Prefrontal cortex dysfunction and depression in atypical parkinsonian syndromes.

Depressive symptoms are common in patients with neurodegenerative disorders. Imaging studies suggest that a disruption of frontal-subcortical pathways may underlie depression associated with basal ganglia disease. This pilot study tested the hypothesis that frontal dysfunction contributes to depression associated with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Depressed patients with MSA (n = 11), PSP (n = 9), and age-matched controls (n = 25) underwent measures of cerebral glucose metabolism applying positron emission tomography with (18)F-fluorodeoxyglucose. Regional metabolism in the patient groups was compared to the normal subjects using the voxel-based statistical parametric mapping. Depressive symptom severity (Hamilton Depression Rating) and degree of locomotor disability (Hoehn & Yahr) were assessed in the patient groups. The association between prefrontal metabolism and the occurrence of depressive symptoms and the degree of locomotor disability was investigated. When compared to controls, MSA patients revealed significant metabolic decreases in bilateral frontal, parietal, and cerebellar cortex and in the left putamen. In PSP patients, significant hypometabolism was demonstrated in bilateral frontal cortex, right thalamus, and midbrain. Depression severity but not the patients' functional condition was significantly associated with dorsolateral prefrontal glucose metabolism in both patient groups. The findings of this pilot study support the hypothesis that depressive symptoms in MSA and PSP are associated with prefrontal dysfunction.     

Secretory immunoglobulin‐A reactivity following increases in workload intensity using the Defined Intensity Stressor Simulation (DISS)

Previous work suggests that secretory immunoglobulin‐A (S‐IgA) reactivity is inversely related to the perceived demands of the stressor. The Defined Intensity Stressor Simulation (DISS) comprises eight stressor modules, and allows for the manipulation of stress either through increasing the number of modules, or increasing the workload of the modules. The current study assessed the effect of increasing the workload of four modules upon S‐IgA reactivity and perceived demands. Participants (N = 14) attended three sessions on consecutive days where they provided a timed saliva sample immediately before and after 5 min on the DISS at low, medium and high workload. Following each session participants recorded their perceptions of the task with regard to workload and levels of stress and arousal. Perceived workload and stress, but not arousal, increased in accordance with increases in workload, however, differential S‐IgA reactivity was observed. Low workload resulted in a slight increase in S‐IgA secretion; medium workload elicited significant up‐regulation, while down‐regulation of S‐IgA occurred following high workload. As DISS is analogous to a variety of working environments it is suggested that the observed S‐IgA reactivity is indicative of how individuals react to multi‐tasking environments when faced with increases in objective or perceived workload demands. As S‐IgA levels are related to protection from illness, down‐regulation of S‐IgA in those who perceive greater demands may lead to greater vulnerability to ill‐health. Copyright © 2005 John Wiley & Sons, Ltd.     

Investigations into the C‐deuteriation of aryl alkyl ketones using urea as a pro‐base in the presence of a deuterium donor

Results are reported on the regioselective C‐deuteriation of a series of enolates derived from the deprotonation of aryl alkyl ketones using dilithiated urea as the pro‐base in the presence of a suitable deuterium donor. Copyright © 2006 John Wiley & Sons, Ltd.     

Adenomyosis:common and uncommon manifestations on sonography and magnetic resonance imaging.

OBJECTIVE: The purpose of this presentation is to show the imaging findings of the common and uncommon variants of adenomyosis as seen on sonography and magnetic resonance imaging (MRI). METHODS: A 3-year database search was performed to identify women who had pelvic sonography and pelvic MRI within a 6-month interval. Images of these cases were retrospectively reviewed. RESULTS: Eighty women were identified. Adenomyosis was diagnosed on MRI, which was used as the reference standard, in 45 of these women. The correct diagnosis was made on sonography in 73% of the cases. CONCLUSIONS: Awareness of the spectrum of imaging features of adenomyosis is important to use sonography effectively for diagnosing this entity and to help avoid misdiagnosis.     

Sick day management using blood 3-hydroxybutyrate (3-OHB) compared with urine ketone monitoring reduces hospital visits in young people with T1DM: a randomized clinical trial.

AIMS: Diabetic ketoacidosis (DKA), a life-threatening acute complication of Type 1 diabetes, may be preventable with frequent monitoring of glycaemia and ketosis along with timely supplemental insulin. This prospective, two-centre study assessed sick day management using blood 3-hydroxybutyrate (3-OHB) monitoring compared with traditional urine ketone testing, aimed at averting emergency assessment and hospitalization. METHODS: One hundred and twenty-three children, adolescents and young adults, aged 3-22 years, and their families received sick day education. Participants were randomized to receive either a blood glucose monitor that also measures blood 3-OHB (blood ketone group, n = 62) or a monitor plus urine ketone strips (urine ketone group, n = 61). All were encouraged to check glucose levels > or = 3 times daily and to check ketones during acute illness or stress, when glucose levels were consistently elevated (> or = 13.9 mmol/l on two consecutive readings), or when symptoms of DKA were present. Frequency of sick days, hyperglycaemia, ketosis, and hospitalization/emergency assessment were ascertained prospectively for 6 months. RESULTS: There were 578 sick days during 21,548 days of follow-up. Participants in the blood ketone group checked ketones significantly more during sick days (276 of 304 episodes, 90.8%) than participants in the urine ketone group (168 of 274 episodes, 61.3%) (P < 0.001). The incidence of hospitalization/emergency assessment was significantly lower in the blood ketone group (38/100 patient-years) compared with the urine ketone group (75/100 patient-years) (P = 0.05). CONCLUSIONS: Blood ketone monitoring during sick days appears acceptable to and preferred by young people with Type 1 diabetes. Routine implementation of blood 3-OHB monitoring for the management of sick days and impending DKA can potentially reduce hospitalization/emergency assessment compared with urine ketone testing and offers potential cost savings.     

Homocysteinylation of low-density lipoproteins (LDL) from subjects with Type 1 diabetes: effect on oxidative damage of human endothelial cells.

BACKGROUND: Homocysteine (Hcy) is an independent risk factor for cardiovascular disease (CVD). Individuals with Type 1 and Type 2 diabetes are more susceptible to the effects of homocysteine than non-diabetic subjects. The interaction between homocysteine-thiolactone (Hcy-thiolactone), a reactive product of Hcy, and low-density lipoproteins (LDL) induces the formation of homocystamide-LDL adducts (Hcy-LDL) and it has been suggested that homocysteinylation could increase atherogenicity of lipoproteins. AIM: The aim of the study was to compare the effect of in vitro homocysteinylation of LDL isolated from healthy control subjects (C-LDL) and from Type 1 diabetic patients (DM-LDL) and to investigate the effect of homocysteinylated LDL (Hcy-C-LDL and Hcy-DM-LDL) on peroxynitrite production of endothelial cells. METHODS: The in vitro homocysteinylation of LDL isolated from control (n = 12) and DM subjects (n = 12) was carried out by incubating lipoproteins with Hcy-thiolactone. The reaction was verified by quantifying the increase in sulphydryl groups (-SH groups) in Hcy-LDL with respect to control LDL. Control and homocysteinylated LDL were incubated with human aortic endothelial cells (HAEC) in culture. Peroxynitrite production in cells treated in different experimental conditions was assayed by a fluorimetric method. RESULTS: The increase in -SH groups after incubation with homocysteine was greater in LDL from diabetic subjects compared with LDL from control subjects (P < 0.001). In addition, peroxynitrite production from HAEC incubated with Hcy-LDL from diabetic patients was greater than after incubation with Hcy-LDL from control subjects and untreated LDL from diabetic patients (P < 0.001). CONCLUSIONS: These results show that LDL from diabetic patients is more susceptible to in vitro homocysteinylation than LDL from non-diabetic individuals and demonstrate that the compositional changes in Hcy-LDL from diabetic subjects have cytotoxic effects on human endothelial cells.     

Is endoscopic one‐piece mucosal resection essential for early gastric cancer?

Background: Endoscopic mucosal resection (EMR) is widely accepted as a minimally invasive treatment for early gastric cancer (EGC) in Japan. However, the criteria for EMR must be strictly adhered to otherwise patients will miss the chance for additional therapy. We assess the important factor in expanding the indication of EMR. Methods: We investigated 1101 EGCs that had been resected by EMR at the National Cancer Center Hospital (NCCH), Tokyo, Japan, according to the indication recommended by Japanese Gastric Cancer Association (JGCA) and the expanded indication proposed by NCCH. Curability and local recurrence of the EMRs were assessed related to the applied indication and the number of resected specimens. Results: The recurrence rate of non‐evaluable resection was higher than that of evaluable resection (P < 0.0001). Eighty‐three lesions among 772 lesions in the JGCA group were non‐evaluable. Thirty‐seven leisons among 329 lesions in the NCCH group were non‐evaluable. There was no difference in the rate of non‐evaluable resection between JGCA and NCCH groups (P = 0.8329). However, the rate of curative resection was lower in the NCCH group than in the JGCA group (P = 0.0009). In piecemeal resection, there was no difference in the rate of non‐evaluable resection between JGCA and NCCH groups (P = 0.0527). In one‐piece resection, the rate of non‐evaluable resection was lower in the NCCH group than the JGCA group (P = 0.0137). Conclusion: Based on our series of cases, we propose one‐piece resection as a gold standard for EMR because it enables accurate histological evaluation, even in the EMR, according to the expanded indication.     

Decreased insulin requirement in relation to GFR in nephropathic Type 1 and insulin-treated Type 2 diabetic patients.

AIMS: In the presence of impaired renal function, patients require less insulin mainly because insulin clearance is prolonged. The aim of this study was to evaluate the insulin requirement related to glomerular filtration rate (GFR) in nephropathic Type 1 and Type 2 diabetic patients. METHODS: In a retrospective study we compared insulin requirement in 20 nephropathic Type 1 diabetic patients and 20 insulin-treated Type 2 diabetic patients from the onset of overt nephropathy until the final stage of renal disease. All patients had proteinuria > 0.5 g/24 h and creatinine clearance >/= 80 ml/min per 1.73 m2 at baseline. Creatinine clearance, urinary protein excretion, glycated haemoglobin and the required insulin doses were determined 3- to 6-monthly, basal C-peptide was measured at the beginning and the end of the observation period. The required insulin doses were evaluated at creatinine clearance rates of 80, 60, 40, 20 and 10 ml/min per 1.73 m2 (or at the initiation of dialysis treatment). RESULTS: The insulin requirement of patients with Type 1 diabetes was reduced from 0.72 +/- 0.16 IU/kg per day at a creatinine clearance rate of 80 ml/min, to 0.45 +/- 0.13 IU/kg per day at a creatinine clearance rate of 10 ml/min (decrement of 38%, P < 0.001). The insulin dose required by Type 2 diabetic patients was reduced from 0.68 +/- 0.28 IU/kg per day at a creatinine clearance rate of 80 ml/min to 0.33 +/- 0.19 IU/kg per day at a clearance rate of 10 ml/min (decrement 51%, P < 0.001). The fall in GFR, urinary protein excretion and glycated haemoglobin levels was similar in the two groups. In patients with Type 2 diabetes, C-peptide levels at the beginning and the end of renal function impairment were 2.2 (0.4-7.3) vs. 2.7 (0.1-4.9) ng/ml (NS). The reduction in insulin requirement was approximately the same in patients with an initial C-peptide level < 1.0 and in those >/= 1.0 ng/ml (decrement 57% vs. 46%). CONCLUSIONS: The reduction in insulin requirement in renal insufficiency is similar in Type 1 and insulin-treated Type 2 diabetic patients. In subjects with Type 2 diabetes, the residual insulin secretion has no impact on the reduction in insulin requirement dependent on the GFR.     

PEUTZ‐JEGHERS SYNDROME ASSOCIATED WITH RENAL AND GASTRIC CANCER THAT DEMONSTRATED AN STK11 MISSENSE MUTATION

A 75‐year‐old male was admitted to the gastroenterology unit of Nagoya City University Hospital due to epigastralgia after surgical treatment for right renal cancer. Endoscopy revealed advanced type 1 gastric cancer in the corpus of the stomach and multiple polypoid lesions in the stomach and duodenum. X‐ray examination of the small intestine using barium showed multiple polyps in the upper jejunum. Faint pigmentation on the palm was also detected. Peutz‐Jeghers syndrome (PJS) was diagnosed, despite a lack of family history. Total gastrectomy, resection of part of the upper jejunum and intraoperative endoscopic polypectomy of duodenal polyps was performed. This is the second reported case of PJS associated with renal cancer. We also detected a missense mutation in the tumor suppressor gene STK11 that, when mutated, is causative for PJS.     

Effect of naringin on bone cells.

Statin, a HMG-CoA reductase inhibitor, was shown to increase BMP-2 gene expression for bone formation, by blocking the mevalonate pathway in cholesterol production. We investigated the effect of naringin, a flavonoid available commonly in citrus fruits, which was also a HMG-CoA reductase inhibitor, in UMR 106 osteoblastic cell line in vitro. The control group consisted of cells cultured without any intervention for different time intervals (24 h, 48 h, and 72 h), whereas the experimental (naringin) group consisted of cells cultured with naringin of different concentrations (0.001 micromol/L, 0.01 micromol/L, and 0.1 micromol/L) for the same time intervals of the control. Colorimetric Tetrazolium (MTT) assay, total protein content assay, and alkaline phosphatase activity were used to measure the cellular activities. Results for the naringin group showed an increase in MTT assay compared with the control and the effect was dose dependent. At high concentration (0.1 micromol), the increases ranged from 60% to 80%. In the total protein content assay, naringin also showed an increase compared with control and the effect was also dose dependent. At high concentration (0.1 micromol), the increases ranged from 9% to 20%. In the alkaline phosphatase activity assay, naringin at high concentration (0.1 micromol) significantly increased the activity up to 20%. In conclusion, naringin significantly increased bone cell activities in vitro. This is the first study specifically attempted to investigate the effect of naringin on bone cell activities. Besides statin, this provided another example of mevalonate pathway blockage in the cholesterol production pathway by HMG-CoA reductase inhibition will increase the bone cell activities.