Characterization of bone pathologies in the ins2+/akita mouse, a new model for diabetes insulindependent: contribution for a better understanding of the disease in humans

Tese de Doutoramento, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2016

Efeito da utilização da levedura desidratada de álcool em dietas para tilápia-do-nilo

Este trabalho teve como objetivo avaliar o efeito da levedura desidratada de álcool (Saccharomyces cerevisae) como substituto do suplemento vitamínico, em dietas de tilápia-do-nilo (Oreochromis niloticus). Trezentos alevinos machos, sexualmente revertidos, com peso médio de 1,5 g, foram distribuídos igualmente em 20 aquários de fibra de vidro, equipados com filtro biológico. Cinco dietas isoprotéicas com 32% de proteína bruta na primeira fase (40 dias) e com 28% de proteína bruta na segunda fase (74 dias) foram fornecidas ad libitum, duas vezes ao dia. A dieta-controle não conti-nha levedura, e as demais apresentavam 10% de levedura. O delineamento foi inteiramente casualizado, com cinco tratamentos e quatro repetições. Não houve influência significativa dos tratamentos sobre o ganho de peso e taxa de crescimento específico. Foi observada, nos peixes alimentados com dietas sem suplemento vitamínico, alta mortalidade. Os peixes que receberam levedura apresentaram menor conteúdo corporal de proteína, e maior, de lipídeos. A levedura desidratada de álcool pode ser usada como fonte de vitaminas hidrossolúveis em dietas para alevinos de tilápia-do-nilo.

Grip strength and functional recovery after hip fracture: An observational study in elderly population

Muscle strength is a common issue in fragility syndrome and sarcopenia, both of them involved in the pathogenesis of falls and fractures. The objective is to study the relationship between hand grip strength and functional recovery after hip fracture surgery. This prospective observational study included patients aged 65. years and older who were admitted to hospital for hip fracture surgery during a 12 month period. Functional status (Barthel Index), mental status (Cruz Roja Index), hand grip strength, 25/OH-Vitamin D plasmatic levels were evaluated at admission. Follow-up was performed 3. months after discharge to assess functional status and survival. Correlations between hand grip strength and the rest of variables were evaluated. Univariate and multivariate analyses were further applied. Mean age of subjects was 85.1. ±. 0.63 years. Out of 127 subjects, 103 were women and 24 were men. Hand grip strength was obtained in 85 patients (76.5%) and, values were between 3.3 and 24.8. kg and 81 patients (95.2%) had values below cut-point of sarcopenia considering European Working Group of Sarcopenia criteria. Hand grip strength at admission shows significant association to Barthel index at three months and functional recovery. It is also associated with age (P <. 0.001) (r = 0.81), sex (P = 0.001), cognitive status by Cruz Roja Index (P <. 0.001) and functional status measured at admission by Barthel Index (P <. 0.01) (r = -0.22). Multivariate analysis confirmed that variables were independently associated to grip strength. Hand grip strength measured at admission in Orthogeriatric Unit after hip fracture is directly related to functional recovery in elderly patients.

Guía de práctica clínica para la enfermedad hepática grasa no alcohólica

Objetivo: Brindar una guía de práctica clínica basada con la evidencia más reciente para el diagnóstico y tratamiento de la Enfermedad Hepática Grasa No alcohólica teniendo en cuenta la efectividad y seguridad de las intervenciones dirigidas a pacientes, personal asistencial, administrativo y entes gubernamentales de cualquier servicio de atención en Colombia. Materiales y métodos: Esta guía fue desarrollada por un equipo multidisciplinario con apoyo de la Asociación Colombiana de Gastroenterología, el Grupo Cochrane ITS y el Instituto de Investigaciones Clínicas de la Universidad Nacional de Colombia. Se desarrollaron preguntas clínicas relevantes y se realizó la búsqueda de guías nacionales e internacionales en bases de datos especializadas. Las guías existentes fueron evaluadas en términos de calidad y aplicabilidad. Una guía cumplió los criterios de adaptación, por lo que se decidió adaptar 3 preguntas clínicas. El Grupo Cochrane realizó la búsqueda sistemática de la literatura. Las tablas de evidencia y recomendaciones fueron realizadas con base a la metodología GRADE. Las recomendaciones de la guía fueron socializadas en una reunión de expertos con entes gubernamentales y pacientes. Resultados: Se desarrolló una guía de práctica clínica basada en la evidencia para el diagnóstico y tratamiento de la Enfermedad Hepática Grasa No alcohólica en Colombia Conclusiones: El diagnóstico y manejo oportuno de la Enfermedad Hepática Grasa No alcohólica contribuirá a disminuir la carga de la enfermedad en Colombia y las enfermedades asociadas

Placental antioxidant enzyme status and lipid peroxidation in pregnant women with type 1 diabetes: The effect of vitamin C and E supplementation

AIM: In view of the increased rates of pre-eclampsia observed in diabetic pregnancy and the lack of ex vivo data on placental biomarkers of oxidative stress in T1 diabetic pregnancy, the aim of the current investigation was to examine placental antioxidant enzyme status and lipid peroxidation in pregnant women with type 1 diabetes. A further objective of the study was to investigate the putative impact of vitamin C and E supplementation on antioxidant enzyme activity and lipid peroxidation in type 1 diabetic placentae.

METHODS: The current study measured levels of antioxidant enzyme [glutathione peroxidase (Gpx), glutathione reductase (Gred), superoxide dismutase (SOD) and catalase] activity and degree of lipid peroxidation (aqueous phase hydroperoxides and 8-iso-prostaglandin F2α) in matched central and peripheral samples from placentae of DAPIT (n=57) participants. Levels of vitamin C and E were assessed in placentae and cord blood.

RESULTS: Peripheral placentae demonstrated significant increases in Gpx and Gred activities in pre-eclamptic in comparison to non-pre-eclamptic women. Vitamin C and E supplementation had no significant effect on cord blood or placental levels of these vitamins, nor on placental antioxidant enzyme activity or degree of lipid peroxidation in comparison to placebo-supplementation.

CONCLUSION: The finding that maternal supplementation with vitamin C/E does not augment cord or placental levels of these vitamins is likely to explain the lack of effect of such supplementation on placental indices including antioxidant enzymes or markers of lipid peroxidation.

Dietary supplementation of vitamin E and -lipoic acid upregulates cell growth and signaling genes in rat myocardium

The efficacy of antioxidant supplementation in the prevention of cardiovascular disease appears equivocal, however the use of more potent antioxidant combinations than those traditionally used may exert a more positive effect. We have shown previously that supplementation of vitamin E and α-lipoic acid increases cardiac performance during post-ischemia reperfusion in older rats and increases Bcl-2 levels in endothelial cells. The purpose of this study was to examine the effects of vitamin E and α-lipoic acid supplementation on myocardial gene expression with a view to determine their mechanism of action. Young male rats received either a control (n=7) or vitamin E and α-lipoic acid supplemented diet (n=8) for 14 weeks. RNA from myocardial tissue was then amplified and samples were pooled within groups and competitively hybridized to 5K oligonucleotide rat microarrays. The relative expression of each gene was then compared to the control sample. Animals that received the antioxidant-supplemented diet exhibited upregulation (>1.5×) of 13 genes in the myocardium with 2 genes downregulated.� �Upregulated genes include those involved in cell growth and maintenance (LynB, Csf1r, Akt2, Tp53), cell signaling (LynB, Csf1r) and signal transduction (Pacsin2, Csf1r). Downregulated genes encode thyroid (Thrsp) and F-actin binding proteins (Nexilin).

Antioxidant supplementation reduces skeletal muscle mitochondrial biogenesis

Purpose: Exercise increases the production of reactive oxygen species (ROS) in skeletal muscle, and athletes often consume antioxidant supplements in the belief they will attenuate ROS-related muscle damage and fatigue during exercise. However, exercise-induced ROS may regulate beneficial skeletal muscle adaptations, such as increased mitochondrial biogenesis. We therefore investigated the effects of long-term antioxidant supplementation with vitamin E and alpha-lipoic acid on changes in markers of mitochondrial biogenesis in the skeletal muscle of exercise-trained and sedentary rats. Methods: Male Wistar rats were divided into four groups: 1) sedentary control diet, 2) sedentary antioxidant diet, 3) exercise control diet, and 4) exercise antioxidant diet. Animals ran on a treadmill 4 d.wk(-1) at similar to 70% V (over dot)O(2max) for up to 90 min.d(-1) for 14 wk. Results: Consistent with the augmentation of skeletal muscle mitochondrial biogenesis and antioxidant defenses, after training there were significant increases in peroxisome proliferator-activated receptor F coactivator 1 alpha (PGC-1 alpha) messenger RNA (mRNA) and protein, cytochrome C oxidase subunit IV (COX IV) and cytochrome C protein abundance, citrate synthase activity, Nfe2l2, and SOD2 protein (P < 0.05). Antioxidant supplementation reduced PGC-1 alpha mRNA, PGC-1 alpha and COX IV protein, and citrate synthase enzyme activity (P < 0.05) in both sedentary and exercise-trained rats. Conclusions: Vitamin E and alpha-lipoic acid supplementation suppresses skeletal muscle mitochondrial biogenesis, regardless of training status.

The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability

BACKGROUND: Migraine is a prevalent and debilitating disease that may, in part, arise because of disruption in neurovascular endothelia caused by elevated homocysteine. This study examined the homocysteine-lowering effects of vitamin supplementation on migraine disability, frequency and severity and whether MTHFRC677T genotype influenced treatment response. METHODS: This was a randomized, double-blind placebo, controlled trial of 6 months of daily vitamin supplementation (i.e. 2 mg of folic acid, 25 mg vitamin B6, and 400 microg of vitamin B12) in 52 patients diagnosed with migraine with aura. FINDINGS: Vitamin supplementation reduced homocysteine by 39% (approximately 4 mumol/l) compared with baseline, a reduction that was greater then placebo (P=0.001). Vitamin supplementation also reduced the prevalence of migraine disability from 60% at baseline to 30% after 6 months (P=0.01), whereas no reduction was observed for the placebo group (P>0.1). Headache frequency and pain severity were also reduced (P<0.05), whereas there was no reduction in the placebo group (P>0.1). In this patient group the treatment effect on both homocysteine levels and migraine disability was associated with MTHFRC677T genotype whereby carriers of the C allele experienced a greater response compared with TT genotypes (P<0.05). INTERPRETATION: This study provides some early evidence that lowering homocysteine through vitamin supplementation reduces migraine disability in a subgroup of patients. Larger trials are now warranted to establish whether vitamin therapy is a safe, inexpensive and effective prophylactic option for treatment of migraine and whether efficacy is dependant on MTHFRC677T genotype.

Effect of deprivation of vitamin A on the basic proteins of the nuclei of rat testes

The relative concentrations of the major histones, namely, H1, TH1, H2A, H2B, H3 and H4 are not significantly changed in the testes of the vitamin A-deficient rats, as compared to those in the normal controls. But the testis-specific protein, TP, which is synthesized at the mid-spermatid stage, is markedly reduced in the testes of the deficient rats. On supplementation of the deficient rats with retinyl acetate for 28 days, there was a 50% recovery in the relative concentration of the TP with respect to the total amounts of H1 and TH1.

Effect of depletion of vitamin A, followed by supplementation with retinyl acetate or retinoic acid, on regeneration of rat liver

After partial hepatectomy the net increase in tissue weight and in RNA, DNA and proteins in the regenerating liver was markedly less in vitamin A-deleted or retinoic acid-supplemented male rats, compared with the corresponding normal control or retinyl acetate-supplemented ones.

Antioxidant supplementation and immunoendocrine responses to prolonged exercise

Davison, Glen, et al., 'Antioxidant supplementation and immunoendocrine responses to prolonged exercise', Medicine and Science in Sports and Exercise, (2007) 39(4) pp.645-652 RAE2008

Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete.

BACKGROUND: Current data suggest that physiologic doses of vitamin B-6 have no significant homocysteine-lowering effect. It is possible that an effect of vitamin B-6 was missed in previous trials because of a much greater effect of folic acid, vitamin B-12, or both. OBJECTIVE: The aim of this study was to investigate the effect of low-dose vitamin B-6 supplementation on fasting total homocysteine (tHcy) concentrations in healthy elderly persons who were made replete with folate and riboflavin. DESIGN: Twenty-two healthy elderly persons aged 63-80 y were supplemented with a low dose of vitamin B-6 (1.6 mg/d) for 12 wk in a randomized, double-blind, placebo-controlled trial after repletion with folic acid (400 microg/d for 6 wk) and riboflavin (1.6 mg/d for 18 wk); none of the subjects had a vitamin B-12 deficiency. RESULTS: Folic acid supplementation lowered fasting tHcy by 19.6% (P