Effect of weight loss and exercise on angiogenic factors in the circulation and in adipose tissue in obese subjects

Background:

Vascular growth is a prerequisite for adipose tissue (AT) development and expansion. Some AT cytokines and hormones have effects on vascular development, like vascular endothelial growth factor (VEGF‐A), angiopoietin (ANG‐1), ANG‐2 and angiopoietin‐like protein‐4 (ANGPTL‐4).

Methods:

In this study, the independent and combined effects of diet‐induced weight loss and exercise on AT gene expression and proteins levels of those angiogenic factors were investigated. Seventy‐nine obese males and females were randomized to: 1. Exercise‐only (EXO; 12‐weeks exercise without diet‐restriction), 2. Hypocaloric diet (DIO; 8‐weeks very low energy diet (VLED) + 4‐weeks weight maintenance diet) and 3. Hypocaloric diet and exercise (DEX; 8‐weeks VLED + 4‐weeks weight maintenance diet combined with exercise throughout the 12 weeks). Blood samples and fat biopsies were taken before and after the intervention.

Results:

Weight loss was 3.5 kg in the EXO group and 12.3 kg in the DIO and DEX groups. VEGF‐A protein was non‐significantly reduced in the weight loss groups. ANG‐1 protein levels were significantly reduced 22‐25% after all three interventions (P < 0.01). The ANG‐1/ANG‐2 ratio was also decreased in all three groups (P < 0.05) by 27‐38%. ANGPTL‐4 was increased in the EXO group (15%, P < 0.05) and 9% (P < 0.05) in the DIO group. VEGF‐A, ANG‐1, and ANGPTL‐4 were all expressed in human AT, but only ANGPTL‐4 was influenced by the interventions.

Conclusions:

Our data show that serum VEGF‐A, ANG‐1, ANG‐2, and ANGPTL‐4 levels are influenced by weight changes, indicating the involvement of these factors in the obese state. Moreover, it was found that weight loss generally was associated with a reduced angiogenic activity in the circulation.     

Iron and iron/manganese ratio in forage from Icelandic sheep farms: relation to scrapie

This study was undertaken in order to examine whether any connection existed between the amounts of iron in forage and the sporadic occurrence of scrapie observed in certain parts of Iceland. As iron and manganese are considered antagonistic in plants, calculation of the Fe/Mn ratios was also included by using results from Mn determination earlier performed in the same samples. Forage samples (n = 170) from the summer harvests of 2001–2003, were collected from 47 farms for iron and manganese analysis. The farms were divided into four categories: 1. Scrapie-free farms in scrapie-free areas (n = 9); 2. Scrapie-free farms in scrapie-afflicted areas (n = 17); 3. Scrapie-prone farms (earlier scrapie-afflicted, restocked farms) (n = 12); 4. Scrapie-afflicted farms (n = 9). Farms in categories 1 and 2 are collectively referred to as scrapie-free farms. The mean iron concentration in forage samples from scrapie-afflicted farms was significantly higher than in forage samples from farms in the other scrapie categories (P = 0.001). The mean Fe/Mn ratio in forage from scrapie-afflicted farms was significantly higher than in forage from scrapie-free and scrapie-prone farms (P < 0.001). The results indicated relative dominance of iron over manganese in forage from scrapie-afflicted farms as compared to farms in the other categories. Thus thorough knowledge of iron, along with manganese, in soil and vegetation on sheep farms could be a pivot in studies on sporadic scrapie.     

Scanning electron microscopy and gramicidin patch clamp recordings of microvillous receptor neurons dissociated from the rat vomeronasal organ

Vomeronasal organs from female rats were dissociated and isolated microvillous receptor neurons were studied. The isolated receptor neurons kept the typical bipolar shape which they have in situ as observed by scanning electron microscopy. We applied the perforated patch-clamp technique using the cation-selective ionophore gramicidin on freshly isolated and well differentiated receptor neurons. The mean resting potential was -58+/-14 mV (n=39). The contribution of the sodium pump current to the resting potential was demonstrated by lowering the K+ concentration in the bath or by application of 100 microM dihydro-ouabain. The input resistance was in the range of 1-6 GOmega and depolarizing current pulses of a few pA were sufficient to trigger overshooting action potentials. In voltage clamp conditions a fast transient sodium inward current and a sustained outward potassium current were activated by membrane depolarization. These observations indicate that freshly isolated vomeronasal receptor neurons of rats can be recorded, using gramicidin, with little modification of the intracellular content. Their electrophysiological properties are very similar to those observed in situ. Four out of eight female vomeronasal receptor cells were depolarized by diluted rat male urine.      

Electron paramagnetic resonance study of the migratory ant Pachycondyla marginata abdomens

Electron paramagnetic resonance was used to investigate the magnetic material present in abdomens of Pachycondyla marginata ants. A g congruent with 4.3 resonance of high-spin ferric ions and a very narrow g congruent with 2 line are observed. Two principal resonance broad lines, one with g > 4.5 (LF) and the other in the region of g congruent with 2 (HF), were associated with the biomineralization process. The resonance field shift between these two lines, HF and LF, associated with magnetic nanoparticles indicates the presence of cluster structures containing on average three single units of magnetite-based nanoparticles. Analysis of the temperature dependence of the HF resonance linewidths supports the model picture of isolated magnetite nanostructures of approximately 13 nm in diameter with a magnetic energy of 544 K. These particles are shown to present a superparamagnetic behavior at room temperature. The use of these superparamagnetic particle properties for the magnetoreception process of the ants is suggested.     

Single median maxillary central incisor: new data and mutation review

BACKGROUND: Single median maxillary central incisor (SMMCI) is a rare anomaly that may occur alone or associated with other conditions, frequently as part of the holoprosencephaly (HPE) spectrum. However, it has been suggested that SMMCI alone, or associated with some midline defects, may be considered a different entity from HPE (OMIM: 147250). Families with SMMCI, without HPE cases, are difficult to counsel for the risk of HPE in future generations because the same midline defects described as part of the "SMMCI syndrome" can also be part of the HPE spectrum. METHODS: We screened five cases of SMMCI for mutations in three HPE genes, SHH, TGIF, and SIX3. RESULTS: A missense mutation c.686C>T was found in the gene SIX3 of one patient, which did not differ from the accepted 20% of known HPE gene mutations among all HPE cases. Our results and an extensive literature review of gene mutations in patients with SMMCI showed that 27/28 of them were in HPE genes: SHH (n = 21), SIX3 (n = 3), TGIF (n = 1), GLI2 (n = 1), and PTCH (n = 1), and only one in the SALL4 gene. CONCLUSIONS: The clinical findings in patients with SMMCI without HPE in families with mutations in HPE genes cannot be distinguished from the findings reported in the SMMCI syndrome. Therefore, persons with SMMCI and their relatives should be carefully investigated for related midline disorders, especially of the HPE spectrum, and all known HPE genes screened.     

Designs for clinical trials with time-to-event outcomes based on stopping guidelines for lack of benefit

Background

We present the design, methods and population characteristics of a large community trial that assessed the efficacy of a weekly supplement containing vitamin A or beta-carotene, at recommended dietary levels, in reducing maternal mortality from early gestation through 12 weeks postpartum. We identify challenges faced and report solutions in implementing an intervention trial under low-resource, rural conditions, including the importance of population choice in promoting generalizability, maintaining rigorous data quality control to reduce inter- and intra- worker variation, and optimizing efficiencies in information and resources flow from and to the field.

Methods

This trial was a double-masked, cluster-randomized, dual intervention, placebo-controlled trial in a contiguous rural area of ~435 sq km with a population of ~650,000 in Gaibandha and Rangpur Districts of Northwestern Bangladesh. Approximately 120,000 married women of reproductive age underwent 5-weekly home surveillance, of whom ~60,000 were detected as pregnant, enrolled into the trial and gave birth to ~44,000 live-born infants. Upon enrollment, at ~ 9 weeks' gestation, pregnant women received a weekly oral supplement containing vitamin A (7000 ug retinol equivalents (RE)), beta-carotene (42 mg, or ~7000 ug RE) or a placebo through 12 weeks postpartum, according to prior randomized allocation of their cluster of residence. Systems described include enlistment and 5-weekly home surveillance for pregnancy based on menstrual history and urine testing, weekly supervised supplementation, periodic risk factor interviews, maternal and infant vital outcome monitoring, birth defect surveillance and clinical/biochemical substudies.

Results

The primary outcome was pregnancy-related mortality assessed for 3 months following parturition. Secondary outcomes included fetal loss due to miscarriage or stillbirth, infant mortality under three months of age, maternal obstetric and infectious morbidity, infant infectious morbidity, maternal and infant micronutrient status, fetal and infant growth and prematurity, external birth defects and postnatal infant growth to 3 months of age.

Conclusion

Aspects of study site selection and its "resonance" with national and rural qualities of Bangladesh, the trial's design, methods and allocation group comparability achieved by randomization, field procedures and innovative approaches to solving challenges in trial conduct are described and discussed. This trial is registered with http://Clinicaltrials.gov as protocol NCT00198822.