Inhibition of the Monocarboxylate Transporter 1 (MCT1) Promotes 3T3-L1 Adipocyte Proliferation and Enhances Insulin Sensitivity.

Enlarged, hypertrophic adipocytes are less responsive to insulin and are a hallmark feature of obesity, contributing to many of the negative metabolic consequences of excess adipose tissue. Although the mechanisms remain unclear, the adipocyte size appears to be inversely correlated with insulin sensitivity and glucose tolerance, wherein smaller adipocytes are insulin-sensitive and larger adipocytes develop insulin resistance and exhibit an impaired glucose uptake. Thus, pharmacological strategies aimed at regulating adipocyte hypertrophy (increase in adipocyte size) in favor of promoting hyperplasia (increase in adipocyte number) have the potential to improve adipocyte insulin sensitivity and provide therapeutic benefits in the context of metabolic disorders. As white adipose tissue can metabolize large amounts of glucose to lactate, using transcriptomics and in vitro characterization we explore the functional consequences of inhibiting monocarboxylate transporter 1 (MCT1) activity in fully differentiated adipocytes. Our studies show that the pharmacological inhibition of MCT1, a key regulator of the cellular metabolism and proliferation, promotes the re-entry of mature adipocytes into the cell cycle. Furthermore, we demonstrate that inhibitor-treated adipocytes exhibit an enhanced insulin-stimulated glucose uptake as compared with untreated adipocytes, and that this outcome is dependent on the cyclin-dependent kinase 1 (CDK1) activity. In summary, we identify a mechanism though which MCT1 inhibition improves the insulin sensitivity of mature adipocytes by inducing cell cycle re-entry. These results provide the foundation for future studies investigating the role MCT1 plays in adipocyte hyperplasia, and its therapeutic potential as a drug target for obesity and metabolic disease.

Molecular basis for maize as a risk factor for esophageal cancer in a South African population via a prostaglandin E2 positive feedback mechanism.

The incidence of squamous cancer of the esophagus varies up to a hundredfold in different regions of the world. In Transkei, South Africa, a particularly high incidence of the disease is observed. We have previously proposed an association between a maize-rich diet and elevated levels of intragastric prostaglandin E2 production (PGE(2)). Here we investigate the molecular mechanisms by which a high-maize diet could lead to increased incidence of squamous cancer of the esophagus. We confirm that levels of PGE(2) are high (606.8 pg/ml) in the gastric fluid of individuals from Transkei. We also show that treatment of esophageal cells with linoleic acid, which is found at high levels in maize and is a precursor to PGE(2), leads to increased cell proliferation. Similarly, treatment of cells with PGE(2) or with gastric fluid from Transkeians also leads to increased proliferation. Our data suggest that the high levels of PGE(2) associated with a maize-rich diet stimulate cell division and induce the enzyme COX 2, resulting in a positive feedback mechanism that predisposes the esophagus to carcinoma.

Public engagement on ethical principles in allocating scarce resources during an influenza pandemic.

OBJECTIVES: To investigate the views of students, support staff and academic staff at the University of Alberta in Edmonton, Canada on the allocation of scarce resources during an influenza pandemic to discover if there were any shared values. METHODS: A web-based questionnaire was circulated to students, support staff and academic staff asking them how they would rank the priority of eleven different groups for access to scarce resources. They were also asked to select one of seven priority access plans. RESULTS: The highest priority was given to health care workers by 89% of respondents, closely followed by emergency workers (85%). Only 12.7% of respondents gave politicians high priority. Respondents favored the "Save the most lives" priority access (39.9%) (N=5220). CONCLUSION: Current policies in place for the allocation of scarce resources during an influenza pandemic may not properly reflect the views of the general public. Further public consultation should be undertaken in order to uncover how they would allocate scarce resources.

Endogenous control genes in prostate cells: evaluation of gene expression using 'real-time' quantitative polymerase chain reaction.

OBJECTIVE: Our aims were to measure the level of expression of Abelson (ABL1), ß-glucuronidase (GUS) and glucose-6-phosphate dehydrogenase (G6PD) genes in exfoliated urine cells from healthy and transrectal ultrasound biopsy patients with elevated prostate-specific antigen levels and/or abnormal digital rectal examinations or urinary symptoms indicative of prostate problems, as well as in archived formalin-fixed paraffin-embedded prostate materials. MATERIALS AND METHODS: Real-time quantitative polymerase chain reaction (RQ-PCR) was used to evaluate the suitability of the 3 control genes, i.e. ABL1, GUS and G6PD, as control genes for prostate cancer cells. Exfoliated urine cells from 30 healthy males, 53 male patients, 138 cases of archived paraffin-embedded prostate tissues and 3 prostate cell lines were sampled. All cells were lysed in guanidine isothiocyanate buffer from which RNA was extracted and converted to cDNA by random hexamer priming. RQ-PCR was performed using TaqMan chemistries. RESULTS: There was no significant difference in the level of expression for each of the 3 control genes in the cell lines. There was a significant difference in GUS transcript level between patients and healthy controls in both urine and prostate tissue sections (p < 0.05). G6PD transcript numbers also differed significantly from those of GUS in the prostate cell lines and tissue sections (p < 0.05). The transcript numbers of all the control genes were significantly reduced in aged samples (p < 0.001). CONCLUSION: The ABL1 gene was the most stable control gene in both clinical specimens and cell lines. Therefore, we recommend its use to enable standardization and interlaboratory comparisons for the RQ-PCR of prostatic tumour markers.

Willingness of university nursing students to volunteer during a pandemic.

OBJECTIVE: The global threat of an influenza pandemic continues to grow and thus universities have begun emergency preparedness planning. This study examined stakeholder's knowledge, risk-perception, and willingness to volunteer. DESIGN AND SAMPLE: The design of this study is a cross-sectional survey. Questionnaires were sent to 1,512 nursing students and were returned by 484, yielding a response rate of 32% for this subgroup. Nursing students may be a much-needed human resource in the event of an influenza pandemic. MEASURES: The measurement tool was a Web-based questionnaire regarding pandemic influenza designed by a subgroup of researchers on the Public Health Response Committee. RESULTS: Most nursing students (67.9%) said they were likely to volunteer in the event of a pandemic if they were able to do so. An even higher number (77.4%) said they would volunteer if provided protective garments. Overall, 70.7% of students supported the proposition that nursing students have a professional obligation to volunteer during a pandemic. Nursing students indicated that they have had a wealth of volunteer experience in the past and they would apply this service ethic to a pandemic situation. CONCLUSIONS: Emergency preparedness competencies should be integrated into existing nursing curricula and other health science programs. University administrations need to engage in planning to create protocol for recruitment, practice, and protection of volunteers.

Information satisfaction in breast and prostate cancer patients: implications for quality of life.

OBJECTIVES: This study aimed to assess information needs and levels of information satisfaction in breast and prostate cancer patients. It further examined relationships between information satisfaction and multi-dimensional quality of life (QoL). METHODS: An adapted Information Satisfaction Questionnaire (ISQ, 2004) and the Functional Assessment of Cancer Therapy QoL questionnaire (FACT-G, 1993) were randomly distributed to cancer patients during oncology clinic visits (breast cancer, n=102; prostate cancer, n=112). Hierarchal regression analyses examined information satisfaction as a predictor of global QoL and its four dimensions (i.e. physical, social, emotional, and functional well-being). RESULTS: High levels of information needs and desire for decision involvement were identified, with patients expressing a considerable degree of information satisfaction. After controlling for demographic and illness factors, information satisfaction explained 21% of the variance in global QoL, 12% in physical well-being, 13% in social well-being, 8% in emotional well-being, and 10% in functional well-being (all p<0.001). CONCLUSIONS: This study highlights the importance of information satisfaction for perceived QoL in individuals with cancer. It is clearly important to identify specific information requirements during the diagnosis and treatment process in order to provide information that is congruent with patients' needs.

Willingness to volunteer during an influenza pandemic: perspectives from students and staff at a large Canadian university.

BACKGROUND: A future influenza pandemic will require greater demand on numerous essential services and a reduced capacity to meet that demand. Recruitment of volunteers is an important issue for pre-pandemic planning. OBJECTIVES: To identify factors and attitudes towards volunteerism in the event of a pandemic of influenza. PARTICIPANTS/METHODS: A 42-item web-questionnaire was administered to all faculty, staff and students at the University of Alberta. Respondents indicated their willingness to volunteer. Responses were dichotomized and logistic regression models were developed to capture the association between willingness to volunteer and (i) demographic and information source variables, (ii) risk perception and general knowledge, and (iii) volunteering attitudes and priority access variables. RESULTS: Many factors predicted willingness to volunteer and several involved interactions with other variables. Individuals who were older, relied on University Health Centre information and who had past volunteerism experience were generally more likely to be willing to volunteer. Those willing to volunteer were more likely to think spread could be prevented by covering mouth when coughing/sneezing, and treatment would include drinking fluids. Those who thought influenza would be treated by antibiotics were less willing to volunteer. Likely volunteers thought that healthcare students should be encouraged to volunteer if there was a healthcare worker shortage. CONCLUSION: This study provides guidance for those who are preparing universities to deal with pandemic influenza. The results suggest factors that might be important in the recruitment of volunteers during an influenza pandemic and these factors might be relevant for other sectors as well.

Nursing students' general knowledge and risk perception of pandemic influenza.

The threat of an influenza pandemic continues to grow, and various institutions have started planning initiatives to manage the potentially high rates of mortality, morbidity and absenteeism. The authors surveyed nursing students at the University of Alberta to determine their general knowledge of, and perception of risk associated with, pandemic influenza. The results indicated that there are many misconceptions about the nature of a potential influenza pandemic that affect nursing students' perceptions of personal and familial risk. It is imperative that nursing students receive adequate information, education and preparation along with the necessary personal protection equipment if they are going to be relied upon as a labour reserve in the event of a pandemic.

Estimation of systemic complement C3 activity in age-related macular degeneration.

OBJECTIVES: To determine the role of systemic complement activation in the pathogenesis of age-related macular degeneration and to examine whether serum C3a des Arg reflects systemic complement activation, independent of individual complement component levels. METHODS: Plasma complement C3a des Arg levels and a single nucleotide polymorphism at position 402 of the complement factor H gene (CFH) were determined in 3 groups of subjects: 42 subjects with early age-related maculopathy, 42 subjects with neovascular (wet) age-related macular degeneration, and a control group of 38 subjects with no clinical evidence of age-related changes at the macula. RESULTS: The median (range) of plasma complement C3a des Arg levels in the age-related maculopathy and neovascular age-related macular degeneration groups were 52.6 (2.8-198.1) ng/mL and 60.9 (3.1-173.1) ng/mL, respectively. The levels were significantly raised compared with the control group (n = 38), which had a median (range) plasma complement C3a des Arg level of 40.3 (6.1-81.7) ng/mL (analysis of variance, P = .02). The concentration of plasma C3a des Arg did not differ significantly between those with different CFH genotypes (P = .07). CONCLUSION: Systemic activation of the complement system may contribute to the pathogenesis of age-related macular degeneration independent of CFH polymorphism. CLINICAL RELEVANCE: The results of this study may be relevant to aiming new treatment strategies toward reducing systemic low-grade inflammation.

Medical students and pandemic influenza.

To assess knowledge of pandemic influenza, we administered a questionnaire to all medical students at the University of Alberta; 354 (69%) of 510 students responded. Data from questionnaires such as this could help determine the role of medical students during a public health emergency.

Bruch's membrane and the vascular intima: is there a common basis for age-related changes and disease?

Several clinical and epidemiological studies have concurrently illuminated established cardiovascular risk factors in age-related macular degeneration (AMD), raising the possibility that cardiovascular disease and AMD may share a similar pathogenic process. The vascular intima and the Bruch's membrane share several age-related changes and are the seat of many common molecules. Diseases of these structures may represent parallel responses to the tissue injury induced by multiple intercalated factors such as genetic variations, oxidative stress, inappropriately directed immune response or inflammatory disease complex. However, there are marked differences in the age-related changes in these two structures. The strategic location of the Bruch's membrane between the retinal pigment epithelium and the choriocapillaris can at least partially explain the differential susceptibility of AMD to cardiovascular risk factors. Unlike the vascular wall that is exposed to changes from the endothelium, the Bruch's membrane is subject to changes from both the endothelium (choriocapillaris) and epithelium (retinal pigment epithelium). Moreover, although both the vascular wall and Bruch's membrane become lipid laden with age, the lipid composition is characteristically different. This review examines the morphological and biochemical alterations in the senescent Bruch's membrane and its analogy to the vascular wall to evaluate the concurrence of atherosclerosis and AMD.