Commensal Flora, is it an Unwelcomed Companion as a Triggering Factor of Autoimmune Pancreatitis?

The etiopathogenesis of many autoimmune disorders has not been identified. The aim of this paper is to focus on the involvement of bacterial exposure, as an environmental factor, in the pathogenesis of autoimmune pancreatitis (AIP), which is broadly categorized as autoimmune disorders involving pancreatic lesions. Avirulent and/or commensal bacteria, which may have an important role(s) as initiating/progressing factors in the pathogenesis of autoimmune disorder AIP, will be emphasized

Bazedoxifene, a selective estrogen receptor modulator, reduces cerebral aneurysm rupture in Ovariectomized rats.

BackgroundEstrogen deficiency is thought to be responsible for the higher frequency of aneurysmal subarachnoid hemorrhage in post- than premenopausal women. Estrogen replacement therapy appears to reduce this risk but is associated with significant side effects. We tested our hypothesis that bazedoxifene, a clinically used selective estrogen receptor (ER) modulator with fewer estrogenic side effects, reduces cerebral aneurysm rupture in a new model of ovariectomized rats.MethodsTen-week-old female Sprague-Dawley rats were subjected to ovariectomy, hemodynamic changes, and hypertension to induce aneurysms (ovariectomized aneurysm rats) and treated with vehicle or with 0.3 or 1.0 mg/kg/day bazedoxifene. They were compared with sham-ovariectomized rats subjected to hypertension and hemodynamic changes (HT rats). The vasoprotective effects of bazedoxifene and the mechanisms underlying its efficacy were analyzed.ResultsDuring 12 weeks of observation, the incidence of aneurysm rupture was 52% in ovariectomized rats. With no effect on the blood pressure, treatment with 0.3 or 1.0 mg/kg/day bazedoxifene lowered this rate to 11 and 17%, almost the same as in HT rats (17%). In ovariectomized rats, the mRNA level of ERα, ERβ, and the tissue inhibitor of metalloproteinase-2 was downregulated in the cerebral artery prone to rupture at 5 weeks after aneurysm induction; the mRNA level of interleukin-1β and the matrix metalloproteinase-9 was upregulated. In HT rats, bazedoxifene restored the mRNA level of ERα and ERβ and decreased the level of interleukin-1β and matrix metalloproteinase-9. These findings suggest that bazedoxifene was protective against aneurysmal rupture by alleviating the vascular inflammation and degradation exacerbated by the decrease in ERα and ERβ.ConclusionsOur observation that bazedoxifene decreased the incidence of aneurysmal rupture in ovariectomized rats warrants further studies to validate this response in humans

A New Microarray System to Detect Streptococcus pneumoniae Serotypes

Streptococcus pneumoniae, one of the most common gram-positive pathogens to colonize the human upper respiratory tract, is responsible for many severe infections, including meningitis and bacteremia. A 23-valent pneumococcal vaccine is available to protect against the 23 S. pneumoniae serotypes responsible for 90% of reported bacteremic infections. Unfortunately, current S. pneumoniae serotype testing requires a large panel of expensive antisera, assay results may be subjective, and serotype cross-reactions are common. For this study, we designed an oligonucleotide-based DNA microarray to identify glycosyltransferase gene sequences specific to each vaccine-related serotype. Out of 56 isolates representing different serotypes, only one isolate, representing serotype 23A, was not detected correctly as it could not be distinguished from serotype 23F. Our data suggest that the microarray provides a more cost-effective and reliable way of monitoring pneumococcal capsular types

Comparison between early and late carotid endarterectomy for symptomatic carotid stenosis in relation to oxidized low-density lipoprotein and plaque vulnerability

ObjectiveAlthough carotid endarterectomy (CEA), the gold standard in stroke prevention, has been performed in the late stage after the insult, its optimal timing remains unclear. Using biomarkers in plaque and plasma, we evaluated oxidative stress and plaque vulnerability between early and late CEA in symptomatic patients.MethodsWe compared symptomatic stroke patients who underwent early CEA within 4 weeks of the last insult (group A; n = 15) with those who received CEA in the late stage beyond 4 weeks from the last symptom (group B; n = 57). They were divided into vulnerable (group Av, n = 13; group Bv, n = 33) and stable (group As, n = 2; group Bs, n = 24) subgroups according to the pathologic findings on their plaques. We studied the relationships among their primary symptoms, clinical findings, oxidized low-density lipoprotein levels, and gelatinase A (matrix metalloproteinase [MMP]-9) activity in their plaques and plasma.ResultsGroup A had a variety of symptoms; there was no difference in the outcome of CEA between groups A and B. The plaque and plasma oxidized low-density lipoprotein levels were higher in group A than in group B (P < .05). The incidence of pathologically vulnerable plaque was higher in group A than in group B. Plaque oxidized low-density lipoprotein levels and MMP-9 activity were similar in group Av and group Bv and were higher in those groups than in group As and Bs.ConclusionsWe first demonstrated that vulnerable plaques in patients subjected to early CEA manifested a remarkable increase in oxidized low-density lipoprotein and MMP-9 activation. Our findings suggest that early CEA may be beneficial in the aspect of oxidative stress

Ways of improving three-dimensional CT angiography images of cervical and cerebral vascular lesions

We evaluated various ways of improving the image clarity of three-dimensional CT angiography (3D-CTA) for the diagnosis of cervical and cerebral vascular disease in sixty-seven patients (36 males and 31 females). The mean age was 61.4 years, with a rang of 17 to 89 years. The patients were examined with a helical CT scanner (TCT-X vision GX) after intravenous bolus injection of 90 ml nonionic contrast medium (300 mgI/ml) at the rate of 3ml/sec. Intracranial and cervical 3D-CTA were performed 60 and 12 times, respectively. Our findings were as follows : 1. Reduction of the pre-scanning delay time from 18 to 10 sec after the injection of the contrast medium eliminates much of the cavernous sinus from the image and makes it easier to distinguish the intracavernous internal carotid artery in intracranial 3D-CTA. In cervical 3D-CTA, reduction of the pre-scanning delay time from 15 to 9 sec delays imaging of the jugular vein and makes it easy to distinguish the bifurcation of the common carotid artery. 2. A subtraction image on 3D-CTA is useful for detecting of vascular lesions adjacent to bone, such as lesions on the internal carotid artery. 3. By producing a stereo picture, a closer three-dimensional relationship between the vascular lesion and the vessel circumference organization can be recognized. 4. Vascular lesions can be clearly visualized from inside the artery using a 3D-CT endoscopic image. We were able to obtain a great deal of detailed information from 3D-CTA images with these modifications and we believe they enhance diagnostic accuracy of the technique

ジョクソウ ニ タイスル ラップ リョウホウ ノ ココロミ : ポリエンカビニリデンセイ ショクヒン ホウソウヨウ フィルム オ モチイタ ジョクソウ チリョウ

A food wrap film was used as a part of therapeutic materials for 34 decubitus ulcers in 29 patients, 15 males and 14 females, who were hospitalized in our departments from June 2000 to May 2001. Basic diseases of the patients consisted of 10 cerebrovascular diseases, 4 cephalic injury sequelae, 3 spinal diseases, 3 femur fractures, and 9 other diseases. Treatment of the decubitus ulcers was done everyday mostly according to Toriyabe’s method. Firstly, the bedsore was rinsed with physiological saline without applying pressure. Then, the ulcer including surrounding skin was covered with plastic food wrap (polyvinylidene chloride food wrapping film). Edge of the film was fixed to the skin with non-woven fabric tape. The results were evaluated by measuring two-dimensional sizes of the ulcers every two to four weeks. Reduction rate of the ulcer was calculated following formula : ((1-present size (maximal diameter×perpendicular size)/original size (maximal diameter×perpendicular size)×100)) (%) in 19 lesions followed more than one month. An average reduction rate was 43.7% at 3 months and 87.9% at 7 months after starting the food wrap film therapy. Moreover, 3 lesions got complete healing during the observation period. We strongly recommend the food wrap film therapy for the treatment of decubitus ulcers because it is simple to handle and extremely inexpensive, as well as effective

Bile-induced DNA strand breaks and biochemical analysis of bile acids in an experimental model of anomalous arrangement of the pancreaticobiliary ducts

A canine experimental model for the anomalous arrangement of the pancreaticobiliary ducts (APBD) was made to investigate the effects of bile acids on carcinogenesis. Seven adult mongrel dogs underwent dorsal pancreatico-cholecystostomy to serve as a functional model for APBD, and six dogs underwent the same procedure with the pancreatic duct ligated as a control group. Bile from the gallbladder was taken 14 months after surgery for bile acid analysis by HPLC. DNA strand breaks in HeLa cells induced by the bile were also investigated in situ by nick translation method. As a result, the fraction of cholic acid tended to be lower, and that of deoxycholic acid slightly higher in APBD-dogs (N.S.). The ursodeoxycholic acid percentage in APBD-dogs significantly decreased compared with that in the control and normal dogs (p<0.05). Extremely high frequency of DNA strand breaks was shown in only two out of seven APBD-dogs. In those two dogs, the cholic acid percentage decreased and that of deoxycholic acid increased extremely. These findings suggest that the alteration of the bile composition in APBD caused frequent DNA strand breaks and repair which might lead to gene mutation and biliary tract carcinoma

Treatment with the PPARγ Agonist Pioglitazone in the Early Post-ischemia Phase Inhibits Pro-inflammatory Responses and Promotes Neurogenesis Via the Activation of Innate- and Bone Marrow-Derived Stem Cells in Rats

Neurogenesis is essential for a good post-stroke outcome. Exogenous stem cells are currently being tested to promote neurogenesis after stroke. Elsewhere, we demonstrated that treatment with the PPARγ agonist pioglitazone (PGZ) before cerebral ischemia induction reduced brain damage and activated survival-related genes in ovariectomized (OVX) rats. Here, we tested our hypothesis that post-ischemia treatment with PGZ inhibits brain damage and contributes to neurogenesis via activated stem cells. Bone marrow (BM) cells of 7-week-old Wistar female rats were replaced with BM cells from green fluorescent protein-transgenic (GFP+BM) rats. Three weeks later, they were ovariectomized (OVX/GFP+BM rats). We subjected 7-week-old Wistar male and 13-week-old OVX/GFP+BM rats to 90-min cerebral ischemia. Male and OVX/GFP+BM rats were divided into two groups, one was treated with PGZ (2.5 mg/kg/day) and the other served as the vehicle control (VC). In both male and OVX/GFP+BM rats, post-ischemia treatment with PGZ reduced neurological deficits and the infarct volume. In male rats, PGZ decreased the mRNA level of IL-6 and M1-like macrophages after 24 h. In OVX/GFP+BM rats, PGZ augmented the proliferation of resident stem cells in the subventricular zone (SVZ) and the recruitment of GFP+BM stem cells on days 7–14. Both types of proliferated stem cells migrated from the SVZ into the peri-infarct area. There, they differentiated into mature neurons, glia, and blood vessels in association with activated Akt, MAP2, and VEGF. Post-ischemia treatment with PGZ may offer a new avenue for stroke treatment through contribution to neuroprotection and neurogenesis