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Paramylon is a novel β-glucan that is stored by Euglena gracilis Z, which is a unicellular photosynthesizing green alga with characteristics of both animals and plants. Recent studies have indicated that paramylon functions as an immunomodulator or a dietary fiber. Currently, chronic kidney disease (CKD) is a global health problem, and there is no effective preventive treatment for CKD progression. However, paramylon may suppress the progression of CKD via the elimination of uremic toxins or modulation of gut microbiota, leading to the alleviation of inflammation. The aim of this study was to evaluate the effect of paramylon in CKD rat model. Eight-week-old male Wistar rats with a 5/6 nephrectomy were given either a normal diet or a diet containing 5% paramylon for 8 weeks. Proteinuria was measured intermittently. Serum and kidney tissues were harvested after sacrifice. We performed a renal molecular and histopathological investigation, serum metabolome analysis, and gut microbiome analysis. The results showed that paramylon attenuated renal function, glomerulosclerosis, tubulointerstitial injury, and podocyte injury in the CKD rat model. Renal fibrosis, tubulointerstitial inflammatory cell infiltration, and proinflammatory cytokine gene expression levels tended to be suppressed with paramylon treatment. Further, paramylon inhibited the accumulation of uremic toxins, including tricarboxylic acid (TCA) cycle-related metabolites and modulated a part of CKD-related gut microbiota in the CKD rat model. In conclusion, we suggest that paramylon mainly inhibited the absorption of non-microbiota-derived uremic solutes, leading to protect renal injury via anti-inflammatory and anti-fibrotic effects. Paramylon may be a novel compound that can act against CKD progression., Competing Interests: Ms. Ayaka Nakashima and Dr. Kengo Suzuki are employees of euglena Co., Ltd. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLoS ONE policies on sharing data and materials.

Background: TAFRO syndrome is a systemic inflammatory disorder that manifests as thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). Renal dysfunction is frequently complicated with TAFRO syndrome, however, it is challenging to perform kidney biopsy in patients with TAFRO syndrome in the presence of thrombocytopenia. Renal histology in TAFRO syndrome mainly shows membranoproliferative glomerulonephritis (MPGN)-like lesions or thrombotic microangiopathy (TMA)-like glomerulopathy. We review our case and previous reports of TAFRO syndrome with kidney biopsy findings and discuss the renal pathophysiology of TAFRO syndrome., Case Presentation: We describe a previously healthy 48- year-old woman with TAFRO syndrome. Kidney biopsy performed before the treatment showed diffuse global endocapillary proliferative changes with endothelial cell swelling, double contours of partial capillary walls, and mesangiolysis, consistent with TMA-like glomerulopathy. Glucocorticoid therapy including steroid pulse was ineffective and she developed anasarca, renal dysfunction and oliguria. Hemodialysis was required. However, the anti-Interleukin (IL)-6 receptor antibody (tocilizumab) therapy was very effective. An increase in urinary volume was achieved about 2 weeks after the tocilizumab therapy and hemodialysis was discontinued. To investigate the renal pathophysiology of TAFRO syndrome, we performed immunohistological staining of vascular endothelial growth factor (VEGF)-A, CD34, and D2-40, in our case and a normal control kidney. Glomerular VEGF-A was especially positive in podocytes both, in the control and in the case, with no significant difference and there was a significant increase of VEGF-A staining area in the cortical peritubular capillaries in the case. Both glomerular and renal cortical CD34 expression were significantly decreased in our case. D2-40 expression in cortex was not significantly different., Conclusions: We reviewed our case and other 10 previous reports about renal biopsy findings in TAFRO syndrome and found that glomerular microangiopathy was a common finding. IL-6-VEGF-axis-induced glomerular microangiopathy may play a crucial role in developing acute kidney injury in TAFRO syndrome and the anti-IL-6 receptor antibody therapy may be useful for TAFRO syndrome refractory to glucocorticoids. About the pathophysiology of VEGF in TAFRO syndrome, VEGF balance in the glomerulus and perhaps in the peritubular capillary system as well may be critical. Further investigation is needed.

The palliative care team's roles are to provide a symptom relief to cancer patients, help them accept their medical conditions, and offer advice regarding the selection of appropriate medical treatments to suit their needs. Seeking the comfort of their homes, patients prefer a home care of superior medical care provided at hospitals. In 2008, 25 of the end-stage cancer patients at hospitals were expressed their desires to have a home medical care, and 10 of them were allowed to do so. We considered the following contributing factors that a patient should have for a smooth transition from hospital care to home medical care: (1) life expectancy of more than 2 months, (2) no progressive breathing difficulties experienced daily, (3) good awareness of medical condition among patients and families, (4) living with someone who has a good understanding of the condition, (5) availability of an appropriate hospital in case of a sudden change in medical requirements, and (6) good collaboration between emergency care hospitals, home physicians, and visiting nurses. To treat the end-stage cancer patients at home, there is a need for information sharing and a joint training of physicians specialized in cancer therapy, palliative care teams, home physicians, and visiting nurses. This would ensure a sustainable "face-to-face collaboration" in community health care.

Rupture of adrenal pheochromocytoma is extremely rare and can be lethal because of dramatic changes in the circulation. We describe a 58-year-old Japanese man who suffered rupture of a pheochromocytoma. The patient was referred to our hospital because of severe hypertension (256/127 mmHg) and a left adrenal tumor. T2-weighted magnetic resonance imaging showed high signal intensity in the 50-mm left adrenal tumor. Endocrinological examinations showed elevated plasma and urinary catecholamine levels. These findings suggested that the left adrenal tumor was a pheochromocytoma. Phentolamine mesilate was administered intravenously. This resulted in a decrease of the systolic blood pressure to 100 mmHg. On the third hospital day, the patient complained of left back pain, and abdominal computed tomography showed rupture of the pheochromocytoma. Pulmonary congestion and effusion, and paralytic small-intestinal ileus occurred. Blood pressure was controlled, small-intestinal decompression was done with a Miller-Abbot tube, and body water was controlled by fluid replacement. After the general condition of the patient had became stable, laparoscopic adrenalectomy was performed. Phentolamine mesilate is a useful α-adrenergic blocker. However, care is needed with its administration, because rupture of pheochromocytoma may be related to a decrease in blood pressure induced by phentolamine mesilate.

Purpose: In hypertensive patients with diabetes, antihypertensive therapy is important in reducing the risk of macro- and microvascular complications. In contrast to the guidelines issued by the American Diabetes Association (ADA) in and after 2002, the guidelines issued by the Japanese Society of Hypertension (JSH) in 2000 and 2004 maintained the traditional view that beta-blockers and thiazides should be rated as second-line drugs. However, both sets of guidelines recommended angiotensin converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) as first-line agents for such patients., Methods: We examined the use of antihypertensives in hypertensive patients with and without diabetes using the prescription data for 1999, 2002 and 2005 from three Japanese university hospitals., Results: When compared with 1999, the proportion of patients with and without diabetes using ARBs was dramatically increased in 2005 from 1.5 to 55% and from 1.5 to 40%, while that of angiotensin converting enzyme inhibitors decreased from 52 to 32% and 35 to 23%, respectively. A relatively stable proportion of patients (around 10% with and without diabetes) used beta-blockers and around 60% of patients with and without diabetes used calcium channel blockers (CCBs) and very few (<5%) used thiazides., Conclusions: The rapid increase in use of ARBs and under-use of thiazides may be explained by the fee schedule in the Japanese health insurance system. The paucity of large-scale clinical trials may also hinder evaluation of the traditional view of the role of beta-blockers and thiazides in treatment of Japanese patients with diabetes.

Objective: We investigated the clinical characteristics of intensive insulin therapy in Japanese type 2 diabetes patients who commenced intensive insulin therapy during the in-hospital diabetes education program at Tokai university hospital., Methods: 81 type 2 diabetes patients who received intensive insulin therapy and in-hospital diabetes education program were examined their clinical features., Results: Intensive insulin therapy maintained HbA(1C) below 7% at all time points during the 2-year follow-up, though it was not necessary to increase the insulin dose, thus highlighting the clinical utility of the therapy in preventing diabetic complications. Insulin therapy could be withdrawn from more than 25% of patients. The diabetic morbid period was shorter and urinary C-peptide level at admission was higher in patients of the withdrawal group than those of the non-withdrawal group, suggesting that patients with well maintained pancreatic β cell reserve could be withdrawn from insulin therapy., Conclusions: Based on our results of the efficacy of strict glycemic control for preventing the development and progression of diabetic complications, we recommend early introduction of intensive insulin therapy to achieve better glycemic control.

Objective: To determine the clinical usefulness of long-term intensive insulin therapy in Japanese patients with type 2 diabetes., Patients and Methods: Various clinical indicators and potential of withdrawal from insulin therapy were investigated in 20 type 2 diabetic patients receiving treatment in the outpatient clinic over a period of 8 years after starting intensive insulin therapy between April 1997 and March 1999., Results: The mean glycated hemoglobin (HbA1c) was approximately 6.5%, and there was no significant increase in insulin dose over a period of 8 years after commencement of intensive insulin therapy. Withdrawal from insulin therapy could be sustained in previously untreated patients., Conclusion: Our results indicated the clinical usefulness of intensive insulin therapy over the long term in Japanese patients with type 2 diabetes and that such therapy could be especially useful for previously untreated patients.

We retrospectively investigated 2,093 renal biopsy procedures performed between 1976 and 2000 at Tokai University Hospital. The study period was divided into 5-year intervals, and the frequencies of each renal disease, age and sex of patients were compared across the study period. Clinical diagnosis was based on WHO criteria. A total of 2,093 patients aged 8 months to 84 years underwent renal biopsy during the study period. The percentage of elderly patients who underwent renal biopsy increased from 1.2% in 1976 - 1980 to 9.9% in 1996 - 2000. IgAN was the most common disease in every 5-year period. CresGN showed an increase from 1 patient (0.3%) in 1976 - 1980 to 15 patients (4.0%) in 1996 - 2000. In contrast, the number of patients with PGN or BRH, MPGN significantly decreased during the study period. Although the criteria for renal biopsy and renal diseases detected are expected to change in the future, renal biopsy will remain an essential procedure for making a definite diagnosis, selection of optimum treatment, and prediction of prognosis.

Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome of variable tissue hyporesponsiveness to thyroid hormone (TH). Its characteristics are a high level of TH and inappropriate lack of TSH suppression. RTH is mainly categorized as generalized RTH (GRTH), pituitary RTH (PRTH), and peripheral tissue RTH (PTRTH). Untreated subjects with GRTH usually achieve a normal metabolic state. We describe a 21-year-old Japanese woman with GRTH and coincidental chronic thyroiditis. Physical examination revealed palpable goiter, congenital alopecia on top of the head, and short stature. She showed elevated levels of free triiodothyronine (FT3) and free thyroxine (FT4), and an inappropriately normal level of TSH. Anti-thyroglobulin and anti-thyroid peroxidase antibodies were positive. A TRH stimulation test showed a normal TSH response. The patient received the standardized diagnostic protocol, administration of incremental doses of liothyronine (L-T3). The peak TSH level after the TRH stimulation test gradually decreased. The patient showed low sensitivity to TH in terms of bone metabolism, protein catabolism, lipid metabolism, and urine magnesium metabolism. Sequence analysis of the TR beta gene was performed with informed consent, and this revealed a novel heterozygous mutation at codon 347 resulting in a GGG (glycine) to GCG (alanine) substitution (G347A). The patient was diagnosed as having GRTH with chronic thyroiditis, and carrying a novel mutation, G347A, of the TR beta gene.

Objective: Membranous nephropathy (MN) is the most common cause of adult-onset nephrotic syndrome and its management is still controversial. The aim of this study was to determine the effectiveness of corticosteroid-alone therapy for controlling proteinuria in MN., Methods: Twenty-three patients, which had moderate proteinuria (admission 24-hour urinary protein excretion 1.0 to 3.5 g/day) with primary MN were studied retrospectively., Results: Thirteen patients received corticosteroid-alone therapy combined with rest and dietary therapy (steroid group), while the other 10 patients were treated with rest and diet alone (non-steroid group). These two groups did not differ with respect to their laboratory features at the time of admission. After discharge, 5 of 13 patients of the steroid group dropped out . Therefore, only 8 patients could be followed up. As the result, 5 of 8 patients (62.5%) achieved complete remission (CR) and 3 of 8 patients (37.5%) had incomplete remission (ICR), so none of the patients failed to improve. On the other hand, 3 of 10 patients of the non-steroid group dropped out. Then, 7 patients were followed up. None of the 7 patients showed improvement during follow-up and 5 of these 7 patients were started on corticosteroids. Finally, as this result, 4 of 5 patients (80%) could achieve CR by 2 years after hospital discharge. Moreover, in the remaining 2 patients from the non-steroid group, no remission could be achieved even 2 years after discharge., Conclusion: These results suggest that long-term corticosteroid-alone therapy is beneficial for controlling proteinuria in patients with MN.

As for Isehara City Visiting Nursing Liaison Congress, we investigated and analyzed the actual conditions of visiting nursing care development at Isehara city by using the NADA nursing diagnosis. It is desirable that a visiting nurse should have skills in evacuation, suction of the respiratory tract, rehabilitation, prevention of complications and an early detection of a poor condition of the patient. In addition, we found that it is also desirable that a visiting nurse fulfill a leadership function in coordinating to support home-care, have a communication skill to anticipate potential problems of patients and counsel his or her family concerns in a short period of time.

Background: In development of progressive extracellular matrix accumulation, connective tissue growth factor (CTGF) may act as a downstream mediator of transforming growth factor-beta 1 (TGF-beta 1). However, the association and the correlation of these cytokines and extracellular matrix accumulation in human diabetic nephropathy (DN) is not fully understood., Methods: To explore the possible involvement of TGF-beta 1 and CTGF in extracellular matrix accumulation in DN, high-resolution in situ hybridization with digoxigenin-labeled antisense oligonucleotides to CTGF, TGF-beta 1 and type IV collagen mRNAs were performed in DN and in histologically normal human kidney (NHK). To quantify expression of each mRNA, the fraction of all nuclear cells that were positively stained in the cytoplasm was determined in at least 10 randomly selected cross-sections of nonsclerotic glomeruli., Results: Both in DN and in NHK, CTGF, TGF-beta 1 and type IV collagen mRNAs were mainly expressed by glomerular mesangial, visceral epithelial and parietal epithelial cells. The percentages of positive glomerular resident cells were significantly higher for each mRNA in DN compared with NHK. Especially, the expression of CTGF mRNA was also notably increased in case of DN with only mild histopathologic lesions. The extent of expression of each mRNA was significantly correlated to that of each other mRNA examined., Conclusion: Our study indicated that CTGF and TGF-beta may play an important role in glomerular histopathologic change in DN.

Objective: The receptor for advanced glycation end-products (RAGE) is one of several advanced glycation end-product (AGE)-specific cellular receptors. To evaluate the relationship between AGE and RAGE in renal tissues of diabetic nephropathy (DN), we examined the levels of expression of AGE protein and of RAGE mRNA. We also investigated the relationships among the degree of mesangial expansion and the expression of AGE and RAGE mRNA., Patients and Methods: Renal biopsy tissues were obtained from 20 patients with DN. We performed immunohistochemical staining using monoclonal anti-AGE antibody and in situ hybridization using non-radioactive oligonucleotide RAGE probe on these tissues. We also examined five control renal samples. We evaluated the intensity of positive anti-AGE antibody staining and the percentage of cells positive for RAGE mRNA. We also measured the total glomerular area and mesangial area in glomeruli using an automatic image analyzer. We then calculated the percentage of mesangial area as a proportion of the total glomerular area (%Mes)., Results: Anti-AGE antibody was detected in the expanded mesangial matrix in DN but not in control samples. RAGE mRNA expression was detected mainly in glomerular intrinsic cells, including glomerular mesangial and epithelial cells, in both DN and control. %Mes correlated significantly with both the intensity of anti-AGE antibody positive staining and the percentage of cells positive for RAGE mRNA., Conclusions: Our findings suggest that both AGE and RAGE are associated with the development and progression of DN.

We experienced a case of rheumatoid arthritis with nephrotic syndrome. A renal biopsy specimen from this patient showed various renal histological changes. The patient was a 50-year-old man who was diagnosed as having rheumatoid arthritis in 1987. We performed a renal biopsy because he had persistent proteinuria from March in 2002. The renal biopsy specimen showed amyloid AA and P protein deposition in the glomeruli. Moreover mild mesangial proliferation was recognized. IgA-deposition in the mesangial area, and granular-deposition of IgG along the glomerular capillary wall were also observed. In electron microscopy, electron dense deposits were recognized in the mesangial area and subepithelium of the glomerular basement membrane. From these findings, we diagnosed amyloid nephropathy, IgA nephritis and membranous nephropathy. Renal biopsy of patients with RA is useful not only for precise diagnosis, but also for selection of the appropriate treatment.

In order to clarify the present status of care-managers, a questionnaire was sent to 1,714 care-managers working in Kanagawa Prefecture in June 2002. The aspects investigated included their background, amount of care-management and degree of achievement, conditions of employment, opinion poll and training system. The response rate was 45.6% (782 out of 1,714). Concerning the total number of users in care at present, 37% of care-managers had less than 30 people, 24% from 31 to 50 and, surprisingly, 39% had more than 51 people. However, 42% answered that less than 30 was an appropriate number of users, 52% said 31 to 50 and only 6% answered that more than 51 people was an appropriate number. The conferences of users service representative were held only 8%. Concerning the burden of care-management, 87% of them answered the evaluation of every month and 86% did the conferences of users service representative. The cases requiring much time for the support, had problems not only the users but also in the household, who lacked the understanding and judgment for long-term care insurance. Most care-managers needed information on the available services and newly open care-service institutions. 27% of care-managers satisfied their care-management, 25% dissatisfied and the remainder were neither off nor on. The satisfaction to the care-management correlated well with the intelligibility of the management leader, motivation regarding care management and the degree of satisfaction with their income. It is concluded that the number of users per care-manager is too large, and that unfortunately it might further increase in the future. The conferences of users service representative were extremely held too low. It is also showed that information of the other service office and informal service with the exception of long-term care insurance are required.

Connective tissue growth factor (CTGF) is a cysteine-rich member of a new family of growth regulators. It is an important factor in the pathogenesis of mesangial matrix accumulation and progressive glomerulosclerosis. The present study was designed to elucidate the role of CTGF in diabetic nephropathy (DN), immunoglobulin A nephropathy (IgA-N), membranous nephropathy (MN), and minimal change nephrotic syndrome (MCNS). We evaluated the expression and localization of CTGF mRNA in surgically excised renal tissue samples from 10 patients with DN, 10 with IgA-N, 10 with MN, 10 with MCNS, and 10 normal human kidney (NHK) tissue samples, by using high-resolution in situ hybridization with digoxigenin-labelled oligonucleotide. To quantify CTGF mRNA expression, we counted all nuclei, and nuclei surrounded by CTGF-positive cytoplasm, in at least 10 randomly selected cross-sections of non-sclerotic glomeruli, and expressed the results as a percentage of total glomerular cells. In all glomeruli, CTGF mRNA was expressed mainly in glomerular intrinsic cells, including glomerular mesangial and epithelial cells and some cells of Bowman's capsule. The percentage of cells positive for CTGF mRNA was significantly higher in DN and IgA-N than in MN, MCNS and NHK. However, there was no significant difference in the percentage of CTGF mRNA-positive cells between DN and IgA-N. Our study indicates that CTGF may play an important role in the development and progression of glomerulosclerosis in DN and IgA-N, which are both accompanied by mesangial matrix expansion and comprise two major causes of end-stage renal failure.

Background/aim: Progressive expansion of mesangial matrix and glomerular basement membrane thickening represent alterations in the balance between synthesis and degradation of glomerular extracellular matrix (ECM) protein and are hallmarks of diabetic nephropathy. In order to elucidate the basis for this imbalance between the synthesis and the degradation of ECM in renal tissues from patients of type 1 diabetes mellitus (type 1D) with diabetic nephropathy (DN), we examined the expression of alpha1 chain of type IV collagen (IV-C), matrix metalloproteinase-2 and -3 (MMP-2, MMP-3), tissue inhibitor of metalloproteinase-1 (TIMP-1) and beta-actin mRNA using a high-resolution in situ hybridization with digoxigenin-labeled oligonucleotide., Methods: Patients were divided into two groups based on both of degree of mesangial expansion using electron microscopic point counting morphometric methods and duration of type 1D: 7 'fast-track' patients were selected for their very rapid development of DN structural changes and 8 'slow-track' patients for their very slow development of DN structural changes. Seven normal human kidney (NHK) tissues were used as controls., Results: Positive cells for each mRNA were observed in glomerular resident cells, including glomerular mesangial, epithelial and endothelial cells and cells of Bowman's capsule. The percentage of glomerular cells positive for IV-C, MMP-2 and MMP-3 mRNA was significantly greater in the 'slow-track' vs. 'fast-track' patients. No significant differences in percentage positive cells was seen for beta-actin mRNA. Furthermore, to elucidate the total number of positive cells per glomerulus for each mRNA, we estimated total cell number of glomerulus using morphometric techniques on light microscopy tissues. The total cell number per glomerulus was significantly greater in 'fast-track' than that in 'slow-track' patients and NHK. The total number of positive cells per glomerulus for MMP-2 in NHK was significantly greater than that in 'slow-track' and 'fast-track' patients., Conclusions: Thus, IV-C, MMP-2, MMP-3 and TIMP-1 mRNA are expressed in resident glomerular cells in renal tissues from NHK and type 1D. Glomerular alterations in these in situ mRNA expressions sufficient to explain ECM accumulation and DN risk were not uncovered. These largely negative results could be due to methodologic quantitative imprecision or could indicate that post-translational differences account for ECM imbalance in DN. However, these studies make it clear that unraveling the nature of the ECM production/removal imbalance in DN will require careful consideration of alterations in glomerular cell number., (Copyright 2002 S. Karger AG, Basel)

Objective: To evaluate the usefulness of renal biopsy in the overall management of patients with diabetes mellitus (DM), we examined the relationship between the clinical parameters and histopathological findings of renal biopsy samples., Methods: Renal biopsy specimens were obtained from 109 type 2 diabetic patients with proteinuria. Samples were divided into the following two groups: Diabetic Nephropathy (DN) group (n=80) had typical diabetic lesions without other renal diseases, complication group (n=29) had diabetic lesions with other renal diseases. Furthermore, DN group was subdivided into two subgroups: slow progressive group (SP group, n=32), the level of serum creatinine (s-Cr) was normal at the time of renal biopsy and three years after renal biopsy, and fast progressive group (FP group, n=14), the level of s-Cr was normal at the time of renal biopsy but more than doubled three years after renal biopsy., Results: The level of total protein was significantly lower and HbA1c significantly higher in the DN group than in the Complication group. However, other clinical parameters were not significantly different between the two groups. Urinary protein, systolic and diastolic blood pressure in FP group were significantly higher than in SP group. The percentage of sclerotic glomeruli, the severity of mesangial expansion, tubular injury and cell infiltration were significantly greater in FP than in SP group., Conclusions: Our results indicated that a complete evaluation of renal pathology in DM could not be made by clinical parameters only, and that the progression of DN could be accurately predicted by histopathological evaluation. Therefore, this study emphasizes the importance of renal biopsy in the overall management of patients with DM and/or DN.