Protective effects of sodium ferulate on flap transplantation via anti-inflammatory modulation and oxidative stress inhibition.

Ischemia-reperfusion injury (IRI) has brought attention to flap failure in reconstructive surgery. To improve the prognosis of skin transplantation, we performed experimental IRI by surgical obstruction of blood flow and used sodium ferulate (SF) to prevent IRI in rats. After SF treatment, the morphological and histological changes of the skin flaps were observed by H&E and Masson's trichrome staining. We also detected the expression levels of COX-1, HO-1, and Ki67 by immunohistochemical and western blot analysis. Moreover, enzyme-linked immunosorbent assay was used to identify the content of tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), malondialdehyde (MDA), and nitric oxide (NO) in peripheral blood and skin tissue. Compared with the model group, SF treatment significantly improved the recovered flap area (%) and promoted collagen synthesis. Cyclooxygenase-2 (COX-2) expression was significantly inhibited by heme oxygenase-1 (HO-1) induction after SF treatment. Furthermore, SF significantly inhibited the levels of TNF-α in peripheral blood, MPO and MDA in the skin tissue, and the increased synthesis of NO. Our results showed the protective effects of SF on IRI after flap transplantation and we believe that the protective effects of SF was closely related to the alleviation of the inflammatory response and the inhibition of the oxidative stress injury.

Protective effects of sodium ferulate on flap transplantation via anti-inflammatory modulation and oxidative stress inhibition

Ischemia-reperfusion injury (IRI) has brought attention to flap failure in reconstructive surgery. To improve the prognosis of skin transplantation, we performed experimental IRI by surgical obstruction of blood flow and used sodium ferulate (SF) to prevent IRI in rats. After SF treatment, the morphological and histological changes of the skin flaps were observed by H&E and Masson's trichrome staining. We also detected the expression levels of COX-1, HO-1, and Ki67 by immunohistochemical and western blot analysis. Moreover, enzyme-linked immunosorbent assay was used to identify the content of tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), malondialdehyde (MDA), and nitric oxide (NO) in peripheral blood and skin tissue. Compared with the model group, SF treatment significantly improved the recovered flap area (%) and promoted collagen synthesis. Cyclooxygenase-2 (COX-2) expression was significantly inhibited by heme oxygenase-1 (HO-1) induction after SF treatment. Furthermore, SF significantly inhibited the levels of TNF-α in peripheral blood, MPO and MDA in the skin tissue, and the increased synthesis of NO. Our results showed the protective effects of SF on IRI after flap transplantation and we believe that the protective effects of SF was closely related to the alleviation of the inflammatory response and the inhibition of the oxidative stress injury.

MRS as an Aid to Diagnose Malignant Transformation in Low-Grade Gliomas with Increasing Contrast Enhancement.

BACKGROUND AND PURPOSE: Increased contrast enhancement has been used as a marker of malignant transformation in low-grade gliomas. This marker has been found to have limited accuracy because many low-grade gliomas with increased contrast enhancement remain grade II. We aimed to investigate whether MR spectroscopy can contribute to the diagnosis of malignant transformation in low-grade gliomas with increased contrast enhancement. MATERIALS AND METHODS: Patients with low-grade gliomas who had contemporaneous MR spectroscopy and histopathology for tumor regions with increased contrast enhancement between 2004 and 2015 were retrospectively reviewed. Clinical data collected were sex and age, Karnofsky Performance Scale, histologic subtypes, isocitrate dehydrogenase 1 mutation status, disease duration, adjuvant therapy, and post-radiation therapy duration. Imaging data collected were contrast-enhancement size, whole-tumor size, MR spectroscopy metabolite ratios, and tumor grades of regions with increased contrast enhancement. Diagnostic values of these factors on malignant transformation of low-grade gliomas were statistically analyzed. RESULTS: A total of 86 patients with 96 MR spectroscopy studies were included. Tumor grades associated with increased contrast enhancement were grade II (n = 42), grade III (n = 27), and grade IV (n = 27). On multivariate analysis, the NAA/Cho ratio was the only significant factor (P < .001; OR, 7.1; 95% CI, 3.2-16.1) diagnostic of malignant transformation. With 0.222 as the cutoff value, the sensitivity, specificity, and accuracy of NAA/Cho for diagnosing malignant transformation were 94.4%, 83.3%, and 89.6%, respectively. CONCLUSIONS: MR spectroscopy complements conventional MR imaging in the diagnosis of malignant transformation in a subgroup of low-grade gliomas with increased contrast enhancement.

Gastrointestinal involvement of primary skin diseases.

Less is known about gastrointestinal (GI) involvement of primary skin diseases due to the difference in embryology, histology, microbiology and physiology between integument and alimentary tract. Oesophagus, following the oropharyngeal mucosa, is the most common GI segment affected by primary skin diseases, especially by eosinophilic oesophagitis, lichen planus and autoimmune bullous dermatoses like pemphigus vulgaris, mucosal membrane pemphigoid and epidermolysis bullosa acquisita. Eosinophilic oesophagitis is an emerging chronic atopic disease with oesophageal dysfunction as the typical presentation, and oesophageal narrowing, rings and stricture as late complications. Oesophageal lichen planus mainly involves the proximal to mid-oesophagus in elderly aged women with long-term oral mucosal lesions. In acute attack of pemphigus vulgaris, oesophageal involvement is not uncommon but often neglected and may cause sloughing oesophagitis (oesophagitis dissecans superficialis) with acute GI bleeding in rare cases. GI manifestation of hereditary bradykininergic angio-oedema with colicky acute abdomen mostly affects small intestine, usually in the absence of pruritus or urticaria, and is more severe and long-lasting than the acquired histaminergic form. Strong evidence supports association between inflammatory bowel disease, especially Crohn disease, and hidradenitis suppurativa/acne inversa. Patients with vitiligo need surveillance of autoimmune liver disease, autoimmune atrophic gastritis or coeliac disease when corresponding symptoms become suspect. Melanoma is the most common primary tumour metastatic to the GI tract, with small intestine predominantly targeted. Gastrointestinal involvement is not uncommon in disseminated mycosis fungoides. Extramammary Paget's disease is an intraepidermal adenocarcinoma of controversial origin, and a high association between the anogenital occurrence and colorectal adenocarcinoma has been reported. As GI tract is the largest organ system with multidimensional functions, dermatologists in daily practice should be aware of the gastrointestinal morbidities related to primary skin diseases for an early diagnosis and treatment.

MiR-181b modulates EGFR-dependent VCAM-1 expression and monocyte adhesion in glioblastoma.

Tumor-associated macrophages (TAMs) originate as circulating monocytes, and are recruited to gliomas, where they facilitate tumor growth and migration. Understanding the interaction between TAM and cancer cells may identify therapeutic targets for glioblastoma multiforme (GBM). Vascular cell adhesion molecule-1 (VCAM-1) is a cytokine-induced adhesion molecule expressed on the surface of cancer cells, which is involved in interactions with immune cells. Analysis of the glioma patient database and tissue immunohistochemistry showed that VCAM-1 expression correlated with the clinico-pathological grade of gliomas. Here, we found that VCAM-1 expression correlated positively with monocyte adhesion to GBM, and knockdown of VCAM-1 abolished the enhancement of monocyte adhesion. Importantly, upregulation of VCAM-1 is dependent on epidermal-growth-factor-receptor (EGFR) expression, and inhibition of EGFR effectively reduced VCAM-1 expression and monocyte adhesion activity. Moreover, GBM possessing higher EGFR levels (U251 cells) had higher VCAM-1 levels compared to GBMs with lower levels of EGFR (GL261 cells). Using two- and three-dimensional cultures, we found that monocyte adhesion to GBM occurs via integrin α4ß1, which promotes tumor growth and invasion activity. Increased proliferation and tumor necrosis factor-α and IFN-γ levels were also observed in the adherent monocytes. Using a genetic modification approach, we demonstrated that VCAM-1 expression and monocyte adhesion were regulated by the miR-181 family, and lower levels of miR-181b correlated with high-grade glioma patients. Our results also demonstrated that miR-181b/protein phosphatase 2A-modulated SP-1 de-phosphorylation, which mediated the EGFR-dependent VCAM-1 expression and monocyte adhesion to GBM. We also found that the EGFR-dependent VCAM-1 expression is mediated by the p38/STAT3 signaling pathway. Our study suggested that VCAM-1 is a critical modulator of EGFR-dependent interaction of monocytes with GBM, which raises the possibility of developing effective and improved therapies for GBM.

Assessment of angiographic vascularity of meningiomas with dynamic susceptibility contrast-enhanced perfusion-weighted imaging and diffusion tensor imaging.

BACKGROUND AND PURPOSE: The roles of DTI and dynamic susceptibility contrast-enhanced-PWI in predicting the angiographic vascularity of meningiomas have not been studied. We aimed to investigate if these 2 techniques could reflect the angiographic vascularity of meningiomas. MATERIALS AND METHODS: Thirty-two consecutive patients with meningiomas who had preoperative dynamic susceptibility contrast-enhanced-PWI, DTI, and conventional angiography were retrospectively included. The correlations between angiographic vascularity of meningiomas, classified with a 4-point grading scale, and the clinical or imaging variables-age and sex of patient, as well as size, CBV, fractional anisotropy, and ADC of meningiomas-were analyzed. The meningiomas were dichotomized into high-vascularity and low-vascularity groups. The differences in clinical and imaging variables between the 2 groups were compared. Receiver operating characteristic curve analysis was used to determine the diagnostic performance of these variables. RESULTS: In meningiomas, angiographic vascularity correlated positively with CBV but negatively with fractional anisotropy. High-vascularity meningiomas demonstrated significantly higher CBV but lower fractional anisotropy as compared with low-vascularity meningiomas. In differentiating between the 2 groups, the area under the curve values were 0.991 for CBV and 0.934 for fractional anisotropy on receiver operating characteristic curve analysis. CONCLUSIONS: CBV and fractional anisotropy correlate well with angiographic vascularity of meningiomas. They may differentiate between low-vascularity and high-vascularity meningiomas.

Differentiation of primary central nervous system lymphomas and glioblastomas: comparisons of diagnostic performance of dynamic susceptibility contrast-enhanced perfusion MR imaging without and with contrast-leakage correction.

BACKGROUND AND PURPOSE: Contrast leakage results in underestimation of the CBV of brain tumors. Our aim was to compare the diagnostic performance of DSC perfusion MR imaging without and with mathematic contrast-leakage correction in differentiating PCNSLs and glioblastomas. MATERIALS AND METHODS: Perfusion parameters-CBV, corrected CBV, and leakage coefficient-were measured in enhancing tumor portions and contralateral NAWM of 15 PCNSLs and 20 glioblastomas, respectively. The ratios of CBV and corrected CBV were calculated by dividing the tumor values by those obtained from contralateral NAWM. A paired t test was used to compare tumor K2 and NAWM K2, as well as tumor CBV ratios without and with leakage correction. Comparisons of CBV, corrected CBV, and K2 between PCNSLs and glioblastomas were done by using a 2-sample t test. The diagnostic performance of DSC perfusion MR imaging without and with contrast-leakage correction was assessed with receiver operating characteristic curve analysis. RESULTS: PCNSLs and glioblastomas demonstrated higher K2 than those in their contralateral NAWM. Corrected CBV ratios were significantly higher than the uncorrected ones for both tumors. PCNSLs had lower CBV ratios (P < .001), lower corrected CBV ratios (P < .001), and higher K2 (P = .001) compared with glioblastomas. In differentiating between PCNSLs and glioblastomas, the area under the curve of the CBV ratio, corrected CBV ratio, and K2 were 0.984, 0.940, and 0.788, respectively. CONCLUSIONS: PCNSL can be differentiated from glioblastoma with CBV ratios, corrected CBV ratios, and K2. CBV without contrast-leakage correction seems to have the best diagnostic performance in differentiating the 2 tumors.

Neuronavigation-guided focused ultrasound-induced blood-brain barrier opening: a preliminary study in swine.

BACKGROUND AND PURPOSE: FUS-induced BBB opening is a promising technique for noninvasive and local delivery of drugs into the brain. Here we propose the novel use of a neuronavigation system to guide the FUS-induced BBB opening procedure and investigate its feasibility in vivo in large animals. MATERIALS AND METHODS: We developed an interface between the neuronavigator and FUS to allow guidance of the focal energy produced by the FUS transducer. The system was tested in 29 swine by more than 40 sonication procedures and evaluated by MR imaging. Gd-DTPA concentration was quantitated in vivo by MR imaging R1 relaxometry and compared with ICP-OES assay. Brain histology after FUS exposure was investigated using H&E and TUNEL staining. RESULTS: Neuronavigation could successfully guide the focal beam, with precision comparable to neurosurgical stereotactic procedures (2.3 ± 0.9 mm). A FUS pressure of 0.43 MPa resulted in consistent BBB opening. Neuronavigation-guided BBB opening increased Gd-DTPA deposition by up to 1.83 mmol/L (a 140% increase). MR relaxometry demonstrated high correlation with ICP-OES measurements (r(2) = 0.822), suggesting that Gd-DTPA deposition can be directly measured by imaging. CONCLUSIONS: Neuronavigation provides sufficient precision for guiding FUS to temporally and locally open the BBB. Gd-DTPA deposition in the brain can be quantified by MR relaxometry, providing a potential tool for the in vivo quantification of therapeutic agents in CNS disease treatment.

Differentiation of pyogenic brain abscesses from necrotic glioblastomas with use of susceptibility-weighted imaging.

BACKGROUND AND PURPOSE: A common imaging finding in brain abscess and necrotic glioblastoma is a T2 hypointense margin. The features of this hypointense rim on SWI have not been previously described, to our knowledge. We aimed to differentiate abscesses from glioblastomas by assessing the morphology of their lesion margin by using SWI. MATERIALS AND METHODS: T2WI and SWI were performed in 12 abscesses and 20 rim-enhancing glioblastomas. On T2WI and SWI, the prevalence and the border types (complete versus incomplete) of hypointense rims were qualitatively assessed. On SWI, the contour (smooth versus irregular) and the location of hypointense rims relative to the contrast-enhancing rims as well as the prevalence of the "dual rim sign," defined as 2 concentric rims at lesion margins with the outer one being hypointense and the inner one hyperintense relative to cavity contents, were also analyzed. RESULTS: Prevalence and the border types of the hypointense rims on T2WI were not different between abscesses and glioblastomas. On SWI, there were significantly more hypointense rims that were complete (P < .001) and smooth (P < .001), having the same location as the contrast-enhancing rims (P < .001) for abscesses. A dual rim sign was present in 9 of 12 abscesses but absent in all glioblastomas (P < .001). CONCLUSIONS: SWI may be helpful in differentiating pyogenic abscesses from necrotic glioblastomas. The dual rim sign is the most specific imaging feature distinguishing the 2.

Differentiation of tumefactive demyelinating lesions from high-grade gliomas with the use of diffusion tensor imaging.

BACKGROUND AND PURPOSE: TDLs may be indistinguishable from high-grade gliomas on conventional MR imaging. The role of DTI in differentiating TDLs from high-grade gliomas is not clear, and quantitative comparison between the 2 has not been reported. Here we aimed to differentiate TDLs from high-grade gliomas by using DTI. MATERIALS AND METHODS: DTI was performed in 8 TDLs and 13 high-grade gliomas. The presence of 3 findings (ie, intralesional hyperintensities on the FA map, restricted diffusion in the lesion periphery, and a perilesional hyperintense FA rim) was assessed by visual inspection. The FA and MD values were measured in the central nonenhancing portion, peripheral enhancing portion, and perilesional edema for each lesion and compared between the 2 groups respectively. RESULTS: TDLs had a significantly higher incidence of intralesional hyperintensities on FA maps (P = .049) but a lower incidence of a perilesional hyperintense FA rim (P < .001), compared with those of high-grade gliomas on visual inspection. TDLs had significantly higher FA (P = .004) and lower MD (P = .001) values in the peripheral enhancing portions of the lesions compared with those of high-grade gliomas. In perilesional edema, FA values were significantly higher in high-grade gliomas (P = .001). CONCLUSIONS: DTI is helpful in differentiating TDLs from high-grade gliomas by using visual inspection and quantitative analysis.

Differentiation of brain abscesses from necrotic glioblastomas and cystic metastatic brain tumors with diffusion tensor imaging.

BACKGROUND AND PURPOSE: The differentiation of abscesses from glioblastomas and metastases may not always be possible on the basis of DWI. Our hypothesis was that differences in diffusion properties as detected by DTI allow differentiation of abscess from glioblastomas and metastasis. Furthermore, diagnostic performance of tensor metrics quantifying anisotropy or tensor shapes is better than that of ADC in measuring mean diffusivity for this purpose. MATERIALS AND METHODS: DTI was performed in 15 abscesses, 15 necrotic glioblastomas, and 26 cystic metastases. In each lesion, manually segmented into 4 regions of interest (ie, cystic cavity, enhancing rim, and immediate [edema most adjacent to the enhancing rim] and distant zones of edema), FA, ADC, C(l), C(p), and C(s) values were measured and statistically compared among groups and evaluated with ROC curve analysis. The presence of a hyperintense FA rim (a rim of edematous tissue that was hyperintense on the FA map) was assessed visually. RESULTS: Abscess was significantly different from glioblastoma for all tensor metrics measured in the cystic cavity and immediate zone of edema and for all except C(l) in the enhancing rim. Abscess was significantly different from metastasis for all tensor metrics measured in the cystic cavity and enhancing rim and for FA, ADC, and C(l) in immediate zone of edema. The incidence of a hyperintense FA rim was significantly higher in glioblastoma and metastasis compared with abscess. The 3 tensor metrics with the highest performance in differentiating abscess from glioblastoma and metastasis were FA, C(l), and C(s) of the cystic cavity. CONCLUSIONS: DTI is able to differentiate abscess from glioblastoma and metastasis. FA, C(l), and C(s) outperformed ADC in diagnostic performance comparisons.

Suicide in Asia.

Suicide is a major problem worldwide, and suicides in Asian countries account for as much as 60% of all suicides in the world. There are many unique features in suicides within this ethnically-diverse continent, from the methods used, to the putative risk factors. Much research still needs to be done to guide efficacious and culturally relevant interventions in suicide prevention; existing literature suggests a strong focus for programmes that address restricting access to pesticides, increasing crisis counseling activities, improving the accessibility and delivery of mental health services, and promoting responsible media reporting of suicide and related issues. There is a need for coordinated national suicide plans to be developed that are sensitive to the socioeconomic and cultural factors in the local context.

Differentiation between classic and atypical meningiomas with use of diffusion tensor imaging.

BACKGROUND AND PURPOSE: The differentiation between classic and atypical meningiomas may have implications in preoperative planning but may not be possible on the basis of conventional MR imaging. Our hypothesis was that classic and atypical meningiomas have different patterns of intratumoral water diffusion that will allow for differentiation between them. MATERIALS AND METHODS: Preoperative diffusion tensor imaging (DTI) was performed in 12 classic and 12 atypical meningiomas. Signal intensity of solid-enhancing tumor regions on diffusion-weighted trace images and apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps was assessed. Regions of interest (ROIs) were placed in solid-enhancing regions, peritumoral edema, and contralateral normal-appearing white matter (NAWM) to measure tensor metrics including major (lambda(1)), intermediate (lambda(2)) and minor eigenvalues (lambda(3)) and FA and ADC values. Distribution of tensor shapes within enhancing tumors was calculated for all tumors. Differences between classic and atypical meningiomas in tumor signal intensity, intratumoral and peritumoral tensor metrics, as well as tensor shapes distribution were statistically analyzed. RESULTS: A significantly greater proportion of atypical meningiomas were isointense and hypointense on ADC maps (P = .007). Classic meningiomas had significantly lower FA (P = .012), higher ADC (P = .011), greater lambda(2) (P = .020) and lambda(3) (P = .003). There was significantly more spherical diffusion in classic than in atypical meningiomas (P = .020). All diffusion tensor metrics for peritumoral edema of the 2 tumor groups did not differ. CONCLUSION: DTI showed that intratumoral microscopic water motion is less organized in classic than in atypical meningiomas. This feature may allow for noninvasive differentiation between classic and atypical meningiomas.

Primary cerebral lymphoma and glioblastoma multiforme: differences in diffusion characteristics evaluated with diffusion tensor imaging.

BACKGROUND AND PURPOSE: Differentiating between primary cerebral lymphoma and glioblastoma multiforme (GBM) based on conventional MR imaging sequences may be impossible. Our hypothesis was that there are significant differences in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) between lymphoma and GBM, which will allow for differentiation between them. MATERIALS AND METHODS: Preoperative diffusion tensor imaging (DTI) was performed in 10 patients with lymphoma and 10 patients with GBM. Regions of interest were placed in only solid-enhancing tumor areas and the contralateral normal-appearing white matter (NAWM) to measure the FA and ADC values. The differences in FA and ADC between lymphoma and GBM, as well as between solid-enhancing areas of each tumor type and contralateral NAWM, were analyzed statistically. Cutoff values of FA, FA ratio, ADC, and ADC ratio for distinguishing lymphomas from GBMs were determined by receiver operating characteristic curve analysis. RESULTS: FA and ADC values of lymphoma were significantly decreased compared with NAWM. Mean FA, FA ratio, ADC (x10(-3) mm(2)/s), and ADC ratios were 0.140 +/- 0.024, 0.25 +/- 0.04, 0.630 +/- 0.155, and 0.83 +/- 0.14 for lymphoma, respectively, and 0.229 +/- 0.069, 0.40 +/- 0.12, 0.963 +/- 0.119, and 1.26 +/- 0.13 for GBM, respectively. All of the values were significantly different between lymphomas and GBM. Cutoff values to differentiate lymphomas from GBM were 0.192 for FA, 0.33 for FA ratio, 0.818 for ADC, and 1.06 for ADC ratio. CONCLUSIONS: The FA and ADC of primary cerebral lymphoma were significantly lower than those of GBM. DTI is able to differentiate lymphomas from GBM.

Reoperation for recurrent trigeminal neuralgia after microvascular decompression.

BACKGROUND: Microvascular decompression (MVD) is an effective technique for those who have trigeminal neuralgia (TN) but cannot tolerate, or show no response to medicine. Though the initial success rate is high, some patients may develop severe recurrent neuralgia, especially after a longer period of follow-up. The efficacy of reoperation needs to be evaluated. To know the possible risk factors of recurrence after initial MVD is mandatory to the management of recurrent TN. METHODS: Among the 80 cases of TN treated with MVD, five cases showed severe recurrent symptoms within a follow-up period from 9 months-4 years. The symptoms recurred on the same side of the face, and were unresponsive to medical treatment. Brain computed tomography (CT) and magnetic resonance imaging (MRI) may reveal the etiology of recurrence. Repeat decompression of the trigeminal nerve was the main goal of reoperation, which was done via a suboccipital approach. RESULTS: Over the past 17 years, 80 MVDs for TN have been performed at Chang Gung Memorial Hospital. There were five cases of serious postoperative recurrence, which could not be relieved by medicine. Recurrence occurred 1 day-12 months after the initial surgery. Three cases were due to vascular compression, while two were caused by the local effect of Teflon felt. Reoperation produced complete remission in four patients, and partial remission in one. CONCLUSIONS: An increasing number of patients may experience severe recurrent TN after initial MVD during a long period of follow-up. Reoperation is safe and beneficial for these patients, but the results are dependent on the etiology of the recurrence. Further vascular compression of the trigeminal nerve can be relieved by MVD. Otherwise, in cases of severe adhesion caused by Teflon, complete microneural lysis can achieve satisfactory results.