Over-expressions of AMPK subunits in ovarian carcinomas with significant clinical implications

ABSTRACT: BACKGROUND: AMP-activated protein kinase (AMPK) has recently been considered as a potential target for cancer therapy. However, the expression status of various subunits of the heterotrimeric AMPK in human cancers is rarely reported. We decided to determine their expressions in ovarian carcinomas and their relationships with the disease. METHODS: Expressions and locations of the AMPK-alpha1, -alpha2, -beta1, -beta2, -gamma1 and -gamma2 were detected by quantitative PCR (Q-PCR) and immunohistochemical staining (IHC). Their expression levels in ovarian tumors were compared with normal controls and also correlated with clinicopathological parameters. RESULTS: Except AMPK-alpha1, expressions of the other five AMPK subunits are significantly higher in ovarian carcinomas as determined by Q-PCR. Although IHC detection of AMPK-gamma1 and -gamma2 were not successful, over-expressions of AMPK-alpha2, -beta1, and -beta2 were further confirmed by IHC. Over-expressions of various AMPK subunits occurred independently and were mainly detected in the cytoplasm. Interestingly, AMPK-alpha2 and -beta1 were also detected in the nucleus and cell membrane, respectively. Clinical correlation analyses indicate that expressions of different AMPK subunits are associated with different subtypes of carcinoma. High expression of AMPK-alpha2 is significantly associated with endometrioid carcinomas. On the other hand, high expressions of AMPK-beta and -gamma subunits are associated with mucinous and serous carcinomas, respectively. Furthermore, high expressions of AMPK-beta1 and -gamma2 are also associated with early and late stages of disease, respectively. Finally, patients with high expression of AMPK-alpha2 had better prognosis. CONCLUSIONS: Aberrant expressions of AMPK subunits may play important roles in ovarian carcinogenesis. Each AMPK subunit may have its own function other than just a component of the AMPK molecule. Correlations with clinical parameters suggest that expressions of AMPK subunits have different clinical implications in ovarian cancer development.     

A systematic approach for identifying and presenting mechanistic evidence in human health assessments

Clear documentation of literature search and presentation methodologies can improve transparency in chemical hazard assessments. We sought to improve clarity for the scientific support for cancer mechanisms of action using a systematic approach to literature retrieval, selection, and presentation of studies. The general question was “What are the mechanisms by which a chemical may cause carcinogenicity in the target tissue?”. Di(2-ethylhexyl)phthalate was used as a case study chemical with a complex database of >3000 publications. Relevant mechanistic events were identified from published reviews. The PubMed search strategy included relevant synonyms and wildcards for DEHP and its metabolites, mechanistic events, and species of interest. Tiered exclusion/inclusion criteria for study pertinence were defined, and applied to the retrieved literature. Manual curation was conducted for mechanistic events with large literature databases. Literature trees documented identification and selection of the literature evidence. The selected studies were summarized in evidence tables accompanied by succinct narratives. Primary publications were deposited into the Health and Environmental Research Online (http://hero.epa.gov/) database and identified by pertinence criteria and key terms to permit organized retrieval. This approach contributes to human health assessment by effectively managing a large volume of literature, improving transparency, and facilitating subsequent synthesis of information across studies.     

Reduction in nocturnal functional bladder capacity is a common factor in the pathogenesis of refractory nocturnal enuresis

OBJECTIVE: To evaluate the diurnal and nocturnal bladder reservoir function in patients with refractory primary nocturnal enuresis (PNE). PATIENTS AND METHODS: Ninety-five children (68 boys, 27 girls, mean age 9.3 years) with significant PNE (>/=3 wet nights/week) that was refractory to treatment with desmopressin +/- an enuretic alarm were assessed using detailed recording of voiding frequency and urinary volume both day and night, natural filling cystometry during the day and continuous cystometry with simultaneous electroencephalogram monitoring during sleep at night. RESULTS: Patients could be broadly categorized into two groups. Group A comprised those with normal daytime urodynamics and functional bladder capacity (FBC) on detailed frequency-volume recording, but who developed marked detrusor instability associated with a significant reduction in nocturnal FBC and small-volume voiding only after sleep at night (33 patients, 35%); and group B, those with abnormal daytime urodynamics and with reduced FBC and small-volume voiding both day and night, but who somehow managed to mask their bladder symptoms during the day (62 patients, 65%). There was no evidence of nocturnal polyuria in either group and the ratios of day : night urinary output volumes for type A and type B patients were 1.48 and 1.99, respectively. CONCLUSION: A reduction in nocturnal FBC, either occurring only after sleep at night in association with the appearance of detrusor instability in patients with normal daytime urodynamics and FBC, or as a manifestation of occult voiding dysfunction or bladder outlet obstruction that affects the bladder reservoir function both day and night, appears to be a common factor and probably the main cause for a mismatch between nocturnal urine output and bladder storage capacity in patients with severe bed-wetting that was refractory to treatment.     

股骨转子间骨折与股骨颈骨折内固定失效后行人工髋关节置换术的比较

目的将股骨转子间骨折行动力髋部螺钉(DHS)内固定术后的人工髋关节置换术与股骨颈骨折AO螺钉内固定术后行全髋关节置换术的临床结果相比较,总结股骨转子间骨折行DHS内固定术后的人工髋关节置换术经验以及治疗过程中的困难和随访结果。方法将1984年6月～2001年8月有完整资料的19例股骨转子间骨折行DHS内固定术后和配对的19例股骨颈骨折AO螺钉内固定术后行人工髋关节置换术的结果进行比较。使用SPSS软件中的配对T检验方法对本组病人的年龄、性别、DHS失效的原因、骨折至关节置换术时间、早期并发症、失血、手术时间及临床Harris的评分进行统计分析。结果在DHS组中,术后早期并发症(术中股骨近端骨折或术后髋关节脱位)的发生率明显高于AO螺钉组(0.01相似文献   

Personal tragedy or system failure: a qualitative analysis of narratives of caregivers of people with severe mental illness in Hong Kong and Taiwan

BACKGROUND: Most studies agree that mental illness brings a heavy objective and subjective burden of care on the family and especially the caregivers. However, very little attention has been paid to the wider context in which this burden is shaped and sustained. MATERIAL: In-depth interviews were conducted with 11 caregivers in Hong Kong and Taiwan and subsequent analysis identified four major themes: mystical knowledge beyond understanding, persistent self-blame and lay explanation, inertia of caregivers and non-responsive service system, and unsatisfying encounters with medical staff. DISCUSSION: The results of the study indicate that these families did not get the services they needed. In spite of recounting many system failures, most respondents attributed their situation to tragedy and misfortune at personal and family levels. Such a discourse is closely connected to a wider context of health and social care. The Hong Kong subjects complained more, felt more helpless, and had more persistent self-blame and lay explanation than the Taiwanese subjects. CONCLUSIONS: To reduce such experiences, this paper calls for inclusive policies for the family, new education strategies and reflections on the roles of mental health professionals in empowerment and advocacy beyond conventional treatment, counseling and education.     

Reduced semantic fluency as an additional screening tool for subjects with questionable dementia

BACKGROUND: Subjective memory complaints in subjects with mild cognitive impairment may represent a genuine decline in episodic memory. This paper evaluates the neuropsychological correlates of the semantic fluency test in subjects with questionable dementia (QD). METHODS: A total of 331 Chinese subjects (118 normal controls, NC, 150 with QD and 63 with mild Alzheimer's disease, AD) were assessed with the Category Verbal Fluency Test (CVFT), the AD Assessment Scale-cognitive subscale (ADAS-Cog), and digit and verbal span tests. CVFT performance was evaluated in each Clinical Dementia Rating (CDR) group. The total number of exemplars, the subcategory and the category size generated were evaluated. Neuropsychological correlates of CVFT scores were computed. RESULTS: Significant differences in CVFT performance were found between the different CDR groups. The subjects with QD had intermediate scores compared to the NC and AD subjects (1-way ANOVA, p < 0.001, post-hoc Bonferroni comparisons). In NC the CVFT scores were significantly associated with ADAS-Cog total, and immediate and delayed recall scores (partial correlations controlled for age and education, p < 0.005). In the QD group the CVFT scores were correlated with ADAS-Cog total, and immediate recall and object naming scores (partial correlation controlled for age and education, p < 0.005). Regression analysis revealed that age and delayed recall were significant predictors of CVFT performance in NCs. In the QD group, age, ADAS-Cog immediate recall and object naming scores predicted the CVFT performance. CONCLUSIONS: The CVFT was impaired in the subjects with QD. Apart from episodic memory, semantic memory deficits also occur early in AD. The different cognitive predictors of CVFT scores in the NC and QD groups suggest that the test is associated with specific psychological functions at different stages of cognitive impairment.     

Curcumin attenuates the expression and secretion of RANTES after spinal cord injury in vivo and lipopolysaccharide-induced astrocyte reactivation in vitro

Curcumin has been proposed for treatment of various neuroinflammatory and neurodegenerative conditions, including post-traumatic inflammation during acute spinal cord injury (SCI). In this study, we examined whether curcumin anti-inflammation involves regulation of astrocyte reactivation, with special focus on the injury-induced RANTES (regulated on expression normal T-cell expressed and secreted) from astrocytes in acute SCI. Male Sprague-Dawley (SD) rats were subjected to impact injury of the spinal cord followed by treatment with curcumin (40 mg/kg i.p.). RANTES and inducible nitric oxide synthase expression as well as RANTES-positive astrocytes were all induced by injury accompanied by the elevation of lipid peroxidation, and attenuated by the curcumin treatment. In primary cultured rat astrocytes challenged with lipopolysaccharide (LPS) to mimic astrocyte reactivation following SCI, LPS induces robust increase of RANTES expression and the effect was also reduced by 1 μM curcumin treatment. Furthermore, cortical neurons cultured with astrocyte conditioned medium (ACM) conditioned with both LPS and curcumin (LPS-curcumin/ACM), which characteristically exhibited decreased RANTES expression when compared with ACM from astrocytes treated with LPS alone (LPS/ACM), showed higher level of cell viability and lower level of cell death as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction activity assay and lactate dehydrogenase release assay, respectively. Knockdown of RANTES expression by siRNA (siRANTES) shows reduced RANTES expression and release from LPS-reactivated astrocytes, and ACM obtained from this condition (LPS-siRANTES/ACM) becomes less cytotoxic as compared with the LPS-ACM. Therefore, curcumin reduction of robust RANTES production in reactivated astrocytes both in vitro and in vivo may contribute to its neuroprotection and potential application in SCI.     

Endoscopic submucosal dissection versus local excision for early rectal neoplasms: a comparative study

Background  

Transanal local excision (LE) is a well-established treatment option for early rectal neoplasms not amenable to complete colonoscopic removal. Endoscopic submucosal dissection (ESD) has been introduced recently as a novel procedure that enables en bloc resection of large rectal neoplasms. To date, no report comparing the two approaches can be found in the literature. This study aimed to compare the short-term clinical outcomes between ESD and LE for early rectal neoplasms.     

Risk of deep vein thrombosis following laparoscopic rectosigmoid cancer resection in chinese patients

OBJECTIVE: The aim of this study was to evaluate the incidence of postoperative deep vein thrombosis (DVT) in Chinese patients who underwent laparoscopic resection of rectal or sigmoid cancer in the absence of thromboprophylaxis. METHODS: Patients with adenocarcinoma of the sigmoid colon or rectum scheduled for laparoscopic resection were recruited. Neither chemoprophylaxis nor mechanical methods against DVT were employed. They were scheduled to have routine duplex ultrasound of both lower limbs perioperatively. RESULTS: In a 12-month period, 50 patients were recruited. Postoperative DVT occurred in 19 (38%) patients. None needed anticoagulation. Complete resolution of the thrombus was noted in 10 (53%) patients 12 weeks after operation, and in six patients 36 weeks after operation. Female sex was identified as being associated with a higher incidence of DVT. Age, smoking, preoperative neoadjuvant chemoirradiation, preoperative metastasis, duration of operation, conversion and postoperative complications did not appear to be risk factors for DVT. CONCLUSION: The incidence of asymptomatic calf vein DVT is relatively high after laparoscopic resection for rectosigmoid cancers in the Chinese population. However, complete resolution occurred without the use of anticoagulant therapy in the majority of cases. It is thus difficult to advocate the routine use of anticoagulant prophylaxis.