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Emergency medicine residency director perceptions of the resident selection process

OBJECTIVE: To assess perceptions of emergency medicine (EM) program directors (PDs) of the resident selection process. METHODS: PDs of 120 EM residencies were mailed a 22 question survey immediately following the 1999 match. (Applicants interviewing in more than one specialty and post-interview communications were areas of interest). Non-respondents received a second mailing. RESULTS: Ninety-eight (81. 7%) completed surveys were returned. Five PDs felt that interviewing in more than one specialty was ethically wrong, while most felt multi-specialty interviews were a system byproduct (42%) or that there was nothing wrong (41%). Eighty-one percent of PDs felt the applicant's rank order would be negatively affected if the applicant disclosed interviewing in >1 specialty. Forty-seven percent of PDs (always or frequently) told applicants to keep in touch if interested in the program. However, 88% of PDs were skeptical or did not believe an applicant's communicated intent to rank the program 'high,' nor did this communication influence an applicant's rank order (75%). Forty-two percent of PDs reported informal commitments by applicants. PDs frequently felt lied to by applicants (always (4%), frequently (42%), sometimes (42%)). Applicants often ask how the program intends to rank them. Highly ranked applicants receive positive responses from 61% of PDs vs. 33% of PDs who give negative responses to low ranked applicants. Ten percent of PDs offer residency positions outside of the match. CONCLUSIONS: Applicants who interview in >1 specialty are viewed negatively by PDs. Post-interview communications by applicants are viewed with skepticism. Gamesmanship is practiced commonly during the resident selection process.

Journal Article↗

Advantages of pyruvate over lactate in peritoneal dialysis solutions.

This review discusses effects of both lactate and pyruvate, and high glucose in peritoneal dialysis solutions (PDS) on leukocytes, mainly on intracellular pH ([pH](i)), glucose metabolic pathways, and apoptosis. Lactate-based PDS (L-PDS) are bioincompatible primarily due to the low pH, high lactate, and glucose excess in both individual and combination. High lactate in an acidi milieu would induce severe intracellular acidosis of leukocytes, and high glucose may disturb glucose metabolic pathways and activate protein kinase C (PKC) and nuclear factor-kappa B (NF-kappaB) of the cells, leading to apoptosis. Pyruvate-based PDS (P-PDS) are novel experimental PDS. Evidence shows that P-PDS are superior in biocompatibility. Pyruvate protection of cells has been confirmed in many fields besides the PDS area. Although the underlying mechanism whereby P-PDS preserve cell function is not fully understood, it may be associated with the maintenance of [pH](i) close to physiological, due to its low buffering capacity, improvement of cellular glucose metabolic pathways and redox state, and sustainment of intracellular calcium ([Ca2+]i) homeostasis in high glucose concentrations. It may also inhibit PKC and NF-kappaB activation in high glucose. In addition, pyruvate is a strong antioxidant, a scavenger of hydrogen peroxide (H2O2). However, exogenous pyruvate in PDS could not be an energy source for cells and also the Crabtree effect might not occur in neutrophils. Pyruvate is a hopeful candidate of buffers in PDS in the near future. Further observation of P-PDS is strongly needed with peritoneal cells to verify the cell protection both in vitro and in vivo before clinic trials.

Apoptosis↗

Postpartum anoestrus is reduced by increasing the within-day milking to suckling interval in dual purpose cows.

In the dual purpose milk/beef production system practised in Mexico, the cows are milked once a day in the presence of the calf and then the calf suckles for the next 1-8 h. It was hypothesised that the imposition of milking and suckling in close succession contributes to the long postpartum anoestrous periods experienced by cows in this system. Therefore, separating these two inhibiting factors, by delaying the start of suckling after milking would lower the impact on the hypothalamus-hypophysial axis and allow it to recover more readily. This hypothesis was tested in two experiments using Bostaurus x Bosindicus cows which weighed 541.3 +/- 12.7 kg (mean +/- S.E.M.; experiment 1) and 537.8 +/- 10.6 kg (experiment 2) and had a body condition score of 5-6 (scale 1-9) at calving. The cows and calves were maintained on separate pastures and the cows were offered concentrate supplements. Experiment 1 was conducted in the dry season and cows were offered a daily supplement of 3 kg of 17% crude protein (CP) concentrates plus 1 kg molasses per cow. Experiment 2 was conducted during the wet season and the nutritional supplement consisted of only 1 kg of 17% CP plus 1 kg molasses per cow per day. Each experiment lasted for the first 100 days postpartum and the cows were not mated during this time. Cows were hand-milked once a day in the presence of the calf to stimulate milk let-down. In experiment 1, 30 multiparous cows were assigned at random by date of calving, to one of three treatments: controlled suckling (CS; n = 10), delayed suckling (DS; n = 10) and prolonged delayed suckling (PDS; n = 10). The suckling period on all treatments lasted for 2 h and started at 0 h (CS), 4 h (DS) or 8 h (PDS) after milking. In experiment, 34 multiparous cows were assigned at random to three treatments: CS (n = 11), PDS (n = 11) or prolonged delayed short suckling (PDSS; n = 12), in this last treatment the suckling period was reduced to only 30 min. In both experiments, one quarter of the udder of cows on treatment CS was not milked but all the udder was milked on the other treatments. Body weights of cows and calves and cow milk yields were recorded. Weekly blood samples were collected for plasma progesterone assay to detect the first postpartum corpus luteum. Data were analysed by ANOVA and chi-square test. Cows in experiment 1 had similar weight changes during the first 100 days postpartum. Milk production was higher for DS (8.0 +/- 0.7 kg per day) and PDS (7.0 +/- 0.5 kg per day) cows than for CS (5.2 +/- 0.7 kg per day) cows (P < 0.01). Calf daily gain was greater (P < 0.05) for PDS (827 +/- 35 g per day), than CS (702 +/- 26 g per day) or DS (715 +/- 29 g per day). The proportion of cows ovulating during the first 100 days postpartum were 50.0, 70.0 and 100.0%, for CS, DS and PDS, respectively (P < 0.05). The intervals from calving to first significant rise in progesterone were 70.4 +/- 1.6, 72.1 +/- 1.3 and 64.6 +/- 1.5 days for CS, DS and PDS (P > 0.05), respectively. In experiment 2, cow body weight during the first 100 days postpartum did not differ between treatments. Milk production was not significantly different between CS (7.3 +/- 1.0 kg per day) and PDSS (6.8 +/- 1.0 kg per day), but was higher (P < 0.05) for CS than PDS (5.2 +/- 1.0 kg per day). Calf daily gain was lower for CS (576 +/- 31 g per day; P < 0.05) than PDS (779 +/- 38 g per day) and PDSS (780 +/- 20 g per day). The proportion of cows ovulating was higher (P < 0.05) for treatments PDS (100%) and CS (81.8%) than PDSS (50%). Calving to first ovulation interval was shorter (P < 0.05) for PDS (57.3 +/- 4.5 days) and PDSS (49.7 +/- 3.0 days) cows than CS (72.1 +/- 3.5 days) cows. It is concluded that delaying suckling for 8 h after milking, increases the proportion of cows ovulating within 100 days of calving, shortened the calving to first ovulation interval and improved calf performance without adversely affecting cow milk yield or body weight change.

Anestrus↗

Heritage characteristics reported by a group of African-Americans who exhibit the pigment dispersion syndrome: a case-control study.

PURPOSE: To investigate the racial heritage of a group of African-Americans who exhibit the pigment dispersion syndrome (PDS). SUBJECTS AND METHODS: Ten unrelated African-American PDS patients (age range 13-59) from a primary eye care population in Chicago, Illinois, USA, were interviewed to determine their racial heritage. Since Caucasian and Native American heritage were commonly reported, 101 unaffected African-American control subjects (age range 18-55) were also interviewed to determine the reported frequency of these specific racial heritage characteristics. RESULTS: Some degree of Caucasian heritage was reported by 100% of the PDS subjects and by 46.5% of controls. Native American heritage was reported by 90% of the PDS subjects and by 71.3% of controls. Based on these data, the PDS subjects were significantly more likely to report Caucasian heritage (Fisher's exact test, P=0.001) but they were not significantly more likely to report Native American heritage (P=0.282). In addition, the PDS subjects were significantly more likely to report Caucasian heritage from both parents (P=0.024) and more likely to report a combination of both Caucasian and Native American heritage (P=0.0006) than corresponding controls. In general, the PDS subjects had 'light' or 'medium' complexions. CONCLUSION: Results from this analysis are consistent with the hypothesis that non-African heritage, particularly Caucasian, is likely to be prevalent in the background of African-Americans who exhibit PDS. It is suggested that non-African heritage may not only be important for the transference of PDS causing genes, but it may also influence factors such as degree of iris pigmentation and rigidity which could influence iris contour and the subsequent expression of PDS in those who are genetically predisposed. Further investigation is needed to study the factors that influence the expression and severity of PDS among African-Americans, a population which traditionally has been considered to be rarely affected by this condition.

Adolescent↗

Evaluation of the personal dental services (wave 1) for Lambeth, Southwark and Lewisham primary care trusts--Part 1: Retrospective analyses of registration data and access issues.

AIM/OBJECTIVE: The purpose of the study was to undertake analyses of registration data for the personal dental services (PDS) of Lambeth, Southwark and Lewisham primary care trusts and relate the analyses to the PDS goal of increasing uptake of dental services. METHOD: Secondary analyses of registration statistics provided by the Dental Practice Board were undertaken for both 1 years pre-PDS (October 1997 to September 1998) and post-PDS (October 1998 to March 2003) periods. Three sets of analyses were undertaken to consider different aspects of changing registrations: (1) Absolute numbers of patients registered at each time interval; (2) Rates of change in numbers of patients registered for the entire period after the introduction of PDS; and (3) Rates of change in numbers of patients registered for the most recent 3 years of available data. RESULTS: There was a significant increase in the numbers of children registered under capitation, post-PDS as compared to the pre-PDS level (all ages and both genders combined). Post-PDS, the rate of increase for the children was approximately one additional child per practice per month (0.96, 95% CI 0.41-1.52). Similarly there was a significant trend for increasing adults registrations over time of about two and a half adults per practice per month (2.42, 95% CI 0.90-3.95). There was no evidence of a change in registrations for children or adults in total over the most recent period of 3 years. CONCLUSIONS: The analysis of the absolute numbers of registered patients each month indicated that the PDS practices had more children registered than before the implementation of the PDS scheme, but not adults. Overall post-implementation there was a trend for increasing registrations in both children and adults, but the most recent data indicated a plateau effect. Further consideration of facilitators to achieve PDS goals of improved uptake of services is required, particularly as they relate to local contexts.

Adolescent↗

Protein synthesis inhibitors and the chemical chaperone TMAO reverse endoplasmic reticulum perturbation induced by overexpression of the iodide transporter pendrin.

An outcome of overloading of the endoplasmic reticulum (ER) folding machinery is a perturbation in ER function and the formation of intracellular aggregates. The latter is a key pathogenic factor in numerous diseases known as ER storage diseases. Here, we report that heterologous overexpression of the green fluorescent protein-tagged iodide transporter pendrin (GFP-PDS) perturbs folding and degradation processes in the ER. Pendrin (PDS) is a chloride-iodide transporter found in thyroid cells. Mutations in PDS can cause its retention in the ER and are associated with Pendred syndrome. Biochemical and live-cell analyses demonstrated that wild-type GFP-PDS is predominantly retained in perinuclear aggregates and in ER membranes, causing their collapse and vesiculation. Inhibition of protein synthesis by cycloheximide (CHX) or puromycin caused dissociation of the GFP-PDS aggregates and returned the ER to its normal reticular morphology. Blocking protein synthesis promoted folding and export of ER-retained GFP-PDS, as demonstrated by surface-biotinylation analysis and by CHX- or puromycin-induced accumulation of YFP-PDS in the Golgi apparatus during a 20 degrees C temperature-block experiment. The chemical chaperone trimethylamine-N-oxide (TMAO) also reversed the GFP-PDS-mediated ER collapse and vesiculation, suggesting that exposed hydrophobic stretches of misfolded or aggregated GFP-PDS may contribute to ER retention. These data suggest that GFP-PDS is a slow-folding protein with a propensity to form aggregates when overexpressed. Thus, we describe a system for the reversible induction of ER stress that is based entirely on the heterologous overexpression of GFP-PDS.

Animals↗

Pyruvate-based peritoneal dialysate preserves neutrophilic oxygen consumption.

AIM: To investigate effects of pyruvate- or lactate-based peritoneal dialysis solutions (P-PDS or L-PDS) on neutrophilic oxygen consumption and the role of the extracellular pH (pHe) in cells' oxygen uptake. METHODS: Human neutrophils were incubated in P-PDS or L-PDS containing pyruvate or lactate 35-38 mmol.L-1 at various pHe, respectively. Oxygen consumption rates by opsonized zymosan (OZ)-stimulated cells were measured polarographically, using a Clark-type oxygen electrode. RESULTS: L-PDS at an initial pH 5.2 dramatically inhibited the rate of oxygen consumption (2.2 nmol.min-1/10(6) cells) by neutrophils, while the equally acidic P-PDS markedly improved the rate (6.4 nmol.min-1/10(6) cells) (P < 0.01). However, P-PDS at pHe 5.2 severely impaired the rate by cells, the same as pHe 5.2 L-PDS. CONCLUSION: P-PDS preserved an oxygen consumption rate by OZ-stimulated human neutrophils, but in an acidi milieu it comparably deteriorated the ability of cells to consume oxygen, indicating that the pHe of PDS plays an essential role in cellular oxidative metabolism. The superior biocompatibility of an acidic P-PDS was associated with its lower buffering capacity.

Dialysis Solutions↗

Peritoneal dialysis solutions disturb the balance of apoptosis and proliferation of peritoneal cells in chronic dialysis model.

The present study investigated variation in apoptosis and proliferation, and the balance between apoptosis and proliferation, for peritoneal mesothelial cells (MCs) after exposure to peritoneal dialysis solution (PDS) in vivo. We implanted 32 male Sprague-Dawley rats (4 groups; n = 8 in each group) with catheters and intraperitoneally infused the animals with 20 mL Dianeal 1.36%, 2.27%, or 3.86% (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.) PDS twice daily for eight consecutive weeks, using saline as a control. At the end of the eighth week, samples of peritoneal membrane were fixed and sliced. Expression of apoptosis was checked with TUNEL kits (Boehringer Mannheim, Mannheim, Germany), and expression of proliferative cell nuclear antigen (PCNA) was checked by immunohistochemistry [streptoavidin-biotin-peroxidase complex (SABC) method]. The ratio of MC apoptosis to proliferation was measured from the same slices using the dual-stain combination of TUNEL and SABC. Cells positive for apoptosis and PCNA were counted for all samples by light microscopy in 50 consecutive grids (10 x by 40). Peritoneal dialysis solution was found to significantly induce MC apoptosis as compared with control at the end of the eighth week. The degree of apoptosis was proportional to the concentration of glucose in the PDS. The 1.36% PDS, but not the 2.27% or 3.86%, significantly stimulated the expression of PCNA. The degree of PCNA expression was negatively related to the glucose concentration of the PDS. The MC apoptosis: PCNA ratio was significantly higher for 3.86% and 2.27% PDS than for the control, but no significant difference was seen between 1.36% PDS and control. We conclude that glucose-based PDS may induce apoptosis and disturb the balance of MC apoptosis and proliferation, and that 1.36% PDS damages the balance less than does 2.27% or 3.86% PDS. These effects may be partly due to pH, calcium, hyperosmolality, and glucose degradation products (GDPs). Loss of balance between MC proliferation and apoptosis--induced by unphysiologic PDS--may be one of the major causes of peritoneal membrane failure during long-term continuous ambulatory peritoneal dialysis.

Animals↗

Correlation of power Doppler sonography with vascularity of the synovial tissue of the knee joint in patients with osteoarthritis and rheumatoid arthritis.

OBJECTIVE: To examine the significance of power Doppler sonography (PDS) in the diagnosis of synovial hypertrophy of the knee joint by verifying and comparing the PDS findings with histopathologic findings of synovial membrane vascularity. METHODS: The knee joints of 23 patients who were undergoing arthroplasty of the knee joint because of osteoarthritis or rheumatoid arthritis were examined with ultrasound before arthroplasty. The vascularity of the synovial membrane was classified semiquantitatively using PDS. A sample of synovial tissue was obtained during the arthroplasty, and the vascularity of the synovial tissue was evaluated by immunohistochemistry (factor VIII) and was graded qualitatively by a pathologist who was unaware of the PDS findings. The visual qualitative grading by the examiner was controlled by analyzing PDS images and histologic samples using a digital image evaluation system. RESULTS: The correlation between the qualitative PDS results and the qualitative grading of the vascularity by the pathologist was 0.89 by Spearman's rho (P < 0.01). The Pearson correlation coefficient between the digital analysis of the PDS images and the digital analysis of the tissue sections was 0.81 (P < 0.01). Digital image analysis and qualitative grading by the examiner had a correlation of 0.89 by Spearman's p (P < 0.01) for the PDS images. The correlation between the qualitative estimation of vascularity by the pathologist and the digital image analysis was 0.88 by Spearman's rho (P < 0.01). CONCLUSION: In the present study, PDS proved to be a reliable diagnostic method for qualitative grading of the vascularity of the synovial tissue. In clinical practice, PDS allows further differentiation of the hypertrophic synovium.

Adult↗

[Family history of glaucoma and risk factors in pigmentary glaucoma. A new clinical study].

BACKGROUND: Whether a family history of glaucoma (FHG) in patients with pigmentary glaucoma (PG) is a prognostical indicator, is unknown. Therefore the aim of this study was to evaluate the influence of FHG on the severity of the disease in PG and pigment dispersion syndrome (PDS). Furthermore risk factors in PG and PDS were evaluated. METHODS: The findings of 207 patients with PG and PDS, who were able to give information about FHG, were evaluated (149 PG, 43 PDS with ocular hypertension (OH), 15 PDS without OH). RESULTS: Significance of FHG: FHG was found in 39.1%, and in one third of the patients more than one relative had the disease. FHG was found in PG not more frequent than in PDS. Pigmentary glaucomas in advanced stages of the disease did not have a higher incidence of FHG than patients in beginning stages. Out of 207 patients with PG and PDS 71% were male and 29% female (p < 0.001). In patients with FHG the share of men was 64.2% and not significantly different to the group without FHG with 75.4%. The sex distribution in parents and grandparents having a glaucomatous disease was 1:1. RISK FACTORS: The pf1p4nts with and without FHG in PDS with and without OH, PG, and within the different stages of visual field loss, showed no significant differences in risk factors, for example in maximum intraocular pressure, refraction and cup-disc ratio. Myopia: Patients with PG had a significantly higher myopia than patients with PDS (p < 0.01). The higher the myopia, the earlier the disease was diagnosed (p = 0.008). Krukenberg spindle: During miotic therapy the Krukenberg spindle decreased in the upper half of the cornea. Time of diagnosis: PG was diagnosed at a higher age compared to PDS. CONCLUSION: FHG does not influence the severity of the disease in PG. Family history of glaucoma is a risk factor in patients with PG, but no prognostical indicator. Patients with FHG do not have primarily larger cup-disc ratios than patients without FHG. Myopia is a risk factor.

Adolescent↗

Impact of postdischarge surveillance on surgical site infection rates for several surgical procedures: results from the nosocomial surveillance network in The Netherlands.

OBJECTIVE: To compare the number of surgical site infections (SSIs) registered after hospital discharge with respect to various surgical procedures and to identify the procedures for which postdischarge surveillance (PDS) is most important. DESIGN: Prospective SSI surveillance with voluntary PDS. Recommended methods for PDS in the Dutch national nosocomial surveillance network are addition of a special registration card to the outpatient medical record, on which the surgeon notes clinical symptoms and whether a patient developed an SSI according to the definitions; an alternative method is examination of the outpatient medical record. SETTING: Hospitals participating in the Dutch national nosocomial surveillance network between 1996 and 2004. RESULTS: We collected data on 131,798 surgical procedures performed in 64 of the 98 Dutch hospitals. PDS was performed according to one of the recommended methods for 31,134 operations (24%) and according to another active method for 32,589 operations (25%), and passive PDS was performed for 68,075 operations (52%). Relatively more SSIs were recorded after discharge for cases in which PDS was performed according to a recommended method (43%), compared with cases in which another active PDS method was used (30%) and cases in which passive PDS was used (25%). The highest rate of SSI after discharge was found for appendectomy (79% of operations), followed by knee prosthesis surgery (64%), mastectomy (61%), femoropopliteal or femorotibial bypass (53%), and abdominal hysterectomy (53%). CONCLUSIONS: For certain surgical procedures, most SSIs develop after discharge. SSI rates will be underestimated if no PDS is performed. We believe we have found a feasible and sensitive method for PDS that, if patients routinely return to the hospital for a postdischarge follow-up visit, might be suitable for use internationally.

Community Networks↗

Prodos is a conserved transcriptional regulator that interacts with dTAF(II)16 in Drosophila melanogaster.

The transcription factor TFIID is a multiprotein complex that includes the TATA box binding protein (TBP) and a number of associated factors, TAF(II). Prodos (PDS) is a conserved protein that exhibits a histone fold domain (HFD). In yeast two-hybrid tests using PDS as bait, we cloned the Drosophila TAF(II), dTAF(II)16, as a specific PDS target. dTAF(II)16 is closely related to human TAF(II)30 and to another recently discovered Drosophila TAF, dTAF(II)24. PDS and dTAF(II)24 do not interact, however, thus establishing a functional difference between these dTAFs. The PDS-dTAF(II)16 interaction is mediated by the HFD motif in PDS and the N terminus in dTAF(II)16, as indicated by yeast two-hybrid assays with protein fragments. Luciferase-reported transcription tests in transfected cells show that PDS or an HFD-containing fragment activates transcription only with the help of dTAF(II)16 and TBP. Consistent with this, the eye phenotype of flies expressing a sev-Ras1 construct is modulated by PDS and dTAF(II)16 in a gene dosage-dependent manner. Finally, we show that PDS function is required for cell viability in somatic mosaics. These findings indicate that PDS is a novel transcriptional coactivator that associates with a member of the general transcription factor TFIID.

Amino Acid Sequence↗

Restoration of advanced spermatogenic cells in the experimentally regressed rat testis: quantitative relationship to testosterone concentration within the testis.

We examined the effect of exogenously administered testosterone (T) on the quantitative restoration of advanced spermatogenic cells in adult rat testes rendered azoospermic by treating rats with polydimethylsiloxane (PDS) implants of T and estradiol (E). Experimental rats received PDS-TE implants for an initial 8-week period; control rats received empty implants. By 8 weeks of PDS-TE treatment, rats became severely oligospermic, and the T concentration within the seminiferous tubule fluid (STF) was reduced approximately 80% (from 57.8 ng/ml in controls to 9.6 ng/ml). After the initial 8-week PDS-TE treatment, PDS-TE implants were removed from one group of rats; a second group of PDS-TE-implanted rats received an additional PDS-T implant of 24 cm. Eight weeks after the removal of PDS-TE implants or the implantation of additional T, testis weight and numbers of advanced spermatogenic cells were restored to those of control rats. The STF T concentration 8 weeks after the removal of PDS-TE implants also was restored to that in control rats. In contrast, the STF T concentration increased to only 40% of control values in the rats that received an additional T implant. Despite this 60% reduction in T concentration compared to the control value, advanced spermatogenic cell number was restored to a value indistinguishable from that of intact controls. These observations indicate that spermatogenesis can be quantitatively restored in PDS-TE-implanted rats with exogenously administered T, and moreover, that this restoration does not require the high T concentration found in the STF of intact control rats.

Animals↗

Risk factors for development of pre-diabetic state from normal glucose regulation.

As a strategy to prevent the progression of diabetes mellitus, it is important to screen out the subjects who will develop a pre-diabetic state (PDS) in the future. To find out the potential risk factors for PDS, we employed the values of fasting plasma glucose and hemoglobin A1c (HbA1c), which are routinely measured in our health checkup. We selected 3,879 individuals who had normal glucose regulation at both fasting plasma glucose < 6.1 mmol/l and HbA1c < 5.5% in 1997 and investigated whether they would develop PDS in the next 5 years. PDS is defined at fasting plasma glucose >or= 6.1 mmol/l and HbA1c >or= 5.5%. Among 3,879 individuals, 21 developed PDS and 2,128 maintained normal glucose regulation in 2001. The remaining 1,730 subjects fit one of the two criteria for PDS. The parameters measured in 1997, including fasting plasma glucose, HbA1c, triglyceride, alanine aminotransferase, gamma-glutamyltranspeptidas, cholinesterase, uric acid, red blood cells, hemoglobin, percent body fat and diastolic blood pressure, were significantly higher in the individuals who developed PDS than in those who maintained normal glucose regulation. On the other hand, hematocrit was significantly lower in PDS than in normal glucose regulation. Logistic regression analysis identified alanine aminotransferase >or= 40 U/l, triglyceride >or= 1.69 mmol/l, low-density lipoprotein cholesterol >or= 3.62 mmol/l and hematocrit < 38% as valuable factors for predicting the development of PDS. The present study demonstrates that the subjects with high risks for PDS could be identified from several clinical parameters and that they should be encouraged to improve their living habits not to develop diabetes mellitus.

Alanine Transaminase↗

[Effect of ligustrazine peritoneal dialysate on CD40 expression of rat peritoneal mesothellial cells].

OBJECTIVE: To explore the effect of Ligustrazine (LGZ) affecting the expression of CD40 on mesothelial cells (MC). METHODS: Rat's peritoneal MC isolated from peritoneal cavity were cultured and maintained under the defined conditions in vitro. They were cultured with 4.25% peritoneal dialysis solution (PDS), 4.25% PDS added LGZ (40 mg/L), 4.25% PDS added IFN-gamma (100 u/ml) and 4.25% PDS added IFN-gamma and LGZ for 30 min, the DMEM/F12 cultural medium was taken as control. The expression of CD40 on MC was detected by reverse transcript polymerase chain reaction (RT-PCR) and flow cytometry analysis. RESULTS: MC cultured in vitro expressed CD40 markedly, the expression of CD40 mRNA and its protein was markedly up-regulated following stimulation with 4.25% PDS or IFN-gamma and 4.25% PDS. LGZ (40 mg/L) could reduce the expression of CD40 mRNA and its protein significantly as it was added in 4.25% PDS and 4.25% PDS with IFN-gamma. CONCLUSION: The PDS stimulates the expression of CD40 on MC. LGZ has the function of down-regulating the expression of CD40 on MC. During long-term continuous ambulatory peritoneal dialysis, it might be helpful to alleviate chronic inflammatory reaction by adding LGZ into standard PDS, therefore prevent or retard the occurence and development of peritoneal fibrosis.

Animals↗

Peritoneal dialysis solutions contract arteries through endothelium-independent prostanoid pathways.

Conventional peritoneal dialysis solution (PDS) relaxes visceral and parietal peritoneal arterioles (microvessels) by unclear mechanisms. The present study was originally designed to investigate the mechanisms of PDS-mediated vascular reactivity. Surprisingly, our preliminary data indicated that PDS induces contraction in large vessels such as the aorta. That result contrasts with the relaxation observed in the microvasculature. We therefore extended the study to (1) determine the effect of PDS on the superior mesenteric artery (SMA), (2) confirm the PDS-induced contraction in the aorta, and (3) determine if a prostanoid and nitric oxide are involved in the observed PDS-induced vessel response. Rat SMA rings with intact endothelium and aortic rings with and without endothelium were prepared and placed in baths filled with a non vasoactive physiologic salt solution (PSS), or with PSS plus mefenamic acid (MFA, a cyclo-oxygenase inhibitor), or PSS plus NG-monomethyl-L-arginine (L-NMMA, an inhibitor of nitric oxide synthase) under a force transducer. We recorded changes in tension throughout the protocols. After equilibration, the baths were filled with a conventional glucose-based PDS (Delflex 2.5%: Fresenius Medical Care, Bad Homburg, Germany) with and without MFA or L-NMMA for 30 minutes. The rings were then washed, contracted with phenylephrine, and relaxed with acetylcholine to verify the presence or absence of endothelium. In both SMA and aorta, PDS induced contraction. That contraction was suppressed by MFA [SMA: 0.57 g vs. 0.13 g (+/- 0.035 g); aorta: 0.88 g vs. 0.27 g (+/- 0.035 g); p < 0.05 by analysis of variance (ANOVA)]. Aortic contraction induced by PDS was not altered by L-NMMA. Conventional PDS induces contraction in large vessels, in contrast to its action of relaxation in microvessels. Vascular reactivity in large vessels involves the production of a constrictor prostanoid in the vascular smooth muscle. Peritoneal dialysis solutions do not induce NO in aortic endothelium. Peritoneal dialysis solution-induced, prostanoid-mediated contraction of smooth muscle may contribute to a worsening of hypertension and the premature uterine contractions observed in the rare cohort of pregnant uremic patients on peritoneal dialysis.

Animals↗

Peritoneal dialysis solution pH and Ca2+ concentration regulate peritoneal macrophage and mesothelial cell activation.

We evaluated the in vitro effects of pH and Ca2+ concentration of peritoneal dialysis solution (PDS) on (1) the release of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8) from peritoneal macrophages (PM0) and peritoneal mesothelial cells (PMC); (2) the release of IL-6 and IL-8 by PMC; and (3) the PM0 and PMC intracellular Ca2+ concentration. Aliquots of 5 x 10(6) PM0 and PMC were incubated (2 hr, 37 degrees C) in 1 ml of physiologic growth medium (RPMI 1640) and in 1 ml of four different PDS (1.36 g/dl glucose): (1) type A PDS (pH 5.5, Ca2+ 1.75 mM), (2) type B PDS (pH 5.5, Ca2+ 1.25 mM), (3) type C PDS (bicarbonate buffered pH 7.4, Ca2+ 1.75 mmol/L, and (4) type D PDS (bicarbonate buffered pH 7.4, Ca2+ 1.25 mM); each was stimulated with S. epidermidis. Results showed that type A PDS samples induced an average 60% increase in PM0 and PMC cytoplasmic levels and in cytokine release, whereas with type B PDS samples there was a 90% decrease. Type C PDS samples did not modify the PM0 and PMC IL-6 and IL-8 production, whereas a 3-fold rise in the production of IL-1 and TNF-alpha by PM0 was seen; this was associated with an increase in PM0 and PMC Ca2+ cytoplasmic levels. When type D PDS samples were incubated, however, there was an average 40% decrease in PM0 and PMC cytoplasmic Ca2+ levels and in cytokine release.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗

Block of spontaneous termination of paroxysmal depolarizations by forskolin (buccal ganglia, Helix pomatia).

Effects of cAMP-activated protein kinases (PKA) on epileptic activity are at present studied in a model nervous system. Identified neurons in the buccal ganglia of the snail Helix pomatia were recorded with intracellular microelectrodes in a continuously perfused experimental chamber. Epileptiform activity appeared regularly in neuron B3 when the saline contained pentylenetetrazol (20-40 mM). Epileptiform activity consisted of a series of paroxysmal depolarization shifts (PDS). Epileptiform activity was quantified by calculating the percentage of PDS-duration of PDS-periods. High percentage of PDS-duration was regularly found 15-30 min after the start of treatment with pentylenetetrazol. Subsequently, percentage of PDS decreased spontaneously. Adding forskolin (50 microM) to the pentylenetetrazol-containing solution increased percentage of PDS-duration. The increase during forskolin corresponded to the amount of decrease which had taken place spontaneously before. During application of forskolin for up to 4 h, spontaneous PDS decrease was absent, i.e., epileptiform activity corresponded to status epilepticus. Forskolin was not able to induce epileptiform activity when applied without pentylenetetrazol. 1,6-Dideoxy-forskolin (50 microM) did not accelerate epileptiform activity. When pentylenetetrazol was applied twice (1 h each) separated by 2.5 h of control conditions, PDS decrease obtained during the first application was found to be largely preserved during control conditions. When forskolin was applied for 30 min in between both applications of pentylenetetrazol, the second response to pentylenetetrazol did not show a preserved PDS decrease. Results suggest that forskolin blocks an endogenous antiepileptic process and that activation of PKA can maintain epileptic activity and induce status epilepticus.

Action Potentials↗