The Effects of Dietary Intervention and Macrophage-Activating Factor Supplementation on Cognitive Function in Elderly Users of Outpatient Rehabilitation.

BACKGROUND: Age, genetic, and environmental factors are noted to contribute to dementia risk. Neuroplasticity, protection from degeneration and cell death, and early intervention are desirable for preventing dementia. The linkage between neurons and microglia has been a research focus. In this study, we examined the effects of dietary modification (a reduction in advanced glycation end products [AGEs]) and macrophage-activating factor (MAF; a macrophage regulator) supplementation on cognitive function in elderly participants undergoing rehabilitation. METHODS: Participants were older than 60 years of age and had been attending a daycare rehabilitation facility for at least three months without cognitive dysfunction, severe anemia, terminal cancer, or neurodegenerative diseases such as Parkinson's disease. The exercise protocol at the rehabilitation facility was not changed during the study period. Forty-three participates were randomly divided into three groups: a control group receiving placebo, a group receiving dietary guidance, and a group receiving dietary guidance and MAF supplementation. The amyloid-ß40/42 ratio, dietary AGE intake, plasma AGE levels, dietary caloric intake, and mild cognitive impairment (MCI) screen test were evaluated. RESULTS: Four participants withdrew from the study. MCI screening scores significantly improved in the MAF supplementation group, especially after 6 months. Dietary modulation was also more effective than placebo at improving cognitive function after 12 months. Only the control group exhibited significantly increased plasma AGEs while the dietary modulation and MAF supplementation groups showed no change in plasma AGEs after 12 months. CONCLUSIONS: MAF supplementation improved cognitive function, especially after 6 months, in elderly people undergoing rehabilitation. Dietary modulation was also effective for improving cognitive function after 12 months compared to that in the control group. It was difficult to supervise meals during dietary guidance at the daycare service. However, simple guidance could show improvements in cognitive function through diet.

The effect of Chlorella supplementation in pregnant women with low-grade inflammation.

Pregnancy dramatically changes maternal metabolism and the microbiome. Low-grade inflammation can cause maternal complications and fetal abnormalities. The objective of this open-label, randomized, controlled study was to evaluate the efficacy and safety of orally administered Chlorella, a green alga that is commercially available as a dietary supplement with rich nutrients and dietary fiber for pregnant women with low-grade inflammation. Patients with C-reactive protein levels >0.05 mg/dL (16 weeks gestation, n = 22) were enrolled and randomly allocated to the Chlorella group (n = 10) or control group (n = 12). We conducted blood biochemical tests at 25, 30, and 35 weeks gestation and evaluated the evacuation status (symptoms depending on the Rome IV C2 criteria and laxative usage), side effects, and complications throughout the investigation. We also monitored the status of the offspring. The Chlorella group (n = 0) showed a significantly lower rate of constipation than the control group (n = 8). This study demonstrated the beneficial effects and safety of Chlorella supplementation in pregnant women, which prevented constipation and unnecessary laxative administration.

Case Study of Homeopathic Bowel Nosode Remedies for Dysbiotic Japanese Patients.

BACKGROUND: The composition of intestinal microbiota is very important in human health. Gastrointestinal disturbances are among the symptoms commonly reported by individuals diagnosed with chronic diseases, such as inflammatory bowel disease, autism, and chronic fatigue syndrome. The effects of probiotics and prebiotics for dysbiosis have been reported in many studies. Bowel nosodes are homeopathic remedies made from human gut microbiota. OBJECTIVE: Bowel nosodes made from the intestinal bacteria of European patients from the 1900s were administered to Japanese patients suffering from gastrointestinal disturbances, such as constipation and diarrhea, to determine their therapeutic efficacy. METHODS: Twenty-eight outpatients from Yoko Clinic (11 males, 17 females; age range, 4-72 years) were enrolled in this study. One nosode remedy was selected for each case. Patients took six pills for 2 days. After a month, the effect of each treatment was evaluated using the Glasgow Homeopathic Hospital Outcome Scale (grade +4 to -4). RESULTS: Patient number of each grade was +4 (N = 2), +3 (N = 4), +2 (N = 7), +1 (N = 3), 0 (N = 7), with no negative grades. Of the 23 patients analyzed, 69.6% showed some type of improvement, and no harmful effects from taking bowel nosodes were observed; 26% of patients showed major improvement or were "cured." CONCLUSION: It is difficult to find correct constitutional remedies as they often require high-level techniques and time. Since there are only 11 main bowel nosode remedies, they are easier to choose from and cheaper to use and develop than classical constitutional remedies. Herein, 69.6% of dysbiotic patients taking bowel nosodes showed improvements, and no harmful effects were reported by any patient. These results suggest that the homeopathic bowel nosodes are a useful method for controlling gastrointestinal disturbances.

A 10-patient case study on the influence of two different probiotics on individual intestinal microbiota.

BACKGROUND: Probiotics increase beneficial microbiota and improve chronic conditions, such as atopic diseases, irritable bowel disease, and obesity. However, because there are so many probiotics, it is unknown which probiotics might have more of an effect on intestinal microbiota. OBJECTIVE: To understand how two different types of probiotics influence human intestinal microbiota, human fecal microbiota were analyzed after ingestion of each of the probiotics. MATERIALS AND METHODS: Ten outpatients were enrolled. Study A: Five patients took Lactobacillus buchneri (SU) for 4 weeks and mixed probiotics (NS) for the following 4 weeks. Study B: One year after study A, the other five patients took NS for 4 weeks at first and SU for the following 4 weeks. Fecal samples were collected before and after the outpatients took each of the two probiotics and were then analyzed. RESULTS: Study A: Three of the five patients had a decreased percentage of beneficial bacteria (Lactobacillales, Bifidobacteria species) after taking SU (change [expressed as mean±standard deviation] from 13.7%±7.1% to 4.0%±3.5%), whereas the remaining two patients showed an increased percentage (from 16.8%±3.4% to 30.4%±4.6%). After taking NS, the three patients who had a decreased percentage of beneficial bacteria after taking SU increased (from 4.0%±3.5% to 8.0%±2.1%), whereas the two patients who had increased beneficial bacteria after taking SU showed a decreased percentage (from 30.4%±4.6% to 16.4%±7.4%). Study B: All five patients had increased beneficial bacteria after taking NS (from 9.9%±2.9% to 14.5%±4.8%). After taking SU, all five patients had decreased bacteria (14.5%±4.8% to 10.9%±5.8%). CONCLUSION: The two probiotics studied had different influences. Probiotics should be selected not only for their quality but also for compatibility with each intestinal bacterial flora.

Effect of thermal therapy using hot water bottles on brain natriuretic Peptide in chronic hemodialysis patients.

INTRODUCTION: The use of repeated thermal therapy for improving the symptoms of chronic heart failure (CHF) has been recently demonstrated. Usually, thermal therapy requires an infrared dry sauna. However, it is difficult for small clinics to acquire such an expensive and extensive system. The present study assessed the efficacy of its substitution with hot water bottles. Moreover, there are no prior studies demonstrating the efficacy of thermal therapy in hemodialysis patients with CHF. METHODS: Plasma brain natriuretic peptide (BNP) levels were evaluated in 98 hemodialysis patients in a clinic. Nine patients whose BNP levels were >500 pg/mL agreed to be enrolled in the study and received thermal therapy using hot water bottles. RESULTS: Plasma BNP levels, a potential marker for CHF, tended to decrease (891 ± 448 to 680 ± 339 pg/mL), but the difference was not significant (P = 0.0845). The oral temperature changed from 36.44 ± 0.45°C to 37.04 ± 0.48°C (+0.597°C, P < 0.0001). No side effects were experienced during the therapy. Moreover, most patients had an improvement in their symptoms and the ability to perform activities of daily living. CONCLUSION: Thermal therapy using hot water bottles is very safe and tends to reduce plasma BNP levels in hemodialysis patients with CHF.

Effects of eicosapentaenoic acid supplementation on immunoglobulin A nephropathy.

Eicosapentaenoic acid (EPA), which is purified from fish oil, attenuates inflammatory responses by decreasing eicosanoid and cytokine production. EPA reportedly improves renal survival in patients with immunoglobulin (Ig)A nephropathy; however, this is unconfirmed. We studied the effects of EPA on IgA nephropathy patients. Eighteen biopsy-confirmed IgA nephropathy patients (aged 31 +/- 3 years) were enrolled. The prognoses based on glomerular findings were good (N = 5), relatively poor (N = 12), and poor (N = 1). EPA was administered at 1.8 g/day for 12 months. Five biopsy-confirmed IgA nephropathy patients were enrolled as control subjects. Administration of other drugs used to treat IgA nephropathy was not changed. The estimated creatinine clearance (eCCr), serum creatinine (Cr) concentration, urinary protein creatinine ratio (U/P), and other clinical parameters were checked. In the EPA group, the Cr went from 0.8 +/- 0.2 mg/dL to 0.7 +/- 0.2 mg/dL after 12 months of EPA treatment, and the U/P went from 550 +/- 580 mg/g Cr to 330 +/- 920 mg/g Cr. The values did not differ significantly; however, Cr and U/P tended to improve, with no adverse effects from the EPA. The eCCr improved significantly (99 +/- 7-110 +/- 8 mL/min, P = 0.001) in the EPA group, but not in the control group (126 +/- 12-120 +/- 13, P > 0.05). The effect of EPA in patients with IgA nephropathy is not pronounced, but these results suggest that EPA is a safe and worthwhile supplement to the drugs used to treat this disease.

Colon irrigation causes lymphocyte movement from gut-associated lymphatic tissues to peripheral blood.

It is well established that the intestine is an important site responsible for the local immune system. It is speculated that people suffering from constipation and carrying fecal residues in the intestine may have a decreased function of this immune system. In this study, colon irrigation, which is cleansing of the colon using a simple hydrotherapy instrument, was performed in 10 subjects with or without the disease. The number of leukocytes and their demarcation were then evaluated. The number and ratio of lymphocytes increased significantly after irrigation. This result suggested that colon irrigation might induce lymphocyte transmigration from gut-associated lymphatic tissues into the circulation, which may improve colon and immune system function.

Plasma S100A12 concentrations in peritoneal dialysis patients and subclinical chronic inflammatory disease.

S100A12 is a ligand for the receptor for advanced glycation end products. It has been shown that S100A12 induces expression of adhesion molecules, and mediates activation and migration of monocytes/macrophages. Circulating S100A12 may be involved in chronic inflammation. We previously reported increased S100A12 levels in patients with non-insulin-dependent diabetes mellitus and hemodialysis. A high peritoneal solute transport rate may be associated with encapsulating peritoneal sclerosis and mortality. We measured plasma S100A12 levels in peritoneal dialysis patients and evaluated a possible relation between the increased plasma S100A12 levels in peritoneal dialysis patients and the high peritoneal solute transport rate. Subjects included 36 patients (mean age +/- SE, 46.0 +/- 12.0 years) with no apparent infection and no malignancy who had been undergoing peritoneal dialysis for 36.5 +/- 3.9 months. We developed an enzyme-linked immunosorbent assay system to measure plasma S100A12 levels. A peritoneal equilibrium test was performed and subjects were categorized as high and high-average (H) (n = 14) or low and low-average (L) (n = 22) transporters. Plasma S100A12 concentrations were significantly higher in peritoneal dialysis patients (21.6 +/- 3.0 ng/mL) than in control subjects (n = 42; 10.8 +/- 1.0 ng/mL). Plasma S100A12 concentrations were also higher in the H group (28.2 +/- 6.1 ng/mL) than in the L group (14.2 +/- 2.0 ng/mL). These results suggest that S100A12 may be a sensitive marker of subclinical inflammation and that an increased S100A12 level may be related to the high peritoneal solute transport rate.

Miliary tuberculosis with hypercalcemia, and a false abdominal aortic aneurysm, but no pulmonary findings.

A 69-year-old man with a 10-year history of diabetes mellitus and 1-year history of steroid treatment for nonspecific interstitial pneumonia presented with a nightly fever of over 39 degrees C after surgery for a false abdominal aortic aneurysm. Hypercalcemia was detected, despite acute renal dysfunction. There was no laboratory evidence of collagen disease or infection including tuberculosis. Polymerase chain reaction (PCR)-based amplification of DNA from a bone marrow biopsy specimen revealed Mycobacterium tuberculosis. Antituberculous chemotherapy was initiated. Early bone marrow biopsy and the use of new techniques such as PCR can avoid delay in initiating the proper treatment for compromised patients.

Predominant tubulointerstitial nephritis in a patient with systemic lupus nephritis.

In most cases of systemic lupus erythematosus (SLE), glomerular lesions are the main renal complication. Although tubulointerstitial lesions are often associated with severe glomerular lesions, predominant or isolated tubulointerstitial injury in the presence of minimal glomerular abnormalities with SLE, so-called predominant tubulointerstitial lupus nephritis, is rare. Only ten cases are reported in the English literature. Herein, we describe the case of a 64-year-old man with SLE who presented with acute renal deterioration attributable to acute tubulointerstitial nephritis. Renal biopsy showed diffuse infiltration of inflammatory mononuclear cells in the interstitium and tubulitis without significant glomerular lesions. Immunofluorescence study revealed positive staining for IgG, C3, and C1q along the renal tubular basement membrane (TBM). Electron microscopy also showed electron-dense deposits in the TBM. Other causes of tubulointerstitial injury, such as drug use and infection, were ruled out. Taking these findings together with the presence of antitubular basement membrane antibody, predominant tubulointerstitial lupus nephritis was diagnosed. Treatment with oral corticosteroids for 6 weeks improved renal function. Even after tapering of the corticosteroid, renal function and serological markers of SLE activity have remained stable in this patient for more than 12 months.

Comparison of the effects of quinapril and losartan on carotid artery intima-media thickness in patients with mild-to-moderate arterial hypertension.

BACKGROUND: Ultrasonographic evidence of increased carotid intima-media thickness (IMT) is known to be associated with generalized atherosclerosis. Therapeutic blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme (ACE) inhibitors reportedly reduces carotid IMT in humans. However, there has been no head-to-head comparison of the effects of ACE inhibitor and angiotensin receptor blocker (ARB), a newer type of RAS inhibitor, on carotid IMT. METHODS: 57 hypertensive patients were randomly assigned to treatment with one of two antihypertensive drugs: ACE inhibitor (quinapril; n = 25, group Q) or ARB (losartan; n = 18, group L). RESULTS: After 1 year of treatment, a similar decrease in mean blood pressure was observed in all groups. Carotid IMT was decreased significantly in group Q (10% decrease, p < 0.05) but did not change in group L. There were no significant changes in other atherosclerotic factors between these two groups. CONCLUSION: Our findings suggest that the antiatherosclerotic effect of quinapril is more potent than that of losartan in hypertensive patients. This effect appears unrelated to the drug's antihypertensive action or to traditional atherosclerotic factors.

Acute tubulointerstitial nephritis associated with autoimmune-related pancreatitis.

Various etiologic factors have been identified in tubulointerstitial nephritis (TIN), including allergic drug reaction, infection, and immune-mediated disease. Immune-mediated TIN without significant glomerular involvement has been reported to occur as a renal complication secondary to Sjögren's syndrome, lupus nephritis, and antitubular basement membrane antibody-related disease. We present a first case of acute TIN associated with autoimmune-related pancreatitis (AIP). A 64-year-old man was referred to our division from a surgeon for the close examination of renal dysfunction. The pancreatic and biliary imaging showed segmental narrowing of the pancreatic duct with localized swelling of the pancreatic head, suggesting the carcinoma of the pancreatic head at that time. However, the laboratory findings also showed renal dysfunction with high level of serum immunoglobulin G and hypocomplementemia. Renal biopsy was performed to investigate the etiology of the renal dysfunction. The renal biopsy specimen showed acute TIN. The patient had no drug history, which may cause TIN. Oral corticosteroid therapy improved the renal function as well as histological damage, the pancreatic imaging study, and the laboratory tests of pancreatic and hepatobiliary enzyme. Although the pancreatic biopsy has not performed in our patient, his clinical course confirmed us that AIP was the final diagnosis for his pancreatic lesion. Despite further examination, there was no evidence of other autoimmune-related diseases such as Sjögren's syndrome. To our knowledge, this is the first report of acute TIN associated with AIP. We suggest that AIP may be an etiologic factor in some cases of TIN.

Regulation of glucose transporter (GLUT1) gene expression by angiotensin II in mesangial cells: involvement of HB-EGF and EGF receptor transactivation.

In the development of diabetic nephropathy, angiotensin (Ang) II is thought to exert numerous actions on the glomerulus, and especially on the mesangium. However, the role(s) played by Ang II in the glucose metabolism per se in mesangial cells remains unclear. Ang II, at least via its type 1 receptor (AT1-R)-mediated effect, phosphorylates extracellular signal regulated kinase (ERK) by transactivation of epidermal growth factor receptors (EGF-Rs) via the Ca2+ or protein kinase C (PKC) pathways. Our objective in the present study was to assess the effect of Ang II on glucose transporter 1 (GLUT1) gene expression and to clarify the involvement of EGF-R in Ang II-mediated GLUT1 mRNA expression in glomerular mesangial cells. The results showed that Ang II upregulated GLUT1 mRNA accumulation in a time- and dose-dependent manner (peaking at 12 h; approximately 3.8-fold vs. control), and this upregulation was completely inhibited by the PKC inhibitor calphostin-C. The Ang Il-induced GLUT1 expression was significantly inhibited by the EGF-R inhibitor AG1478 (approximately 80% inhibition), by inactivation of ERK by PD98059, and by pretreatment with heparin and the metalloproteinase (MMP) inhibitor batimastat. On the other hand, phorbol ester markedly upregulated GLUT1 mRNA (approximately 8.6-fold). Batimostat and AG1478 significantly reduced the phorbol ester-induced GLUT1 mRNA expression (approximately 72 and approximately 69% inhibition, respectively). In conclusion, PKC-mediated heparin-binding (HB)-EGF/EGF transactivation followed by ERK activation plays a predominant role in the induction of GLUT1 expression by Ang II.

Involvement of HB-EGF and EGF receptor transactivation in TGF-beta-mediated fibronectin expression in mesangial cells.

BACKGROUND: Gq-coupled receptors are known to transactivate epidermal growth factor receptor (EGFR) via the Ca2+ and PKC pathways to phosphorylate extracellular signal-regulated kinase (ERK). METHODS: We studied the involvement of EGFR in transforming growth factor-beta (TGF-beta)-mediated fibronectin (FN) expression using glomerular mesangial cells. RESULTS: TGF-beta up-regulated FN mRNA accumulation in a time- and dose-dependent manner, which was completely inhibited by phosphatidylcholine-phospholipase C (PC-PLC) inhibitor and PKC inhibitors (calphostin-C and staurosporin). The EGFR inhibitor AG1478 completely abolished TGF-beta-mediated FN expression. ERK inactivation by PD98059, and p38MAPK inhibitor SB203580 also showed significant inhibitory effects. Addition of neutralizing anti-heparin-binding EGF-like growth factor (HB-EGF) antibody, pretreatment with heparin and the metalloproteinase (MMP) inhibitor batimastat blocked FN expression. In mesangial cells stably transfected with a chimera containing HB-EGF and alkaline phosphatase (ALP) genes, ALP activity in incubation medium was rapidly increased by TGF-beta (2.1-fold at 0.5 min) and reached a 3.7-fold increase at two minutes, which was abolished by calphostin-C or batimastat. TGF-beta phosphorylated EGFR, ERK and p38MAPK in a PKC- and MMP-dependent manner. Smad2 phosphorylation by TGF-beta was not affected by AG1478, and HB-EGF did not activate Smad2. FN mRNA stability was not affected by TGF-beta. Cycloheximde did not interfere with TGF-beta-mediated FN expression. CONCLUSIONS: The present study demonstrated that HB-EGF processed and released via PC-PLC-PKC signaling is an intermediate molecule for TGF-beta-mediated EGFR transactivation, and subsequent activation of ERK and p38MAPK is involved in FN expression via transcriptional regulation without requiring new protein synthesis.