A long-term transdermal nitric oxide donor improves uteroplacental circulation in women with preeclampsia.

OBJECTIVE: To determine the effects of long-term transdermal administration (range, 4-30 days; mean +/- SD, 11.1+/-7.2 days) of isosorbide dinitrate, a nitric oxide donor, in preeclamptic women. METHODS: We studied uterine and fetoplacental circulation of 12 preeclamptic women with oligohydramnios and an elevated pulsatility index in the uterine arteries. RESULTS: Transdermal isosorbide dinitrate significantly suppressed the blood pressure of patients. Pulsed Doppler ultrasonography revealed that the average pulsatility index in the uterine arteries was significantly reduced by treatment with isosorbide dinitrate (P < .003). The average pulsatility index in the umbilical artery was also significantly reduced (P < .004). Furthermore, the size of the amniotic fluid pocket increased approximately 4-fold by treatment with isosorbide dinitrate. CONCLUSIONS: Long-term transdermal administration of isosorbide dinitrate improves fetoplacental circulation and may be effective therapy for avoiding maternal hypertension and oligohydramnios in some preeclamptic women.     

Pontine venous congestion caused by dural carotid-cavernous fistula: report of two cases

This is a report of two patients in whom a pontine venous congestion occurred with a dural carotid-cavernous fistula (CCF), an extremely rare complication. This is the first such report. We underscore the importance of early diagnosis and treatment of dural CCFs. Received 16 October 1995; Revision received 15 January 1996; Accepted 29 July 1996     

The expression of thymic stromal lymphopoietin in patients and animal models with eosinophilic otitis media

Objective: In the present study, we aimed to clarify the expression of thymic stromal lymphopoietin (TSLP), a key trigger of Th2-type allergic disease, in the middle ear mucosa of eosinophilic otitis media (EOM).

Methods: An immunohistological study of TSLP was conducted in patients with EOM and in animal models of EOM constructed by intraperitoneal and intratympanic injection of ovalbumin for 7 and 14 days. In addition, the messenger RNA (mRNA) expression of TSLP in the middle ear mucosa of the animal models was analyzed using real-time PCR, and was compared with that of the control animals.

Results: Immunoreactivities for TSLP were observed in the middle ear mucosa around the tympanic ostium of the eustachian tube of patients with EOM. In the animal model, strong immunoreactivity for TSLP was also observed in the eustachian tube epithelium, and mRNA expression of TSLP in the seven-day stimulated animals was significantly higher than that in the controls.

Conclusion: The present study indicates that the presence of epithelium-derived TSLP in the eustachian tubes plays an important role in the onset of EOM.     

Periostin expression in neoplastic and non-neoplastic diseases of bone and joint

Background

Periostin is a matricellular protein that is expressed in bone and joint tissues. To determine the expression of periostin in primary bone tumours and to assess whether it plays a role in tumour progression, we carried out immunohistochemistry and ELISA for periostin in a range of neoplastic and non-neoplastic bone and joint lesions.

Methods

140 formalin-fixed paraffin-embedded sections of bone tumours and tumour-like lesions were stained by an indirect immunoperoxidase technique with a polyclonal anti-periostin antibody. Periostin expression was also assessed in rheumatoid arthritis (RA) and non-inflammatory osteoarthritis (OA) synovium and synovial fluid immunohistochemistry and ELISA respectively.

Results

Periostin was most strongly expressed in osteoid/woven bone of neoplastic and non-neoplastic bone-forming lesions, including osteoblastoma, osteosarcoma, fibrous dysplasia, osteofibrous dysplasia, fracture callus and myositis ossificans, and mineralised chondroid matrix/woven bone in chondroblastoma and clear cell chondrosarcoma. Reactive host bone at the edge of growing tumours, particularly in areas of increased vascularity and fibrosis, also stained strongly for periostin. Vascular elements in RA synovium strongly expressed periostin, and synovial fluid levels of periostin were higher in RA than OA.

Conclusions

In keeping with its known role in modulating the synthesis of collagen and other extracellular matrix proteins in bone, strong periostin expression was noted in benign and malignant lesions forming an osteoid or osteoid-like matrix. Periostin was also noted in other bone tumours and was found in areas of reactive bone and increased vascularity at the edge of growing tumours, consistent with its involvement in tissue remodelling and angiogenesis associated with tumour progression.

     

Combined effect of cabozantinib and gefitinib in crizotinib‐resistant lung tumors harboring ROS1 fusions

The ROS1 tyrosine kinase inhibitor (TKI) crizotinib has shown dramatic effects in patients with non‐small cell lung cancer (NSCLC) harboring ROS1 fusion genes. However, patients inevitably develop resistance to this agent. Therefore, a new treatment strategy is required for lung tumors with ROS1 fusion genes. In the present study, lung cancer cell lines, HCC78 harboring SLC34A2‐ROS1 and ABC‐20 harboring CD74‐ROS1, were used as cell line‐based resistance models. Crizotinib‐resistant HCC78R cells were established from HCC78. We comprehensively screened the resistant cells using a phosphor‐receptor tyrosine kinase array and RNA sequence analysis by next‐generation sequencing. HCC78R cells showed upregulation of HB‐EGF and activation of epidermal growth factor receptor (EGFR) phosphorylation and the EGFR signaling pathway. Recombinant HB‐EGF or EGF rendered HCC78 cells or ABC‐20 cells resistant to crizotinib. RNA sequence analysis by next‐generation sequencing revealed the upregulation of AXL in HCC78R cells. HCC78R cells showed marked sensitivity to EGFR‐TKI or anti‐EGFR antibody treatment in vitro. Combinations of an AXL inhibitor, cabozantinib or gilteritinib, and an EGFR‐TKI were more effective against HCC78R cells than monotherapy with an EGFR‐TKI or AXL inhibitor. The combination of cabozantinib and gefitinib effectively inhibited the growth of HCC78R tumors in an in vivo xenograft model of NOG mice. The results of this study indicated that HB‐EGF/EGFR and AXL play roles in crizotinib resistance in lung cancers harboring ROS1 fusions. The combination of cabozantinib and EGFR‐TKI may represent a useful alternative treatment strategy for patients with advanced NSCLC harboring ROS1 fusion genes.     

Spasmolytic effects of prostaglandin E1 on serotonin-induced bronchoconstriction and pulmonary hypertension in dogs

In this study, we simultaneously evaluated the spasmolytic effectsof prostaglandin E₁ (PGE₁) on serotonin-induced bronchoconstrictionand pulmonary hypertension. Eleven mongrel dogs (8–12kg) anaesthetized with pentobarbital were assigned to two groups:saline (n=4) and PGE₁ (n=7). Bronchoconstriction and pulmonaryhypertension were elicited with serotonin 10 µg kg^–1+ 1 mg kg^–1 h^–1 and assessed as the percentage changein bronchial cross-sectional area (BCA) measured by bronchoscopyand pulmonary vascular resistance (PVR), respectively. Thirtyminutes after starting the serotonin infusion, saline or PGE₁0 (saline), 0.01, 0.1, 1.0 or 10 µg kg^–1 i.v. wasgiven. %BCA and %PVR (basal=100%) were assessed before and 30min after serotonin, and 30 and 60 min after saline (salinegroup) or 5 min after each dose of PGE₁ (PGE₁ group). In thesaline group, pulmonary hypertension and bronchoconstrictionwere stable. In the PGE₁ group, PGE₁ at     

BMP-2-producing L cells induce osteogenesis in vivo and in vitro

A high level of expression of the humanbone morphogenetic protein-2 (hBMP-2) gene was found in L cells under control of a cytomegalovirus enhancer and a chicken -actin promoter. The induction of osteogenesis in vitro was examined by treating the stromal cell lines MC3T3-E1, ST2, and OP9 with either conditioned medium (CM) from hBMP-2 L cell transfectants, or with retinoic acid. BMP-2 CM induced alkaline phosphatase (ALP) activity in all three cell lines at different levels, with ALP activity in the OP9 cell line being approximately one-tenth that in the other cell lines. Serum induced ALP activity synergistically with BMP-2 CM. Retinoic acid strongly induced ALP activity only in the ST2 cell line. The different responses of stromal cell lines to BMP-2 CM and retinoic acid characterized stromal and preosteoblastic cells. In an in vivo analysis, BMP-2-producing L cells were injected into the foreleg and thigh muscles of nude mice, resulting in ectopic bone formation.     

Novel assessment tool based on laser speckle contrast imaging to diagnose severe ischemia in the lower limb for patients with peripheral arterial disease

Objective

We propose a new assessment tool to diagnose severe ischemia of the lower limb in peripheral arterial disease, using laser speckle contrast imaging to evaluate heating‐induced microcirculatory fluctuations in the proximal and distal sites of the dorsal foot.

Study Design

A cross‐sectional study.

Methods

We recorded the slope describing the behavior of perfusion values (decrease or plateau) following the initial, heating‐induced increase in perfusion in 63 feet of patients with clinical signs of peripheral arterial disease.

Results

The plateau and decrease groups were defined as having perfusion slopes of <0.20 and ≥0.20 PU/min, respectively. Transcutaneous oxygen tension was significantly lower (P < 0.001) in the plateau than in the decrease group (8 vs. 45 mmHg), indicating more severe ischemia. The laser speckle contrast imaging thermal load test discriminated transcutaneous oxygen tension <30 mmHg with good sensitivity (78.7%) and specificity (96.2%), and an area under the curve of 0.908.

Conclusions

Both transcutaneous oxygen tension and the laser speckle contrast imaging thermal load test are useful in diagnosing severe ischemia in the foot. Lasers Surg. Med. 49:645–651, 2017. © 2017. The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.