Altered gut microbiota and its association with inflammation in patients with chronic thromboembolic pulmonary hypertension: a single-center observational study in Japan.

BACKGROUND: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is considered to be associated with chronic inflammation; however, the underlying mechanism remains unclear. Recently, altered gut microbiota were found in patients with pulmonary arterial hypertension (PAH) and in experimental PAH models. The aim of this study was to characterize the gut microbiota in patients with CTEPH and assess the relationship between gut dysbiosis and inflammation in CTEPH. METHODS: In this observational study, fecal samples were collected from 11 patients with CTEPH and 22 healthy participants. The abundance of gut microbiota in these fecal samples was assessed using 16S ribosomal ribonucleic acid (rRNA) gene sequencing. Inflammatory cytokine and endotoxin levels were also assessed in patients with CTEPH and control participants. RESULTS: The levels of serum tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and macrophage inflammatory protein (MIP)-1α were elevated in patients with CTEPH. Plasma endotoxin levels were significantly increased in patients with CTEPH (P < 0.001), and were positively correlated with TNF-α, IL-6, IL-8, and MIP-1α levels. The 16S rRNA gene sequencing and the principal coordinate analysis revealed the distinction in the gut microbiota between patients with CTEPH (P < 0.01) and control participants as well as the decreased bacterial alpha-diversity in patients with CTEPH. A random forest analysis for predicting the distinction in gut microbiota revealed an accuracy of 80.3%. CONCLUSION: The composition of the gut microbiota in patients with CTEPH was distinct from that of healthy participants, which may be associated with the elevated inflammatory cytokines and endotoxins in CTEPH.

Rare cause of severe anemia due to pyogenic granuloma in the jejunum.

BACKGROUND: Pyogenic granuloma (PG) is a polypoid lobular capillary hemangioma rarely observed in the gastrointestinal tract. Only a few cases in the small bowel have been described in the literature. CASE PRESENTATION: A 58-year-old man had been suffering from general fatigue and severe anemia. Esophagogastroduodenoscopy and colonoscopy did not reveal any significant bleeding. Abdominal computer tomography revealed a hypervascular tumor in the small intestine. Oral double-balloon endoscopy (DBE) detected a polypoid lesion (2 cm in diameter) in the jejunum. We performed laparoscopic-assisted partial resection of the jejunum. The histological features of the tumor were consistent with PG. The patient's anemia gradually improved without the need for oral iron after surgery. CONCLUSION: In this case report, we present a case of pyogenic granuloma in in the jejunum that was detected by DBE.

Elevated level of urinary tellurium is a potential risk for increase of blood pressure in humans and mice.

BACKGROUND: People worldwide are routinely exposed to tellurium mainly via dietary ingestion. There has been no study to clarify the contribution of tellurium to blood pressure in humans or animals. METHODS: In this cross-sectional study conducted in a general population of 2592 residents in Japan, the associations of urinary tellurium levels with blood pressure and prevalence of hypertension were investigated. The potential sources of tellurium were also investigated. An interventional study in mice confirmed the effect of tellurium exposure on blood pressure. RESULTS: Linear and logistic regression analyses with consideration of confounders including urinary sodium-potassium ratio showed significant positive associations of urinary tellurium level with prevalence of hypertension and blood pressure. Cereals/beans and vegetables/fruits were determined to be potential dietary sources of tellurium exposure. Intermediary analysis suggested that increased intake of cereals/beans, but not that of vegetables/fruits, is positively associated with the tellurium-mediated risk of hypertension. Correspondingly, the mouse study showed that exposure to a putative human-equivalent dose of tellurium via drinking water increased blood pressure with an elevated level of urinary tellurium. The temporally increased blood pressure was decreased to the normal level by a break of tellurium exposure with a reduced level of urinary tellurium. CONCLUSIONS: The interdisciplinary approach provided the first evidence that tellurium exposure is a potential risk for increase of blood pressure. Since the human urinary tellurium level in this study is comparable with the levels in general populations in other Asian and European countries in previous studies, exposure to tellurium may be a latent universal risk for hypertension.

Inhibition of the SET8 Pathway Ameliorates Lung Fibrosis Even Through Fibroblast Dedifferentiation.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown etiopathogenesis. The activation of extracellular matrix (ECM)-producing myofibroblasts plays a key role in fibrotic tissue remodeling. The dedifferentiation of myofibroblasts has attracted considerable attention as a promising target for the development of effective therapeutic interventions against IPF. Here, we screened a small library of epigenetics-related inhibitors using dedifferentiation assay of lung myofibroblasts prepared from a patient at the terminal stages of IPF and chose UNC0379. The inhibition of SET8, a histone H4 lysine 20 (H4K20) monomethyltransferase, by UNC0379 markedly suppressed the expression of α-smooth muscle actin (SMA) and ED-A-fibronectin in myofibroblasts. In IPF myofibroblasts, SET8 expression and H4K20 monomethylation (H4K20me1) levels, which were significantly higher than those in normal human lung fibroblasts, were reduced upon treatment with UNC0379. Hence, the changes in the expression of the two fibrotic markers clearly correlated with those in SET8 expression and H4K20me1 level. Furthermore, in a mouse model of bleomycin (BLM)-induced lung fibrosis, the intratracheal administration of UNC0379 at an early fibrotic stage markedly ameliorated the histopathological changes associated with collagen deposition in the lungs. However, treatment with UNC0379 did not significantly affect the number of proinflammatory cells or cytokine production in the bronchoalveolar lavage fluids from mice treated with BLM. In the BLM-injured lung, SET8 was predominantly localized to the nuclei of α-SMA-positive cells, which colocalized with H4K20me1. Taken together, our results indicate that the inhibition of SET8 resulting in myofibroblast dedifferentiation may partly mitigate lung fibrosis without affecting the inflammatory responses.

Neurogenic bladder in patients with cervical compressive myelopathy.

We examined the urinary disturbances in 56 consecutive patients with cervical compressive myelopathy using the latest International Continence Society classification. Of the 56 patients with cervical compressive myelopathy, 29 (52%) had some urinary subjective complaints, whereas the remaining 27 (48%) had none. Urologic examination indicated that 8 of these 29 (28%) patients with urinary complaints had urologic disorders other than neurogenic bladder. Of the remaining 21 patients, only 6 (25%) were judged to have neurogenic bladder on urodynamic study. Urodynamic study may be of limited value in diagnosing urinary disturbance in cervical myelopathy. Further, four cases (83%) showed underactive bladder activity in voiding phase, and only one case (17%) showed overactive bladder activity in filling phase. These results were contrary to those of previous studies indicating that cervical compressive myelopathy is associated with overactive bladder activity in filling phase. There were no significant differences in motor or sensory Japanese Orthopedic Association scores between the patients with and without urinary complaints. However, the patients with urinary complaints had significantly longer durations of myelopathy and delayed motor evoked potential latencies than those without urinary complaints. After surgery, 19 of the 21 (90%) patients with urinary complaints showed recovery from urinary disturbance. Operations in patients with cervical myelopathy were also effective against urinary disturbance. Urinary complaints may be an indication for surgical treatment despite the results of urodynamic study.

Diagnosis of thoracic outlet syndrome by magnetic stimulation of the brachial plexus.

The abductor pollicis brevis (APB) and abductor digiti minimi (ADM) compound muscle action potential (CMAP) latencies, and median and ulnar motor conduction velocities (MCVs), obtained by magnetic stimulation of the brachial plexus, were evaluated for the diagnosis of thoracic outlet syndrome (TOS). These measurements were compared in three groups of limbs: (1) the symptomatic limbs of patients with TOS (symptomatic group), (2) the asymptomatic con-tralateral limbs of these patients (asymptomatic group), and (3) the limbs of healthy control subjects (control group). Although no significant differences were observed in MCVs among the three groups, the APB CMAP latency in the sym-ptomatic group (12.0 +/- 1.2 ms) was significantly prolonged compared with that in the control group (10.4 +/- 0.64 ms; P < 0.01), and the ADM CMAP latency in the symptomatic group (11.0 +/- 0.82 ms) was also significantly prolonged compared with that in the control group (10.1 +/- 0.59 ms; P < 0.01). The possibility is suggested that the evaluation of APB and ADM CMAP latencies by magnetic stimulation of the brachial plexus may be helpful for the diagnosis of TOS.