Giant broad ligament leiomyoma with postoperative infection diagnosed with contrast-enhanced ultrasound: Case report and literature review.

A 33-year-old woman of giant broad ligament leiomyoma with myxoid degeneration was misdiagnosed as ovarian tumor. The patient underwent a transabdominal myomectomy and developed a pelvic infection after operation diagnosed with contrast-enhanced ultrasound. She was cured and ultimately discharged after symptomatic treatment. Only 21 cases of giant broad ligament leiomyomas with a diameter larger than 12 cm were included. The present systematic review aimed to increase awareness of the clinical characteristics and treatment methods of giant broad ligament leiomyoma, and reduce the rates of misdiagnosis and postoperative complications.

tPA Mobilizes Immune Cells That Exacerbate Hemorrhagic Transformation in Stroke.

RATIONALE: Hemorrhagic complications represent a major limitation of intravenous thrombolysis using tPA (tissue-type plasminogen activator) in patients with ischemic stroke. The expression of tPA receptors on immune cells raises the question of what effects tPA exerts on these cells and whether these effects contribute to thrombolysis-related hemorrhagic transformation. OBJECTIVE: We aim to determine the impact of tPA on immune cells and investigate the association between observed immune alteration with hemorrhagic transformation in ischemic stroke patients and in a rat model of embolic stroke. METHODS AND RESULTS: Paired blood samples were collected before and 1 hour after tPA infusion from 71 patients with ischemic stroke. Control blood samples were collected from 27 ischemic stroke patients without tPA treatment. A rat embolic middle cerebral artery occlusion model was adopted to investigate the underlying mechanisms of hemorrhagic transformation. We report that tPA induces a swift surge of circulating neutrophils and T cells with profoundly altered molecular features in ischemic stroke patients and a rat model of focal embolic stroke. tPA exacerbates endothelial injury, increases adhesion and migration of neutrophils and T cells, which are associated with brain hemorrhage in rats subjected to embolic stroke. Genetic ablation of annexin A2 in neutrophils and T cells diminishes the effect of tPA on these cells. Decoupling the interaction between mobilized neutrophils/T cells and the neurovascular unit, achieved via a S1PR (sphingosine-1-phosphate receptor) 1 modulator RP101075 and a CCL2 (C-C motif chemokine ligand 2) synthesis inhibitor bindarit, which block lymphocyte egress and myeloid cell recruitment, respectively, attenuates hemorrhagic transformation and improves neurological function after tPA thrombolysis. CONCLUSIONS: Our findings suggest that immune invasion of the neurovascular unit represents a previously unrecognized mechanism underlying tPA-mediated brain hemorrhage, which can be overcome by precise immune modulation during thrombolytic therapy.

Inhibition of activator protein 1 attenuates neuroinflammation and brain injury after experimental intracerebral hemorrhage.

AIMS: Intracerebral hemorrhage (ICH) is a devastating type of stroke without specific treatment. Activator protein 1 (AP-1), as a gene regulator, initiates cytokine expression in response to environmental stimuli. In this study, we investigated the relationship between AP-1 and neuroinflammation-associated brain injury triggered by ICH. METHODS: Intracerebral hemorrhage mice were developed by autologous blood or collagenase infusion. We measured the dynamics of AP-1 in mouse brain tissues during neuroinflammation formation after ICH. The effects of the AP-1 inhibitor SR11302 on brain injury and neuroinflammation as well as the underlying mechanisms were investigated in vivo and in vitro. RESULTS: AP-1 was significantly upregulated in mouse brain tissue as early as 6 hours after ICH, accompanied by elevations in proinflammatory factors, including interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α. Inhibition of AP-1 using SR11302 reduced neurodeficits and brain edema at day 3 after ICH. SR11302 ablated microglial IL-6 and TNF-α production and brain-infiltrating leukocytes in ICH mice. In addition, SR11302 treatment diminished thrombin-induced production of IL-6 and TNF-α in cultured microglia. CONCLUSIONS: Inhibition of AP-1 curbs neuroinflammation and reduces brain injury following ICH.

CYP2C19 polymorphisms and antiplatelet effects of clopidogrel in acute ischemic stroke in China.

BACKGROUND AND PURPOSE: Little research regarding genotypes and clopidogrel response related to acute ischemic stroke has been published. This study was conducted to investigate whether the polymorphisms of receptors or enzymes involved in the metabolic process of clopidogrel affect clopidogrel response and prognosis related to acute stroke. METHODS: A total of 259 patients with acute ischemic stroke were enrolled in this study; all received follow-up evaluations 3 and 6 months after clopidogrel treatment. CYP2C19, CYP3A4, and P2Y12 were screened. The adenosine diphosphate-induced platelet aggregation test, the National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) were used, and blood vascular events were evaluated. RESULTS: The difference before and after clopidogrel treatment on adenosine diphosphate-induced platelet aggregation was significantly smaller in patients carrying 1 or 2 CYP2C19 loss-of-function alleles (*2, *3) compared with patients carrying none. Patients with none had better outcomes than patients with CYP2C19 loss-of-function alleles, as demonstrated by NIHSS and mRS scores at 3 and 6 months after treatment. Regression analysis showed that CYP2C19 was an independent predictor of clopidogrel resistance. CONCLUSIONS: CYP2C19 genotypes had significant impact on clopidogrel response and prognosis of patients with stroke. Clinical Trial Registration Information- URL: http://www.chictr.org/. Unique Identifier: ChiCTR-OCH-12002681.

[Clone and construction of plant expression vector of AeSS gene in Aralia elata].

OBJECTIVE: To clone Aralia elata squalene synthase gene (designated as AeSS) and construct plant expression vector for transgenic research. METHODS: Isolated squalene synthase from Aralia elata with specific primers by RT-PCR and inserted AeSS gene into the plant expression vector pBI121. RESULTS: The full-length cDNA of AeSS (Genebank accession Number: GU354313) was 1 261 bp and contained a 1 245 bp open reading frame (ORF) encoding a polypeptide of 414 amino acids. The plant expression vector pAeSS was constructed by inserted AeSS gene into the downstream of 35 S promoter of plant expression vector pBI121. CONCLUSION: AeSS gene was cloned and plant expression vector was constructed for future research.

[Relationship between expression of nestin in experimental brain contusion and injury time].

OBJECTIVE: To observe the alteration of nestin intervals in the experimental traumatic brain injury and investigate its relation to the injury intervals. METHODS: The rat brain contusion was conducted by falling impact injury. After various survival interval (0.5, 6, 12 h and 1, 3, 7, 14, 28 d), immunohistochemical SP method was used for observing the expression of nestin in the cortex, hippocampal dentate gyrus and the corpus callosum on injury side. RESULTS: Expression of nestin positive cells increased at 0.5 h and reached the maximum level in 7 d after brain contusion, then the expression decreased gradually. The intensity of nestin staining in the the cortex and the hippocampal dentate gyrus decreased to normal on 28 d. As to the corpus callosum of injury side it remained weak on 28 d. CONCLUSION: The changes of nestin immunohistochemical staining can be used as an index for forensic estimation of early injury time.

Early decrease in serum IV-7S levels during IFN treatment predicts anti-fibrogenic effect in nonresponders with chronic hepatitis C.

BACKGROUND: We evaluated whether early changes in serum levels of fibrogenic markers during interferon (IFN) treatment can predict long-term anti-fibrogenic effects in patients with chronic hepatitis C (CHC). METHODS: We retrospectively examined the serum levels of N-terminal peptide of type III procollagen (P-III-NP) and 7S domain of type IV collagen (IV-7S) in 56 patients with CHC who were revealed to be IFN-nonresponders. We measured these markers before (T0) and 1 month (T1) after the commencement of IFN therapy, at the end of 24 weeks' IFN therapy (T24), and 1 year (T24-1) and more than 2 years (T24-2) after the cessation of IFN therapy. We also measured these markers twice, at intervals of more than 2 years, in 43 IFN-untreated patients with CHC as controls. RESULTS: In nonresponders, both P-III-NP and IV-7S levels at T24-2 were significantly decreased compared with those at T0. P-III-NP levels at T1 were significantly decreased compared with those at T0, and remained at significantly low levels until the end of the observation period. IV-7S levels at T1 were not significantly different from those at T0. In patients whose IV-7S levels at T24-2 were decreased compared with those at T0, IV-7S levels at T1 were significantly lower than those at T0. In patients whose IV-7S levels at T24-2 were elevated or unchanged compared with those at T0, IV-7S levels at T1 were significantly higher than those at T0. In untreated patients, both P-III-NP and IV-7S levels at more than 2 years after the initial time were significantly increased compared with those at the initial time. CONCLUSIONS: An early decrease in IV-7S levels after IFN treatment is a useful indicator of anti-fibrogenic effects in nonresponders.

Differential mechanism and site of action of CCK on the pancreatic secretion and growth in rats.

Recent studies demonstrated that cholecystokinin (CCK) at physiological levels stimulates pancreatic enzyme secretion via a capsaicin-sensitive afferent vagal pathway. This study examined whether chemical ablation of afferent vagal fibers influences pancreatic growth and secretion in rats. Bilateral subdiaphragmatic vagal trunks were exposed, and capsaicin solution was applied. Pancreatic wet weight and pancreatic secretion and growth in response to endogenous and exogenous CCK were examined 7 days after capsaicin treatment. Perivagal application of capsaicin increased plasma CCK levels and significantly increased pancreatic wet weight compared with those in the control rats. Oral administration of CCK-1 receptor antagonist loxiglumide prevented the increase in pancreatic wet weight after capsaicin treatment. In addition, continuous intraduodenal infusion of trypsin prevented the increase in plasma CCK levels and pancreatic wet weight after capsaicin treatment. There were no significant differences in the expression levels of CCK-1 receptor mRNA and protein in the pancreas in capsaicin-treated and control rats. Intraduodenal administration of camostat or intravenous infusion of CCK-8 stimulated pancreatic secretion in control rats but not in capsaicin-treated rats. In contrast, repeated oral administrations of camostat or intraperitoneal injections of CCK-8 significantly increased pancreatic wet weight in both capsaicin-treated and control rats. Present results suggest that perivagal application of capsaicin stimulates pancreatic growth via an increase in endogenous CCK and that exogenous and endogenous CCK stimulate pancreatic growth not via vagal afferent fibers but directly in rats.

Treatment for hyperglycemia promotes pancreatic regeneration in rats without CCK-1 receptor gene expression.

INTRODUCTION AND AIM: Recent studies have suggested that CCK is not essential for normal pancreatic growth in mice. We examined whether the treatment of hyperglycemia participates in a non-CCK-1-receptor-mediated mechanism of pancreatic regeneration after partial (30%) pancreatectomy (Px) with use of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model for type 2 diabetes mellitus without CCK-1 receptor gene expression. METHODOLOGY: Male OLETF rats were divided into five groups at 24 weeks of age. The first group was killed to examine the pancreas at 24 weeks of age (PrePx). The second group underwent a midline laparotomy and received a standard rat chow (ShamPx). The remaining three groups of rats received one of the following three treatments after Px: a standard rat chow (PxC), a diet containing acarbose (PxA), or a standard rat chow and once-daily subcutaneous injection of insulin (PxI) for 8 weeks. RESULTS: PxC rats had significantly higher serum glucose levels than did PxA and PxI rats. Pancreatic weight and pancreatic contents of protein in PxA and PxI rats were significantly higher than in PxC rats. The pancreas in PxC rats was atrophic, and marked inflammatory cell infiltration was observed in the pancreas. In addition, tumor necrosis factor-alpha (TNFalpha) was expressed in the inflammatory cells, acinar cells, and islets in PxC rats. However, histologic alterations, including expression of TNFalpha, remained at a minimum in PxA and PxI rats. CONCLUSION: We conclude that the control of serum glucose levels plays an important role in preventing pancreatic atrophy and participates in the non-CCK-1-receptor-mediated mechanisms of pancreatic growth in rats.

Troglitazone stimulates pancreatic growth in normal rats.

INTRODUCTION: Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-activated nuclear transcription factors belonging to the nuclear hormone receptors. Troglitazone, a specific ligand for PPAR-gamma is shown to regulate not only lipids and glucose metabolism, but also cell cycle, differentiation, and apoptosis. AIM: To examine the effect of chronic oral administration of troglitazone on the age-related changes of insulin resistance, plasma CCK levels, and pancreatic growth in normal rats. METHODOLOGY: A troglitazone-rich diet (0.2%) was given from 12 to 28 weeks of age or from 12 or 28 weeks of age to 72 weeks of age. RESULTS: Fasting serum glucose concentrations in control rats increased progressively with age, which was almost completely prevented by troglitazone treatment. Serum insulin concentrations and pancreatic insulin content in the control rat markedly increased at 28 weeks of age but decreased at 72 weeks of age. These parameters in troglitazone-treated rats remained at nearly the same concentrations at all ages. Insulin concentration relative to DNA in the control rats increased with age, whereas in the troglitazone-treated rats it remained at nearly the same concentrations throughout the observation periods and was significantly lower than that in the controls. Insulin resistance in control rats showed a great increase at 72 weeks of age, whereas it was nearly the same at all ages in troglitazone-treated rats and was significantly lower than those in the control rats. Plasma cholecystokinin concentrations in control rats slightly but insignificantly increased with age, whereas pancreatic weight decreased age-dependently when corrected for body weight. Although troglitazone treatment appeared to decrease plasma cholecystokinin concentrations compared with those in the control rats, it significantly increased pancreatic weight and prevented age-dependent decrease. Troglitazone treatment significantly increased pancreatic protein and DNA contents, but the protein per DNA ratio, an indicator of cellular size, remained at nearly the same concentrations at all ages. The contour of the islets in the control rats at 72 weeks of age was somewhat irregular with structural disarrangement and fibrosis. Moreover, the islets were separated into small sections (cluster) by fibrosis. Troglitazone treatment prevented or reversed these age-related changes of the islets to those in rats at 12 weeks of age. CONCLUSION: Our results indicate that troglitazone stimulates pancreatic growth in the normal rat not only by reducing insulin resistance and improving glucose metabolism, but also by suppressing fibrosis of the islets.