CURRENT STATUS OF DOUBLE BALLOON ENDOSCOPY

Yamamoto and colleagues have developed a novel insertion method of the endoscope, the ‘double balloon method’ for enteroscopy and, recently, a specialized system for the ‘double balloon method’ has been commercialized by Fujinon. The double balloon endoscopy enables visualization of the entire small bowel and also allows for interventional therapy in the small intestine. This method could be used either from the oral or anal approach. Observation of an affected area with controlled movement of the endoscope enables interventions, including biopsies, hemostasis, balloon dilatation, stent placement, polypectomy, and endoscopic mucosal resection. The procedure is safe and useful, and it provides high diagnostic yields and therapeutic capabilities.     

Effects of renin-angiotensin system blockade on macrophage infiltration in patients with hypertensive nephrosclerosis.

The mechanisms of hypertensive nephrosclerosis are not fully understood. In experimental models of the disease, inflammatory reactions such as macrophage infiltration play an important role. In human hypertensive nephrosclerosis, however, there have been few studies examining the role of inflammation histologically. We investigated whether the number of infiltrating macrophages was increased in human hypertensive nephrosclerosis, and evaluated the effects of a blockade of the renin-angiotensin system on clinical and histological findings. We examined macrophage infiltration using immunohistochemistry in renal biopsy specimens obtained from 16 patients with hypertensive nephrosclerosis, 5 patients with IgA nephropathy, 5 patients with membranous nephropathy, and 5 patients with minimal change nephrotic syndrome. The number of infiltrating macrophages in glomeruli was significantly larger in the patients with hypertensive nephrosclerosis than in those with minimal change nephrotic syndrome. The patients with hypertensive nephrosclerosis were divided into groups based on their use of antihypertensive agents at the time of renal biopsy. We investigated the effects of antihypertensive agents on clinical findings, macrophage infiltration, and monocyte chemoattractant protein-1 expression. There was no difference in clinical findings between the hypertensive groups. The numbers of infiltrating macrophages and monocyte chemoattractant protein-1-positive cells in glomeruli were significantly smaller in patients treated with an angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor blocker, whereas calcium channel blockers had no influence on histological findings. In conclusion, inflammation is involved in the progression of human hypertensive nephrosclerosis and the inflammatory process is inhibited by blocking the renin-angiotensin system.     

Effect of nasal continuous positive airway pressure treatment on plasma adrenomedullin levels in patients with obstructive sleep apnea syndrome: roles of nocturnal hypoxia and oxidant stress.

Obstructive sleep apnea syndrome (OSAS) is recognized as one of the risk factors of hypertension and cardiovascular disorders. In the current study, we hypothesized that the hypoxic stress and oxidative stress caused by obstructive sleep apnea would increase circulating adrenomedullin (ADM) levels in untreated OSAS patients as compared to an age and body mass index (BMI)-matched control group and an age-matched, but normal-BMI control group. We further hypothesized that nasal continuous positive airway pressure (nCPAP) treatment may decrease OSAS-induced hypoxic stress, oxidative stress and ADM levels. To examine these hypotheses, we measured circulating ADM and reactive oxygen species (ROS) from leukocytes before and after nCPAP therapy in OSAS patients. The circulating levels of ADM and amount of ROS in untreated OSAS patients were significantly greater than those in the controls. No differences in ADM levels were found between the increased-BMI controls and normal-BMI controls. We observed that nCPAP treatment decreased sleep apneas, nocturnal oxyhemoglobin desaturation, the circulating ADM, and ROS production by leukocytes in OSAS patients. The ADM levels were associated with the magnitude of oxyhemoglobin desaturation rather than the number of sleep apneas. These observations suggest that nCPAP therapy could reduce OSAS-induced nocturnal hypoxemia, generation of ROS, and ADM in patients with OSAS.     

Association of the GNAS1 gene variant with hypertension is dependent on alcohol consumption.

The beta-adrenoceptor (beta-AR)-stimulatory guanine nucleotide-binding (Gs) protein system has been shown to play important roles in the cardiovascular system. The gene encoding the alpha-subunit of Gs proteins (GNAS1) is a candidate genetic determinant for hypertension. Because alcohol consumption is known to affect blood pressure partly through the beta-AR-Gs protein system, we examined the possible interaction between GNAS1 T393C polymorphism and drinking status in the association with hypertension in the present study. As a result, a non-significant but reasonable trend supporting the presence of an interaction was shown (p = 0.076). In line with this trend, the T393C polymorphism significantly interacted with drinking status in the association with systolic blood pressure (p = 0.028). Moreover, supporting the presence of an interaction, T allele carriers consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than CC homozygotes in non-drinkers and light drinkers. In contrast, CC homozygotes consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than T allele carriers in moderate to heavy drinkers. The present study also showed a significant interaction between the T393C polymorphism and drinking status in the association with pulse pressure (p = 0.026), reflected by a significant association between the T393C polymorphism and pulse pressure in moderate to heavy drinkers (p = 0.026). These findings may be helpful in conducting further molecular and biological studies on the relationship among the effects of alcohol, the beta-AR-Gs protein system, and hypertension.     

Amlodipine-induced reduction of oxidative stress in the brain is associated with sympatho-inhibitory effects in stroke-prone spontaneously hypertensive rats.

Amlodipine is a dihydropyridine calcium channel blocker that is widely used for the treatment of hypertensive patients and has an antioxidant effect on vessels in vitro. The aim of the present study was to examine whether treatment with amlodipine reduced oxidative stress in the brains of stroke-prone spontaneously hypertensive rats (SHRSP). The animals received amlodipine, nicardipine or hydralazine for 30 days in their drinking water. Levels of thiobarbituric acid-reactive substances (TBARS) in the brain (cortex, cerebellum, hypothalamus, and brainstem) were measured before and after each treatment. Systolic blood pressure decreased to similar levels in the amlodipine-, nicardipine-, and hydralazine-treated groups. Urinary norepinephrine excretion was significantly reduced in SHRSP after treatment with amlodipine, but not with nicardipine or hydralazine. Levels of TBARS in the cortex, cerebellum, hypothalamus, and brainstem were significantly higher in SHRSP than in Wistar-Kyoto rats (WKY), and were reduced in amlodipine-treated, but not in nicardipine- or hydralazine-treated, SHRSP. Electron spin resonance spectroscopy revealed increased levels of reactive oxygen species in the brains of SHRSP, which were reduced by treatment with amlodipine. Intracisternal infusion of amlodipine also reduced systolic blood pressure, urinary norepinephrine excretion, and the levels of TBARS in the brain. These results suggested that oxidative stress in the brain was enhanced in SHRSP compared with WKY rats. In addition, antihypertensive treatment with amlodipine reduced oxidative stress in all areas of the brain examined and decreased blood pressure without a reflex increase in sympathetic nerve activity in SHRSP.     

Lethal midline granuloma (peripheral T-cell lymphoma) after lymphomatoid papulosis.

A Japanese woman with an 8-year history of lymphomatoid papulosis (LP) had lethal midline granuloma (LMG) develop at the age of 51 years. There were histologic similarities between LP and LMG seen in this patient. Surface phenotypic studies on nasal and cutaneous lesions demonstrated a population of T-cells expressing CD2, CD4, CD25, CD30, and histocompatibility antigen-DR (HLA-DR). Genotypic analyses of nasal and skin biopsy specimens disclosed a clonal rearrangement of the beta T-cell receptor gene with the same rearrangement pattern. These data indicate that this patient had LMG characterized by clonal peripheral T-cell lymphoma, which probably resulted from progression of the LP.     

A muscle-derived factor antagonizes the neurotoxicity of glutamate in dissociated cell cultures of chick telencephalic neurons.

Excitatory amino acids including glutamate are known to reveal considerable neurotoxicity in various nervous systems. Our previous studies revealed that the chick muscle extract contains a factor which promotes the survival of telencephalic neurons. Further investigations clearly showed that this extract contains the factor that antagonizes the neurotoxicity of glutamate in a dissociated telencephalic neuronal culture system optimized for detection of the toxicity. This factor reduced at least the toxicity mediated by non-N-methyl-D-aspartate (non-NMDA) receptor.     

Effects of Ageing on the Oral Absorption of d-Xylose in Rats: Analysis of Gastrointestinal Disposition

The effects of ageing on the oral (gastrointestinal) absorption of d -xylose were investigated by analysing the gastrointestinal disposition after oral administration to young (9 weeks) and old (53 weeks) rats. A linear model assuming first-order gastric emptying followed by first-order intestinal absorption was fitted to remaining fraction vs time profiles for the stomach and small intestine to estimate the gastric emptying rate constant (k_g) and the intestinal absorption rate constant (k_a). In young and old rats, k_g values were 0·087 ± 0·008 and 0·070 ± 0·007 min^?1, respectively, and k_a values were 0·020 ± 0·002 and 0·018 ± 0·002 min^?1 suggesting an insignificant effect on ageing on the rate of oral absorption. The average intestinal lumen volume (V_av) was unchanged with ageing, and so was the apparent intestinal membrane permeability clearance (CL_app) as the product of k_a and V_av. However, the small intestinal transit time (T_si) was suggested to be twice that in older rats (171 min) than in young rats (78 min) by the analysis of gastrointestinal disposition of inulin, a non-absorbable marker. It was also shown that our preceding finding of an increase in the fraction absorbed of D-xylose with ageing can be solely ascribable to the delay in intestinal transit. Thus, among various determinants of oral absorption, only T_si was found to be altered with ageing. The CL_a,app and k_a of passively absorbed drugs such as D-xylose may be generally unchanged, and the fraction absorbed may increase with ageing by the delay in intestinal transit.