Cuprophane Membranes Research Articles

Substantiation of the composition of a semi-solid dosage form with a probiotic component for use in dermatology

One of the important issues in the pharmaceutical development of a semisolid preparation for dermal use is the scientific and experimental justification for choosing the base-carrier of active substances.
 The aim of this study was to experimentally substantiate the choice of rational combination of excipients in the development of a semisolid dosage form with a probiotic component for use in dermatology.
 Materials and methods. Hydrophilic gelling agents were used as excipients in the study: Sepiplus 400, Aristoflex AVC, Carbopol 934, hydroxyethylcellulose HEC, sodium alginate. Physical and chemical, pharmaco-technological and microbiological methods were used to select the optimal basis. Colloidal stability was determined using a laboratory centrifuge at a speed of 6000 rpm for 5 min, an electronic thermometer and a water bath laboratory. Thermostability was determined in the thermostat at (40±2) °C for 24 hours. Investigation of the rheological properties of the samples was performed using a Rheolab QC (Anton Paar, Austria) rheoviscometer using a system of coaxial cylinders C-CC27/SS. The kinetics of water absorption of the samples were studied by dialysis through a semipermeable Cuprophan membrane, Type 150 pm at a temperature of (34±2) °C. The number of viable lactobacilli cells was determined by surface seeding on Petri dishes with dense MRS medium.
 Research results. The results of the study of the number of viable lactobacilli cells showed that the lowest number of viable cells was in sample based on HEC. Tests for thermostability and colloidal stability showed that for sample No. 5 based on sodium alginate, stratification was observed in the experiment, which indicates its instability. These samples were excluded. Samples on Sepiplus 400 and Aristoflex AVC on a set of rheological features have advantages both consumer and technological; and sample on t Aristoflex AVC has the best indicators of osmotic activity and the viability of cells in the dynamics for this study.
 Conclusions. As a result of physical and chemical (organoleptic, colloidal and thermostability), pharmaco-technological (osmotic and structural and mechanical properties) and microbiological studies (number of viable lactobacilli cells) studies it was found that further work should be carried out with a sample based on gelling agent Aristoflex AVC, which has the most optimal performance in this development for a semisolid dosage form with a probiotic component for use in dermatology

Single- and multiple-dose pharmacokinetics and total removal of colistin in a patient with acute kidney injury undergoing extended daily dialysis

Sir, The emergence of multidrug-resistant bacteria has recently renewed interest in colistin, which was first introduced in 1959. For intravenous administration, not colistin itself, but its inactive prodrug colistin methanesulfonate (CMS) is administered. As 70% of CMS is excreted unchanged in the urine, its t1 2 increases with a decline in glomerular filtration rate (GFR) to up to 14 h in patients with a GFR ,15 mL/min. Additionally, a larger fraction of the CMS dose is converted into colistin with decreasing renal function. Thus, dose reduction is recommended with decreasing GFR. Data from 1968 on four patients treated with twice-weekly dialysis for 11–16 h using a cuprophane membrane are the foundation for current dosing regimens in chronic haemodialysis. In these patients a dose of 1 million units every 48 h is recommended. Data on dosing in critically ill patients undergoing extended dialysis are missing. We here report for the first time, singleand multiple-dose pharmacokinetics of colistin in a critically ill patient undergoing extended dialysis. Written informed consent was obtained from the patient’s mother for publication of this study. Ethical approval for reporting this case was obtained from the Medical School Hannover. A patient aged between 30 and 40 years (height 163 cm, weight 53 kg) was admitted to our intensive care unit (ICU) for rapidly progressive respiratory failure. The patient had undergone lung transplantation for pulmonary hypertension 10 months earlier. The patient’s post-transplant course had been complicated by acute rejection and an Aspergillus fumigatus infection. On admission, the patient required non-invasive ventilation. Bronchoalveolar lavage revealed a multiresistant Klebsiella pneumoniae in addition to the previously known Aspergillus. Endotracheal intubation was required owing to worsening respiratory failure. Extended dialysis for acute kidney injury was started. As the K. pneumoniae was only susceptible to colistin, we initiated treatment with 3 million units every 8 h after an initial dose of 6 million units. Blood samples were taken at regular intervals on day 1 and day 9 of treatment. Colistin and CMS concentrations were determined separately by HPLC combined with tandem mass spectrometry, as recently used in its modified form. The average dialysis time between day 1 and day 9 was 552 min; mean blood and dialysate flow were 191 mL/min and 121 mL/ min, respectively. After a loading dose of 6 million units, peak levels of colistin and CMS were 10.01 mg/mL and 24.76 mg/mL, respectively. The lowest plasma concentrations on day 1 were 3.83 mg/mL for colistin and ,0.1 mg/mL for CMS. Extended dialysis with the above-mentioned specifications led to a reduction of peak colistin levels (Figure 1). After 9 days of treatment with 3 million units every 8 h there was neither an accumulation of colistin (peak level day 9: 8.96 mg/mL, trough level 2.13 mg/mL) nor an accumulation of CMS (peak level day 9: 11.83 mg/mL, trough level ,0.1 mg/mL). Depending on the blood and dialysate flow, the dialyser clearance of colistin ranged between 54 and 71 mL/min and the CMS clearance between 25 and 62 mL/min. The amount of colistin in the total collected dialysate was 245 mg on day 1 and 191 mg on day 9. Although the patient responded well to this antibiotic therapy, subsequent cerebral aspergillosis could not be treated, leading to the death of the patient after 5 weeks of treatment in the ICU. There are scarce data on the dosing of antibiotics in patients undergoing renal replacement therapy. Our data suggest that extended dialysis eliminates colistin effectively and to a larger extent than regular intermittent outpatient haemodialysis. This is in line with recent data on two critically ill patients undergoing a modern type of intermittent dialysis (1.6 m polymethylacrylate membrane, blood/dialysate flow 300/500 mL/min, duration 4 h), in whom a CMS dialyser clearance of 90 mL/min was reported. Li et al. described a dialyser clearance of 11.9 mL/min for colistin and 11.2 mL/min for CMS in one critically ill patient undergoing continuous venovenous haemodiafiltration, which due to its continuous mode would remove approximately the same amount of the drug. Lastly, dialyser clearance in five patients receiving continuous venovenous haemodiafiltration was recently reported to be 72 mL/min for colistin and 32 mL/min for CMS. Thus, dosing colistin as recommended during regular haemodialysis is inadequate and would result in a significant under-dosing, which could be associated with a substantial risk, especially in critically ill patients in the ICU. A dose of 3 million units every 8 h seems to be adequate for patients undergoing daily extended dialysis for 9 h a day with a high flux 1.3 m dialyser. This dose of 9 million units per day did not lead to accumulation of the drug.

The ultrafiltration coefficient: this old 'grand inconnu' in dialysis

Although a wide range of physical principles capable of separating different solutes exist in biochemistry (such as affinity, or size as well as charge retaining columns and others), the removal of uraemic solutes has been almost exclusively performed up to the present with membrane-based systems. Sir Thomas Graham, in the second half of the 1800s, defined the method of separating various fluids by diffusion through a membrane with the term ‘dialysis’[1]. Galen in the second century of our era already claimed that the skin resembles a sieve and ‘sweating purifies the body, … by low-effort exercise, baths and the summer heat’ [De Symptomatum Causis Libri III, Claudii Galeni Opera Omnia (II)][2], and ancient Romans used the skin as a natural membrane to rid their bodies of poisonous urinal substances in the Therms and public baths. Well into the 20th century, artificial kidneys, based on membrane devices were adopted and the pioneer work by Abel, Rowntree and Turner [3], as well as that of Haas [4], was followed by the rotatory drum dialyser of Willem Kolff [5] and the vertical drum one of Nils Alwall [6]. Finally, the hollow fibre dialysers gained adepts and a widespread use of cuprophane membranes for a very long period of time (from the 1970s to the 1990s) has been followed by the introduction of high-flux membranes that have invaded most of the dialysis units worldwide to the present. It became quite clear from the very beginning that membranes differ in their clearance capacities of the different solutes, basically depending on thickness and pore size. However, increasing the pore size and reducing thickness is almost forcedly associated to a water permeability increase. The open dialysate circuit settings used during the era of low-permeability membranes had to be secured by the addition of ultrafiltration controllers, which closed the dialysis circuit [7], and are mandatory when using high-flux membranes (highly permeable to water) particularly if convective techniques are utilized. Defining water permeability of a dialyser was considered important from the beginning and is even more important with the high-flux dialysers. Water permeability of a dialyser was defined by its ultrafiltration coefficient, which is displayed in the notice of the given dialyser. The coefficient of ultrafiltration (KUF) was first defined by the amount of fluid (V) in mL crossing the dialyser membrane per time (T) in hours and pressure (P) in mmHg: KUF=VT×P The perception that renal physicians have of KUF has changed over time. Senior nephrologists considered KUF as a constant and took it into account in dialysis prescription in the low-permeability era [8]; it was common to hear comments on the different KUF or ‘slope’ of one dialyser in regard to another one in clinics and the consequences that this might have to the treatment and to the patient. Among senior physicians, only those particularly interested on the topic knew that KUF was not always a constant as its value may vary over a certain range of filtration rate. Young nephrologists, who have only lived the ultrafiltration controller era, have just ignored KUF. They simply did not need it. Nevertheless, the importance of KUF of the early times has remained in many aspects, including the approval of new devices by the regulatory agencies such as the US Food and Drugs Administration (FDA) [9] or its equivalent in Europe, the European Medicines Agency (EMA), a prerequisite to use them in clinics in all these countries. Indeed, the recent randomized, controlled trials on haemodiafiltration [10–12] and particularly that of Maduell et al. [12] providing evidence that high convective volume may improve survival has given a renewed protagonism to KUF, as it influences the convective capacities of the dialysis setting. KUF remains, though, the old ‘grand inconnu’. In the present editorial comment, we want to present a refurbished KUF to society, going in-depth into the factors influencing KUF and its calculation, and then coming back with as simple as possible methods to obtain it for easy clinical use.

Cuprophan膜におけるβ2-microglobulinとacute phase reactantの動向

Cuprophan膜におけるβ2-microglobulinとacute phase reactantの動向

Serum metalloproteinases MMP-2, MMP-9 and metalloproteinase tissue inhibitors TIMP-1 and TIMP-2 in patients on hemodialysis

We assessed the effect of hemodialysis (HD) and chronic kidney disease (CKD) on the serum levels of metalloproteinase-2 (MMP-2), MMP-9 and metalloproteinase tissue inhibitors (TIMP-1) and TIMP-2. 18 patients on regular HD treatment with low-flux, cuprophane membrane, 15 non-dialyzed patients with CKD and 15 healthy controls were sampled. The serum MMP and TIMP concentrations were determined by ELISA assays. MMP-9, TIMP-1, and TIMP-2 serum levels were significantly decreased in HD patients to 32.7 ± 20.1 ng/ml, 178.8 ± 73.0 ng/ml, and 103.4 ± 55.3 ng/ml compared with 482.3 ± 139.5, 367.6 ± 75.5 ng/ml, and 299.7 ± 63.2 ng/ml in patients with CKD and 594.6 ± 154.7 ng/ml, 354.5 ± 81.2 ng/ml, and 272.4 ± 91.8 ng/ml in healthy controls, respectively, (P < 0.001 vs. HD patients). MMP-2 was lower in patients with CKD: 405.6 ± 106.1 ng/ml compared with 516.9 ± 81.7 ng/ml in controls (P = 0.02). The MMP-2/TIMP-2 ratio was increased in HD patients compared with both patients with CKD and controls. In the course of an HD session, MMP-2 and TIMP-1 serum levels were significantly decreased from pre-HD 570.0 ± 256.5 and 178.8 ± 66.9 ng/ml to post-HD 492.6 ± 212.5 and 144.6 ± 44.2 ng/ml (P = 0.004 and 0.013, respectively). However, the MMP-9/TIMP-1 ratio increased from pre-HD 0.15 (2.19) (median, range) to 0.23 (0.33) after a HD session (P = 0.03). CRP was positively correlated with MMP-9 and MMP-9/TIMP-1 ratio in HD patients and patients with CKD (r = 0.67; P = 0.03). The MMP-9/TIMP-1 ratio increased during HD sessions, although their absolute levels were lowered. This change may represent a chronic state of enhanced fibrosis in patients undergoing HD.

Five Decades of Indian Nephrology: A Personal Journey

Impressive accomplishments have been made in Indian nephrology during the last 5 decades. The first renal biopsy performed in 1956 ushered in a new era of modern nephrology practice in India and led to the recognition of nephrology as a distinct specialty. The first hemodialysis facility was established in 1961; presently, there are 950 nephrologists, 850 hospitals equipped with dialysis facilities, and 170 institutions recognized for kidney transplantation, with approximately 3,500 transplantations performed every year. The majority of dialysis units are small minimal-care facilities with fewer than 5 dialysis stations, and more than 85% are in the private sector. Government hospitals provide free treatment to poor patients with chronic kidney disease; however, inadequate funding and lack of health insurance schemes pose serious hurdles in providing renal replacement therapy. In contrast, private/corporate hospitals located in big cities have large units with state-of-the-art dialysis and transplantation facilities, similar to advanced centers of the world, but are accessible to only upper-income groups. Of the estimated 175,000 new patients who develop end-stage renal disease annually, less than 10% are able to gain access to renal replacement therapy. Research in the field of renal diseases has evolved slowly and is focused primarily on tropical conditions. The availability of structured nephrology training programs coupled with excellent diagnostic and therapeutic facilities in some academic institutions and tertiary-care private/corporate hospitals have diminished the need for foreign travel by students, patients, and consultants to a considerable extent. The expansion of therapeutic facilities in India is hampered by only economic constraints, not lack of expertise.

Hemodialysis Modality, Percentage of Body Fat, and Patient Survival

A number of studies have reported lower mortality of overweight hemodialysis patients. This post hoc analysis of an observational prospective single-center study was aimed at elucidating whether both being overweight and surviving longer could result from changes in the hemodialysis modality. The study included a cohort of 242 patients who were gradually switched from cuprophane membrane and acetate dialysis to polysulfone (including high-flux) membranes and bicarbonate dialysis. The analysis involved 12 months of baseline data obtained during the first calendar year after the patients entered the study (1994-2001) and repeated measurements for up to 132 months of follow-up (until 2004). Anthropometric measurements were made during the winter season and the percentage of body fat (%fat) was calculated from triceps, biceps, subscapular, and suprailiac skinfolds (K/DOQI guidelines).Kt/V, normalized protein catabolic rate, and cardiovascular comorbidity were also determined and laboratory analyses undertaken. Significant correlations were found between %fat and bicarbonate dialysate as well as polysulfone membrane and high-flux membrane. The linear mixed model showed dependence of %fat on polysulfone and high-flux membrane (p<0.01) Multivariate Cox regression (time-dependent covariates) found %fat to be an independent factor for longer survival, in addition to polysulfone and high-flux membranes. Changes in hemodialysis modality were followed by both higher body fat percentage and patient survival. The reverse epidemiology of overweight patients might be at least partially the result of the influence of nonnutritional factors, such as a change in hemodialysis modality (introducing biocompatible high-flux and low-flux membranes and bicarbonate dialysis).

Systemic levels of tumor necrosis factor alpha during hemodialysis with cellulosic membranes: no effect of the sterilization procedure.

Extractable constituents of dialyzer membranes (e.g., monomers and beta-glucans) may induce the production of cytokines in vitro. We therefore studied circulating tumor necrosis factor alpha (TNF alpha) levels in 23 stable hemodialysis patients during treatment with dry Cuprophan membranes (ETO-sterilized n = 10, steam-sterilized n = 13) longitudinally over a period of 4 weeks. After 4 weeks, those 5 patients of each group showing the highest TNF alpha levels were switched to steam-sterilized, wet Cuprophan membranes. No significant increase in plasma TNF alpha was observed during hemodialysis with either ETO- or steam-sterilized dry Cuprophan membranes. A substantial TNF alpha increase (> or = 100% compared to pre-HD values), however, was observed during 14 of 84 treatment sessions. In 5 selected patients with ETO-sterilized, dry Cuprophan dialyzers, TNF alpha rose from (mean +/- SEM) 17.2 +/- 3.0 (pre-HD) to 20.9 +/- 6.2 (120 min) and 21.9 +/- 4.5 pg/ml (240 min). Corresponding levels in patients with steam-sterilized, dry Cuprophan were 16.2 +/- 5.4 (pre-HD), 21.9 +/- 6.8 (120 min), and 16.0 +/- 3.7 pg/ml (240 min), respectively. There was no difference between ETO- and steam-sterilized dialyzers. No significant reduction in mean TNF alpha plasma levels or in frequency of elevated peak levels was achieved when these patients were switched to wet Cuprophan dialyzers for another 4 weeks. It is suggested that an induction of elevated TNF alpha levels during hemodialysis is possible but is not observed regularly during treatment with Cuprophan membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in mononuclear cell tumour necrosis factor-alpha (TNF-alpha) response in patients on long term cuprophane haemodialysis.

We have investigated TNF-alpha secretory response of peripheral blood mononuclear cells (PBMC) from 13 uraemic patients undergoing regular haemodialysis with cuprophane membrane (CM). Sixteen healthy subjects and five uraemic patients under conservative therapy were also studied as controls. Cells of haemodialysis patients exhibited increased TNF-alpha release in vitro in the absence of activating stimuli other than culture conditions, as compared with normal and uraemic controls. In contrast to normal cells, this spontaneous secretion of TNF-alpha from dialysis PBMC could not be significantly reduced by addition of polymyxin B to culture medium, thus indicating its independence of trace amount of lipopolysaccharide (LPS) present in the medium as contaminant. Furthermore, predialysis PBMC were considerably more sensitive to stimulation with 10(7) pg/ml of LPS under in vitro culture conditions than normal and uraemic controls. To elucidate a role of direct contact with CM in stimulation of TNF-alpha release from monocytes, PBMC were cultured on CM in vitro. Contact with CM stimulated TNF-alpha secretion from PBMC above the level of cells cultured on tissue culture plastic. This response persisted with time in culture in contrast to a transient LPS-induced TNF-alpha release. Furthermore, PBMC stimulated by contact with CM for 2 days did not lose the capacity to secrete TNF-alpha in response to a subsequent LPS stimulation, while a 2-day treatment of cells with LPS was followed by LPS refractory state. Therefore, direct contact with CM induces in PBMC a long-lasting TNF-alpha response which is not down-regulated by the acquisition of refractoriness in a manner similar to that which occurs in the case of LPS stimulation. These in vitro findings provide a possible explanation of the observation that predialysis PBMC exhibit elevated TNF-alpha secretory capacity.

Reactive oxygen product formation by human neutrophils as an early marker for biocompatibility of dialysis membranes.

Production of reactive oxygen intermediates (ROI) by neutrophils (PMN) in vivo was examined by a whole blood assay using dichlorofluorescein-diacetate (DCFH-DA) in 10 patients each dialysed consecutively with two different dialyser membranes. Haemodialysis (HD) with cuprophan membrane (CM) led to a significantly (P < 0.001) more pronounced ROI production by PMN (2.4 +/- 0.5-fold increase in intracellular oxidation of DCFH-DA) compared with HD with polysulfone membranes (PM; 1.5 +/- 0.2-fold). HD with CM induced a decrease in PMN count by about 90%, whereas PM induced a decrease by only 25% (P < 0.001). In CM patients maximal ROI production coincided with the nadir in PMN count. All patients dialysed with CM showed a clear increase in serum levels of Bb fragments, whereas PM-dialysed patients did not. In this respect, however, no clear time relationship was seen to the kinetics of ROI production, nor to the disappearance of neutrophils from the circulation. Evaluating a direct effect of the dialysis membranes on PMN demonstrated that incubation of neutrophils with hollow fibres of the CM but not of the PM in the absence of plasma induces significant ROI production by PMN. Our study thus indicates that ROI production by PMN during HD correlates to membrane biocompatibility. Furthermore, one might speculate that also independently from but perhaps in addition to complement activation, reactive oxygen products are critically involved in the generation of haemodialysis-associated neutrophil emigration.

Induction of tumour necrosis factor-alpha during haemodialysis. Influence of the membrane type

Some of the secondary clinical effects induced by long-term haemodialysis in patients with end-stage renal failure have been related to an increased production of interleukin-1 (IL-1). We investigated the role of another cytokine which shares a number of biological properties with IL-1, tumour necrosis factor-alpha (TNF-alpha). In long-term haemodialysed patients, we found at the beginning of the dialysis increased plasma TNF-alpha levels and enhanced monocyte capacity to produce TNF-alpha spontaneously ex vivo. Non-haemodialysed uraemic patients also presented increased plasma TNF-alpha levels. During dialysis with cellulose acetate (CA) or polysulphone (PS) membranes, plasma TNF-alpha levels and the spontaneous and lipopolysaccharide-induced production of TNF-alpha by monocytes remained at predialysis levels. In contrast, when cuprophane membranes were used, there was a significant increase in plasma TNF-alpha levels and in both spontaneous (10-fold) and lipopolysaccharide-induced (seven-fold) ex vivo TNF-alpha production by monocytes. These results suggest that monocytes are stimulated during haemodialysis with the poorly biocompatible cuprophane membrane.

Nerve Conduction Studies and Prediction of Mortality in Hemodialysis Patients

Background. The electrophysiological aspects of uremic neuropathy have been studied extensively, but never for prediction of mortality. In order to assess the parameters of nerve conduction study (NCS) as predictors of mortality in hemodialysis patients, a post hoc analysis of a prospective observation study was made. Methods. We examined conventional electrophysiological parameters (motor nerve conduction velocity [MCV], terminal latency [TL], and F wave latency of the peroneal nerve, as well as sensory nerve conduction velocity [SCV] of the sural nerve) in 75 nondiabetic patients. Hemodialysis modality (bicarbonate dialysis and biocompatible membranes), Kt/V, comorbidity (ischemic heart disease and congestive heart failure), and clinical and laboratory parameters were also evaluated. Survival was analyzed using the Cox proportional hazard model. Results. SCV was significantly higher (t-test, p < 0.01) in the group of patients treated with polysulfone compared to those using cuprophane membranes. On the other hand, MCV significantly correlated with Kt/V (Pearson, r = 0.388; p < 0.01). Multivariate Cox regression revealed only MCV as a significant predictor of mortality in this group of hemodialysis patients (HR = 0.92; CI (0.86–0.99); p < 0.05). Conclusion. Only MCV was a significant mortality risk predictor among NCS parameters. This parameter correlates significantly with dialysis dose. SCV was related to the use of biocompatible membranes, indicating the complexity of polyneuropathy in dialysis patients.

Should Cuprophane Membranes Continue to Be Used for Chronic Hemodialysis?

Seminars in DialysisVolume 5, Issue 2 p. 113-114 Should Cuprophane Membranes Continue to Be Used for Chronic Hemodialysis? Steve J. Schwab, Corresponding Author Steve J. Schwab Department of Medicine, Division of Nephrology, Duke University Medical Center, Durham, North CarolinaSteve J. Schwab, MD, Associate Director, Division of Nephrology, Duke University Hospital, Box 3014, Durham, NC 27710.Search for more papers by this author Steve J. Schwab, Corresponding Author Steve J. Schwab Department of Medicine, Division of Nephrology, Duke University Medical Center, Durham, North CarolinaSteve J. Schwab, MD, Associate Director, Division of Nephrology, Duke University Hospital, Box 3014, Durham, NC 27710.Search for more papers by this author First published: April 1992 https://doi.org/10.1111/j.1525-139X.1992.tb00125.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume5, Issue2April 1992Pages 113-114 RelatedInformation

Should Cuprophane Membranes Continue to Be Used for Chronic Hemodialysis?

Seminars in DialysisVolume 5, Issue 2 p. 115-116 Should Cuprophane Membranes Continue to Be Used for Chronic Hemodialysis? Peter Ivanovich, Corresponding Author Peter Ivanovich Department of Medicine, Northwestern University, and Department of Veterans Affairs, Lakeside Medical Center, Chicago, IllinoisPeter Ivanovich, MD, Section of Nephrology, VA Lakeside Medical Center, 333 E. Huron Street, Chicago, IL 60611.Search for more papers by this authorSalim K. Mujais, Salim K. Mujais Department of Medicine, Northwestern University, and Department of Veterans Affairs, Lakeside Medical Center, Chicago, IllinoisSearch for more papers by this author Peter Ivanovich, Corresponding Author Peter Ivanovich Department of Medicine, Northwestern University, and Department of Veterans Affairs, Lakeside Medical Center, Chicago, IllinoisPeter Ivanovich, MD, Section of Nephrology, VA Lakeside Medical Center, 333 E. Huron Street, Chicago, IL 60611.Search for more papers by this authorSalim K. Mujais, Salim K. Mujais Department of Medicine, Northwestern University, and Department of Veterans Affairs, Lakeside Medical Center, Chicago, IllinoisSearch for more papers by this author First published: April 1992 https://doi.org/10.1111/j.1525-139X.1992.tb00126.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume5, Issue2April 1992Pages 115-116 RelatedInformation

Should Cuprophane Membranes Continue to Be Used for Chronic Hemodialysis?

Seminars in DialysisVolume 5, Issue 2 p. 116-118 Should Cuprophane Membranes Continue to Be Used for Chronic Hemodialysis? Sidney M. Kobrin, Corresponding Author Sidney M. Kobrin Renal Electrolyte Section, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PennsylvaniaSidney M. Kobrin, MD, 700 Clinical Research Building, University of Pennsylvania, 422 Curie Boulevard, Philadelphia, PA 19104-6144.Search for more papers by this author Sidney M. Kobrin, Corresponding Author Sidney M. Kobrin Renal Electrolyte Section, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PennsylvaniaSidney M. Kobrin, MD, 700 Clinical Research Building, University of Pennsylvania, 422 Curie Boulevard, Philadelphia, PA 19104-6144.Search for more papers by this author First published: April 1992 https://doi.org/10.1111/j.1525-139X.1992.tb00127.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume5, Issue2April 1992Pages 116-118 RelatedInformation

Cuprophane membrane permeability to urea studied by optical interference method

Investigation of the mechanisms of transportation through the biological membranes is of interest mainly in biology and medicine. Besides the cognitive value, the aim of such studies is to find new technologies of producing synthetic membranes of desired characteristics to be used in modern methods of medical therapy. The paper reports on the cuprophane membrane permeability to urea studied by very sensitive method of optical interference.

Expression of granzyme A in human polymorphonuclear neutrophils

Polymorphonuclear neutrophils (PMNs) are the first line of defence against invading pathogens. They contain a multitude of antimicrobial and potentially cytotoxic substances packed in granules and secretory vesicles. Here, we show that granzyme A (GzmA) is constitutively expressed in human PMNs, but not in the promyelocytic cell line HL-60, by performing flow cytometry, western blot, enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. To further track the intracellular localization of GzmA, we performed subcellular fractionation and found GzmA to be present in peroxidase-negative granules. Finally, stimulation with opsonized Escherichia coli or the bioincompatible haemodialysis membrane cuprophane led to up-regulation of GzmA expression at the transcriptional level as well as at the translational level. In conclusion, we provide clear evidence that GzmA is constitutively expressed in human PMNs and can be up-regulated upon stimulation. These findings may also indicate a role for GzmA in PMNs in defence against invading pathogens.

The evaluation of hemodialysis adequacy during the use of different dialysis membranes

Hemodialysis efficacy that significantly influences morbidity and mortality of patients can be evaluated by different widely used indices of adequacy. The aim of the study was to evaluate the adequacy of hemodialysis in the group of patients on maintenance hemodialysis and to examine the influence of different dialysis membranes on the indices of adequacy and frequency of symptoms and complications developing during dialysis treatment. The study involved 14 patients dialyzed in three successive months with three different types of dialyzers: E3 (Hemomed)--cuprophane membrane, 1.3 m2, F6 (Hemomed)--polysulfone membrane, 1.3 m2, CM23 (Zdravlje)--cuprophane membrane, 1.25 m2. Each type of dialyzers was used during one month, meaning during 12 successive 4-hour hemodialyses. Mean value of Kt/V index was 1.39 +/- 0.21 for E3 dialyzer, 1.18 +/- 0.24 for F6 dialyzer and 1.44 +/- 0.25 for CM23 dialyzer. The difference between the indices was statistically significant (p < 0.05). Mean protein catabolic rate (PCRn) ranged between 1.6 and 1.7 and no significant difference was found between the dialyzers used. The frequency of hypertension episodes was similar during the hemodialysis with different dialyzers, but the incidence of different symptoms and hypotension episodes was significantly lower during hemodialysis with polysulfone membrane. Hemodialysis with three examined types of dialyzers enabled acceptable dialysis adequacy. Dialyzers with cuprophane membrane enabled significantly higher Kt/V index, but the incidence of symptoms and hypotension was significantly lower during hemodialysis with polysulfone membrane.

Oxidation of proteins adsorbed on hemodialysis membranes and model materials

The cleaning of cellulosic hemodialysis membrane Cuprophan and model materials (glass; polystyrene and polypropylene, as such and surface-oxidized), conditioned by adsorption of blood plasma proteins (HSA, fibrinogen, IgG) was investigated in vitro. Sodium hypochlorite (NaClO) and Renalin, a product containing hydrogen peroxide and peroxyacetic acid, were used as cleaning reagents. X-ray photoelectron spectroscopy and the use of radiolabeled fibrinogen demonstrated the presence of varying amounts of a polypeptidic residue, with sulfur brought to a high oxidation stage (sulfonate-like). The trends were the same for the three proteins regarding the effectiveness of the oxidizer and the influence of the surface properties. NaClO was much more effective than Renalin to remove the adsorbed proteins. The proteins adsorbed on Cuprophan were more sensitive to the oxidizers, when compared with proteins adsorbed on other materials. This may be due to both the lower protein-surface affinity, as indicated by radiochemical measurements, and the sensitivity of the material itself to the oxidizer, as revealed by weight loss measurements. These results support the attribution of hemocompatibility improvement after regeneration of Cuprophan with Renalin to the masking of the activating surface by a residue from previously adsorbed proteins.

Increased Levels of Soluble TNF-α Receptors and Cellular Adhesion Molecules in Patients Undergoing Bioincompatible Hemodialysis

Background: The study aimed to differentiate the effects of hemodialysis (HD) and chronic renal failure (CRF) on the levels of circulating tumor necrosis factor-α (TNF-α) and TNF-α receptors p55 and p75, soluble vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), soluble endothelial-leukocyte adhesion molecule-1 (sE-selectin) and sP-selectin in 18 patients on regular HD treatment with cuprophane membrane in relation to 15 non-dialyzed CRF patients and 15 healthy controls. Methods: The serum concentrations were determined with standard ELISA assays. Results: Blood serum p75 and p55 were approximately tenfold increased in CRF (36.7 ± 6.2 and 27.1 ± 5.6 ng/ml) and HD patients (45.6 ± 18.4 and 28.7 ± 5.9 ng/ml) before the HD session (HD 0), during (HD 20) the session (45.7 ± 18.4 and 28.5 ± 7.3 ng/ml) and after (HD 240) the HD session (52.1 ± 17.4 and 30.9 ± 8.2 ng/ml) in comparison to control values (5.6 ± 1.3 and 2.4 ± 0.8 ng/ml, respectively) (p < 0.01). The highest increment of p75 at the end of HD session (HD 240) was also significantly higher than at preceding time points (HD 0 and 20) (p < 0.05). However, the remaining study parameters did not change during an HD session. Also, there were no relevant changes in TNF-α levels if (HD 0) 22.7 ± 21.5 ng/ml and (HD 240) 21.1 ± 18.9 ng/ml were compared. Chronic HD status was related to the increase of sVCAM-1 and sICAM-1 levels. Prior to HD, T0 sVCAM-1 and sICAM-1 concentrations were 2,180.4 ± 761.8 and 567.3 ± 218.8 ng/ml, during HD (T20): 2,172.7 ± 759.2 and 602.3 ± 379.9 ng/ml, and after HD (T240): 2,401.6 ± 756.4 and 648.3 ± 183.5 ng/ml, respectively (p < 0.05 vs. controls and CRF patients). sVCAM-1 and sICAM-1 serum levels (1,262.2 ± 472.9 and 165.6 ± 50.4 ng/ml) were similar in CRF patients and healthy controls (854.4 ± 241.5 and 217.6 ± 74.2 ng/ml, respectively). Even though serum sE- and sP-selectin in CRF patients did not differ from the control (39.8 ± 21.3 vs. 42.1 ± 18.9 ng/ml and 187.9 ± 66.9 vs. 198.8 ± 62.2 ng/ml, respectively), their levels were increased in HD patients up to 111.9 ± 54.6 and 453.2 ± 231.1 ng/ml in patients prior to HD, 118.7 ± 66.2 and 350.8 ± 114.8 ng/ml during the HD session and then 132.3 ± 61.1 and 368.3 ± 126.6 ng/ml, respectively, after its completion (p < 0.05 in comparison with CRF patients and controls). Conclusions: The increased circulating TNF-α receptors appear more associated with the uremic milieu than HD-related systemic inflammation, whereas increased soluble cellular adhesion molecules in patients undergoing bioincompatible HD may be related to the enhanced systemic inflammation specifically due to maintenance HD.