Semi-individualised Chinese medicine treatment as an adjuvant management for diabetic nephropathy: a pilot add-on, randomised, controlled, multicentre, open-label pragmatic clinical trial

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Increased sialylation of polymeric γ-IgA1 in patients with IgA nephropathy

The mechanism of mesangial IgA deposition is poorly understood in IgA nephropathy (IgAN). Abnormal glycosylation of carbohydrate moieties in the hinge region of the IgA molecule has recently attracted much attention. In this report, we studied galactosylation and sialylation profiles in κ- and γ-IgA1 from patients with IgAN. Total serum IgA1 was isolated from patients with IgAN lgAN or healthy controls by jacalin-affinity chromatography. Six fractions of molecular weight (MW) 50-1,000 kDa were separated by fast protein liquid chromatography (FPLC). Four lectin-binding assays were used to study the sialylation and the presence of terminal galactose or N-acetylgalactosamine (GaINAc) in the O-linked carbohydrate moieties of κ- or γ-IgA1. Maackia amurensis agglutinin (MAA) and Sambucus nigra agglutinin (SNA) lectin recognize α(2,3)- and α(2,6)-linked sialic acid, respectively. Peanut agglutinin (PNA) and Helix aspersa (HA) lectin recognize terminal galactose and GaINAc, respectively. Reduced HA was demonstrated in macromolecular κ or γ-IgA1 (300-825 kDa) isolated from patients with IgAN (P < 0.05 compared with healthy controls). Lambda- but not κ-IgA1 from patients with IgAN bound less to PNA (P < 0.05). The α(2,3)-linked sialic acid content in γ- but not κ-IgA1 of MW 150-610 kDa from patients was higher than that of controls (P < 0.005). The α(2,6)-linked sialic acid content in γ-IgA1 (300-825 kDa) and κ-IgA1 (150-610 kDa) from patients was also higher than that of controls. This unusual glycosylation and sialylation pattern of the γ-IgA1 may have important implications for the pathogenesis of IgAN, as both the masking effect of sialic acid on galactose and the reduced galactosylation will hinder the clearance of macromorecular γ-IgA1 by asialoglycoprotein receptor of hepatocytes. The negative charge from sialic acid may also favor mesangial deposition of macromolecular γ-IgA1 in IgAN. © 2002 Wiley-Liss, Inc.link_to_subscribed_fulltex

Effect of subcutaneous and intraperitoneal administration of recombinant human erythropoietin on blood pressure and vasoactive hormones in patients on continuous ambulatory peritoneal dialysis

The effect of subcutaneous and intraperitoneal administration of recombinant human erythropoietin (rHuEPO) on blood pressure was evaluated in 20 patients with renal failure on continuous ambulatory peritoneal dialysis. The two groups of patients were commenced on a 16-week course of twice weekly rHuEPO by either the subcutaneous (10 patients) or the intraperitoneal route (10 patients). One patient in the latter group was subsequently excluded because of operation and transfusion. The hemoglobulin increased significantly from 6.9 ± 0.3 g/dl to 9.8 ± 0.6 g/dl after subcutaneous rHuEPO treatment (p < 0.01) at an average dose of 84 ± 9 U/kg body weight/week. For the intraperitoneal group, despite a higher average rHuEPO dosage (133 ± 7 U/kg body weight/week), the hemoglobin level was not significantly altered (7.0 ± 0.4 g/dl to 8.0 ± 0.4 g/dl, p < 0.03). During the 16-week period of rHuEPO therapy, an increase in antihypertensive therapy was required more frequently in patients in the intraperitoneal group but the difference between groups failed to reach statistical significance. There was no conclusive evidence that the rise in hematocrit was an independent precipitant of hypertension. Patients who were hypertensive prior to rHuEPO therapy appeared most susceptible to the pressor effects in that 8 of 11 treated hypertensive patients required more intensive antihypertensive treatment during EPO administration whereas none of the untreated patients developed hypertension during the study (Fisher's exact test, p = 0.007). Plasma levels of the vasoactive hormones, atrial natriuretic peptide (ANP), plasma renin activity (PRA), and endothelin (ET) remained unchanged during both subcutaneous and intraperitoneal rHuEPO therapy. These observations suggest that the presence of hypertension predisposes to the pressor effect of EPO, and that the vasoactive hormones ANP, PRA, and ET are unlikely to be involved in the pathophysiology of rHuEPO-induced hypertension.link_to_subscribed_fulltex

Correction of anemia using self-administered daily subcutaneous erythropoietin in uremic patients on continuous ambulatory peritoneal dialysis

We studied the effects of self-administered, daily, low-dose, subcutaneous (SC) erythropoietin (EPO) therapy in 15 uremic patients on continuous ambulatory peritoneal dialysis (CAPD) for 16 weeks to assess its efficacy and safety. The patients had baseline hemoglobin (Hb) levels of <8 g/dl and were started on 10 u/kg/day of beta-EPO. The dosage of EPO was adjusted every 4 weeks according to hematological response. The patients learned to inject into their thighs themselves. Hb increased significantly from 6.6 ± 0.2 g/dl (mean ± SEM) at week 0 to 9.0 ± 0.3 at week 8 and 10.0 ± 0.4 at week 16 (p < 0.0001). Hematocrit (Hct) increased significantly from 0.20 ± 0.01 at week 0 to 0.27 ± 0.01 at week 8 and 0.29 ± 0.001 at week 16 (p < 0.0001). The mean EPO dose was 10 u/kg/day at week 0 and 10.5 ± 0.4 at week 8 and 10.3 ± 0.5 at week 16. After minor adjustments in antihypertensive therapy had been made no significant differences in mean arterial blood pressure were noted. Six of 15 patients required increased dosage of antihypertensive drugs. All patients were given oral iron supplements. There was a significant decrease in percentage of transferrin saturation and 10 patients required additional intravenous iron supplements. There was no significant difference in the serum levels of creatinine, albumin, potassium, phosphate and urate with EPO treatment. There were no local complications at the sites of injection and the injections themselves were quite painless. We conclude that low-dose SC daily EPO is effective and safe in the correction of anemia in CAPD patients.link_to_subscribed_fulltex

The information needs of breast cancer patients in hong kong and their levels of satisfaction with the provision of information

Background: Information is vital for patients in overcoming cancer and making decisions about their treatment plans, but little is known about the information needs of Chinese breast cancer patients and their satisfaction with the information provided. Objectives: The objectives of this study were to examine the priority of information needs perceived by participants and the demographic and clinical factors that affect the priority of information needs such as prioritization, the utilization of and satisfaction with different sources of information, and satisfaction with the information provided by health care professionals. Methods: A self-administered survey was used, including sources of information, an Information Needs Questionnaire-Chinese version, and patients' satisfaction with the information provided by health care professionals. Results: Participants (n = 374) ranked the likelihood of cure, spread of the disease, and treatment options as the 3 most important information needs. They had mostly been using the information sources available in the hospital. Despite health care professionals being ranked as a highly satisfying source of information, participants perceived different levels of satisfaction with the various types of information provided. Conclusion: Participants perceived information about the illness itself and about treatment as most important. They preferred to use sources available in the hospital, but the satisfaction rates associated with information provided by health care professionals were relatively low. Implications for Practice: This study provides useful information about what patients really want to know and a potential basis for developing more effective models to deliver information and support to breast cancer patients. Identification of the actual needs of these patients can produce better resource allocation and provide health services more efficiently to meet those needs. Copyright © 2010 Lippincott Williams & Wilkins.link_to_subscribed_fulltex

Modulation of intra-pulmonary TGF-β expression by mycophenolate mofetil in lupus prone MRL/lpr mice

We investigated the expression profile of inflammatory cytokines in the lung of lupus-prone MRL/lpr mice and evaluated the therapeutic potential of mycophenolate mofetil (MMF) in reducing pulmonary cytokines in active lupus. Eight-week old female MRL/lpr mice (n = 20) were treated with MMF in vehicle by oral gavage. Disease control MRL/lpr mice (n = 30) or normal control MRL mice (n = 20) received vehicle alone. The mice were sacrificed after eight or 12 weeks of treatment. Gene expression and protein synthesis of IL-1β, MCP-1 and TGF-β1 in lung tissues were determined. We found an increase in the gene expression of IL-1β, MCP-1 and TGF-β1 in lung tissues of untreated MRL/lpr mice compared with MRL mice at either 16 weeks or 20 weeks of age. MMF treatment significantly prolonged the survival of MRL/lpr mice, down-regulated the gene expression of IL-1β, MCP-1 and TGF-β1 in lung tissues at the end of eight or 12 weeks of treatment. Protein synthesis of TGF-β1 was decreased following eight weeks of MMF treatment. We conclude that MMF treatment can reduce the TGF-β1 gene expression and protein synthesis in lung tissues of lupus-prone mice. Our findings provide experimental data suggesting a beneficial potential of MMF therapy in pulmonary involvement of lupus. © 2005 Edward Arnold (Publishers) Ltd.link_to_subscribed_fulltex

CD4-positive cells from patients with IgA nephropathy demonstrate increased mRNA of cytokines that induce the IgA switch and differentiation

IgA nephropathy (IgAN) is characterized by raised serum IgA1 and mesangial IgA1 deposits. We have previously shown increased T-cell activation in IgAN. Recently, transforming growth factor-β (TGF-β) has been shown to induce IgA isotype switch at a clonal level and interleukin 5 (IL5) promotes differentiation into IgA-bearing B cells. In the present study we have examined the TGF-β and IL5 mRNA expression by mitogen-activated CD4-positive T cells from patients with IgAN (n = 25), patients with other primary nephritides (CGN) (n = 24), and healthy control subjects (n = 25). The cytokine genes were analysed by reverse transcription (RT)-polymerase chain reaction (PCR) and were semi-quantitated by normalizing the differences occurring during RT and PCR using a housekeeping gene, β-actin. CDC-positive T cells from IgA nephritic patients expressed a higher level of IL5 mRNA than healthy controls (P < 0.01) and patients with CGN (P < 0.005). CD4-positive T cells from IgA nephritic patients expressed a higher level of TGF-β mRNA than healthy controls (P < 0.01) but no difference was demonstrated on comparison with CGN patients. Elevated TGF-β mRNA expression in patients with CGN probably reflects its other important function as a 'sclerogenic' factor involved in the glomerulosclerosis found in these nephritides. Our data suggest that there is increased expression of cytokine genes which induce the IgA isotype switch and differentiation; these immunological abnormalities may be important in the pathogenesis of IgAN.link_to_subscribed_fulltex