Relations of lysophosphatidylcholine in low-density lipoprotein with serum lipoprotein-associated phospholipase A2, paraoxonase and homocysteine thiolactonase activities in patients with type 2 diabetes mellitus.

AIMS: We studied the relations of lysophosphatidylcholine (lyso-PC) in LDL with serum lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), paraoxonase and homocysteine thiolactonase (HTLase) activities in patients with type 2 diabetes mellitus. METHODS: Lyso-PC was measured by electrospray ionization-liquid chromatography/mass spectrometry. Paraoxonase and HTLase activities were measured with paraoxon and gamma-thiobutyrolactone as substrates, respectively. RESULTS: Serum HTLase and paraoxonase activities were significantly suppressed in diabetic patients (n=96) compared with control (n=25), whereas serum Lp-PLA(2) did not differ in control and diabetic patients. Lyso-PC contents in LDL correlated with serum Lp-PLA(2) activity positively and with serum HTLase activity negatively. Stepwise regression analysis revealed that serum Lp-PLA(2) and HTLase activities independently contributed to lyso-PC contents in LDL. In patients with diabetic nephropathy, lyso-PC contents in LDL were increased with reduced serum HTLase and paraoxonase activities compared with control, while serum Lp-PLA(2) activity did not differ. On the other hand, 3-month treatment with simvastatin reduced both lyso-PC contents in LDL and serum Lp-PLA(2) activity in hypercholesterolemic diabetic patients, while serum HTLase or paraoxonase activities did not change. CONCLUSIONS: Increased lyso-PC contents in LDL were associated with the suppressed HTLase activity, and serum Lp-PLA(2) and HTLase activities may be related to lyso-PC in type 2 diabetic patients.

Cerebral venous thrombosis associated with iron deficiency anemia.

A 55-year-old man presented with generalized seizures and postictal left hemiparesis. Computed tomography scanning of his head showed a low density area in the right frontal lobe. Cerebral angiography demonstrated a partial defect in the superior sagittal sinus and cortical veins, indicating the presence of cerebral venous thrombosis. He had bleeding from a peptic ulcer and the laboratory data revealed iron deficiency anemia concomitant with an elevation of D-dimer and thrombin-antithrombin III complex (TAT). After the anemia resolved with the treatment of the peptic ulcer and iron supplementation, the TAT and D-dimer levels were normalized, and the occluded veins were recanalized. In a cerebral venous thrombosis associated with iron deficiency anemia, treatment for the anemia may improve hypercoagulable state without antithrombotic therapy, although the long-term monitoring of TAT and D-dimer levels is required.

Intravenous calcitriol therapy in an early stage prevents parathyroid gland growth.

BACKGROUND: Both the phenotypic alterations of parathyroid (PT) cells, e.g. down-regulation of the calcium-sensing receptor, and the increase of the PT cell number in nodular hyperplasia are the main causes of refractory secondary hyperparathyroidism. It is of great importance to prevent PT growth in an early stage. METHODS: To examine a more effective method of calcitriol therapy for the prevention of PT hyperplasia, we randomized haemodialysis patients with mild hyperparathyroidism to receive either daily orally administered calcitriol (n = 33) or intravenous calcitriol (n = 27) over a 12-month study period. Calcitriol was modulated so as to keep the serum intact PTH level between 100 and 150 pg/ml. RESULTS: Both groups showed similar reductions of the serum PTH level and similar increases in serum calcium. In both groups, there were no significant changes in the serum phosphate level. Long-term daily oral calcitriol therapy failed to prevent the increase of both maximum PT volume and total volume, as assessed by ultrasonography; however, intravenous calcitriol therapy successfully suppressed this progression. In the daily, oral group, both the bone-specific alkaline phosphatase (BAP) and the N-telopeptide cross-linked of type I collagen (NTX) significantly decreased, which was probably due to the PTH suppression. However, these bone metabolism markers remained stable in the intravenous group. The total dosage of calcitriol during the study was comparable in both groups. CONCLUSIONS: These data indicate that intravenous calcitriol therapy in an early stage of secondary hyperparathyroidism is necessary to prevent PT growth and to keep a good condition of bone metabolism.

Intestinal spirochetosis due to Brachyspira pilosicoli: endoscopic and radiographic features.

We report a 31-year-old patient with intestinal spirochetosis. Colonoscopy revealed edematous mucosa with multiple erythematous spots in the proximal colon. Barium enema examination demonstrated marked edema with luminal narrowing and thumb-printing predominantly in the ascending colon. Numerous spirochetes were detected by histological examinations of biopsy specimens. Polymerase chain reaction (PCR) amplification of the bacterial 16S ribosomal RNA showed the organisms to be Brachyspira pilosicoli.

Factors affecting recurrence in patients with Crohn's disease under nutritional therapy.

PURPOSE: This retrospective study was designed to determine risk factors for recurrence of Crohn's disease under enteral nutrition. METHODS: The clinical course of 145 patients with Crohn's disease, who were primarily induced into remission by total parenteral nutrition, was reviewed. The patients were classified into two groups: enteral nutrition group (n = 98; >/=1,200 kcal/day of enteral nutrition), or nonenteral nutrition group (n = 47;<1,200 kcal/day of enteral nutrition) according to the amount of their daily elemental or polymeric diet. Contributions of enteral nutrition and other clinical variables to the recurrence were analyzed retrospectively. A Crohn's disease activity index of >150 plus an increase in Crohn's disease activity index of >70 from the baseline value was defined as recurrence. RESULTS: Forty-two patients in the enteral nutrition group and 29 patients in the nonenteral nutrition group recurred during periods ranging from 3 to 159 months. The cumulative rate of recurrence was significantly higher in the nonenteral nutrition group than in the enteral nutrition group (P = 0.047). Among the Crohn's disease patients in the enteral nutrition group, penetrating type (relative risk, 3.89; 95 percent confidence interval, 1.58-9.62), colonic involvement (relative risk, 3.10; 95 percent confidence interval, 1.39-6.9), and previous history of surgery (relative risk, 2.48; 95 percent confidence interval, 1.16-5.33) were factors that significantly affected recurrence. In contrast, penetrating type was the only possible factor associated with recurrence in the nonenteral nutrition group (relative risk, 2.75; 95 percent confidence interval, 0.96-7.81). CONCLUSIONS: Among patients with Crohn's disease under maintenance enteral nutrition, the risk of recurrence differs according to the disease type and the site of involvement. The maintenance treatment by enteral nutrition alone seems insufficient for patients with penetrating type or with colonic involvement.

Effect of the non-steroidal anti-inflammatory drug sulindac on colorectal adenomas of uncolectomized familial adenomatous polyposis.

BACKGROUND: The aim of the present study was to elucidate the effect of sulindac on uncolectomized familial adenomatous polyposis (FAP). METHODS: Seven FAP patients (SU group) without proctocolectomy were given sulindac 300 mg/day orally for 12 months. Six FAP patients without sulindac (non-SU group) served as controls. Colorectal lesions were assessed by protrusion index (no. radiolucent areas/cm(2); PI) under barium enema examination and non-polypoid lesion were assessed under chromoscopy prior to and at the end of the observation period. In the SU group, germline adenomatous polyposis coli (APC) mutation was determined by protein truncation test. RESULTS: In the SU group, PI decreased significantly in the distal colon (from 3.0 +/- 1.1 to 1.1 +/- 0.8/cm(2), P < 0.02) and in the proximal colon (from 3.4 +/- 2.4 to 0.9 +/- 1.3/cm(2), P < 0.02). The PI in the non-SU group slightly but significantly increased in the distal colon (from 1.0 +/- 0.8 to 1.2 +/- 0.9/cm(2); P < 0.05) and it remained unchanged in the proximal colon (from 0.6 +/- 0.3 to 0.7 +/- 0.3/cm(2); P > 0.05). Chromoscopy at the end of observation identified non-polypoid lesions in five patients in the SU group, whereas such lesions were not found in the non-SU group (71% vs 0%, P = 0.016). Decrease in PI was not different among distal APC mutation (exons 1-9), proximal APC mutation (exons 10-15) and negative mutation. CONCLUSION: Sulindac reduces colorectal adenomas of protruding type in uncolectomized FAP. The effect of sulindac may be unrelated to genotype of FAP.

Preventive effect of nutritional therapy against postoperative recurrence of Crohn disease, with reference to findings determined by intra-operative enteroscopy.

OBJECTIVE: The aim of this study was to elucidate the predictive value of intra-operative enteroscopy (IOE) and the effect of enteral nutrition (EN) with regard to the postoperative recurrence of Crohn disease (CD). MATERIAL AND METHODS: Forty patients requiring surgery for severe intestinal complications of CD were examined by IOE, and the severity of the remnant small intestine was determined. Patients were subclassified into either an EN group (>1,200 kcal/day) or a non-EN group (<1,200 kcal/day) according to the amount of daily EN intake after surgery. Contributions of IOE findings and EN to postoperative recurrence were analysed retrospectively. RESULTS: IOE identified intestinal lesions in 39 patients and active intestinal lesions in 24 patients. The cumulative rate of postoperative recurrence was significantly higher in patients with cobblestone appearance confirmed by IOE (p=0.006). However, other active intestinal lesions were not related to postoperative recurrence. EN reduced the cumulative rate of postoperative recurrence (p=0.017), especially in patients with penetrating type (p=0.005), in patients who did not have colitis (p=0.051) and in patients who did not have active intestinal lesions confirmed by IOE (p=0.02). CONCLUSIONS: EN is a prophylactic that prevents the postoperative recurrence of small intestinal CD. Patients with the penetrating type of CD, and those who do not have active lesions in the small intestine according to IOE, are candidates for EN after surgery.

Therapeutic efficacy of infliximab on active Crohn's disease under nutritional therapy.

OBJECTIVE: The aim of this investigation was to elucidate retrospectively the therapeutic effect of infliximab in patients with active Crohn's disease (CD) under nutritional therapy. MATERIAL AND METHODS: Using a review of the clinical records in 24 nationwide institutions specializing in inflammatory bowel disease, the short-term effect of infliximab in 97 patients with active CD was retrospectively investigated. The Crohn's disease activity index (CDAI) at baseline and after 2 weeks of a single infliximab administration (5 mg/kg) was compared among patients under total parenteral nutrition (TPN group, n=36), those following an elemental or polymeric diet (EN group, n=49) and those without TPN and EN (NN group, n=12). A decrease in CDAI >or= 70 or a CDAI value <150 at 2 weeks was regarded as effective. RESULTS: There was no difference in CDAI at baseline among the three groups. In each group, CDAI decreased significantly (from 250 (195-290) [median (interquartiles)] to 152 (123-233) in the TPN group, p<0.0001; from 259 (200-325) to 180 (130-238) in the EN group, p<0.0001; from 278 (222-291) to 164 (132-196) in the NN group, p=0.003). Infliximab was effective in 63.9% of patients in the TPN group, in 55.1% of those in the EN group and in 75% of the NN group. There was no statistical difference in efficacy among the three groups (p=0.4). Multivariate logistic regression analysis revealed younger age to be a significant factor related to the efficacy of infliximab. CONCLUSIONS: Infliximab is effective in patients with CD under TPN or EN. Age at infliximab administration may be predictive of response to infliximab.

Parathyroid cell growth in patients with advanced secondary hyperparathyroidism: vitamin D receptor, calcium sensing receptor, and cell cycle regulating factors.

The parathyroid gland (PTG) is a unique endocrine organ in which the quiescent glandular cells begin to proliferate in response to the demand for maintaining calcium (Ca) homeostasis in the progressive course of renal failure, leading to secondary hypereparathyroidism (SHPT). SHPT is characterized with continuous over-secretion of parathyroid hormone (PTH) and high turn-over bone disease, osteitis fibrosa, and the major factors include a deficiency of active vitamin D, hypocalcemia, and phosphate retention. With long-term end-stage renal failure, SHPT becomes resistant to conventional medical treatment such as phosphate binders and active vitamin D supplementation, and the growth of the PTG accelerates with the pattern of hyperplasia changing from diffuse to nodular type. In this process, the sigmoid curve between extracellular Ca concentration (exCa) and the plasma level of PTH shifts to the upper-rightward, indicating both an absolute increase in PTH secretion and the resistance of PT cells to exCa. Many experimental and human studies have revealed down-regulation of vitamin D receptor (VDR), calcium-sensing receptor (CaSR), and retinoid X receptor (RXR) in PT cells. The sustained proliferation of PT cells after obtaining autonomicity is another characteristic feature of SHPT. In this context, it has been demonstrated that the cell cycle is markedly progressed, where the expression of cyclin-dependent kinase inhibitor (CDKI), p21 and p27, is depressed in a VDR-dependent manner. These pathological features are most evident in nodular hyperplasia, in which monoclonal proliferation is obvious, indicating the phenotypic changes have occured in PT cells. It has been observed by Fukagawa and colleagues that pharmacologically high dose of active vitamin D administered orally can cause small-size PTG hyperplasia to regress in patients with advanced SHPT. Successful renal transplantation may also restore VDR and CaSR expressions in the diffuse type, in association with increasing TUNEL-positive cells. Thus, it is important to vigorously treat SHPT when the PT cell proliferation is in the reversible stage of diffuse hyperplasia.

Enteral nutrition as a primary therapy for intestinal lymphangiectasia: value of elemental diet and polymeric diet compared with total parenteral nutrition.

Intestinal lymphangiectasia (IL) is a rare disease requiring oral fat restriction. The aim of this study was to evaluate the efficacy of enteral nutrition compared to that of total parenteral nutrition (TPN). We retrospectively reviewed nine patients with IL presenting with protein-losing enteropathy. Of these, seven patients not responding to a low-fat diet were treated with elemental diet (ED), polymeric diet (PD) containing medium-chain triglycerides, or TPN. Improvement in serum total protein was observed in two of three on ED and in one of two on PD, compared with three of three on TPN. Enteric protein loss was improved in two of two on ED, one of two on PD, and two of two on TPN. Outpatients who continued to receive enteral nutrition maintained a total protein level. Enteral nutirition appears to be as effective as TPN for patients with IL, and it may provide a valid and safe alternative therapy.

Effect of saccharated ferric oxide and iron dextran on the metabolism of phosphorus in rats.

As a means of investigating the physiologic damage to and histologic deterioration of the kidney caused by saccharated ferric oxide (SFO) and iron dextran (ID), we administered these substances intraperitoneally to rats. The rats were divided into 3 groups. Group 1 rats ( n = 7) were given SFO, 28 mg/kg for 9 days and 20 mg/kg for 19 days. Group 2 rats ( n = 5) were given ID, 28 mg/kg for 9 days and 20 mg/kg for 19 days. Group 3 rats (control, n = 9) were given normal saline solution. After 28 days, serum calcium, total protein, and albumin concentrations were significantly lower in the SFO group than in the ID group. Serum phosphorus concentrations were significantly lower in the SFO group than in the control group. Serum iron concentrations were significantly higher in the ID group than in the SFO group or the control, and the fractional excretion of sodium was significantly lower in the ID group than in the control group. The percent tubular reabsorption of phosphorus was significantly greater in the ID group than in the SFO group or the control group, and the theoretical threshold concentration of phosphorus was also significantly lower in the SFO group than in the ID or the control group. Histologic examination of the kidney after treatment revealed neither iron in the tubules nor any structural damage to the tubules. ID was not found to induce hypophosphatemia, whereas SFO did. We believe that the cause of such hypophosphatemia is impaired tubular reabsorption.

[Drug therapy for ulcerative colitis: salazosulfapyridine and 5-ASA].

Aminosalicylates have a wide range of anti-inflammatory and immunomodulatory effects. Oral salazosulfapyridine (SASP) and 5-aminosalicylic acid (5-ASA) are the 'first-line' therapy for induction of remission in mild to moderate active ulcerative colitis (UC). SASP, which is consisted of 5-ASA and sulfapyridine, has greater incidence of side effects. 5-ASA is a therapeutically active compound, while sulfapyridine is related to adverse effects. For this reason, 5-ASA formulas exclusive of sulfapyridine were developed and they enabled higher dose of 5-ASA administration without adverse effects. Topical treatment by 5-ASA enema or SASP suppository should be considered for the treatment of proctitis or distal type of UC. Oral aminosalicylate therapy is also effective for the maintenance of remission in UC. Therefore, aminosalicylates are key drugs for the treatment of UC.

Central and peripheral cardiovascular actions of apelin in conscious rats.

APJ was cloned as an orphan G protein-coupled receptor and shares a close identity with angiotensin II type 1 receptor (AT1R). Apelin is a peptide that has recently been identified as an endogenous ligand of the APJ. Apelin and APJ mRNA are expressed in peripheral tissue and the central nervous system. However, little is known about the effects of apelin in cardiovascular regulation. To examine the central and peripheral role of apelin, we injected the active fragment of apelin [(Pyr1)apelin-13] intracerebroventricularly (ICV, 5 and 20 nmol, n=6) or intravenously (IV, 20 and 50 nmol, n=4 or 5) in conscious rats. ICV injection of (Pyr1)apelin-13 dose-dependently increased mean arterial pressure (MAP) and heart rate (HR) (19+/-3 mm Hg and 162+/-26 bpm at 20 nmol). Pretreatment with ICV injection of the AT1R antagonist (CV-11974, 20 nmol) did not alter the apelin-induced increase in MAP and HR. IV injection of (Pyr1)apelin-13 also dose-dependently increased MAP and HR (13+/-2 mm Hg and 103+/-18 bpm at 50 nmol); however, the peripheral effects of apelin were relatively weak compared to its central effects. Expression of c-fos in the paraventricular nucleus (PVN) of hypothalamus was increased in the rat that received ICV injection of (Pyr1)apelin-13 but not in the rat that received IV injection of (Pyr1)apelin-13. These results suggest that apelin plays a role in both central and peripheral cardiovascular regulation in conscious rats, and that the cardiovascular effects of apelin are not mediated by the AT1R.

Selenium is depleted in Crohn's disease on enteral nutrition.

BACKGROUND/AIMS: [corrected] Selenium is an important trace element and its deficiency has been reported to be associated with cardiomyopathy or gastrointestinal cancer. The aim of this study is to clarify the selenium status in Crohn's disease (CD) on enteral nutrition. METHODS: We measured serum selenium concentrations in 53 patients with CD and compared them with those in 21 healthy controls. Twenty-nine patients were under the treatment by enteral nutrition (EN group), and the remaining 24 patients were free from formulated enteral nutrition (non-EN group). RESULTS: While the serum selenium concentration in the non-EN group was not decreased when compared to controls, the value in the EN group was significantly lower than those in the non-EN group and in controls. Clinical manifestations of selenium deficiency were found in a patient on exclusive enteral nutrition. In the EN group, the serum selenium concentration showed an inverse correlation with the duration and the daily dose of enteral nutrition. In the non-EN group, the serum selenium concentrations were inversely correlated with the Crohn's disease activity index. CONCLUSION: These findings suggest that patients with CD on enteral nutrition are at risk for selenium deficiency and that even patients without enteral nutrition may develop selenium deficiency at the active phase of the disease.

Mesenteric phlebosclerosis: a new disease entity causing ischemic colitis.

PURPOSE: Nonthrombotic stenosis or occlusion of the mesenteric veins is a rare cause of intestinal ischemia. The aim of this study was to describe a new disease entity causing chronic ischemic colitis. METHODS: Seven patients were diagnosed as having mesenteric phlebosclerosis. All seven patients had calcifications in the small mesenteric veins and their intramural branches. No evidence of vasculitis or portal hypertension was recognized. None of the patients had a history of gastrointestinal disease or of prolonged drug use. We report clinical, laboratory, radiographic, endoscopic, and histopathologic findings. RESULTS: Clinical findings included abdominal pain and diarrhea of a gradual onset and chronic course. A positive fecal occult blood test and mild anemia were often found. The patients had linear calcifications and stenosis in the right colon, which were discovered by plain abdominal radiography and barium enema, respectively. Endoscopic findings included edematous, dark colored mucosa and ulcerations. Four patients underwent a subtotal colectomy because of persistent abdominal pain or ileus. The histopathologic findings were macroscopically characterized by a dark purple or dark brown colored colonic surface, the swelling and disappearance of plicae semilunares coli, and marked thickening of the colonic wall, while they were microscopically characterized by marked fibrous thickening of the venous walls with calcifications, marked submucosal fibrosis, deposition of collagen in the mucosa, and foamy macrophages within the vessel walls. CONCLUSIONS: These peculiar lesions have not previously been fully described. The cause and pathogenesis still remain unknown. We conclude that such lesions represent a new clinicopathologic disease entity and propose the term "idiopathic mesenteric phlebosclerosis."