Combined Effects of High-Intensity Aerobic Exercise Training and Ziziphus jujuba Extract on Tissue Nesfatin-1 in Rats.

Nesfatin-1 is involved in metabolic/feeding regulation and prevention of cardiovascular disease. Previous studies have shown that exercise and herb supplementation can influence nesfatin-1 concentration. The present study investigated the effects of high-intensity training (HIT) and Ziziphus jujuba (ZJ) extract on tissue nesfatin-1 in rats. Twenty-eight female rats were randomly assigned to one of four groups i.e. 1) Saline-Control (SC), 2) Saline-High Intensity Training (ST), 3) Ziziphus jujuba-Control (ZJC), and 4) Ziziphus jujuba-High Intensity Training (ZJT). Rats performed exercise on a treadmill and/or administered supplements intragastrically for 6 weeks, depending on group category. Seventy-two hours after the last training session, rats were anesthetized. Blood, hypothafi 2lamus tissue, heart and gastrocnemius muscles were sent to the laboratory for analyses. Significantly higher nesfatin-1 gene expression and concentration and ATP concentration were found in trained rat. HIT increased plasma High Density Lipoprotein (HDL) and insulin concentration and reduced plasma Triglyceride (TG) and cortisol. ZJ increased tissue nesftain-1 gene expression and concentration while only increasing heart ATP. The combination of exercise and ZJ showed an additive effect compared to each intervention alone on hypothalamus, heart and gastrocnemius NUCB2 gene expression, heart and gastrocnemius nesfatin-1 concentration, plasma HDL and cortisol concentration. The authors recommend both interventions as a means to improve cardiovascular health in rats with further work needed to confirm similar findings in homo sapiens.

GLP: A requirement in cell therapies - perspectives for the cardiovascular field.

In biomedical research, enormous progress is being made and new candidates for putative medicinal products emerge. However, most published preclinical data are not conducted according to the standard Good Laboratory Practice (GLP). GLP is mandatory for preclinical analysis of Advanced Therapy Medicinal Products (ATMP) and thereby a prerequisite for planning and conduction of clinical trials. Not inconsiderable numbers of clinical trials are terminated earlier or fail - do inadequate testing strategies or missing specialized assays during the preclinical development contribute to this severe complex of problems? Unfortunately, there is also a lack of access to GLP testing results and OECD (Organisation for Economic Co-operation and Development) GLP guidelines are not yet adjusted to ATMP specialties. Ultimately, GLP offers possibilities to generate reliable and reproducible data. Therefore, this review elucidates different GLP aspects in drug development, speculates on reasons of putative low GLP acceptance in the scientific community and mentions solution proposals.

Eccentric resistance training and ß-hydroxy-ß-methylbutyrate free acid affects muscle PGC-1α expression and serum irisin, nesfatin-1 and resistin in rats.

The hypothalamus controls metabolism and feeding behaviour via several signals with other tissues. Exercise and supplements can change hypothalamic signalling pathways, so the present study investigated the influence of eccentric resistance training and ß-hydroxy-ß-methylbutyrate free acid supplementation on PGC-1α expression, serum irisin, nesfatin-1 and resistin concentrations. Thirty-two male rats (8 weeks old, 200±17 g body mass) were randomly allocated to control, ß-hydroxy-ß-methylbutyrate free acid supplementation (HMB), eccentric resistance training (ERT), and ß-hydroxy-ß-methylbutyrate free acid supplementation plus eccentric resistance training (HMB+ERT) groups. Training groups undertook eccentric resistance training (6 weeks, 3 times a week) and supplement groups consumed ß-hydroxy-ß-methylbutyrate free acid (HMB-FA) orally (76 mg kg-1 day-1). Twenty-four hours after the last training session, serum and triceps brachii muscle samples were collected and sent to the laboratory for analysis. Two-way ANOVA and Pearson correlation were employed (significance level: P<0.05). The results showed that eccentric resistance training increases skeletal muscle PGC-1α gene expression, as well as serum levels of irisin and nesfatin-1 (P=0.001). Eccentric resistance training decreased the serum concentration of resistin (P=0.001). HMB-FA supplementation increased skeletal muscle PGC-1α gene expression (P=0.002), as well as the serum concentration of irisin and nesfatin-1 (P=0.001), but decreased the serum concentration of resistin (P=0.001). Significant correlations were observed between PGC-1α gene expression and serum concentrations of irisin, nesfatin-1 and resistin. HMB-FA supplementation with eccentric resistance training may induce crosstalk between peptide release from other tissues and increases maximal muscle strength. The combination of the two interventions had a more substantial effect than each in isolation.

Dose Quantification in UV Phototherapy.

Ultraviolet light has long been used to alleviate a number of skin conditions, and its efficacy is well known. However, over-exposure to ultraviolet radiation has a number of detrimental effects and thus it is vital to maintain a dose to skin within the therapeutic window. To maximise treatment gain whilst circumventing potential side-effects of over-exposure requires accurate determination of irradiance and skin-dose. This is complicated by the fact that ultraviolet radiation is essentially absorbed at the skin surface, which means that changing orientation of the patient and source can modulate dose received. In addition, irregular patient shapes mean dose must be carefully calibrated. This chapter focuses on methods of determination of dose, clinical protocols for quantifying radiation dose received and mathematical models for estimating these quantities.

Desired and side effects of the supplementation with l-glutamine and l-glutathione in enteric glia of diabetic rats.

BACKGROUND/AIMS: Enteric neuropathy associated with Diabetes Mellitus causes dysfunction in the digestive system, such as: nausea, diarrhea, constipation, vomiting, among others. The aim of this study was to compare the effects of supplementation with 2% l-glutamine and 1% l-glutathione on neurons and enteric glial cells of ileum of diabetic rats. METHODS: Thirty male Wistar rats have been used according to these group distributions: Normoglycemic (N), Normoglycemic supplemented with l-glutamine (NG), Normoglycemic supplemented with l-glutathione (NGO), Diabetic (D), Diabetic supplemented with l-glutamine (DG) and Diabetic supplemented with l-glutathione (DGO). After 120days, the ileum was processed for immunohistochemistry of HuC/D and S100ß. Quantitative and morphometric analysis have been performed. RESULTS: Diabetic rats presented a decrease in the number of neurons when compared to normoglycemic animals. However, diabetes was not associated with a change in glial density. l-Glutathione prevented the neuronal death in diabetic rats. l-Glutathione increased a glial proliferation in diabetic rats. The neuronal area in diabetic rats increased in relation to the normoglycemics. The diabetic rats supplemented with l-glutamine and l-glutathione showed a smaller neuronal area in comparison to diabetic group. The glial cell area was a decreased in the diabetics. The diabetic rats supplemented with l-glutamine and l-glutathione did not have significant difference in the glial cell body area when compared to diabetic rats. CONCLUSION: It is concluded that the usage of l-glutamine and l-glutathione as supplements presents both desired and side effects that are different for the same substance in considering normoglycemic or diabetic animals.

Ultraviolet radiation therapy and UVR dose models.

Ultraviolet radiation (UVR) has been an effective treatment for a number of chronic skin disorders, and its ability to alleviate these conditions has been well documented. Although nonionizing, exposure to ultraviolet (UV) radiation is still damaging to deoxyribonucleic acid integrity, and has a number of unpleasant side effects ranging from erythema (sunburn) to carcinogenesis. As the conditions treated with this therapy tend to be chronic, exposures are repeated and can be high, increasing the lifetime probability of an adverse event or mutagenic effect. Despite the potential detrimental effects, quantitative ultraviolet dosimetry for phototherapy is an underdeveloped area and better dosimetry would allow clinicians to maximize biological effect whilst minimizing the repercussions of overexposure. This review gives a history and insight into the current state of UVR phototherapy, including an overview of biological effects of UVR, a discussion of UVR production, illness treated by this modality, cabin design and the clinical implementation of phototherapy, as well as clinical dose estimation techniques. Several dose models for ultraviolet phototherapy are also examined, and the need for an accurate computational dose estimation method in ultraviolet phototherapy is discussed.

A computational simulation of reflector and tube effects in ultraviolet phototherapy.

While ultraviolet phototherapy is effective at treating a wide range of skin conditions, over exposure to ultraviolet radiation has a number of detrimental effects including but not limited to erythema, ocular damage and even oncogenesis. It is therefore important to quantify and control the dose received in order to maximize the effectiveness of treatment while minimizing the potentially damaging side effects. Recent dose models have been developed for this purpose, incorporating both the irradiance from the phototherapy lamps and the contributions from metallic reflectors. These models have good predictive power, but the situation is complicated by the huge variety of cabin and mirror geometries available. This work simulates a variety of possible treatment configurations to examine the implications these factors have on dose homogeneity and global irradiance, and shows that the relationship between global irradiance and number of tubes is complex and nonlinear. This has implications for both cabin design and treatment planning.

Investigations of cabin design in UV phototherapy.

PURPOSE: UVR phototherapy cabins exist in a huge variety of configurations and geometries. An accurate dose model has been developed which can be used to examine the question of cabin design to investigate factors influencing dose on a patient. METHODS: This work extends the existing dose model to entire cabins and investigates how cabin and reflector geometry influence resultant dose. RESULTS: The model predictions are in line with what is measured. It is found that the length and angle of the reflectors have a large influence on received dose. CONCLUSIONS: The influence of cabin geometry is important in estimating patient dose, and the findings of this work are applicable to future cabin designs.

Reflection modeling in ultraviolet phototherapy.

PURPOSE: Ultraviolet phototherapy is a widely used treatment which has exceptional success with a variety of skin conditions. Over-exposure to ultraviolet radiation (UVR) can however be detrimental and cause side effects such as erythema, photokeratisis, and even skin cancer. Quantifying patient dose is therefore imperative to ensure biologically effective treatment while minimizing negative repercussions. A dose model for treatment would be valuable in achieving these ends. METHODS: Prior work by the authors concentrated on modeling the output of the lamps used in treatment and it was found a line source model described the output from the sources to a high degree. In practice, these lamps are surrounded by reflective anodized aluminum in patient treatment cabins and this work extends the model to quantify specular reflections from these planes on patient dose. RESULTS: The extension of the model to allow for reflected images in addition to tube output shows a remarkably good fit to the actual data measured. CONCLUSIONS: The reflection model yields impressive accuracy and is a good basis for full UVR cabin modeling.

Dose modeling in ultraviolet phototherapy.

PURPOSE: Ultraviolet phototherapy is widely used in the treatment of numerous skin conditions. This treatment is well established and largely beneficial to patients on both physical and psychological levels; however, overexposure to ultraviolet radiation (UVR) can have detrimental effects, such as erythemal responses and ocular damage in addition to the potentially carcinogenic nature of UVR. For these reasons, it is essential to control and quantify the radiation dose incident upon the patient to ensure that it is both biologically effective and has the minimal possible impact on the surrounding unaffected tissue. METHODS: To date, there has been little work on dose modeling, and the output of artificial UVR sources is an area where research has been recommended. This work characterizes these sources by formalizing an approach from first principles and experimentally examining this model. RESULTS: An implementation of a line source model is found to give impressive accuracy and quantifies the output radiation well. CONCLUSIONS: This method could potentially serve as a basis for a full computational dose model for quantifying patient dose.

Do omega-6 and trans fatty acids play a role in complex regional pain syndrome? A pilot study.

OBJECTIVES: The study aims to compare the omega-6 (n-6) and omega-3 (n-3) highly unsaturated fatty acids (HUFA), and trans fatty acid (trans FA) status of Complex Regional Pain Syndrome (CRPS) patients to pain-free controls. DESIGN: Case control study. Setting. The setting was at a multidisciplinary rehabilitation center. PATIENTS: Twenty patients that met the Budapest research diagnostic criteria for CRPS and 15 pain-free control subjects were included in this study. Outcome Measures. Fasting plasma fatty acids were collected from all participants. In CRPS patients, pain was assessed using the McGill Pain Questionnaire-Short Form. In addition, results from the perceived disability (Pain Disability Index), pain-related anxiety (Pain Anxiety Symptom Scale Short Form), depression (Center for Epidemiologic Studies Depression Scale Short Form), and quality of life (Short Form-36 [SF-36]) were evaluated. RESULTS: Compared with controls, CRPS patients demonstrated elevated concentrations of n-6 HUFA and trans FA. No differences in n-3 HUFA concentrations were observed. Plasma concentrations of the n-6 HUFA docosatetraenoic acid were inversely correlated with the "vitality" section of the SF-36. Trans FA concentrations positively correlated with pain-related disability and anxiety. CONCLUSION: These pilot data suggest that elevated n-6 HUFA and trans FA may play a role in CRPS pathogenesis. These findings should be replicated, and more research is needed to explore the clinical significance of low n-6 and trans FA diets with or without concurrent n-3 HUFA supplementation, for the management of CRPS.

Erythrocyte omega-3 and omega-6 polyunsaturated fatty acids and preeclampsia risk in Peruvian women.

OBJECTIVE: This case-control study was conducted in Lima, Peru, from June 1997 through January 1998 to assess whether alteration in maternal erythrocyte omega-3 (n-3) and omega-6 (n-6) fatty acids was associated with increased risk of preeclampsia. METHODS: A total of 99 preeclampsia and 100 normotensive pregnant women were included. Maternal erythrocyte n-3 and n-6 fatty acids were determined using capillary gas chromatography/mass spectrometry and expressed as micromolar (mM) concentrations. We employed logistic regression procedures to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULT: n-3 fatty acids were consistently lower in preeclampsia cases than controls. After adjusting for confounders, the corresponding ORs for preeclampsia across decreasing quartiles of sum of long-chain n-3 fatty acids were 1.0, 3.3, 2.4, and 3.3, respectively (P=0.07 for trend). A similar pattern was observed for eicosapentenoic acid (20:5n-3, EPA) and docosahexenoic acid (22:6n-3, DHA). There was no clear evidence of an association between arachidonic acid (20:4n-6, AA) and preeclampsia risk, the ORs in successively lower quartiles were 1.0, 1.1, 1.0, and 1.5 (P=0.48 for trend). A similar pattern was seen for the sum of long-chain n-6 fatty acids. CONCLUSION: In Peruvian women, low erythrocyte n-3 fatty acids appeared to be associated with an increased risk of preeclampsia.

Normal levels of prepulse inhibition in the euthymic phase of bipolar disorder.

BACKGROUND: Deficits in prepulse inhibition (PPI) of the acoustic startle response have been suggested as a potentially useful endophenotype for schizophrenia spectrum disorders and may explain certain symptoms and cognitive deficits observed in the psychoses. PPI deficits have also been found in mania, but it remains to be confirmed whether this dysfunction is present in the euthymic phase of bipolar disorder. METHOD: Twenty-three adult patients with DSM-IV bipolar disorder were compared to 20 controls on tests of acoustic startle reactivity and PPI of the startle response. Sociodemographic and treatment variables were recorded and symptom scores assessed using the Hamilton Depression Inventory and the Young Mania Rating Scale. RESULTS: Overall, the patient and control groups demonstrated similar levels of startle reactivity and PPI, although there was a trend for the inter-stimulus interval to differentially affect levels of PPI in the two groups. CONCLUSIONS: In contrast to bipolar patients experiencing a manic episode, general levels of PPI were normal in this euthymic sample. Further studies are required to confirm this finding and to determine the mechanisms by which this potential disruption/normalization occurs. It is suggested that an examination of PPI in a high-risk group is required to fully discount dysfunctional PPI as a potentially useful endophenotype for bipolar disorder.