Interrelationship between drug oxidation ureogenesis and gluconeogenesis in isolated hepatocytes

1. The effect of increased ureogenesis--provoked by NH4Cl and ornithine--on gluconeogenesis and aminopyrine oxidation was studied in isolated hepatocytes prepared from 24 hr starved mice; lactate or fructose was used as gluconeogenic precursor. 2. Increased ureogenesis caused about 40% inhibition both on aminopyrine oxidation and gluconeogenesis when lactate was added as gluconeogenic substrate. 3. On the other hand, only 10% inhibition of aminopyrine oxidation and about 15% inhibition of gluconeogenesis were observed when fructose was used as gluconeogenic precursor. 4. Aminopyrine has been reported to inhibit gluconeogenesis from fructose by 30% and from lactate by 85%. The inhibitory effect of the combined addition of aminopyrine, NH4Cl and ornithine on gluconeogenesis was also dependent on the applied gluconeogenic precursor. 5. The provoked ureogenesis by ammonia and ornithine was not inhibited by aminopyrine. N6, O2-dibutyryl cAMP known to cause an increase of gluconeogenesis a decrease of aminopyrine oxidation enhanced the inhibitory action of increased ureogenesis on aminopyrine oxidation and on gluconeogenesis further. 6. The role of NADPH in the regulation of drug oxidation and ureogenesis is underlined.     

Glucocorticoids Affect 24 h Clock Genes Expression in Human Adipose Tissue Explant Cultures

Aims

to examine firstly whether CLOCK exhibits a circadian expression in human visceral (V) and subcutaneous (S) adipose tissue (AT) in vitro as compared with BMAL1 and PER2, and secondly to investigate the possible effect of the glucocorticoid analogue dexamethasone (DEX) on positive and negative clock genes expression.

Subjects and Methods

VAT and SAT biopsies were obtained from morbid obese women (body mass index≥40 kg/m²) (n = 6). In order to investigate rhythmic expression pattern of clock genes and the effect of DEX on CLOCK, PER2 and BMAL1 expression, control AT (without DEX) and AT explants treated with DEX (2 hours) were cultured during 24 h and gene expression was analyzed at the following times: 10:00 h, 14:00 h, 18:00 h, 22:00 h, 02:00 h and 06:00 h, using qRT-PCR.

Results

CLOCK, BMAL1 and PER2 expression exhibited circadian patterns in both VAT and SAT explants that were adjusted to a typical 24 h sinusoidal curve. PER2 expression (negative element) was in antiphase with respect to CLOCK and in phase with BMAL1 expression (both positive elements) in the SAT (situation not present in VAT). A marked effect of DEX exposure on both positive and negative clock genes expression patterns was observed. Indeed, DEX treatment modified the rhythmicity pattern towards altered patterns with a period lower than 24 hours in all genes and in both tissues.

Conclusions

24 h patterns in CLOCK and BMAL1 (positive clock elements) and PER2 (negative element) mRNA levels were observed in human adipose explants. These patterns were altered by dexamethasone exposure.     

Combating Obesity through Healthy Eating Behavior: A Call for System Dynamics Optimization

Poor eating behavior has been identified as one of the core contributory factors of the childhood obesity epidemic. The consequences of obesity on numerous aspects of life are thoroughly explored in the existing literature. For instance, evidence shows that obesity is linked to incidences of diseases such as heart disease, type-2 diabetes, and some cancers, as well as psychosocial problems. To respond to the increasing trends in the UK, in 2008 the government set a target to reverse the prevalence of obesity (POB) back to 2000 levels by 2020. This paper will outline the application of system dynamics (SD) optimization to simulate the effect of changes in the eating behavior of British children (aged 2 to 15 years) on weight and obesity. This study also will identify how long it will take to achieve the government’s target. This paper proposed a simulation model called Intervention Childhood Obesity Dynamics (ICOD) by focusing the interrelations between various strands of knowledge in one complex human weight regulation system. The model offers distinct insights into the dynamics by capturing the complex interdependencies from the causal loop and feedback structure, with the intention to better understand how eating behaviors influence children’s weight, body mass index (BMI), and POB measurement. This study proposed a set of equations that are revised from the original (baseline) equations. The new functions are constructed using a RAMP function of linear decrement in portion size and number of meal variables from 2013 until 2020 in order to achieve the 2020 desired target. Findings from the optimization analysis revealed that the 2020 target won’t be achieved until 2026 at the earliest, six years late. Thus, the model suggested that a longer period may be needed to significantly reduce obesity in this population.     

Erratum to “Random models of Menzerath–Altmann law in genomes” (BioSystems 107(3) (2012) 167–173)

Here we improve the mathematical arguments of Baixeries et al (BioSystems 107(3) (2012) 167–173). The corrections do not alter the conclusion that the random breakage model yields an insufficient fit to the scaling of mean chromosome length as a function of chromosome number in real genomes.     

Exposure to T‐Cycles of 22 and 23 h during Lactation Modifies the Later Dissociation of Motor Activity and Temperature Circadian Rhythms in Rats

Early environmental conditions may affect the development and manifestation of circadian rhythms. This study sought to determine whether the maintenance of rats under different T‐cycles during lactation influences the subsequent degree of dissociation of the circadian rhythms of motor activity and core body temperature. Two groups of 22 day‐old Wistar rats were kept after weaning under T‐cycles of 22 h (T22) or 23 h (T23) for 70 days. Subsequently, they were kept in constant darkness (DD). Half of the animals in each group were born and reared under these experimental conditions, while the other half were reared until weaning under 24 h LD cycles (T24). Rats transferred from T24 to T22 or T23 showed two circadian components in motor activity and temperature, one entrained by light and the other free‐running. In T22, there was also desynchronization between temperature and motor activity. Rats submitted to T23 from birth showed higher stability of the 23 h component than rats transferred from T24 to T23 after weaning. However, in comparison to rats born under T24 and subsequently changed to T22, animals submitted to T22 from birth showed shorter values of the period of the non‐light‐dependent component during T22, more aftereffects when transferred to DD, and a lack of desynchronization between motor activity and temperature. The results suggest that T‐cycles in the early environment may modify overt rhythms by altering the internal coupling of the circadian pacemaker.     

Foraging Behavior Patterns of Sheep and Horses Under a Mixed Species Grazing System

The research objective was to assess the behavior patterns of the Polish Konik horse breed and the Uhruska variety of the Polish Lowland Sheep breed under a mixed-grazing system, and their relationship with climatic factors. The observation included 4 adult horses, 27 ewes with lambs and 10 primiparous ewes. The behavior of the animals and the weather conditions were recorded at 60-min intervals. Horses and sheep displayed similarities in both species-specific behavioral patterns and timing of grazing activity, and the duration of foraging sessions was mostly influenced by time of day, lower temperature and relative humidity. In addition, the two species showed more interest in the watering place in the afternoon, and drinking frequency was mainly dependent on air temperature. The animals that pastured together gradually began to mix, but at first, they remained within their species group. Both animal species can be used for environmental protection and landscape conservation making rational use of pastures within protected areas.     

Extracellular H2O2 and not superoxide determines the compartment-specific activation of transferrin receptor by iron regulatory protein 1

Iron regulatory protein 1 (IRP1) functions as translational regulator that plays a central role in coordinating the cellular iron metabolism by binding to the mRNA of target genes such as the transferrin receptor (TfR)—the major iron uptake protein. Reactive oxygen species such as H₂O₂ and that are both co-released by inflammatory cells modulate IRP1 in opposing directions. While H₂O₂—similar to iron depletion—strongly induces IRP1 via a signalling cascade, inactivates the mRNA binding activity by a direct chemical attack. These findings have raised the question of whether compartmentalization may be an important mechanism for isolating these biological reactants when released from inflammatory cells during the oxygen burst cascade. To address this question, we studied cytosolic IRP1 and its downstream target TfR in conjunction with a tightly controlled biochemical modulation of extracellular and H₂O₂ levels mimicking the oxygen burst cascade of inflammatory cells. We here demonstrate that IRP1 activity and expression of TfR are solely dependent on H₂O₂ when co-released with from xanthine oxidase. Our findings confirm that extracellular H₂O₂ determines the functionality of the IRP1 cluster and its downstream targets while the reactivity of is limited to its compartment of origin.     

Excretion of newly synthesized DNA by tonsil lymphocytes.

The main part of newly synthesized DNA is preferentially released in vitro both by non-stimulated or phytohemagglutinin-stimulated tonsil lymphocytes. Freshly isolated cells excrete DNA faster than phytohemagglutinin-stimulated ones. The acid-precipitable 3H-thymidine lost can be accounted for in the culture medium as labeled, double stranded DNA isolated on hydroxyapatite column.