Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CPD”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed2001

Patterns of DNA damage and photoinhibition in temperate South-Atlantic picophytoplankton exposed to solar ultraviolet radiation.

Natural marine phytoplankton assemblages from Bahía Bustamante (Chubut, Argentina, 45 degrees S, 66.5 degrees W), mainly consisting of cells in the picoplankton size range (0.2-2 microm), were exposed to various UVBR (280-315 nm) and UVAR (315-400 nm) regimes in order to follow wavelength-dependent patterns of cyclobutane pyrimidine dimer (CPD) induction and repair. Simultaneously, UVR induced photosynthetic inhibition was studied in radiocarbon incorporation experiments. Biological weighting functions (BWFs) for photoinhibition and for CPD induction, the latter measured in bare calf thymus DNA, differed in the UVAR region: carbon incorporation was reduced markedly due to UVAR, whereas no measurable UVAR effect was found on CPD formation. In contrast, BWFs for inhibition of photosynthesis and CPD accumulation were fairly similar in the UVBR region, especially above 300 nm. Incubation of phytoplankton under full solar radiation caused rapid CPD accumulation over the day, giving maximum damage levels exceeding 500 CPD MB(-1) at the end of the afternoon. A clear daily pattern of CPD accumulation was found, in keeping with the DNA effective dose measured by a DNA dosimeter. In contrast, UVBR induced photosynthetic inhibition was not dose related and remained nearly constant during the day. Screening of UVBR or UVR did not cause significant CPD removal, indicating that photoreactivation either by PAR or UVAR was of minor importance in these organisms. High CPD levels were found in situ early in the morning, which remained unaffected notwithstanding treatments favoring photorepair. These results imply that a proportion of cells had been killed by UVBR exposure prior to the treatments. Our data suggest that the limited potential for photoreactivation in picophytoplankton assemblages from the southern Atlantic Ocean causes high CPD accumulation as a result of UVBR exposure.

Animals↗
PubMed2000

The xeroderma pigmentosum group C gene leads to selective repair of cyclobutane pyrimidine dimers rather than 6-4 photoproducts.

We investigated the contribution of the xeroderma pigmentosum group C (XPC) gene to DNA repair. We stably transfected XPC cells (XP4PA-SV-EB) with XPC cDNA and selected a partially corrected (XP4PA-SE1) and a fully corrected (XP4PA-SE2) clone. Cell survival after UVC (254 nm) exposure was low for XP4PA-SV-EB, intermediate for XP4PA-SE1, and normal for XP4PA-SE2 cells. XP4PA-SV-EB cells had undetectable XPC mRNA and protein levels. XP4PA-SE1 cells had 130% of normal mRNA but 25% of normal protein levels, whereas XP4PA-SE2 cells had an 18-fold mRNA overexpression and normal XPC protein levels compared with normal cells. We measured cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts (6-4PP) by using specific mAbs and the ELISA technique. XP4PA-SV-EB cells had no detectable removal of CPD or 6-4PP from their global genome by 24 h after 30 J/m(2) UVC exposure. The partially corrected XP4PA-SE1 cells had normal repair of CPD but minimal repair of 6-4PP by 24 h, whereas the fully corrected XP4PA-SE2 cells regained normal CPD and 6-4PP repair capacities. We also exposed pRSVcat plasmid to UVC (to induce CPD and 6-4PP), to UVC + photolyase (to leave only 6-4PP on the plasmid), or to UVB + acetophenone (to induce only CPD). Host cell reactivation of UVB + acetophenone-, but not of UVC + photolyase-treated plasmids was normal in XP4PA-SE1 cells. Thus, increasing XPC gene expression leads to selective repair of CPD in the global genome. Undetectable XPC protein is associated with no repair of CPD or 6-4PP, detectable but subnormal XPC protein levels reconstitute CPD but not 6-4PP repair, and normal XPC protein levels fully reconstitute both CPD and 6-4PP repair.

Animals↗
PubMed1996

Tissue distribution and characterization of soluble and membrane-bound forms of metallocarboxypeptidase D.

Metallocarboxypeptidase D (CPD) is a recently discovered 180-kDa membrane-bound carboxypeptidase E-like enzyme (Song, L. and Fricker, L. D. (1995) J. Biol. Chem. 270, 25007-25013). In the present study, a soluble CPD-like activity has been purified to homogeneity and characterized. On denaturing polyacrylamide gels, the soluble enzyme from bovine pituitary glands appears as two bands of 170 and 135 kDa which are converted to 155 and 115 kDa by endoglycosidase F. Both of the soluble forms of CPD are recognized by an antisera raised against CPD purified from rat brain membranes. The partial N-terminal amino acid sequences of the two soluble forms are identical to each other and to the predicted N terminus of duck gp180. The soluble and membrane forms of CPD have similar pH optima, inhibitor specificities, and kinetic parameters for substrate hydrolysis. CPD-like enzymatic activity is detected in all rat tissues examined, with highest levels in pituitary, brain, and adrenal. Western blot analysis indicates that both soluble and membrane forms of CPD are present in rat brain, heart, liver, and kidney. At least four distinct 100-180-kDa forms of CPD are detected on Western blots, although an antiserum raised against the C-terminal region of rat CPD recognizes only the 180-kDa membrane-bound form. The finding that CPD is widely distributed suggests a broad role for this enzyme in the processing of proteins that transit the secretory pathway.

Animals↗
PubMed1999

Localization of metallocarboxypeptidase D in AtT-20 cells. Potential role in prohormone processing.

Carboxypeptidase D (CPD) is a recently discovered metallocarboxypeptidase that is predominantly located in the trans-Golgi network (TGN), and also cycles between the cell surface and the TGN. In the present study, the intracellular distribution of CPD was examined in AtT-20 cells, a mouse anterior pituitary-derived corticotroph. CPD-containing compartments were isolated using antibodies to the CPD cytosolic tail. The immunopurified vesicles contained TGN proteins (TGN38, furin, syntaxin 6) but not lysosomal or plasma membrane proteins. The CPD-containing vesicles also contained neuropeptide-processing enzymes and adrenocorticotropic hormone, a product of proopiomelanocortin proteolysis. Electron microscopic analysis revealed that CPD is present within the TGN and immature secretory granules but is virtually absent from mature granules, suggesting that CPD is actively removed from the regulated pathway during the process of granule maturation. A second major finding of the present study is that a soluble truncated form of CPD is secreted mainly via the constitutive pathway in AtT-20 cells, indicating that the lumenal domain does not contain signals for the sorting of CPD to mature secretory granules. Taken together, these data are consistent with the proposal that CPD participates in the processing of proteins within the TGN and immature secretory vesicles.

Animals↗
PubMed2003

Palmitoylation of carboxypeptidase D. Implications for intracellular trafficking.

Covalent lipid modifications mediate protein-membrane and protein-protein interactions and are often essential for function. The purposes of this study were to examine the Cys residues of the transmembrane domain of metallocarboxypeptidase D (CPD) that could be a target for palmitoylation and to clarify the function of this modification. CPD is an integral membrane protein that cycles between the trans Golgi network and the plasma membrane. We constructed AtT-20 cells stably expressing various constructs carrying a reporter protein (albumin) fused to a transmembrane domain and the CPD cytoplasmic tail. Some of the constructs contained the three Cys residues present in the CPD transmembrane region, while other constructs contained Ala in place of the Cys. Constructs carrying Cys residues were palmitoylated, while those constructs lacking the Cys residues were not. Because palmitoylation of several proteins affects their association with cholesterol and sphingolipid-rich membrane domains or caveolae, we tested endogenous CPD and several of the reporter constructs for resistance to extraction with Triton X-100. A construct containing the Cys residues of the CPD transmembrane domain was soluble in Triton X-100 as was endogenous palmitoylated CPD, indicating that palmitoylation does not target CPD to detergent-resistant membrane rafts. Interestingly, constructs of CPD that lack palmitoylation sites have an increased half-life, a slightly more diffuse steady-state localization, and a slower rate of exit from the Golgi as compared with constructs containing palmitoylation sites. Thus, the covalent attachment of palmitic acid to the Cys residues of CPD has a functional significance in the trafficking of the protein.

3T3 Cells↗
PubMed2001

Effects of photoreactivation of cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts on ultraviolet mutagenesis in SOS-induced repair-deficient Escherichia coli.

Using purified photolyases for pyrimidine (6-4) pyrimidone photoproducts [(6-4)PP] and cyclobutane pyrimidine dimers (CPD), the effects of photoreactivation on mutagenesis were examined in the supF gene on a plasmid transfected into repair-deficient SOS-induced Escherichia coli host cells. More than 95% of CPD and (6-4)PP were removed from plasmid DNA by treatment with CPD photolyase and (6-4)photolyase, respectively. In each photolyase treatment, base substitutions at dipyrimidine sequences were predominantly observed. Of the single base substitutions observed after CPD photoreactivation, 83% were A:T-->G:C transitions at 5'-TT-3' sites. After (6-4)photolyase treatment, 81% were G:C-->A:T transitions at 5'-CC-3' and 5'-TC-3' sequences. Thus, the major mutagenic photoproducts of single-base substitutions were CPD at 5'-CC-3' or 5'-TC-3' sites and (6-4)PP at 5'-TT-3' sites. Tandem double mutations occurred mainly at 5'-CC-3' sites and were CPD-photoreactivated, suggesting that CPD at 5'-CC-3' was responsible for tandem double mutations. After photoreactivation of both CPD and (6-4)PP, single-base substitutions were primarily G:C-->A:T transitions at 5'-CC-3' or 5'-TC-3' sites and A:T-->G:C transitions at 5'-TT-3' sites, and secondarily G:C-->T:A transversions at 5'-CC-3' sites, G:C-->C:G transversions at 5'-CC-3' sites and A:T-->T:A transversions at 5'-TT-3' sites, which were essentially the same as those observed after photoreactivation of CPD alone, (6-4)PP alone and without photoreactivation. Thus, these transversions were not derived from unknown UV adducts but from incompletely repaired CPD and (6-4)PP.

Base Sequence↗
PubMed2004

Spinal canal narrowing during simulated whiplash.

STUDY DESIGN: A biofidelic whole cervical spine model with muscle force replication was used to evaluate spinal canal pinch diameter (CPD) narrowing during simulated whiplash. OBJECTIVES: To quantify CPD narrowing during simulated whiplash and to determine if whiplash resulted in a narrower post-whiplash CPD. SUMMARY OF BACKGROUND DATA: Spinal cord injuries are uncommon in whiplash patients, although such injuries have been reported in those with narrow canals. It has been hypothesized that increased cerebral spinal fluid pressure during whiplash could injure neural tissues. METHODS: The biofidelic model and a bench-top whiplash apparatus were used to simulate whiplash at 3.5, 5, 6.5, and 8 g accelerations of the T1 vertebra. The CPD was measured in the intact specimen in the neutral posture (neutral posture CPD) and under a 1.5 Nm static extension load (pre-whiplash CPD), during simulated whiplash (dynamic whiplash CPD), and again under a 1.5 Nm extension load following each whiplash simulation (post-whiplash CPD). RESULTS: The average dynamic whiplash CPDs were significantly narrower (P < 0.05) than the corresponding pre-whiplash CPDs at accelerations of 3.5 g and above. The narrowest CPD was observed at C5-C6 during the 6.5 g simulation and was 3.5 mm narrower than the neutral posture CPD. In general, the average post-whiplash CPDs were not significantly narrower than the corresponding pre-whiplash CPDs. CONCLUSIONS: Spinal cord injury during whiplash is unlikely in patients with average normal canal diameters. Cord compression following whiplash due to physiologic extension loading is not likely. Previous clinical studies have found that whiplash patients with narrow canals may be at risk of injury, and our results do not disprove it.

Aged↗
PubMed2005

Continuing professional development--global perspectives: synopsis of a workshop held during the International Association of Dental Research meeting in Gothenburg, Sweden, 2003. Part 2: regulatory and accreditation systems and evidence for improving the performance of the dental team.

This paper is the second in a series of two that report on continuing professional development (CPD). Details of the informants and the methodologies used were reported in the first paper. This paper reports the data and information presented on the topics of regulatory and accreditation systems for CPD and evidence that CPD improves the performance of the oral health team. By June 2003, participation in CPD was mandatory in most of the states of the USA, all Canadian Provinces, the UK and Latvia and was likely to become mandatory in a number of other countries in the near future. A variety of accreditation systems were reported including collecting CPD points, which in some countries were weighted depending on the type of CPD activity, and re-certification examinations. Very few studies for the effectiveness of dental CPD were identified. However, in general it was concluded that there is little evidence for the effectiveness of CPD for the oral health team. The main recommendation from this study is that a systematic review of the effectiveness of CPD in improving the performance of the oral health team and patient based outcomes be undertaken. A range of other research questions was also identified including: how can CPD be best matched to clinicians' needs rather than demands?

Accreditation↗
PubMed1996

Induction of cyclobutane pyrimidine dimer photolyase in cultured fish cells by UVA and blue light.

The cyclobutane pyrimidine dimer (CPD) photolyase in fish cells is known to be regulated by environmental factors, such as light, hydrogen peroxide and growth inhibition. The induction of CPD photolyase by light in cultured goldfish cells was dependent on the wavelength of the light, and UVA and blue light had high inductive activity. The spectrum for CPD photolyase activity was different from that for the induction. Treatment with blue or yellow light for a short time, which did not induce any CPD photolyase, induced high CPD photolyase activity in the presence of the photosensitizers, TPPS (monosulfonated meso-tetraphenyl porphine) and ALPS (aluminum phthalocyanine tetrasulfonate), respectively. These results suggest that the induction of CPD photolyase might be triggered by active oxygen produced by light and cellular photosensitizers. We also found that immediately after treatment with UVA, blue light or a photosensitizer in combination with light, cellular attachment to the substratum was enhanced, as was the CPD photolyase activity. Pretreatment with a flavonoid, quercetin, inhibited both photoinduction of CPD photolyase and enhancement of cellular attachment. Vitamin E inhibited only photoinduction of CPD photolyase activity. Treatment with H7, a strong inhibitor for protein kinase C, after light treatment inhibited photoinduction of CPD photolyase activity, but an analogue of H7, Ha1004, which is a weak inhibitor of protein kinase C, did not have such an effect.

Animals↗
PubMed2001

Tritan colour contrast sensitivity function in refractive multifocal intraocular lenses.

AIMS: To compare tritan colour contrast sensitivity (CCS), without and with glare, in patients with refractive multifocal intraocular lenses (IOLs) and with monofocal intraocular lenses. METHODS: Tritan CCS was determined (Moorfields Vision System, CH Electronics) in 15 eyes (14 patients, 75.7 (+/-6.6) years) with a refractive multifocal IOL (Allergan SA 40N) and in 11 eyes (10 patients, 73.7 (+/-6.4) years) with a monofocal IOL (Allergan SI 40 NB). Measurements were made monocularly under mesopic conditions at a distance of 2 metres from the monitor with best distance refraction plus 0.5 D at 0.5, 1, 3, 6, 11.4, and 22.8 cycles per degree (cpd). The test was then repeated for the multifocal IOLs, adding minus 2.5 D to the best distance refraction to force the patient to use the near focus. Both lenses were also investigated under glare conditions with the same set-up and using the brightness acuity tester (BAT). RESULTS: The tritan CCS function without glare in multifocal lenses through the distance focus was nearly identical to that through the near focus. The following statistically significant differences were measured: the CCS function without glare for the multifocal lens was worse at 0.5 cpd and 1.0 cpd than that of the monofocal lens. In CCS testing of the multifocal group with glare at 6 cpd, the results through the distance focus were better than the results through the near focus. For the CCS function with glare, the values for the distance focus in the multifocal lens were worse than the values for the monofocal lens at 0.5 cpd and 1 cpd. In CCS testing with glare through the near focus and CCS testing through the monofocal lens, the monofocal lens performed better at 0.5 cpd, 1 cpd, 3 cpd, and 6 cpd. CONCLUSION: Refractive multifocal intraocular lenses influence tritan CCS function compared to monofocal lenses.

Aged↗
PubMed2001

Protein phosphatase 2A binds to the cytoplasmic tail of carboxypeptidase D and regulates post-trans-Golgi network trafficking.

Carboxypeptidase D (CPD) is a transmembrane protein that processes proteins in the trans-Golgi network (TGN). A 20-residue region within the cytoplasmic tail of CPD binds protein phosphatase 2A (PP2A). PP2A also binds to the cytoplasmic tails of other secretory pathway proteins: peptidylglycine-(amino)-amidating mono-oxygenase, the cation-independent mannose-6-phosphate receptor and TGN38. The CPD tail is phosphorylated on Thr residues in the AtT-20 cell line. The CPD tail can also be phosphorylated by purified protein kinase A, protein kinase C and casein kinase II. Both the in vitro and the in vivo phosphorylated CPD tail can be dephosphorylated by purified PP2A. The binding of CPD tail peptide to PP2A does not influence phosphatase activity. The rate of transport of CPD from the TGN to the cell surface of AtT-20 cells is decreased 45% by okadaic acid, a PP2A inhibitor. Microinjection of the CPD tail into AtT-20 cells inhibits the transition of CPD from endosomal compartments to the TGN. However, okadaic acid does not affect the rate of budding of CPD from the TGN into nascent vesicles or the rate of uptake from the cell surface into endosomal compartments. These results are consistent with the model that PP2A is involved in the trafficking of proteins between a TGN recycling loop and a cell-surface recycling loop, but is not involved in the individual recycling loops.

Amino Acid Sequence↗
PubMed2000

Cdc25 inhibition and cell cycle arrest by a synthetic thioalkyl vitamin K analogue.

A synthetic vitamin K analogue, 2-(2-mercaptoethanol)-3-methyl-1,4-naphthoquinone or compound 5 (Cpd 5), was found previously to be a potent inhibitor of tumor cell growth. We now demonstrate that Cpd 5 arrested cell cycle progression at both G1 and G2-M. Because of the potential arylating activity of Cpd 5, it might inhibit Cdc25 phosphatases, which contain a cysteine in the catalytic site. To test this hypothesis, we examined the inhibitory activity of Cpd 5 against several cell cycle-relevant protein tyrosine phosphatases and found that Cpd 5 was a potent, selective, and partially competitive inhibitor of Cdc25 phosphatases. Furthermore, Cpd 5 caused time-dependent, irreversible enzyme inhibition, consistent with arylation of the catalytic cysteine in Cdc25. Treatment of cells with Cpd 5 blocked dephosphorylation of the Cdc25C substrate, Cdc2, and its kinase activity. Cpd 5 enhanced tyrosine phosphorylation of both potent regulators of G1 transition, ie., Cdk2 and Cdk4, and decreased the phosphorylation of Rb, an endogenous substrate for Cdk4 kinase. Furthermore, close chemical analogues that lacked in vitro Cdc25 inhibitory activity failed to block cell cycle progression and Cdc2 kinase activity. Cpd 5 did not alter the levels of p53 or the endogenous cyclin-dependent kinase inhibitors, p21 and p16. Our results support the hypothesis that the disruption in cell cycle transition caused by Cpd 5 was attributable to intracellular Cdc25 inhibition. This novel thioalkyl K vitamin analogue could be useful for cell cycle control studies and may provide a valuable pharmacophore for the design of future therapeutics.

Cell Cycle↗
PubMedDate not supplied

Patients' descriptions of specific factors leading to modality selection of chronic peritoneal dialysis or hemodialysis.

OBJECTIVES: There has been increasing interest in understanding how patients with chronic renal failure choose between chronic peritoneal dialysis (CPD) and hemodialysis (HD) for renal replacement therapy. The purpose of the present study was to examine the influences and specific factors that patients identify as significant in choosing a specific dialysis modality for treatment of their end-stage renal disease (ESRD). PATIENTS AND DESIGN: 40 patients (20 CPD, 20 HD) who had started dialysis within the preceding 6 months were randomly selected to participate in the study. A structured interview was conducted with the patients, discussing and exploring what factors patients thought were important in helping them decide their treatment modality. The format of the interview was open-ended. Based on patients' comments, a taxonomy of the specific factors that influenced the patients' decisions was developed. SETTING: The study was conducted in a freestanding CPD unit and two freestanding HD units. RESULTS: All 20 CPD patients reported choosing their treatment modality; only 8 of the 20 HD patients reported having a choice of treatment modality. 18 of the 22 patients who participated in predialysis educational programs opted for CPD. 83% of the patients reported that their physician was important in influencing their treatment choice; however, the CPD patients relied more on written material and the opinions of their spouse/significant other or other family members in making their decisions. Issues of autonomy and control were important for 95% of patients choosing CPD. Both CPD and HD patients cited a variety of treatment-specific factors. The three most frequently cited reasons for choosing CPD were (1) flexibility of schedule (19 patients), (2) convenience of performing CPD in their own home (19 patients), and (3) the option of doing dialysis at night while sleeping (8 patients). The 8 HD patients who selected their treatment modality cited the desirability of having a planned schedule (7 patients) and letting nurses or other take care of them (5 patients). CONCLUSIONS: The present study explored factors perceived by patients as being important in determining their choice of renal replacement therapy. A taxonomy of patient influences and concerns has been developed to provide caregivers with a framework to structure their educational strategies and assist patients with progressive renal failure in making an informed choice of therapeutic modality for their ESRD treatment.

Decision Making↗
PubMedDate not supplied

Adiponectin levels and atherosclerotic risk factors in pediatric chronic peritoneal dialysis patients.

BACKGROUND: Atherosclerotic vascular diseases are the major cause of mortality in patients with end-stage renal disease (ESRD) treated with chronic peritoneal dialysis (CPD), even in children. Adiponectin (ADPN) is a recently discovered adipocyte-derived plasma protein having anti-atherogenic properties. ADPN levels are elevated in ESRD but it has been reported that ESRD patients with low plasma ADPN levels have a high risk of cardiovascular death. OBJECTIVE: To clarify the atherosclerotic risk and especially the significance of ADPN levels in pediatric patients on CPD. DESIGN: Cross-sectional studyin the pediatric peritoneal dialysis unit of a university hospital. PATIENTS: 18 children, aged 12.6 +/- 5.6 years, being treated with CPD and 20 healthy age- and sex-matched control subjects were enrolled in this study. METHODS: Serum ADPN levels and other risk factors, including blood pressure, blood glucose, serum lipid/lipoprotein fractions, apolipoprotein B, C-reactive protein (CRP), lipoprotein(a), and homocysteine levels, were studied in CPD patients and compared to the controls. RESULTS: Serum ADPN levels were three times higher in the CPD group compared to the control subjects, as was previously reported. Apolipoprotein B and CRP levels were also high in the CPD group. No significant difference was found in other atherosclerotic parameters, including lipoprotein(a) and homocysteine levels. Interestingly, we found a negative correlation between log ADPN and creatinine levels among the CPD patients (r = -0.54, p < 0.05). There was no correlation between log ADPN and duration of CPD. Creatinine and low-density lipoprotein levels could account for 54% of the total variation in ADPN levels. CONCLUSION: Among pediatric CPD patients, serum levels of the anti-atherogenic protein, ADPN, were inversely associated with creatinine. ADPN level might be a novel marker to predict prognosis in pediatric CPD patients.

Adiponectin↗
PubMed2005

Australian rural midwives: perspectives on Continuing Professional Development.

INTRODUCTION: Continuing Professional Development (CPD) provides an important counter to workforce pressures affecting rural midwives; however, there is a lack of information about how rural midwives understand and perceive CPD and how this is situated in the practising and social context. This research aimed to explore rural midwives' experiences and perceptions of CPD in context. METHODS: A qualitative approach gathered focus group data on the beliefs, opinions and perceptions of a total of 52 rural midwives (nine focus groups), across three Australian states: Western Australia, Victoria and Tasmania. The focus groups were taped and transcribed verbatim and data was analysed thematically using an inductive approach, with the aid of an NVivo (QSR Software, Durham, UK) computer program. RESULTS: Four key themes emerged from the data: midwives' views of CPD; their motivations for undertaking CPD; the choices they make around CPD; and how context factors facilitate their involvement in CPD. Congruence with issues evident in the literature were: the difficulties associated with role diversity, the need for acquiring key skills before engaging in CPD, and the importance of a culture supportive of ongoing learning. CONCLUSIONS: CPD can be considered an important strategy for the retention and professionalism of midwives. The study findings helped fill a gap in the literature about rural and regional Australian midwives' perspectives on CPD.

Attitude of Health Personnel↗
PubMed1991

The utility of a structured evaluation of elderly patients for continuous peritoneal dialysis.

The elderly comprise an increasing proportion of chronic dialysis patients. Recruiting them for continuous peritoneal dialysis (CPD) would help CPD programs maintain a patient population. We retrospectively studied the ability of a prospective evaluation to predict success with CPD in elderly (age greater than 60 years) patients. PD nurses and a renal social worker assigned scores in 10 categories, which were then averaged to obtain an over-all evaluation score. Scores were from 1-5 with 1 = good, 5 = poor, and 3 = average. Thirty-four elderly patients began CPD during the study period. Evaluation scores were available for 28 of these patients before they began dialysis. Evaluation scores less than 3 predicted success with CPD (2.2 +/- 0.2 versus 3.2 +/- 0.4 in patients transferring to hemodialysis, p less than 0.02). Patient motivation and preference were the categories that predicted success with CPD. Elderly patients were more likely than younger patients (those less than 60 years of age) to decline CPD for social reasons (46% versus 4% respectively, p less than 0.001). Elderly patients required more CPD training time than young patients (4.9 +/- 0.7 days versus 3.3 +/- 0.8 days respectively, p less than 0.01). We conclude that a prospective assessment of elderly patients can predict success with CPD and provide information important to individual structuring of CPD training and follow-up.

Age Factors↗
PubMed1996

Nutritional status in children receiving chronic peritoneal dialysis.

Chronic peritoneal dialysis (CPD), widely used in uremic children, may have contrasting effects on the nutritional status of patients. Metabolic and nutritional abnormalities due to the combined effects of uremia per se, glucose absorption from the dialysate and catabolic factors, such as protein and amino acid losses into dialysate, poor appetite, and recurrent episodes of peritonitis are the most important. Although CPD allows for fewer dietary restrictions and supplies an extra amount of calories by glucose absorbed with the peritoneal fluid, when protein and energy intakes are assessed the protein intake was almost sufficient or more than that prescribed, whereas the energy intake was low. In CPD children the standard deviation score for weight, height, triceps skinfold thickness, and midarm circumference has been reported as more severely impaired in children less than ten years old. Anthropometric parameters did not worsen during CPD treatment. Plasma proteins and albumin are reported as being low in CPD children. The dietary intake and protein losses have been considered to be the most important determinants of the albumin level in CPD patients. The reported average dialysate losses of free amino acids (AA) during CPD in children vary from 0.02 to 0.03 g/kg/day in different studies. The patterns of plasma AA in CPD is represented by reduced levels of branched chain AA and of other essential amino acids and increased concentrations of some nonessential AA. Several factors may influence plasma AA profile: uremia per se, hormonal alterations, protein and AA losses, and dietary intake. A more specific uremic AA pattern is found in muscle, the largest pool of free AA in the body. Studies on muscle AA in adults on CPD are conflicting: some authors have reported several muscle AA alterations, but others have shown an almost normal pattern. Low valine and leucine muscle levels have been reported in children on CPD.

Adolescent↗
PubMed2002

K vitamins, PTP antagonism, and cell growth arrest.

The main function of K vitamins is to act as co-factors for gamma-glutamyl carboxylase. However, they have also recently been shown to inhibit cell growth. We have chemically synthesized a series of K vitamin analogs with various side chains at the 2 or 3 position of the core naphthoquinone structure. The analogs with short thio-ethanol side chains are found to be more potent growth inhibitors in vitro of various tumor cell lines. Cpd 5 or [2-(2-mercaptoethanol)-3-methyl-1,4-naphthoquinone] is one of the most potent. The anti-proliferation activity of these compounds is antagonized by exogenous thiols but not by non-thiol antioxidants. This suggests that the growth inhibition is mediated by sulfhydryl arylation of cellular glutathione and cysteine-containing proteins and not by oxidative stress. The protein tyrosine phosphatases (PTP) are an important group of proteins that contain cysteine at their catalytic site. PTPs regulate mitogenic signal transduction and cell cycle progression. PTP inhibition by Cpd 5 results in prolonged tyrosine phosphorylation and activation of several kinases and transcription factors including EGFR, ERK1/2, and Elk1. Cpd 5 could activate ERK1/2 either by signaling from an activated EGFR, which is upstream in the signaling cascade, or by direct inhibition of ERK1/2 phosphatase(s). Prolonged ERK1/2 phosphorylation strongly correlates with Cpd 5-mediated growth inhibition. Cpd 5 can also bind to and inhibit the Cdc25 family of dual specific phosphatases. As a result, several Cdc25 substrates (Cdk1, Cdk2, Cdk4) involved in cell cycle progression are tyrosine phosphorylated and thereby inhibited by its action. Cpd 5 could also inhibit both normal liver regeneration and hepatoma growth in vivo. DNA synthesis during rat liver regeneration following partial hepatectomy, transplantable rat hepatoma cell growth, and glutathione-S-transferase-pi expressing hepatocytes after administration of the chemical carcinogen diethylnitrosamine, are all inhibited by Cpd 5 administration. The growth inhibitory effect during liver regeneration and transplantable tumor growth is also correlated with ERK1/2 phosphorylation induced by Cpd 5. Thus, Cpd 5-mediated inhibition of PTPs, such as Cdc25 leads to cell growth arrest due to altered activity of key cellular kinases involved in signal transduction and cell cycle progression. This prototype K vitamin analog represents a novel class of growth inhibitor based upon its action as a selective PTP antagonist. It is clearly associated with prolonged ERK1/2 phosphorylation, which is in contrast with the transient ERK1/2 phosphorylation induced by growth stimulatory mitogens.

Animals↗