Abstract
BACKGROUND: Hyperglycemia is common and showed to be risky for poor prognosis in patients with subarachnoid hemorrhage (SAH). However, the causality and mechanism underlying this observation ...are not well established.
OBJECTIVE: To investigate the relationship between hyperglycemia and cerebral vasospasm with its pathogenesis in a rat model of SAH.
METHODS: One-shot SAH model was employed in male Sprague-Dawley rats. Hyperglycemia was triggered by intraperitoneal streptozotocin administration (50 mg/kg) 7 days before SAH induction. The severity of cerebral vasospasm was determined by the cross-sectional area of basilar artery (BA) in male rats randomly assigned to 1 of 4 groups: control, hyperglycemia only, SAH only, and SAH with hyperglycemia. The expression of endothelial nitric oxide synthase (eNOS) and induced nitric oxide synthase (iNOS) in the BA were analyzed by immunohistochemistry.
RESULTS: The mean (standard deviation) blood glucose level was 433.0 (98.3) and 156.5 (31.7) mg/dL in streptozotocin -treated and untreated rats, respectively. Hyperglycemic rats exhibited poorer neurobehavioral performance than normoglycemic rats when subjected to SAH. Hyperglycemia-mediated exacerbation of vasospasm was evident by the greater decrease in the BA cross-sectional area in the hyperglycemic SAH group than in the SAH only group. Furthermore, there was more decreased expression of eNOS and increased expression of iNOS within the vessels of the hyperglycemic SAH rats.
CONCLUSION: Hyperglycemia exacerbated cerebral vasospasm and was associated with poorer neurological outcomes following SAH. Our findings also suggested the nitric oxide pathway as a potential underlying mechanism via the dysregulation of eNOS and iNOS.
A new cyclohexan-1-one, named xylariaone (
1
), was isolated from the fungal strain Xylaria sp. 12F0758. Its structure was elucidated by spectroscopic analyses, including 1D and 2D NMR experiments, ...and by high-resolution fast atom bombardment (HR-FAB-MS) mass spectrometry.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
AIM: TO investigate the prognostic role of isoform 165 vascular endothelial growth factor messenger RNA (VEGF165 mRNA) in noncancerous liver tissues from patients with primary hepatocellular ...carcinoma (HCC). METHODS: Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, VEGF mRNA was determined prospectively in noncancerous liver tissues from 60 consecutive patients with HCC undergoing curative resection. We categorized the patients with VEGF16s mRNA over 0.500 in noncancerous liver tissues as group A, and those below 0.500 as group B. RESULTS: Among the isoforms of VEGF mRNA by multivariate analysis, a higher level of VEGF165 mRNA in noncancerous liver tissue correlated significantly with a higher risk of HCC recurrence (P=0.039) and recurrence-related mortality (P= 0.048), but VEGF121 did not. The other significant predictors of recurrence consisted of vascular permeation (P=0.022), daughter nodules (P=0.033), cellular dedifferentiation (P=0.033), an absent or incomplete capsule (P=0.037). A significant variable of recurrence-related mortality was vascular permeation (P=0.012). As to the clinical manifestations of 16 patients who developed recurrence, the recurrent tumor number over 2, recurrent extent over two-liver segments, and the median survival after recurrence, all significantly correlated with group A patients (P=0.043, 0.043, and 0.048, respectively). However, the presence of extrahepatic metastasis was not (P>0.05). The difference in recurrence after treatment between the two groups had no statistical significance (P>0.05). CONCLUSION: The higher expression of isoform VEGF165 mRNA in noncancerous liver remnant of patients with HCC may be a significant biological indicator of the invasiveness of postoperative recurrence.
AIM: To investigate whether the changes of gap junction gene connexin messenger RNA in the noncancerous liver tissue of patients with hepatocellular carcinoma (HCC) could play a significant role in ...its postresection recurrence. METHODS: Seventy-nine consecutive patients having undergone curative resection for HCC entered this study. Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, connexin (Cx) 26, connexin (Cx) 32 and connexin (Cx) 43 mRNAs were determined prospectively in noncancerous liver tissues from these 79 patients and in the liver tissues from 15 controls. The correlations between connexin mRNA expression and the clinicopathological variables and outcomes (tumor recurrence and recurrence related mortality) were studied. RESULTS: Compared with liver tissues of control patients, the expression of Cx 32 mRNA in noncancerous liver tissues was significantly lower (mean: 0.715 vs control 1.225, P<0.01), whereas the decreased Cx 26 mRNA (mean: 0.700 vs of control 1.205, P>0.05) and increased Cx 43 mRNA (mean: 0.241 vs control 0.100, P>0.05) had no statistical significance. We defined the value of Cx 32 mRNA or Cx 26 mRNA below 0.800 as a lower value. By multivariate analysis for noncancerous livers, a lower value of Cx 32 mRNA correlated significantly with a risk of HCC recurrence and recurrence-related mortality. The lower value of Cx 26 mRNA did not correlate with recurrence and mortality. The increased value of Cx43 mRNA also did not correlate with postoperative recurrence and recurrence-related mortality. By multivariate analysis, other significant predictors of HCC recurrence included vascular permeation, cellular dedifferentiation, and less encaps-ulation. The other significant parameter of recurrence related mortality was vascular permeation. CONCLUSION: The decreased expression of Cx 32 mRNA in noncancerous liver tissues plays a significant role in the prediction of postoperative recurrence of HCC.
AIM: To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma(HCC) recurrence for up to 3 year following curative resection. ...METHODS: A total of 143 patients(83.1% of the 172 participants in the phase Ⅱ study) participated in the follow-up study. Of these patients, 50 had received no treatment, 48 had received 160 mg/d PI-88, and 45 had received 250 mg/d PI-88 during the phase Ⅱ trial. Safety parameters and the following efficacy endpoints were investigated:(1) time to recurrence;(2) diseasefree survival; and(3) overall survival. RESULTS: PI-88 at 160 mg/d delayed the onset and frequency of HCC recurrence, and provided a clinically significant survival advantage for up to 3 years after treatment compared with those of the control group:(1) the recurrence-free rate increased from 50% to 63%, and(2) time to recurrence at the 36 th percentile was postponed by 78%. The efficacy of administering PI-88 at 250 mg/d was confounded by a high dropout rate(11 out of 54 patients). Additionally, subgroup analyses of patients with(1) multiple tumors or a single tumor ≥ 2 cm; and(2) hepatitis B or C revealed that administering PI-88 at 160 mg/d conferred the most significant survival advantage(56.8% improvement in disease-free survival, P = 0.045) for patients with both risk factors for recurrence. CONCLUSION: Administering PI-88 at 160 mg/d is a safe and well-tolerated dosage that may confer significant clinical benefits for patients with HCC.
BACKGROUND
Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) remains a major complication in patients suffering from SAH. In our previous study, we reported that stimulating vascular ...K
+ channel activity prevented the development of cerebral vasospasm. Recent evidence indicates that glyceryl nonivamide (GLNVA), a capsaicin derivative, has a vasorelaxant effect on the aortic vascular smooth muscle due to the release of coronary calcitonin gene-related peptide, which in turn stimulates K
+ channel opening. The purpose of the present study was to examine the preventive effects of GLNVA on vasospasm.
METHODS
New Zealand white rabbits were subjected to experimental SAH by injecting autologous blood into the cisterna magna. GLNVA or vehicle was injected intrathecally immediately after the induction of SAH. All animals were killed by perfusion-fixation at 48 hours after SAH. The basilar arteries were removed and sectioned, and their cross-sectional areas were measured.
RESULTS
The average cross-sectional areas of basilar arteries were reduced by 69% and 71% in the SAH only and SAH plus vehicle groups, respectively, when compared with the healthy controls. After treatment with 0.35, 1.75, and 3.5 mg/kg GLNVA in rabbits subjected to SAH the average cross-sectional area was decreased by 46%, 12% and 2%, respectively, when compared with the healthy controls. The protective effect of GLNVA achieved statistical significance at all dosages. Morphologically, corrugation of the internal elastic lamina of vessels was often observed in the vehicle-treated group, but was not prominent in the GLNVA-treated groups or healthy controls.
CONCLUSION
The findings showed that GLNVA dose-dependently attenuated cerebral vasospasm after SAH in the rabbit. These results suggest that intrathecal administration of GLNVA could be an effective strategy for preventing cerebral vasospasm after SAH.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Sensing tissue acidosis is an important function of the somatosensory nervous system to response to noxious stimuli.
In the pain clinic, acid or soreness sensation is a characteristic sensory ...phenotype of various acute and chronic pain syndromes, such as delayed onset muscle soreness, fibromyalgia, and radicular pain. However, soreness sensation is a sign of successful analgesia for acupuncture and noxipoint therapy. Thus, the nature of acid or soreness sensation is not always nociceptive (or painful) and could be anti-nociceptive. To facilitate the investigation of the molecular and neurobiological mechanisms of soreness sensation, we propose a concept called "sngception (sng- ception)" to describe the response of the somatosensory nervous system to sense tissue acidosis and to distinguish it from nociception. "Sng" is a Taiwanese word that represents the state of soreness while at the same time imitates the natural vocalization of humans feeling sore.
Here we propose sngception as a specific somatosensory function that transmits the acid sensation from the peripheral to the central nervous system. Sngception could partially overlap with nociception, but it could also transmit antinociception, proprioception, and pruriception.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Injectable thermoresponsive hydrogels have the advantages of effective cell delivery and minimal invasion for tissue engineering applications. In this study, we investigated the chondroinductive ...potential of newly developed hyaluronic acid (HA)-modified thermoresponsive poly(N-isopropylacrylamide) (HA-PNIPAAm-CL) hydrogels on enhancing rabbit ADSC (rADSC) chondrogenesis in vitro and in the synovial cavity of rabbit. The HA-mixed PNIPAAm (HA-PNIPAAm-CP) and HA-cross-linked PNIPAAm (HA-PNIPAAm-CL) were fabricated using physical interaction and chemical cross-linking methods, respectively. The in vitro results showed that, compared to unmodified PNIPAAm, both HA-modified hydrogels significantly increased cell viability, chondrogenic marker gene (aggrecan and type II collagen) expression and sulfide glycosaminoglycan (sGAG) formation in embedded rADSCs. However, HA-PNIPAAm-CL showed the highest rADSC viability and chondrogenesis. The chondrogenic effects of HA-modified hydrogels on rADSCs were confirmed in vivo by the intraarticular injection of hydrogel-embedded rADSC constructs into rabbit synovial cavities for 3 weeks and tracing with CM-DiI labeling. Neocartilage formation in the hydrogels was determined by histomorphological staining of GAG and type II collagen. In vivo injected rADSC/HA-PNIPAAm-CL constructs showed more hyaline cartilage formation than that of rADSC/HA-PNIPAAm-CP and rADSC/PNIPAAm constructs in the synovial cavity of rabbit. These results suggest that the HA-PNIPAAm-CL provides a suitable microenvironment to enhance ADSC chondrogenesis for articular cartilage tissue engineering applications.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Fibromyalgia is a chronic disorder characterized by widespread musculoskeletal pain. A common complaint is soreness. However, until now, no assessment tool is available to address soreness and ...evaluate its impact on disease severity. We aimed to establish a questionnaire for soreness assessment and to evaluate its validity in fibromyalgia patients.
Patients diagnosed with fibromyalgia per the American College of Rheumatology criteria (2011) were recruited. The Revised Fibromyalgia Impact Questionnaire with an integration of Soreness Assessment (FIQRS) was established by adding five items pertinent to soreness sensation to the existing FIQR. The participants were asked to evaluate their soreness symptoms by filling out the FIQRS twice. The test-retest reliability and internal consistency were assessed. Construct validity was evaluated by correlations with the FIQR and fibromyalgia symptom severity (SS) score.
Sixty-two patients with fibromyalgia were recruited, including 57 females (91.9%; mean age: 51.4 years). The intraclass correlation coefficient (ICC) of test-retest reliability was 0.92 for the FIQRS overall score. The Cronbach's α of all the items in the FIQRS was 0.93. The correlation coefficient of the FIQRS total score with the FIQR was 0.97 (p < 0.0001) and that with the fibromyalgia SS scale was 0.52 (p < 0.0001).
The FIQRS has good reliability and internal consistency for the assessment of disease impact on fibromyalgia patients, thus providing a reliable tool for soreness evaluation. Future studies are warranted for further validation regarding its correlation with other psychometric properties and life quality measurements.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Osteoporosis is the second most common epidemiologic disease in the aging population worldwide. Previous studies have found that frequent tea drinkers have higher bone mineral density and less hip ...fracture. We previously found that (-)-epigallocatechin gallate (EGCG) (20⁻100 µmol/L) significantly suppressed receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclastogenesis and pit formation via inhibiting NF-κB transcriptional activity and nuclear transport of NF-κB in RAW 264.7 cells and murine primary bone marrow macrophage cells. The most important regulation in osteoclastogenesis is the receptor activator of nuclear factor-kB/RANKL/osteoprotegrin (RANK/RANKL/OPG) pathway. In this study, we used the coculture of RAW 264.7 cells and the feeder cells, ST2, to evaluate how EGCG regulated the RANK/RANKL/OPG pathway in RAW 264.7 cells and ST2 cells. We found EGCG decreased the RANKL/OPG ratio in both mRNA expression and secretory protein levels and eventually decreased osteoclastogenesis by TRAP (+) stain osteoclasts and TRAP activity at low concentrations-1 and 10 µmol/L-via the RANK/RANKL/OPG pathway. The effective concentration can be easily achieved in daily tea consumption. Taken together, our results implicate that EGCG could be an important nutrient in modulating bone resorption.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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