV filter (Alcon) offers any advantage in patients having cataract surgery, as compared with Acrysof SA60 IOL (Alcon). METHODS: This was a prospective analytical study. We studied sixty-four eyes from 32 patients with cataracts. After a random assignment, phacoemulsification with the implant was performed using the Acrysof SN60AT tinted lens in one eye and Acrysof SA60 in the other. A variety of variables was subsequently assessed: contrast sensitivity with a CSV 1000E test, colour perception through a Farnsworth 25 test and subjective measures by a patient survey. Differences between the groups were assessed statistically. RESULTS: The contrast sensitivity results were obtained for 3, 6, 12 and 18 cycles per degree (cpd) frequencies under scotopic conditions, with better results obtained following the use of SN60AT: 0.75 (CSV 1000E test units) for 3 cpd, 0.86 for 6 cpd, 0.54 for 12 cpd and 0.35 for 18 cpd. The differences were statistically significant between the two groups for 3 cpd and 6 cpd. A total of 62.5% of patients using a tinted lens and 50% with SA60 achieved good results in the Farnsworth test; 12.5% and 21% had fair results and 25% and 28.1% respectively had poor results. CONCLUSIONS: We obtained an improvement in favour of the tinted lens for all frequencies, with this being statistically significant at lower frequencies (3 and 6 cpd). No significant differences in the Farnsworth test performance or in the patient survey were found. The tinting provided by the IMPRUV filter brings an increase in contrast sensitivity without affecting colour perception.

Aged↗

Peritonitis in the extended-care facility.

Many patients with end-stage renal disease (ESRD) require admission to an extended-care facility (ECF). Few data are available concerning the development of peritonitis among continuous peritoneal dialysis (CPD) patients residing in an ECF. We retrospectively reviewed the charts of 77 CPD patients admitted to an ECF between November 1993 and 31 August 1997. A total of 25 episodes of peritonitis developed among CPD patients in the ECF during this period for an overall peritonitis rate of 1 episode in 19.8 patient-months. The CPD patients developing peritonitis in the ECF were similar in age and gender to the CPD patients residing in the ECF not developing peritonitis. There were more African-Americans among the group of CPD patients residing in the ECF who developed peritonitis than among the ECF residents who did not develop peritonitis (41% vs. 23%, respectively; P < 0.05). Patients developing peritonitis in the ECF resided in the ECF significantly longer than the remaining CPD patients not developing peritonitis in the ECF (106 vs. 77 days, respectively; P < 0.05). The overall rate of peritonitis in the ECF was lower than that seen in the community (1 episode in 19.8 patient-months vs. 1 episode in 10.0 patient-months, respectively). The rate of gram-positive peritonitis was lower than the rate of gram-positive peritonitis seen in the community setting (1 episode in 54.9 patient-months vs. 1 episode in 14.9 patient-months, respectively). The rate of culture-negative peritonitis was higher among the ECF patients than among patients developing community-acquired peritonitis (1 episode in 61.9 patient-months vs. 1 episode in 106.2 patient-months, respectively). The spectrum of organisms in the ECF was different than the spectrum noted among patients developing hospital-acquired peritonitis. Eleven of the 25 episodes of peritonitis were treated successfully at the ECF while the remaining 14 episodes of peritonitis were treated at an acute-care hospital. Continuous PD therapy was continued following 19 of the 25 episodes (76%), 1 patient transferred to hemodialysis, and 5 patients expired. We conclude that patients develop peritonitis in the ECF less frequently than in the community setting, with the spectrum of organisms different than the spectrum seen in the community and hospital settings. Seventy-six percent of the patients continue CPD therapy following an episode of peritonitis.

Aged↗

[The effect of herbal compound 861 on mRNA levels of MMP-2 and its activities in experimental rats liver fibrosis].

OBJECTIVE: To explore the effect of herbal compound 861 (Cpd 861) on MMP-2 expression and its enzymatic activities, and the antifibrotic mechanism of this herbal compound. METHODS: Forty five female rats were randomly divided into normal control (sham operation) group, common bile duct ligation (BDL) group and Cpd 861 therapeutic group. In the last group, daily gastric feeding of Cpd 861 (9 g/kg.bw) started on day 7 after BDL operation. At 49 days, all animals were sacrificed and mRNA expression of MMP-2 in liver tissue was evaluated by semi-quantitive RT-PCR. In addition, enzymatic activities of MMP-2 were analyzed by zymography. RESULTS: In comparison with model group, MMP-2 mRNA levels in Cpd 861 therapeutic group were significantly decreased. MMP-2 enzymatic activities were not detectable in normal group, slightly elevated in model group, higher in Cpd 861 therapeutic group. CONCLUSIONS: Cpd 861 decreases the mRNA level of MMP-2, but transiently increases the enzymatic activities of MMP-2. The latter effect of Cpd 861 may be mediated by decreasing TIMPs, the inhibitors of MMPs, during resolution stage of fibrosis. This is probably one of the mechanisms whereby herbal Cpd 861 exerted its antifibrotic action in this kind of experimental liver fibrosis.

Animals↗

Effect of citrate feeding on free radical induced changes in experimental urolithiasis.

Feeding calculi producing diet (CPD) to rats for 4 weeks produced calcium oxaltate stones. Supplementation of sodium citrate to CPD (c-CPD) prevented stone formation. Except oxalate, the excretion of calcium, phosphorus and magnesium was restored to normal in c-CPD fed rats. The CPD fed rats exhibited increase in glycolic acid oxidase (GAO) and lactate dehydrogenase (LDH) activities and only GAO activity was partially restored in c-CPD fed rats. Kidney sub-cellular fractions of calculi producing diet (CPD) fed rats showed increased susceptibility for lipid peroxidation in presence of promotors. Antioxidant enzyme activities of superoxide dismutase (SOD), catalase and glutathione peroxidase and antioxidant concentrations of reduced glutathione, total thiols, ascorbic acid and vitamin E were significantly decreased while the xanthine oxidase activity, and concentrations of hydroxyl radical, diene conjugates and hydroperoxides were significantly increased in CPD fed rats. The susceptibility to lipid peroxidation, activities of antioxidant enzymes, and the concentration of antioxidants were not normalized by feeding citrate.

Animals↗

Continuous peritoneal dialysis-associated peritonitis of nosocomial origin.

OBJECTIVE: To describe our experience with nosocomial continuous peritoneal dialysis (CPD)-associated peritonitis focusing on the incidence, possible risk factors, spectrum of organisms, and outcome. DESIGN: Retrospective review of the medical records of our CPD patients admitted to an acute-care hospital between November, 1993 and December, 1994. SETTING: University-associated acute-care hospitals in New Haven, Connecticut. PATIENTS: One hundred and eighty-eight patients maintained on CPD therapy and admitted to an acute-care hospital. RESULTS: Nineteen patients (5%) developing nosocomial peritonitis (NP) were identified from the 408 admissions occurring during the study period. Patients developing NP were older than the hospitalized CPD patients not developing NP (65.5 +/- 14.6 vs 58.4 +/- 14.7 years, p < 0.05). Comorbid diseases including diabetes, peripheral vascular disease, gastrointestinal disease, cardiovascular disease, and human immunodeficiency virus seropositivity were not more common in the patients developing NP. Patients developing NP were hospitalized significantly longer than the CPD patients not developing NP (39.5 +/- 46.5 days vs 12.7 +/- 12.4 days, p < 0.001). The mean serum albumin was lower in the NP patients than in the CPD patients not developing NP (2.35 +/- 0.52 g/dL vs 3.02 +/- 0.60 g/L, p < 0.001). Antecedent antibiotic use and performance of invasive procedures were noted in 89% and 68% of the patients developing NP, respectively. Staphylococcal species, enterococcal species, and gram-negative organisms accounted for 26%, 21%, and 53% of the episodes of NP, respectively. Furthermore, two strains of Enterococcus resistant to vancomycin were cultured. Eight patients developing NP expired, 8 patients continued CPD therapy, 2 patients transferred to hemodialysis, and one patient recovered renal function. CONCLUSION: We conclude that NP is uncommon. Increased age, increased length of hospital stay, and hypoalbuminemia may predispose patients to the development of NP. Further studies with case controls should help to clarify whether antecedent antibiotics or prior performance of invasive procedures predispose patients to the development of nosocomial peritonitis. The spectrum of organisms accounting for NP is different than the spectrum of organisms causing community-acquired CPD-associated peritonitis. Some of these organisms may be resistant to standard antibiotic therapies. Patients developing NP do poorly, with 42% expiring while being treated for NP.

Age Factors↗

Serum albumin in continuous peritoneal dialysis: absence of universal predictors.

Factors shown to affect serum albumin concentration in continuous peritoneal dialysis (CPD) were compared between two CPD populations residing in Greece (patient n = 108) and the United States (patient n = 194). Compared to the U.S. group, the Greek CPD population had higher serum albumin levels (35.1 +/- 4.6 vs 33.9 +/- 5.0 g/L, p = 0.031), was older (61.2 +/- 12.0 vs 52.7 +/- 16.5 years, p < 0.001), and had a greater number of high or high-average peritoneal solute transport types (69.4% vs 52.1%, p = 0.003). The American CPD population had a higher number of diabetics (53.1% vs 27.8%, p < 0.001), higher total Kt/Vurea (2.06 +/- 0.57 vs 1.93 +/- 0.46 weekly, p = 0.046), and higher total creatinine clearance (76.3 +/- 38.7 vs 63.4 +/- 23.5 L/1.73 m2 weekly, p < 0.001), while normalized protein nitrogen appearance values were comparable (0.95 +/- 0.21 in the Greeks vs 0.94 +/- 0.22 g/(kg x 24 hr) in the Americans, NS). A logistic regression model developed in the United States identified advanced age, diabetes, and high/high-average peritoneal solute transport as the predictors of hypoalbuminemia (serum albumin < 35 g/L). This model generated the following areas with 95% confidence intervals (CI) under the receiver operating characteristic (ROC) curve: in the Greek CPD population, ROC area 0.594 (95% CI 0.486-0.702); in the American CPD population, ROC area 0.850 (95% CI 0.810-0.890). In Greek CPD patients serum albumin appears to be affected by factors other than those identified in North America. This complicates comparisons of serum albumin, and probably morbidity and mortality, between CPD populations residing in different parts of the world.

Creatinine↗

Growth inhibition and protein tyrosine phosphorylation in MCF 7 breast cancer cells by a novel K vitamin.

We have now found that the most potent, Cpd 5 [2-(2-mercaptoethanol)-3-methyl-1, 4-napthoquinone], inhibits growth of doxorubicin-resistant and doxorubicin-sensitive breast cancer cells (MCF 7r and MCF 7w) in culture. Growth inhibition by Cpd 5 was antagonized by the thiol antioxidants glutathione and cysteine, but not by catalase or superoxide dismutase, suggesting that growth inhibition is probably via conjugation of cellular thiols. In support of this, we found that Cpd 5 inhibited the activity of thiol containing cellular protein tyrosine phosphatase (PTP) enzyme, with consequent induction of various tyrosine phosphoproteins, but not serine or tyrosine phosphoproteins. The tyrosine phosphorylation was also inhibited by exogenous glutathione or cysteine and could be enhanced by depletion of cellular glutathione by BSO. This effect of Cpd 5 on protein tyrosine phosphorylation was highly selective, however. Tyrosine phosphorylation of EGF-R, Erb-B2, and ERK1/2 was increased, but not that of Insulin-R or JNK. ERK1/2 tyrosine phosphorylation and growth inhibition increased with increasing concentrations of Cpd 5. Furthermore, suppression of Cpd 5-mediated ERK1/2 phosphorylation by an ERK-kinase inhibitor antagonized growth inhibition. These results suggest a strong correlation between ERK1/2 phosphorylation by Cpd 5 and growth inhibition. This novel K-vitamin analog thus inhibits MCF 7 cell growth and induces selective protein tyrosine phosphorylation.

Antineoplastic Agents↗

Mutations affecting cyclic phosphodiesterases and adenylate cyclase in Neurospora.

Two regulatory mutants in orthophosphate-regulated cyclic phosphodiesterase (cPDase), cpd-3 and cpd-4, were isolated and mapped proximal to arg-1 on L.G. IC and distal to arg-12 on L.G. IIR, respectively. cpd-3 showed short aerial hyphae with dense formation of conidia. The morphology was very similar to that of cr-1, cpd-3 and cr-1 had reduced levels of cyclic 3',5'-AMP, adenylate cyclase and cPDases (CPDase I, II and III in low phosphate condition) but had elevated levels of cyclic 3',5'-GMP. Although cr-1 showed an enhanced level and enhanced activation of heat activated cyclic phosphodiesterase (ha-PDE), this enzyme was not activated in cpd-3. cpd-4, nuc-1 and nuc-2 produced neither cPDase I, II, III, alkaline phosphatase nor ribonuclease N1 in low phosphate media. These mutants did not produce aerial hyphae or conidia when grown in low phosphate liquid medium. Activation of ha-PDE occurred in cpd-4, but not in nuc-1 and nuc-2.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Molecular evolution of the photolyase-blue-light photoreceptor family.

The photolyase-blue-light photoreceptor family is composed of cyclobutane pyrimidine dimer (CPD) photolyases, (6-4) photolyases, and blue-light photoreceptors. CPD photolyase and (6-4) photolyase are involved in photoreactivation for CPD and (6-4) photoproducts, respectively. CPD photolyase is classified into two subclasses, class I and II, based on amino acid sequence similarity. Blue-light photoreceptors are essential light detectors for the early development of plants. The amino acid sequence of the receptor is similar to those of the photolyases, although the receptor does not show the activity of photoreactivation. To investigate the functional divergence of the family, the amino acid sequences of the proteins were aligned. The alignment suggested that the recognition mechanisms of the cofactors and the substrate of class I CPD photolyases (class I photolyases) are different from those of class II CPD photolyases (class II photolyases). We reconstructed the phylogenetic trees based on the alignment by the NJ method and the ML method. The phylogenetic analysis suggested that the ancestral gene of the family had encoded CPD photolyase and that the gene duplication of the ancestral proteins had occurred at least eight times before the divergence between eubacteria and eukaryotes.

Amino Acid Sequence↗

Chronic peritoneal dialysis in Turkish children: a multicenter study.

Chronic peritoneal dialysis (CPD) has been utilized in the treatment of children since 1989 in Turkey. The aims of this study were to summarize our experience with CPD in children and to establish a pediatric registry data system in Turkey. Standard questionnaires were sent to all pediatric CPD centers. 514 patients treated between 1989 and 2002 in 12 pediatric centers were enrolled in the study. Reflux nephropathy was the most common (18.1%) cause of renal failure. Mean age at dialysis initiation was 10.1+/-4.6 years. Mean duration of dialysis was 24.1+/-20.5 months. Continuous ambulatory peritoneal dialysis (CAPD) was the first CPD modality for 476 (92.6%) patients, 142 of whom switched to automated peritoneal dialysis (APD) during follow-up. Currently, 47.3% of the patients are still on CPD, 15.4% were transplanted, 13.2% switched to hemodialysis, 16.7% died. The patient and technique survivals were 90% and 95% at one year and 70% and 69% at five years, respectively. The survival was significantly shorter in the youngest age group (0-24 months) compared to those in older age groups (p=0.000). We herein report the first results of the TUPEPD study providing information on demographic data and survival of pediatric CPD patients. As opposed to clear recommendations in favor of APD, there is a clear preponderance of CAPD in our pediatric CPD population. That vesicoureteral reflux (VUR) is still the leading cause of renal failure is a distressing finding. Remarkably lower survival rates and transplantation ratios are as striking and distressing as the high incidence of VUR among the causes of ESRD. We conclude that we must make a great effort to achieve better results and to change these undesirable events.

Adolescent↗

Deficient global genome repair of UV-induced cyclobutane pyrimidine dimers in terminally differentiated myocytes and proliferating fibroblasts from the rat heart.

Nucleotide excision repair (NER) is the principal pathway for the removal of a wide range of DNA helix-distorting lesions. Two NER subpathways have been identified, i.e. global genome repair (GGR) and transcription-coupled repair (TCR). Little is known about the expression of NER pathways in differentiated cells. We assessed the repair of UV-induced cyclobutane pyrimidine dimers (CPD) and 6-4-photoproducts (6-4 PP) in terminally differentiated myocytes and proliferating fibroblasts isolated from the hearts of neonatal rats. Myocytes and fibroblasts were found to carry out efficient removal of 6-4 PP but display poor repair of CPD by GGR. Furthermore, both cell types were found to carry out TCR of CPD, thus mimicking the repair phenotype of established rodent cell lines. The inefficient repair of CPD at the genome overall level occurs in the absence of massive apoptosis, but goes along with an undetectable level of transcription of the p48 gene, known to be mutated in xeroderma pigmentosum group E (XP-E) patients and recently proposed to be essential for repair of CPD in nonexpressed DNA. Taken together, the results suggest that primary non-dividing cardiac myocytes and proliferating fibroblasts from rat heart selectively remove CPD from the transcribed strand of transcriptionally active genes. GGR of CPD is poor due to the absence of p48 expression.

Animals↗