Selective inhibition of cyclooxygenase 2 induces p27kip1 and skp2 in oral squamous cell carcinoma

It has been shown that inhibition of cyclooxygenase 2 (COX-2) may cause growth arrest and reduced tumour formation in some human cancers; however, the mechanism is not fully known. In this study, we used an oral squamous cell carcinoma cell line to study growth inhibition and changes in critical cell cycle-regulating proteins induced by the selective COX-2 inhibitor celecoxib. Using cell viability assay, we established the optimal in vitro inhibitory dose of celecoxib and showed that inhibition of COX-2 markedly induces the expression of p27kip1, p21, waf1, and the F-box protein skp2. These results add new experimental data to our knowledge of the mechanism of cyclooxygenases on neoplastic cells.     

An uncommon presentation of orbital apex syndrome.

BACKGROUND: Bilateral total ophthalmoplegia secondary to a malignancy or infection of the cavernous sinus and orbital apex is an unusual presentation. Bilateral ophthalmoplegia as the initial sign of this type of rhinocerebral pathology is also uncommon. CASE REPORT: A 34-year old Haitian woman presented with bilateral vision loss, ptosis, total ophthalmoplegia, and ocular pain. A physical and neurologic examination, laboratory analysis, chest x-rays, and neurologic imaging studies were requested. Cranial and facial computed tomography (CT) scans showed swelling of the soft tissues proximal to the sphenoid extending into the dorsal sella and prepontine cistern, obliteration of the nasopharyngeal reflection, opacification of the ethmoid and sphenoid sinus, bony destruction of the mid-skull base, and bilateral lymphadenopathy of the neck. Magnetic resonance imaging (MRI) showed the presence of a soft tissue mass causing destruction of the skull base. Involvement of the clivus, cavernous sinuses, and sella with nasopharynx extension was observed. Hypodense centers within nasopharyngeal tissues suggested the presence of necrosis. Differential diagnosis included nasopaharyngeal carcinoma, lymphoma, or an infectious process. The patient did not consent to a biopsy and refused treatment. CONCLUSION: This presentation is a medical emergency. A combination of surgical, medical, or radiological intervention may be required to manage rhino-cerebral diseases responsible for orbital apex syndrome. Despite advances in neurologic imaging, histologic examination of tissue obtained from a biopsy may ultimately be necessary to obtain a precise diagnosis.     

Loss of adenomatous polyposis coli (apc) results in an expanded ciliary marginal zone in the zebrafish eye

The distal region of neural retina (ciliary marginal zone [CMZ]) contains stem cells that produce non‐neural and neuronal progenitors. We provide a detailed gene expression analysis of the eyes of apc mutant zebrafish where the Wnt/β‐catenin pathway is constitutively active. Wnt/β‐catenin signaling leads to an expansion of the CMZ accompanied by a central shift of the retinal identity gene sox2 and the proneural gene atoh7. This suggests an important role for peripheral Wnt/β‐catenin signaling in regulating the expression and localization of neurogenic genes in the central retina. Retinal identity genes rx1 and vsx2, as well as meis1 and pax6a act upstream of Wnt/β‐catenin pathway activation. Peripheral cells that likely contain stem cells can be identified by the expression of follistatin, otx1, and axin2 and the lack of expression of myca and cyclinD1. Our results introduce the zebrafish apc mutation as a new model to study signaling pathways regulating the CMZ. Developmental Dynamics 239:2066–2077, 2010. © 2010 Wiley‐Liss, Inc.     

Resting posterior versus frontal delta/theta EEG activity is associated with extraversion and the COMT VALMET polymorphism

Recent studies suggest that resting posterior versus frontal EEG delta/theta activity (delta/theta Pz–Fz) is both sensitive to pharmacological manipulations of neural dopamine and associated with the agency facet of extraversion (i.e., a motivational disposition comprising enthusiasm, energy, assertiveness, achievement striving and social dominance). These observations suggest that posterior versus frontal resting EEG delta/theta activity may represent a useful marker for investigating the molecular genetic basis of extraversion. The present study aimed to test the novel hypothesis of an association between delta/theta Pz–Fz and a functional polymorphism of the enzyme catechol-O-methyltransferase (COMT VAL¹⁵⁸MET) involved in dopamine catabolism. This was conducted in a large EEG data set from the Brain Resource International Database (BRID; resting EEG from N = 1093 healthy individuals, 382 of which also genotyped for COMT VAL¹⁵⁸MET). In summary, we (1) showed for the first time that the VAL allele is associated with increased delta/theta Pz–Fz; (2) replicated the association between extraversion and delta/theta Pz–Fz in a large, heterogeneous sample including both genders; and (3) documented that the VAL allele of the COMT VAL¹⁵⁸MET is associated with increased extraversion scores, as previously reported for an overlapping BRID sample. This coherent pattern of findings adds further support to the suggestion that the posterior–anterior distribution of resting EEG slow wave activity in the delta/theta range represents a useful tool for probing the dopaminergic basis of extraversion.     

Amyloid and metabolic positron emission tomography imaging of cognitively normal adults with Alzheimer's parents

This study examines the relationship between fibrillar beta-amyloid (Aβ) deposition and reduced glucose metabolism, a proxy for neuronal dysfunction, in cognitively normal (NL) individuals with a parent affected by late-onset Alzheimer's disease (AD). Forty-seven 40–80-year-old NL received positron emission tomography (PET) with ¹¹C-Pittsburgh compound B (PiB) and 18F-fluoro-2-deoxy-d-glucose (FDG). These included 19 NL with a maternal history (MH), 12 NL with a paternal history (PH), and 16 NL with negative family history of AD (NH). Automated regions of interest, statistical parametric mapping, voxel-wise intermodality correlations, and logistic regressions were used to examine cerebral-to-cerebellar PiB and FDG standardized uptake value ratios across groups. The MH group showed higher PiB retention and lower metabolism in AD regions compared with NH and PH, which were negatively correlated in posterior cingulate, frontal, and parieto-temporal regions (Pearson r ≤ −0.57, p ≤ 0.05). No correlations were observed in NH and PH. The combination of Aβ deposition and metabolism yielded accuracy ≥ 69% for MH vs. NH and ≥ 71% for MH vs. PH, with relative risk = 1.9–5.1 (p values < 0.005). NL individuals with AD-affected mothers show co-occurring Aβ increases and hypometabolism in AD-vulnerable regions, suggesting an increased risk for AD.     

Prevalence and Clinical Outcome of Hyperglycemia in the Perioperative Period in Noncardiac Surgery

OBJECTIVE

Hospital hyperglycemia, in individuals with and without diabetes, has been identified as a marker of poor clinical outcome in cardiac surgery patients. However, the impact of perioperative hyperglycemia on clinical outcome in general and noncardiac surgery patients is not known.

RESEARCH DESIGN AND METHODS

This was an observational study with the aim of determining the relationship between pre- and postsurgery blood glucose levels and hospital length of stay (LOS), complications, and mortality in 3,184 noncardiac surgery patients consecutively admitted to Emory University Hospital (Atlanta, GA) between 1 January 2007 and 30 June 2007.

RESULTS

The overall 30-day mortality was 2.3%, with nonsurvivors having significantly higher blood glucose levels before and after surgery (both P < 0.01) than survivors. Perioperative hyperglycemia was associated with increased hospital and intensive care unit LOS (P < 0.001) as well as higher numbers of postoperative cases of pneumonia (P < 0.001), systemic blood infection (P < 0.001), urinary tract infection (P < 0.001), acute renal failure (P = 0.005), and acute myocardial infarction (P = 0.005). In multivariate analysis (adjusted for age, sex, race, and surgery severity), the risk of death increased in proportion to perioperative glucose levels; however, this association was significant only for patients without a history of diabetes (P = 0.008) compared with patients with known diabetes (P = 0.748).

CONCLUSIONS

Perioperative hyperglycemia is associated with increased LOS, hospital complications, and mortality after noncardiac general surgery. Randomized controlled trials are needed to determine whether perioperative diabetes management improves clinical outcome in noncardiac surgery patients.Patients with diabetes are more likely to undergo surgery than are those without diabetes (1,2). Surgery in diabetic patients is associated with longer hospital stay, higher health care resource utilization, and greater perioperative mortality than in nondiabetic subjects (1–3). The higher morbidity and mortality in diabetic patients relates in part to the heightened incidence of comorbid conditions including coronary heart disease, hypertension, and renal insufficiency (4,5), as well as the adverse effects of hyperglycemia in clinical outcome (6–8). Evidence from observational studies suggests that in surgical patients, with and without diabetes, improvement in glycemic control positively affects morbidity and mortality (9,10). The stronger body of evidence comes from the setting of cardiac surgery and critically ill patients admitted to the intensive care unit (ICU). In this setting, perioperative hyperglycemia is associated with an increased rate of deep sternal wound infections, hospital complications, and mortality (11,12), and improvement of glycemic control reduces the rate of postoperative complications, length of hospital stay, and mortality (8,12,13). Similarly, the development of perioperative hyperglycemia has also been shown to be a sensitive predictor of nosocomial infection in small observational studies in general surgery (9,10,14). Few studies, however, have reported on the association between glucose levels and hospital mortality in general surgery patients, and it is not known whether the severity of hyperglycemia and the timing of hyperglycemia before or during the postoperative period lead to the increased mortality and hospital complications. Accordingly, the aim of this study was to determine 1) the relationship between perioperative hyperglycemia and diabetes on clinical outcome (length of hospital stay, need for ICU care, infectious complications, acute renal failure [ARF], respiratory failure, and myocardial infarction) and 2) the impact of perioperative hyperglycemia on survival after adjustment for known prognostic factors in patients undergoing general noncardiac surgery. We hypothesized that general surgery patients with perioperative hyperglycemia would experience higher hospital complications and mortality compared with patients with normal glucose levels.     

Genetic and genomic tools for zebrafish research: the NIH zebrafish initiative.

The National Institutes of Health (NIH) has been a leading advocate of the zebrafish as a model organism for the study of vertebrate development, physiology, and disease. Genomic tools, developed with the support of NIH funding, have made zebrafish even more attractive as a genetic system and have stimulated research using this model. The NIH continues to provide support for new and existing community resources, such as the Zebrafish International Resource Center and the Zebrafish Information Network, research tool development and mutant screens, and a wide array of investigator-initiated studies that are using zebrafish to elucidate many aspects of vertebrate biology.     

Behavioral and emotional disturbances in the offspring of depressed parents with anger attacks

BACKGROUND: To examine the emotional and behavioral characteristics of the offspring of depressed parents with and without anger attacks. METHODS: Forty-three parents who met criteria for major depressive disorder (MDD) completed the Achenbach Child Behavior Checklist - Parent Report Version (CBCL) for each of their birth children (n = 58, age range 6-17 years). Unpaired t tests were used to evaluate the CBCL scale score differences between children of parents with and children of parents without anger attacks. Baseline demographics and clinical differences between the two groups of parents were also evaluated. RESULTS: Parents with anger attacks had a significantly younger age of onset of MDD. Offspring of depressed parents with anger attacks were found to have significantly lower social and school competency scale scores and higher scores for delinquency, attention problems, and aggressive behavior. In addition, this group was found to have a significantly higher total T score (a global measure of psychopathology). CONCLUSIONS: There are some important differences between offspring of depressed parents with and without anger attacks. This finding may be important in identifying and formulating intervention strategies for childhood problems in the offspring of depressed parents.