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Continuous flow peritoneal dialysis: assessment of fluid and solute removal in a high-flow model of "fresh dialysate single pass".

BACKGROUND: Growing concern over the limited capacity of the peritoneal dialysis (PD) system has revived interest in continuous flow peritoneal dialysis (CFPD), a modality in which continuous circulation of PD fluid is maintained at a high flow rate using two separate catheters or one dual-lumen catheter. The CFPD regimen contrasts the "inflow/outflow" regimen, which requires specific times devoted to filling and draining the peritoneum via a single-lumen catheter. Historical data established CFPD capabilities in providing higher solute clearance and ultrafiltration rate (UFR) using either an open loop system with a single pass of fresh PD fluid, or various external purifications of the spent dialysate. OBJECTIVE: To compare, in patients with various peritoneal transport patterns, fluid and solute removal achieved during a standardized program of CFPD versus two control schedules: nightly intermittent peritoneal dialysis (NIPD) and nightly tidal peritoneal dialysis (NTPD). This study focused on small solute clearances and UFR using only isotonic PD solution (Dianeal PD1 1.36%; Baxter Healthcare, Castlebar, Ireland). The model of fresh dialysate, single pass, was used to optimize solute gradients and to characterize the impact of a continuous flow regimen on peritoneal transport characteristics. METHODS: In a crossover trial, 4-hour CFPD sessions were performed at a fixed dialysate flow rate (100 mL/ minute) in 5 patients being treated with automated PD. A hemofiltration monitor (BM25; Baxter Healthcare, Brussels, Belgium) was adapted to the CFPD technique. The peritoneal cavity was filled through a temporary second catheter and simultaneously drained using the permanent peritoneal access. Fluid and solute removal were compared to data obtained from a control period based on 8-hour sessions of NIPD or NTPD using 13 L of isotonic dialysate. RESULTS: High-flow CFPD enhanced the diffusive transport coefficient compared with the alternative flow regimen in patients ranging from low to high transporters. Weekly creatinine clearance increased from 36.9 L (22.3 - 49.6 L) and 37.3 L (27.5 - 45.0 L) with NIPD and NTPD respectively, to 74.9 L (42.3 - 107.5 L) with CFPD. Mean UFR was 2.44 mL/min with CFPD versus 0.92 and 0.89 mL/min with NIPD and NTPD respectively. The mass transfer area coefficient (MTAC) of creatinine with CFPD was 2.5-fold that obtained from the peritoneal equilibration test data. CONCLUSION: Our results confirm that CFPD is highly effective in increasing fluid and solute removal. Furthermore, consistent with historical data, our findings indicate that the enhanced solute transfer is not due only to steeper solute gradients, but also depends on increased MTAC in a wide range of peritoneum transport characteristics.

Biological Transport↗

[Effect of Bushenyiqihexue recipe on the expression of endometrial pinopodes in blastocyst implantation dysfunctional mice].

OBJECTIVE: To observe the effect of Bushenyiqihexue recipe on the expression of endometrial pinopodes in blastocyst implantation dysfunctional mice. METHODS: To induce blastocyst implantation dysfunctional mice model, Kunming mice were injected subcutaneously with mifepristone on day 4 of pregnancy. First, Kunming mice were randomly assigned to the control group, the model group and treated group postcoitally. Every morning from day 1 of pregnancy (Pd1), the treated group was administered the Bushenyiqihexue recipe decoction, while the model group and control group were administered saline orally. On Pd4, the model and treated groups were injected subcutaneously with mifepristone diluted in propylene glycol, while the control group was injected with saline only. The expression of endometrial pinopodes between 21:30 and 22:00 on Pd4 (T1) and between 9:30 and 10:00 on Pd5 (T2) was determined by scanning electron microscopy. RESULTS: Compared with control group (90%, 14.7 +/- 1.4), pregnancy rate (25%) and mean implanted blastocysts (7.7 +/- 1.3) in model group were remarkably reduced (P < 0.05, P < 0.001). Compared with the model group, pregnancy rate (55%) and mean implanted blastocysts (12.3 +/- 0.8) in treated group were significantly improved (P < 0.05, P < 0.01). At T1, abundant developing pinopodes were expressed in endometrial surface in control group, whereas abundant fully developed pinopodes expressed at T2. At T1, only a few pinopodes were expressed locally in endometrial surface in model group, while completely disappeared at T2. At T1, endometrial surface in treated group expressed a lot of developing pinopodes which lagged behind slightly that of the control group in time, whereas many fully developed pinopodes expressed at T2. CONCLUSIONS: Decreased pinopodes expression at T1 and complete loss expression of pinopodes at T2 seem to be the reasons for blastocyst implantation dysfunction induced by mifepristone. It is suggested that Bushenyiqihexue recipe could improve pinopodes expression in endometrial surface, eventually better uterine receptivity and improve the blastocyst implantation.

Animals↗

Do regulatory T-cells play a role in AIDS pathogenesis?

The impairment of adaptive immune responses to HIV and abnormalities in the immune regulatory function mechanisms during HIV infection have been regarded as key issues in AIDS pathogenesis since the early years of the pandemic. However, the multiple mechanisms underlying this impairment are still not fully understood. New emerging information shows that alterations in the number and/or function of regulatory T-cells may contribute to HIV pathogenesis. Thus, pharmacologic manipulation of regulatory T-cells as well as blocking the activity of other immunomodulatory molecules, such as indoleamine 2,3-dioxygenase, glucocorticoid-induced tumor necrosis factor receptor and PD1, might provide a valuable approach to redirect the immune system towards an efficient antiviral response.

Acquired Immunodeficiency Syndrome↗

[Detection of Yersinia ruckeri in rainbow trout in Czechoslovakia].

At the end of 1988 eight rainbow trouts Pd1 and nine rainbow trouts Pd2 were investigated at localities N and D with the increased mortality of rainbow trout. The pathological finding in dead and killed trout corresponded to the changes which are described in the so called ERM (enteric redmouth) salmonids. At the beginning of the year a similar case was found at locality B where 12 rainbow trouts Pd2 were examined. In the same period 15 trouts Pd2 at locality M were examined in which no large pathomorphological changes were observed. From the organs and intestines of locality N trout, from the intestines of locality D trout and the organs of locality B trout, in total 16 bacterial cultures were isolated, the morphological and biochemical characteristics of which correspond to the description of Y. ruckeri (Ross et al., Ewing et al., 1978). Fifteen sorbitol-nonfermenting strains came from the cases with clinical and pathomorphological findings while the only sorbitol-fermenting strain was isolated from a symptom-free carrier. These findings demonstrate that in the Czechoslovak conditions it is not possible to omit the difference in the virulence of sorbitol-fermenting and sorbitol-nonfermenting strains to rainbow trout.

Animals↗

Primary structure of chicken pituitary prolactin deduced from the cDNA sequence. Conserved and specific amino acid residues in the domains of the prolactins.

The perform of chicken prolactin (PRL) deduced from the cDNA sequence contains a signal peptide of 30 amino acid residues followed by a mature PRL of 199 residues. Chicken PRL shows 77, 68, 67, 58, and 31% identity of amino acid sequence with whale, human, ovine, rat, and salmon PRLs, respectively. Elucidation of the primary structure of avian PRL enabled extended analysis of the specific and conserved amino acid residues and domains of the PRL molecules. The mammalian, teleostean, and avian PRLs share 32 common residues, and these conserved residues are observed to cluster in four distinct domains (PD1 to PD4), corresponding to four of five conserved domains of the growth hormones. Of the 32 residues, 8 residues in the PD2 and PD4 domains, including 4 cysteines, are conserved by other members of the growth hormone family, which indicates that these 8 residues may be essential for common structural features of the gene family. On the other hand, 13 other residues distributed among all four domains are conserved almost exclusively in the PRLs, suggesting that these residues are indispensable for specific binding of the PRLs to their receptors.

Amino Acid Sequence↗

[Diagnosis of infectious pancreatic necrosis (IPN) of trout using immunofluorescence].

Until recently, demonstration of infectious pancreatic necrosis was conditioned by the isolation of virus. By means of the immunofluorescence method it is possible to make a rapid and accurate diagnosis, as well as to determine the development of infection. In acute cases, the virus in fry was demonstrated mainly in the cytoplasm of epithelial cells of guts; in Pd1-2 trout, the virus was proved in the cytoplasm of epithelial cells of primary kidney tubules and in the cytoplasm of epithelial cells of pancreatic acini. In all cases the virus occurrence demonstrated by immunofluorescence was in correlation with the results achieved by cultivation methods.

Animals↗

Alkalosis and hypomagnesaemia: unwanted effects of a low-calcium CAPD solution.

We studied 43 CAPD patients for 4 months during the change from a high-calcium dialysis fluid (Baxter PD1) to a low-calcium fluid (Baxter PD4), which also contained low magnesium (0.25 mmol/l) and high lactate concentrations (40 mmol/l). Serum calcium fell significantly as did the incidence of hypercalcaemia, whilst the proportion of patients taking calcium-containing phosphate binders increased. There was a non-significant increase in serum i-PTH levels but the proportion with i-PTH > 150 pg/ml (normal range 10-65 pg/ml) increased significantly. There was a significant fall in serum magnesium level and seven patients developed hypomagnesaemia. Serum bicarbonate increased significantly and progressively and 17 patients were alkalotic at 4 months, five severely (bicarbonate 35-40 mmol/l). One patient developed recurrent episodes of painful subcutaneous and periarticular calcification, which may have been related to the alkalosis. Initial serum bicarbonate levels correlated significantly with dialysis adequacy assessed by daily Kt/V (r = 0.458, P = 0.002). The relationship to adequacy was abolished during the period of use of the high-lactate dialysis fluid. Use of low-magnesium CAPD fluids must be supported by regular monitoring of serum magnesium levels. The high lactate concentration in such fluids may not be appropriate and is potentially hazardous when individualization of dialysis dose demands the use of relatively high exchange volumes. Low serum bicarbonate levels in CAPD patients reflect inadequate dialysis, which use of these fluids serves to mask.

Adult↗

Prevalence rates of diagnosis of asthma in general population samples of northern and central Italy.

In order to assess the distribution of asthma in Italy in the 1980s, we have compared the findings of three general population surveys carried out in the North and the Centre of the country. Two cross-sectional investigations were performed in the Po Delta area (North Italy), 6 yrs apart: 1) 3,285 subjects, aged 8-64 yrs, in 1980-1982 (PD1); and 2) 2,841 subjects, aged 8-73 yrs, in 1988-1991 (PD2). One cross-sectional survey was carried out in Pisa (Central Italy): 3,866 subjects, aged 5-90 yrs, in 1985-1988 (PI1). For this analysis we have used data from the standardized questionnaires of those subjects between 18-64 yrs, who were currently employed. The prevalence rate of ever asthma was 3.3-5.5%, that of current asthma 1.3-2.9%; almost all of the diagnoses were confirmed by a doctor. Taking into account only doctor-confirmed asthma, the age of onset of manifestations was most frequently over 18 yrs (41-79%). It also occurred more frequently after the onset of employment. As regards smoking, whilst most asthmatic males were current or former smokers (70-86%), most asthmatic females were nonsmokers. However, the situation changed in PD2, where females showed the same pattern as males. Considering asthmatic subjects with skin-prick test reactivity (data available only in PD2), the vast majority (67% in males, 75% in females) had an age of disease onset under 18 yrs. In conclusion, the prevalence of asthma in Italy in the 1980s was similar to that in other European countries and was affected by atopy and smoking differently in the two sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Photodynamic therapy of extracellular matrix stimulates endothelial cell growth by inactivation of matrix-associated transforming growth factor-beta.

Photodynamic therapy (PDT), the production of cytotoxic free-radical moieties by light activation of photosensitizer dyes, is a novel approach to inhibit experimental intimal hyperplasia. Local eradication of vascular cells with this method in vivo is followed by expedient reendothelialization, and PDT of extracellular matrix (ECM) in vitro stimulates endothelial cell (EC) growth. This in vitro study explored one possible mechanism underlying these findings by investigating the effects of PDT on matrix-associated transforming growth factor-beta (TGF-beta), a potent inhibitor of EC growth. The ECM deposited by EC on tissue culture plates contained 85.4 +/- 10.2 pg/10 cm2 of TGF-beta, as measured by an ELISA. In contrast, after PDT of ECM, levels of TGF-beta could be barely be detected (0.2 +/- 0.5 pg/10 cm2). The functional consequence of this observation was demonstrated by the finding that PD1 of plates coated with a fibronectin-TGF-beta complex stimulated EC mitogenesis (102.3% +/- 19.3%, p < 0.0005) compared with the untreated control (44.1% +/- 13.5%). The inhibitory effect of ECM-associated TGF-beta on EC was further delineated by blocking its activity with a specific antibody. Whereas the antibody did not affect EC mitogenesis or PDT-treated matrix or matrix-free plates (101% +/- 8.8%, 105.6% +/- 9.8%), EC mitogenesis growing on ECM was significantly enhanced (125.9%, 17.5%, p < 0.05). Finally, SDS-PAGE analysis of PDT-treated TGF-beta in solution demonstrated that the PDT-mediated loss of TGF-beta activity was not associated with changes in its molecular weight. These data demonstrate that increased EC proliferation on PDT-treated matrix is, at least in part, mediated by inactivation of TGF-beta. PDT-removal of this EC growth inhibitor in the intima provides a mechanism by which PDT of the vascular wall could potentiate endothelial regrowth, a factor which may promote proper healing and result in the inhibition of intimal hyperplasia.

Animals↗

Propionyl-CoA carboxylase subunit B regulates anti-tumor T cells in a pancreatic cancer mouse model.

Most human pancreatic ductal adenocarcinoma (PDAC) are not infiltrated with cytotoxic T cells and are highly resistant to immunotherapy. Over 90% of PDAC have oncogenic KRAS mutations, and phosphoinositide 3-kinases (PI3Ks) are direct effectors of KRAS. Our previous study demonstrated that ablation of Pik3ca in KPC (KrasG12D; Trp53R172H; Pdx1-Cre) pancreatic cancer cells induced host T cells to infiltrate and completely eliminate the tumors in a syngeneic orthotopic implantation mouse model. Now, we show that implantation of Pik3ca-/- KPC (named &#x3b1;KO) cancer cells induces clonal enrichment of cytotoxic T cells infiltrating the pancreatic tumors. To identify potential molecules that can regulate the activity of these anti-tumor T cells, we conducted an in vivo genome-wide gene-deletion screen using &#x3b1;KO cells implanted in the mouse pancreas. The result shows that deletion of propionyl-CoA carboxylase subunit B gene (Pccb) in &#x3b1;KO cells (named p-&#x3b1;KO) leads to immune evasion, tumor progression, and death of host mice. Surprisingly, p-&#x3b1;KO tumors are still infiltrated with clonally enriched CD8+ T cells but they are inactive against tumor cells. However, blockade of PD-L1/PD1 interaction reactivated these clonally enriched T cells infiltrating p-&#x3b1;KO tumors, leading to slower tumor progression and improve survival of host mice. These results indicate that Pccb can modulate the activity of cytotoxic T cells infiltrating some pancreatic cancers and this understanding may lead to improvement in immunotherapy for this difficult-to-treat cancer.

Animals↗