Circadian Rhythms of Plasma Concentrations of Na+ and K+ and Their Urinary Excretion in Normal and Diabetic Rats

The effects of streptozotocin induced diabetes (50 mg/Kg) on the circadian rhythms in the excretion of sodium and potassium as well as their plasma concentration rhythms were investigated. Control (C) and diabetic (D) rats were studied during a light-dark (12h:12h) cycle and fed ad libitum. Statistically significant circadian rhythms were found for sodium and potassium excretion in C rats. The orthophases of both rhythms occurred in the dark phase, the potassium one occurring before that of sodium. In D rats there is increased excretion of both sodium and potassium with the rhythmicity maintained for sodium excretion only, which has an earlier orthophase than in the C rats. Plasma sodium and potassium concentrations showed a statistically significant circadian pattern in C rats, with orthophase in the light phase. This rhythmicity only appears in plasma potassium concentration for D rats, with orthophase at the end of the dark phase. The results in diabetic rats may suggest that the glomerular filtration rate (GFR) and/or tubular reabsorption rhythms are still contributing to the sodium excretory rhythm, and that the loss of the circadian rhythm in sodium plasma concentration has no influence on the sodium excretion rhythm. Nevertheless, the loss of the potassium excretion rhythm may suggest a disruption of the variations in the secretory process, as this excretion seems to be independent of the plasma potassium concentration rhythm, which is not lost in D rats.     

Improved screening test for abnormal hemoglobins from dried blood samples

Summary A method is described wherin blood samples taken from adults or newborns and dried on filter paper can be used for hemoglobin analysis within 2 years after sampling. The samples are eluted in 8 M urea in the presence of 5% 2-mercaptoethanol and 2% of the neutral detergent Nonidet P-40. Then the individual , , , and chains are separated by means of electrofocusing in 8 M urea-PAA gels. Up to 96 samples can be applied to a gel using multiple syringes. Several hundred samples can be analyzed daily by one person. This method may be especially useful for preventive programs against sickle cell anemia as well as for human mutation monitoring systems.Abbreviations used in this paper PAA polyacrylamide - PAG polyacrylamide gel - TCA trichloroacetic acid - PKU phenylketonuria     

Direct and Indirect Effects of Climate on Demography and Early Growth of Pinus sylvestris at the Rear Edge: Changing Roles of Biotic and Abiotic Factors

Global change triggers shifts in forest composition, with warming and aridification being particularly threatening for the populations located at the rear edge of the species distributions. This is the case of Scots pine (Pinus sylvestris) in the Mediterranean Basin where uncertainties in relation to its dynamics under these changing scenarios are still high. We analysed the relative effect of climate on the recruitment patterns of Scots pine and its interactions with local biotic and abiotic variables at different spatial scales. Number of seedlings and saplings was surveyed, and their annual shoot growth measured in 96 plots located across altitudinal gradients in three different regions in the Iberian Peninsula. We found a significant influence of climate on demography and performance of recruits, with a non-linear effect of temperature on the presence of juveniles, and a positive effect of precipitation on their survival. Abundance of juveniles of P. sylvestris that underwent their first summer drought was skewed towards higher altitudes than the altitudinal mean range of the conspecific adults and the optimum elevation for seedlings'' emergence. At local level, light availability did not influence juveniles'' density, but it enhanced their growth. Biotic interactions were found between juveniles and the herb cover (competition) and between the number of newly emerged seedlings and shrubs (facilitation). Results also highlighted the indirect effect that climate exerts over the local factors, modulating the interactions with the pre-existing vegetation that were more evident at more stressful sites. This multiscale approach improves our understanding of the dynamics of these marginal populations and some management criteria can be inferred to boost their conservation under the current global warming.     

Circadian Rhythms of Plasma Concentrations of Na+ and K+ and Their Urinary Excretion in Normal and Diabetic Rats

The effects of streptozotocin induced diabetes (50 mg/Kg) on the circadian rhythms in the excretion of sodium and potassium as well as their plasma concentration rhythms were investigated. Control (C) and diabetic (D) rats were studied during a light-dark (12h:12h) cycle and fed ad libitum. Statistically significant circadian rhythms were found for sodium and potassium excretion in C rats. The orthophases of both rhythms occurred in the dark phase, the potassium one occurring before that of sodium. In D rats there is increased excretion of both sodium and potassium with the rhythmicity maintained for sodium excretion only, which has an earlier orthophase than in the C rats. Plasma sodium and potassium concentrations showed a statistically significant circadian pattern in C rats, with orthophase in the light phase. This rhythmicity only appears in plasma potassium concentration for D rats, with orthophase at the end of the dark phase. The results in diabetic rats may suggest that the glomerular filtration rate (GFR) and/or tubular reabsorption rhythms are still contributing to the sodium excretory rhythm, and that the loss of the circadian rhythm in sodium plasma concentration has no influence on the sodium excretion rhythm. Nevertheless, the loss of the potassium excretion rhythm may suggest a disruption of the variations in the secretory process, as this excretion seems to be independent of the plasma potassium concentration rhythm, which is not lost in D rats.     

Tumor-based rhythms of anticancer efficacy in experimental models

Experimental tumor models constitute a prerequisite toward chronotherapy testing in cancer patients. Studies in experimental models are required to understand the relation between tumor rhythms and antitumor treatments efficacy. In healthy tissues, cell proliferation, and differentiation processes are regulated precisely and exhibit marked circadian rhythmicity. Experimental and human tumors can retain circadian rhythms or display altered oscillations. Healthy tissues can also display rhythm modifications, possibly related to cancer stage. Cellular rhythms modulate the metabolism of cytotoxic agents and the cellular response to them; hence, they determine the chronopharmacology of anticancer drugs. Circadian rhythms in host tolerability and/or cancer chemotherapy efficacy have been demonstrated with nontoxic doses of drugs in several experimental tumor models, while in other ones a circadian-time effect was only seen within a specific dose range. The usual coupling between tolerability and efficacy rhythms of anticancer agents has resulted in significant improvement of their therapeutic index. Results of laboratory animal studies have been extrapolated to the design of clinical cancer therapy trials involving a chronobiological approach.     

Enzymatic hydrolysis of lime-pretreated corn stover and investigation of the HCH-1 Model: inhibition pattern, degree of inhibition, validity of simplified HCH-1 Model

The inhibition pattern was identified for a reaction system composed of Trichoderma reesei cellulase enzyme complex and lime-pretreated corn stover. Also, the glucose inhibition effect was quantified for the aforementioned reaction system over a range of enzyme loadings and substrate concentrations. Lastly, the range of substrate concentrations and enzyme loadings were identified in which the linear form of the simplified HCH-1 Model is valid. The HCH-1 Model is a modified Michaelis-Menton Model with non-competitive inhibition and the fraction of insoluble substrate available to bind with enzyme. With a high enzyme loading, the HCH-1 Model can be integrated and simplified in such a way that sugar conversion is linearly proportional to the logarithm of enzyme loading. A wide range of enzyme loadings (0.25-50 FPU/g dry biomass) and substrate concentrations (10-100g/L) were investigated. All experiments were conducted with an excess cellobiase loading to ensure the experimental results were not influenced by cellobiose inhibition. A non-competitive inhibition pattern was identified for the corn stover-cellulase reaction system, thereby validating the assumptions of the HCH-1 Model. At a substrate concentration of 10 g/L, glucose inhibition parameters of 0.986 and 0.979 were measured for enzyme loadings of 2 FPU/g dry biomass and 50 FPU/g dry biomass, respectively. At 5 FPU/g dry biomass, glucose inhibition parameters of 0.985 and 0.853 were measured for substrate concentrations of 10 and 100g/L, respectively. The linear form of the HCH-1 Model predicted biomass digestibility for lime-pretreated corn stover over an enzyme loading range of 0.25-50 FPU/g dry biomass and substrate concentration range of 10-100g/L.     

<Emphasis Type="Italic">Burkholderia</Emphasis> Hep_Hag autotransporter (BuHA) proteins elicit a strong antibody response during experimental glanders but not human melioidosis

Background  

The bacterial biothreat agents Burkholderia mallei and Burkholderia pseudomallei are the cause of glanders and melioidosis, respectively. Genomic and epidemiological studies have shown that B. mallei is a recently emerged, host restricted clone of B. pseudomallei.     

Bone formation rather than inflammation reflects Ankylosing Spondylitis activity on PET-CT: a pilot study

Introduction

Positron Emission Tomography - Computer Tomography (PET-CT) is an interesting imaging technique to visualize Ankylosing Spondylitis (AS) activity using specific PET tracers. Previous studies have shown that the PET tracers [¹⁸F]FDG and [¹¹C](R)PK11195 can target inflammation (synovitis) in rheumatoid arthritis (RA) and may therefore be useful in AS. Another interesting tracer for AS is [¹⁸F]Fluoride, which targets bone formation. In a pilot setting, the potential of PET-CT in imaging AS activity was tested using different tracers, with Magnetic Resonance Imaging (MRI) and conventional radiographs as reference.

Methods

In a stepwise approach different PET tracers were investigated. First, whole body [¹⁸F]FDG and [¹¹C](R)PK11195 PET-CT scans were obtained of ten AS patients fulfilling the modified New York criteria. According to the BASDAI five of these patients had low and five had high disease activity. Secondly, an extra PET-CT scan using [¹⁸F]Fluoride was made of two additional AS patients with high disease activity. MRI scans of the total spine and sacroiliac joints were performed, and conventional radiographs of the total spine and sacroiliac joints were available for all patients. Scans and radiographs were visually scored by two observers blinded for clinical data.

Results

No increased [¹⁸F]FDG and [¹¹C](R)PK11195 uptake was noticed on PET-CT scans of the first 10 patients. In contrast, MRI demonstrated a total of five bone edema lesions in three out of 10 patients. In the two additional AS patients scanned with [¹⁸F]Fluoride PET-CT, [¹⁸F]Fluoride depicted 17 regions with increased uptake in both vertebral column and sacroiliac joints. In contrast, [¹⁸F]FDG depicted only three lesions, with an uptake of five times lower compared to [¹⁸F]Fluoride, and again no [¹¹C](R)PK11195 positive lesions were found. In these two patients, MRI detected nine lesions and six out of nine matched with the anatomical position of [¹⁸F]Fluoride uptake. Conventional radiographs showed structural bony changes in 11 out of 17 [¹⁸F]Fluoride PET positive lesions.

Conclusions

Our PET-CT data suggest that AS activity is reflected by bone activity (formation) rather than inflammation. The results also show the potential value of PET-CT for imaging AS activity using the bone tracer [¹⁸F]Fluoride. In contrast to active RA, inflammation tracers [¹⁸F]FDG and [¹¹C](R)PK11195 appeared to be less useful for AS imaging.     

A new species of Chiliotrichiopsis (Asteraceae: Astereae) from Peru

Chiliotrichiopsis peruviana Nesom, H. Rob. & Granda, a new species from Dept. Ayacucho in southwestern Peru, is described and illustrated. It is the only rayless species of the genus, now expanded to four species, and the only one that occurs outside of Argentina.Chiliotrichiopsis is one of six shrubby South American genera of Astereae (subtribe Hinterhuberinae) with paleate receptacles. Observations on morphology and a key to these genera provide perspective for the generic placement of the new species.     

Neuronal differentiation is triggered by oleic acid synthesized and released by astrocytes

Unlike in the adult brain, the newborn brain specifically takes up serum albumin during the postnatal period, coinciding with the stage of maximal brain development. Here we report that albumin stimulates oleic acid synthesis by astrocytes from the main metabolic substrates available during brain development. Oleic acid released by astrocytes is used by neurons for the synthesis of phospholipids and is specifically incorporated into growth cones. Oleic acid promotes axonal growth, neuronal clustering, and expression of the axonal growth-associated protein-43, GAP-43; all these observations indicating neuronal differentiation. The effect of oleic acid on GAP-43 synthesis is brought about by the activation of protein kinase C, since it was prevented by inhibitors of this kinase, such as H-7, polymyxin or sphingosine. The expression of GAP-43 was significantly increased in neurons co-cultured with astrocytes by the presence of albumin indicating that neuronal differentiation takes place in the presence of oleic acid synthesized and released by astrocytes in situ. In conclusion, during brain development the presence of albumin could play an important role by triggering the synthesis and release of oleic acid by astrocytes, which induces neuronal differentiation.