Effects of coenzyme Q10 and alpha-tocopherol administration on their tissue levels in the mouse: elevation of mitochondrial alpha-tocopherol by coenzyme Q10.

Coenzyme Q (CoQ) was previously demonstrated in vitro to indirectly act as an antioxidant in respiring mitochondria by regenerating alpha-tocopherol from its phenoxyl radical. The objective of this study was to determine whether CoQ has a similar sparing effect on alpha-tocopherol in vivo. Mice were administered CoQ10 (123 mg/kg/day) alone, or alpha-tocopherol (200 mg/kg/day) alone, or both, for 13 weeks, after which the amounts of CoQ10, CoQ9 and alpha-tocopherol were determined by HPLC in the serum as well as homogenates and mitochondria of liver, kidney, heart, upper hindlimb skeletal muscle and brain. Administration of CoQ10 and alpha-tocopherol, alone or together, increased the corresponding levels of CoQ10 and alpha-tocopherol in the serum. Supplementation with CoQ10 also elevated the amounts of the predominant homologue CoQ9 in the serum and the mitochondria. A notable effect of CoQ10 intake was the enhancement of alpha-tocopherol in mitochondria. alpha-Tocopherol administration resulted in an elevation of alpha-tocopherol content in the homogenates of nearly all tissues and their mitochondria. Results of this study thus indicate that relatively long-term administration of CoQ10 or alpha-tocopherol can result in an elevation of their concentrations in the tissues of the mouse. More importantly, CoQ10 intake has a sparing effect on alpha-tocopherol in mitochondria in vivo.     

Overexpression of glutamate-cysteine ligase extends life span in Drosophila melanogaster

The hypothesis that overexpression of glutamate-cysteine ligase (GCL), which catalyzes the rate-limiting reaction in de novo glutathione biosynthesis, could extend life span was tested in the fruit fly, Drosophila melanogaster. The GAL4-UAS binary transgenic system was used to generate flies overexpressing either the catalytic (GCLc) or modulatory (GCLm) subunit of this enzyme, in a global or neuronally targeted pattern. The GCL protein content of the central nervous system was elevated dramatically in the presence of either global or neuronal drivers. GCL activity was increased in the whole body or in heads, respectively, of GCLc transgenic flies containing global or neuronal drivers. The glutathione content of fly homogenates was increased by overexpression of GCLc or GCLm, particularly in flies overexpressing either subunit globally, or in the heads of GCLc flies possessing neuronal drivers. Neuronal overexpression of GCLc in a long-lived background extended mean and maximum life spans up to 50%, without affecting the rate of oxygen consumption by the flies. In contrast, global overexpression of GCLm extended the mean life span only up to 24%. These results demonstrate that enhancement of the glutathione biosynthetic capability, particularly in neuronal tissues, can extend the life span of flies, and thus support the oxidative stress hypothesis of aging.     

Concurrent administration of coenzyme Q10 and alpha-tocopherol improves learning in aged mice

The main purpose of this study was to determine whether supplemental intake of coenzyme Q10 (CoQ) (ubiquinone-10) or alpha-tocopherol, either alone or together, could improve brain function of aged mice, as reflected in their cognitive or psychomotor performance. Separate groups of aged mice (24 months) were administered either CoQ (123 mg/kg/day), or alpha-tocopherol acetate (200 mg/kg/day), or both, or the vehicle (soybean oil) via gavage for a period of 14 weeks. Three weeks following the initiation of these treatments, mice were given a battery of age-sensitive behavioral tests for the assessment of learning, recent memory, and psychomotor function. In a test that required the mice to rapidly identify and remember the correct arm of a T-maze, and to respond preemptively in order to avoid an electric shock, the intake of alpha-tocopherol plus CoQ resulted in more rapid learning compared to the control group. Learning was not significantly improved in the mice receiving CoQ or alpha-tocopherol alone. None of the treatments resulted in a significant improvement of psychomotor performance in the old mice. In a separate study, treatment with higher doses of CoQ alone (250 or 500 mg/kg/day) for 14 weeks failed to produce effects comparable to those of the combination of alpha-tocopherol and CoQ. The apparent interaction of CoQ and alpha-tocopherol treatments is consistent with the previous suggestion, based on biochemical studies, that coenzyme Q and alpha-tocopherol act in concert. Overall, the findings suggest that concurrent supplementation of alpha-tocopherol with CoQ is more likely to be effective as a potential treatment for age-related learning deficits than supplementation with CoQ or alpha-tocopherol alone.     

Quantification of the magnification and distortion effects of a pediatric flexible video-bronchoscope

Background

Flexible video bronchoscopes, in particular the Olympus BF Type 3C160, are commonly used in pediatric respiratory medicine. There is no data on the magnification and distortion effects of these bronchoscopes yet important clinical decisions are made from the images. The aim of this study was to systematically describe the magnification and distortion of flexible bronchoscope images taken at various distances from the object.

Methods

Using images of known objects and processing these by digital video and computer programs both magnification and distortion scales were derived.

Results

Magnification changes as a linear function between 100 mm (×1) and 10 mm (×9.55) and then as an exponential function between 10 mm and 3 mm (×40) from the object. Magnification depends on the axis of orientation of the object to the optic axis or geometrical axis of the bronchoscope. Magnification also varies across the field of view with the central magnification being 39% greater than at the periphery of the field of view at 15 mm from the object. However, in the paediatric situation the diameter of the orifices is usually less than 10 mm and thus this limits the exposure to these peripheral limits of magnification reduction. Intraclass correlations for measurements and repeatability studies between instruments are very high, r = 0.96. Distortion occurs as both barrel and geometric types but both types are heterogeneous across the field of view. Distortion of geometric type ranges up to 30% at 3 mm from the object but may be as low as 5% depending on the position of the object in relation to the optic axis.

Conclusion

We conclude that the optimal working distance range is between 40 and 10 mm from the object. However the clinician should be cognisant of both variations in magnification and distortion in clinical judgements.     

Mechanisms of aging: an appraisal of the oxidative stress hypothesis

The main purpose of this article is to provide a critical overview of the currently available evidence bearing on the validity of the oxidative stress hypothesis of aging, which postulates that senescence-associated attenuations in physiological functions are caused by molecular oxidative damage. Several lines of correlative evidence support the predictions of the hypothesis, e.g., macromolecular oxidative damage increases with age and tends to be associated with life expectancy of organisms. Nevertheless, a direct link between oxidative stress and aging has not as yet been established. Single gene mutations have been reported to extend the life spans of lower organisms, such as nematodes and insects; however, such prolongations of chronological clock time survival are usually associated with decreases in the rate of metabolism and reproductive output without affecting the metabolic potential, i.e., the total amount of energy consumed during life. Studies on genetic manipulations of the aging process have often been conducted on relatively short-lived strains that are physiologically weak, whereby life-span extensions can not be unambiguously assigned to a slowing effect on the rate of aging. It is concluded that although there is considerable evidence implicating oxidative stress in the aging process, additional evidence is needed to clearly define the nature of the involvement.     

Barriers and Facilitators for Type-2 Diabetes Management in South Asians: A Systematic Review

Objective

Although South Asian populations have among the highest burden of type 2 diabetes in the world, their diabetes management remains poor. We systematically reviewed studies on South Asian patient’s perspectives on the barriers and facilitators to diabetes management.

Methods

We conducted a literature search using OVID, CINHAL and EMBASE (January, 1990 –February, 2014) evaluating the core components of diabetes management: interactions with health care providers, diet, exercise, and medication adherence. South Asian patients were self-reported as Indian, Pakistani, Malaysian-Indian or Bangladeshi origin. From 208 abstracts reviewed, 20 studies were included (19 qualitative including mixed methods studies, 1 questionnaire). Barriers and facilitators were extracted and combined using qualitative synthesis.

Results

All studies included barriers and few facilitators were identified. Language and communication discordance with the healthcare provider was a significant barrier to receiving and understanding diabetes education. There was inconsistent willingness to partake in self-management with preference for following their physician’s guidance. Barriers to adopting a diabetic diet were lack of specific details on South Asian tailored diabetic diet; social responsibilities to continue with a traditional diet, and misconceptions on the components of the diabetic diet. For exercise, South Asian patients were concerned with lack of gender specific exercise facilities and fear of injury or worsening health with exercise. Patients reported a lack of understanding about diabetes medication management, preference for folk and phytotherapy, and concerns about the long-term safety of diabetes medications. Facilitators included trust in care providers, use of culturally appropriate exercise and dietary advice and increasing family involvement. Overall themes for the barriers included lack of knowledge and misperceptions as well as lack of cultural adaptation to diabetes management.

Conclusion

Diabetes programs that focus on improving communication, addressing prevailing misconceptions, and culture specific strategies may be useful for improving diabetes management for South Asians.     

Expression Profiles of Different Cytokine Genes in Peripheral Blood Mononuclear Cells of Goats Infected Experimentally with Native Strain of Mycobacterium Avium Subsp. Paratuberculosis

Paratuberculosis (ParaTB), caused by Mycobacterium avium subspecies paratuberculosis (MAP) is a chronic enteritis of ruminants and may contribute to Crohn's disease in humans. Key features of host immunity to MAP infection include an early pro-inflammatory (Th1-like) response that eventually gives way to a predominant anti-inflammatory (Th2-like) response. Many studies have been conducted to understand the underlying mechanism of misdirected host immune response, however, these studies mainly focused on cattle. The present study is the first attempt to test the hypothesis of shift in Th1 to Th2 like responses during the progression of ParaTB in caprine species (small ruminant). Ten healthy male kids (<6 months old) of the same breed were selected for this study. Of the 10 kids, 6 were experimentally infected with native strain (S5) of MAP (“Indian Bison Type”) and the remaining 4 kids were control. Kids were monitored for a period of 12 months post infection (MPI) and were tested for establishment of infection. Expression levels of IFNG, IL2, IL12, IL4, and IL10 genes were estimated before infection and at 4, 8, and 12 MPI in stimulated peripheral blood mononuclear cells (PBMCs) of infected and control kids. The study demonstrated the expression of IFNG and IL2 as classic Th1-like pro-inflammatory signatures; whereas, IL10 exhibited itself as classical Th2-like signature. The study also reports unexpected lowered expression of the IL12 gene simultaneously with increased expression of IFNG, lowered expression of the IL2 gene (compared to IFNG), and suppressed expression of the IL4.     

Role of epithelial mesenchymal transition (EMT) in chronic obstructive pulmonary disease (COPD)

Small airway fibrosis is the main contributor to physiological airway dysfunction in COPD. One potential mechanism contributing to small airway fibrosis is epithelial mesenchymal transition (EMT). When associated with angiogenesis (so called EMT-Type-3) it may well also be the link with the development of cancer, which is closely associated with COPD and predominantly in large airways. In a recent study published in Respiratory Research, Qin Wang and colleagues investigated the role of urokinase plasminogen activator receptor (uPAR) in EMT in small airway epithelium of COPD patients. However, there are some issues with the paper which we wish to comment on.