Marker Of Metabolic Activity Research Articles

Molecular Imaging of Invasive Pulmonary Aspergillosis Using ImmunoPET/MRI: The Future Looks Bright.

Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of immuno-compromised humans caused by the ubiquitous environmental mold Aspergillus. Biomarker tests for the disease lack sensitivity and specificity, and culture of the fungus from invasive lung biopsy is slow, insensitive, and undesirable in critically ill patients. A computed tomogram (CT) of the chest offers a simple non-intrusive diagnostic procedure for rapid decision making, and so is used in many hematology units to drive antifungal treatment. However, radiological indicators that raise the suspicion of IPA are either transient signs in the early stages of the disease or not specific for Aspergillus infection, with other angio-invasive molds or bacterial pathogens producing comparable radiological manifestations in a chest CT. Improvements to the specificity of radiographic imaging of IPA have been attempted by coupling CT and positron emission tomography (PET) with [18F]fluorodeoxyglucose ([18F]FDG), a marker of metabolic activity well suited to cancer imaging, but with limited use in invasive fungal disease diagnostics due to its inability to differentiate between infectious etiologies, cancer, and inflammation. Bioluminescence imaging using single genetically modified strains of Aspergillus fumigatus has enabled in vivo monitoring of IPA in animal models of disease. For in vivo detection of Aspergillus lung infections in humans, radiolabeled Aspergillus-specific monoclonal antibodies, and iron siderophores, hold enormous potential for clinical diagnosis. This review examines the different experimental technologies used to image IPA, and recent advances in state-of-the-art molecular imaging of IPA using antibody-guided PET/magnetic resonance imaging (immunoPET/MRI).

Co-Cultured Continuously Bioluminescent Human Cells as Bioreporters for the Detection of Prodrug Therapeutic Impact Pre- and Post-Metabolism

Modern drug discovery workflows require assay systems capable of replicating the complex interactions of multiple tissue types, but that can still function under high throughput conditions. In this work, we evaluate the use of substrate-free autobioluminescence in human cell lines to support the performance of these assays with reduced economical and logistical restrictions relative to substrate-requiring bioluminescent reporter systems. The use of autobioluminescence was found to support assay functionality similar to existing luciferase reporter targets. The autobioluminescent assay format was observed to correlate strongly with general metabolic activity markers such as ATP content and the presence of reactive oxygen species, but not with secondary markers such as glutathione depletion. At the transcriptional level, autobioluminescent dynamics were most closely associated with expression of the CYP1A1 phase I detoxification pathway. These results suggest constitutively autobioluminescent cells can function as general metabolic activity bioreporters, while pairing expression of the autobioluminescent phenotype to detoxification pathway specific promoters could create more specific sensor systems.

Bone Mineral Density and Molecular Genetic Markers of Bone Remodeling in Blood of Cosmonauts after Long-term Missions on Board the International Space Station

The results of the investigation of the bone system of 24 Russian cosmonauts after long-term (124–199 days) missions on board the International space station (ISS) are presented. Functional adaptation of the bone system involves some complex changes in the metabolic activity of osteoblasts and osteoclasts, such as alterations of the serum concentrations of osteocalcin, tartrate-resistant acid phosphatase (TRAP), osteoprotegerin, and the activator ligand of the receptor of nuclear factor kappa-B (RANKL); in addition, in peripheral blood leucocytes, there are changes in the expression of genes regulating the development of skeletal system and bone mineral metabolism. Significant variability in the mineral density of femoral neck and molecular genetic markers studied after long-term space flights indicates individual variability of the balance of the processes of bone remodeling, bone formation and resorption. Significant bone mass losses in the femoral bone of cosmonauts are associated with more pronounced changes in the markers of metabolic activity of osteoclasts.

Temperature and photoperiod as environmental cues affect body mass and thermoregulation in Chinese bulbuls, Pycnonotus sinensis.

Seasonal changes in temperature and photoperiod are important environmental cues used by small birds to adjust their body mass (Mb) and thermogenesis. However, the relative importance of these cues with respect to seasonal adjustments in Mb and thermogenesis is difficult to distinguish. In particular, the effects of temperature and photoperiod on energy metabolism and thermoregulation are not well known in many passerines. To address this problem, we measured the effects of temperature and photoperiod on Mb, energy intake, resting metabolic rate (RMR), organ mass and physiological and biochemical markers of metabolic activity in the Chinese bulbul (Pycnonotus sinensis). Groups of Chinese bulbuls were acclimated in a laboratory to the following conditions: (1) warm and long photoperiod, (2) warm and short photoperiod, (3) cold and long photoperiod, and (4) cold and short photoperiod, for 4 weeks. The results indicate that Chinese bulbuls exhibit adaptive physiological regulation when exposed to different temperatures and photoperiods. Mb, RMR, gross energy intake and digestible energy intake were higher in cold-acclimated than in warm-acclimated bulbuls, and in the short photoperiod than in the long photoperiod. The resultant flexibility in energy intake and RMR allows Chinese bulbuls exposed to different temperatures and photoperiods to adjust their energy balance and thermogenesis accordingly. Cold-acclimated birds had heightened state-4 respiration and cytochrome c oxidase activity in their liver and muscle tissue compared with warm-acclimated birds indicating the cellular mechanisms underlying their adaptive thermogenesis. Temperature appears to be a primary cue for adjusting energy budget and thermogenic ability in Chinese bulbuls; photoperiod appears to intensify temperature-induced changes in energy metabolism and thermoregulation.

Relationships between interspecific differences in the mass of internal organs, biochemical markers of metabolic activity, and the thermogenic properties of three small passerines

The capacity for thermogenesis is considered part of an animal’s adaptive strategy for survival, and basal metabolic rate (BMR) is one of the fundamental physiological standards for assessing the energy cost of thermoregulation in endotherms. BMR has been shown to be a highly flexible phenotypic trait both between, and within, species, but the metabolic mechanisms involved in the regulation of BMR, which range from variation in organ mass to biochemical adjustments, remain unclear. In this study, we investigated the relationship between organ mass, biochemical markers of metabolic tissue activity, and thermogenesis, in three species of small passerines: wild Bramblings (Fringilla montifringilla), Little Buntings (Emberiza pusilla) and Eurasian Tree Sparrows (Passer montanus), caught in Wenzhou, southeastern China. Oxygen consumption was measured using an open-circuit respirometry system. Mitochondrial state-4 respiration and cytochrome c oxidase (COX) activity in liver and pectoral muscle were measured with a Clark electrode. Our results show that Eurasian Tree Sparrows had significantly higher BMR, digestive organ mass, mitochondrial state-4 respiration capacity and COX activity in liver and muscle, than Bramblings and Little Buntings. Furthermore, interspecific differences in BMR were strongly correlated with those indigestive tract mass, state-4 respiration and COX activity. Our findings suggest that the digestive organ mass, state-4 respiration and COX activity play an important role in determining interspecific differences in BMR.

MRI and thallium features of pigmented villonodular synovitis and giant cell tumours of tendon sheaths: a retrospective single centre study of imaging and literature review.

The purpose of this study was to characterize the MRI and thallium-201 ((201)TI) scintigraphy attributes of pigmented villonodular synovitis (PVNS) and giant cell tumours of tendon sheaths (GCTTS). The epidemiology of these uncommon lesions was also assessed and less commonly encountered pathology reported on including multifocality, necrosis and concurrent malignancy. A retrospective single centre review of MRI and (201)TI scintigraphy findings for 83 surgically proven or biopsy-proven consecutive cases of PVNS was undertaken. Radiological findings including lesion size, (201)TI uptake (as a marker of metabolic activity), location, extent and patient demographics were correlated with biopsy and surgical specimen histology. Typical appearances are described, as well as less common imaging manifestations. The study period encompassed all patients presenting or referred to a tertiary bone and soft-tissue tumour referral centre with PVNS or GCTTS between 1 January 2007 and the 1 December 2013. Lesions occur most commonly around the knee joint in the fourth decade of life, with younger patients showing a tendency to occur in the hip. Features of PVNS and GTTS include bone erosion, ligamentous and cartilage replacement, muscle infiltration and multifocality. MR signal characteristics were variable but post-contrast enhancement was near-universal. 14 of 83 cases showed no uptake of (201)TI and revealed a statistically significant smaller average axial dimension of 19.8 mm than lesions displaying active (201)TI uptake of 36.4 mm, p = 0.016. Four lesions demonstrated central necrosis on gross histology, two of each from both the (201)TI-avid and (201)TI-non-avid groups. MR is the imaging modality of choice when considering the diagnosis of these uncommon tumours. (201)TI scintigraphy as a marker of metabolic activity further adds minimal value although small lesions can appear to lack (201)TI avidity. This article depicts typical imaging findings of PVNS/GCTTS and also a subset of lesions that demonstrate no uptake on metabolic functional imaging, namely smaller sized lesions irrespective of anatomical location. This represents an important departure from previously documented imaging manifestations, whereby an absence of isotope accumulation suggested exclusion of these lesions from the differential diagnosis. These findings have important implications when considering the diagnosis of these uncommon lesions and may be important when interpreting post-treatment response. We suggest that further investigation, for example, with MRI is valuable in order to clarify potential post-treatment response, as well as the use of alternate functional imaging modalities such as positron emission tomography (PET), to further corroborate these findings.

Decreased baroreflex sensitivity is linked to sympathovagal imbalance, body fat mass and altered cardiometabolic profile in pre-obesity and obesity

ObjectiveThough decreased baroreflex sensitivity (BRS), the predictor of cardiac morbidities and mortality has been reported in obesity, the mechanisms and metabolic biomarkers influencing BRS have not been studied. We aimed to assess the difference in cardiovascular (CV) risk profile in pre-obesity and obesity, and the contribution of body composition and cardiometabolic factors to CV risks in these two conditions. MethodsObesity indices, body composition, blood pressure variability and autonomic function test parameters were recorded in 223 subjects divided into controls (n=72), pre-obese (n=77) and obese (n=74) groups. Insulin resistance (HOMA-IR), atherogenic index (AI), leptin, adiponectin, inflammatory and oxidative stress parameters were measured. Association and independent contribution of altered cardiometabolic parameters with BRS were performed by Pearson’s correlation and multiple regression analysis, respectively. ResultsBRS was significantly decreased in pre-obese and obese group compared to controls. Sympathovagal imbalance (SVI) in the form of increased sympathetic and decreased parasympathetic cardiac drives was observed in pre-obesity and obesity. There was significant difference in general markers of obesity (body mass index, and waist-to-hip ratio), between pre-obese and obese group, however no such difference was observed in body composition and cardiometabolic parameters between the two groups. AI, high sensitive C-reactive protein (hs-CRP) and ratio of basal metabolism to body fat (BM/BF) in pre-obese group, and AI, HOMA-IR, leptin, adiponectin, ratio of basal metabolism to body weight (BM/BW), BM/BF, inflammatory and oxidative stress markers in obese group had independent contribution to BRS. Among these metabolic biomarkers, BRS had maximum association with leptin (β=0.532, p=0.000) in the obese group and hs-CRP (β=0.445, p=0.022) in the pre-obese group. ConclusionsThe present study demonstrates decreased BRS, an important marker of increased CV risk in pre-obesity and obesity. The intensity of cardiometabolic derangements and CV risk was comparable between pre-obese and obese subjects. BM/BF ratio appears to be a better marker of metabolic activity in pre-obesity and obesity. SVI and increased basal metabolism appear to be the physiological link between metabolic derangements and CV risks in both pre-obesity and obesity.

Additive effects of maternal iron deficiency and prenatal immune activation on adult behaviors in rat offspring.

Both iron deficiency (ID) and infection are common during pregnancy and studies have described altered brain development in offspring as a result of these individual maternal exposures. Given their high global incidence, these two insults may occur simultaneously during pregnancy. We recently described a rat model which pairs dietary ID during pregnancy and prenatal immune activation. Pregnant rats were placed on iron sufficient (IS) or ID diets from embryonic day 2 (E2) until postnatal day 7, and administered the bacterial endotoxin, lipopolysaccharide (LPS) or saline on E15/16. In this model, LPS administration on E15 caused greater induction of the pro-inflammatory cytokines, interleukin-6 and tumor necrosis factor-α, in ID dams compared to IS dams. This suggested that the combination of prenatal immune activation on a background of maternal ID might have more adverse neurodevelopmental consequences for the offspring than exposure to either insult alone. In this study we used this model to determine whether combined exposure to maternal ID and prenatal immune activation interact to affect juvenile and adult behaviors in the offspring. We assessed behaviors relevant to deficits in humans or animals that have been associated with exposure to either maternal ID or prenatal immune activation alone. Adult offspring from ID dams displayed significant deficits in pre-pulse inhibition of acoustic startle and in passive avoidance learning, together with increases in cytochrome oxidase immunohistochemistry, a marker of metabolic activity, in the ventral hippocampus immediately after passive avoidance testing. Offspring from LPS treated dams showed a significant increase in social behavior with unfamiliar rats, and subtle locomotor changes during exploration in an open field and in response to amphetamine. Surprisingly, there was no interaction between effects of the two insults on the behaviors assessed, and few observed alterations in juvenile behavior. Our findings show that long-term effects of maternal ID and prenatal LPS were additive, such that offspring exposed to both insults displayed more adult behavioral abnormalities than offspring exposed to one alone.

Metabolic imaging of ischemic stroke: the present and future.

Measures of cerebral metabolism may be useful in the selection of patients for reperfusion therapies and as end points in clinical trials. However, there are currently no clinically routine techniques that provide such data directly. We review how imaging modalities in current clinical use may provide surrogate markers of metabolic activity. Promising techniques for metabolic imaging that are currently in the pipeline are reviewed.

Methylglyoxal and glyoxalase I in atherosclerosis

Cardiovascular disease, caused predominantly by atherosclerotic plaque rupture, remains one of the leading causes of death. However, the mechanism of plaque rupture remains largely unknown. Recent studies have linked high metabolic activity in inflamed atherosclerotic plaques to the development of plaque rupture. AGEs (advanced glycation end-products) are known to be formed as a result of high metabolic activity and are higher in rupture-prone than stable plaques. Furthermore, AGEs seem to be more than mere markers of metabolic activity, as recent studies have elucidated that AGEs and their major precursor, MG (methylglyoxal), may have an important role in the progression of atherosclerosis and plaque rupture. MG can be detoxified by Glo1 (glyoxalase I), thereby preventing the accumulation of MG and MG-derived AGEs. In the present review, data concerning MG, Glo1 and AGEs in the context of plaque phenotype are discussed.

Combining 123I-Metaiodobenzylguanidine SPECT/CT and 18F-FDG PET/CT for the Assessment of Brown Adipose Tissue Activity in Humans During Cold Exposure

Brown adipose tissue (BAT) has become a focus of research in the hope of finding a new target to fight obesity. Metabolic BAT activity can be visualized with (18)F-FDG PET/CT. Furthermore, the sympathetic innervation of BAT can be visualized with the radiolabeled norepinephrine analog (123)I-metaiodobenzylguanidine ((123)I-MIBG). We aimed to determine whether (123)I-MIBG SPECT/CT and (18)F-FDG PET/CT identify the same anatomic regions as active BAT in adult humans. Furthermore, we investigated whether the magnitude of BAT activity measured by these techniques correlated. Finally, we tried to establish the optimal time interval between (123)I-MIBG administration and subsequent SPECT/CT acquisition to visualize sympathetic stimulation of BAT. Ten lean (body mass index, 19-25 kg/m(2)), healthy Caucasian men (age, 18-32 y) underwent one (18)F-FDG PET/CT and two (123)I-MIBG-SPECT/CT scans within a 2-wk interval. On 2 separate occasions, the subjects were exposed to mild cold (17°C) for 2 h after an overnight fast. After 1 h of cold exposure, (18)F-FDG (one occasion) or (123)I-MIBG (other occasion) was administered. (18)F-FDG PET/CT was performed at 1 h after (18)F-FDG administration, and (123)I-MIBG-SPECT/CT was performed at 4 and 24 h after (123)I-MIBG injection. (18)F-FDG uptake in BAT was observed in 8 of 10 subjects, whereas (123)I-MIBG uptake was observed in 7 of 10 subjects in both the SPECT/CT scans acquired at 4 h after (123)I-MIBG administration and the SPECT/CT scans acquired at 24 h after (123)I-MIBG administration. All subjects who showed (123)I-MIBG uptake in BAT also showed (18)F-FDG uptake in BAT. There was no statistically significant correlation between maximal standardized uptake value of (18)F-FDG and semiquantitative uptake of (123)I-MIBG at 4 h after administration. However, a positive correlation was found between the maximal standardized uptake value of (18)F-FDG and semiquantitative uptake of (123)I-MIBG at 24 h after administration (r = 0.64, P = 0.04). (123)I-MIBG SPECT/CT, as a marker of sympathetic activity, and (18)F-FDG PET/CT, as a marker of metabolic activity, identified the same anatomic regions as active BAT. Moreover, when (123)I-MIBG SPECT/CT was performed at 24 h after (123)I-MIBG administration, the magnitude of BAT activity measured with these techniques correlated strongly. This finding not only supports that BAT activity in humans is sympathetically influenced but also identifies (123)I-MIBG SPECT/CT, when performed 24 h after (123)I-MIBG injection, as a method to visualize and quantify sympathetic stimulation of BAT.

Neocortical synaptic proliferation following forebrain-dependent trace associative learning.

Many behavioral studies have suggested that learning induces neocortical synaptic modifications. However, neocortical synaptic modifications following forebrain-dependent trace associative learning has not been closely examined. Acquisition of whisker-trace-eyeblink (WTEB) conditioning, a forebrain-dependent trace associative task, has been reported to modulate the expression of cytochrome oxidase, a marker for metabolic activity, in the conditioned barrels, suggesting that trace associative conditioning induces neocortical synaptic plasticity. However, neocortical synaptic plasticity has never been directly examined following this trace associative task. To assess neocortical synaptic modifications, the present study examined synapsin I expression following WTEB conditioning. Synapsin I is part of a phosphoprotein family involved in neuronal regulation of neurotransmitter release that also exhibits an expression pattern closely correlating to synapse number. Findings from this study demonstrated that synapsin I expression is elevated in primary somatosensory neocortex in trace-paired-conditioned mice compared with unpaired-conditioned (stimulation-control) mice and naïve mice, suggesting that WTEB conditioning induces synaptic proliferation. Additional findings from the present study examining cytochrome oxidase expression replicated previous findings demonstrating that WTEB conditioning induces a learning-specific expansion of the cytochrome oxidase staining expression for conditioned barrels. Together, these results suggest that synaptic proliferation is contributing to the learning-induced metabolic augmentation previously observed in conditioned barrels following WTEB conditioning. Furthermore, these results suggest that trace associative learning facilitates neocortical synaptic modification.

Protein‐based stable isotope probing (protein‐SIP) in functional metaproteomics

The community phenotype as the sum of molecular functions of organisms living in consortia strongly depends on interactions within these communities. Therefore, the analyses of the most significant molecules in terms of the phenotype, the proteins, have to be performed on samples without disrupting the meta-species environment. Due to the increasing genomic information, proteins provide insights into a potential molecular function and the phylogenetic structure of the community. Unfortunately, the lists of identified proteins are often based first on the technical capacity of the used methods or instruments, and second on the interpretation of them by the assignment of molecular functions to proteins in databases. Especially in non-model organisms the functions of many proteins are often not known and an increasing number of studies indicate a significant amount of uncertainty. To decrease the dependency on assumptions and to enable functional insights by metaproteome approaches, the metabolic labeling from an isotopically labeled substrate can be used. Since the metabolites deriving from the substrate are very rarely species-specific, the incorporation of the stable isotope into proteins can be used as a surrogate marker for metabolic activity. The degree of incorporation can be determined accurately on the peptide level by mass spectrometry; additionally, the peptide sequence provides information on the metabolic active species. Thereby, protein-stable isotope probing (protein-SIP) adds functional information to metaproteome approaches. The classical metaproteome approaches will be reviewed with an emphasis on their attempts towards functional interpretation. The gain from functional insights into metaproteomics by using metabolic labeling of stable isotopes of carbon, nitrogen, and sulfur is reviewed with a focus on the techniques of measurement, calculation of incorporation and data processing.

Effect of follicular fluid oxidative stress parameters on intracytoplasmic sperm injection outcome

Objective. The purpose of this study was to evaluate the association between the follicular fluid (FF) reactive oxygen species (ROS) levels, total antioxidant capacity (TAC) and ROS-TAC score and pregnancy after intracytoplasmic sperm injection (ICSI).Methods. A total of 138 consecutive women who had ICSI were included in this study. FF ROS and TAC were measured by enhanced chemiluminescence and colorimetric assay, respectively, and then the ROS-TAC score was calculated.Results. Out of the 138 included patients, 42 (30%) achieved pregnancy after ICSI. Log ROS, TAC, and the ROS-TAC score were not significantly different across diagnoses. Pregnant cycles were associated with significantly lower ROS (P < 0.001), higher TAC (P < 0.001) and higher ROS-TAC scores (P < 0.001). After adjusting for age, there was a significant positive correlation between log ROS and the number of follicles on the day of HCG administration (correlation 0.20, 95% CI: 0.02, 0.39) as well as the number of oocytes retrieved (correlation 0.18, 0.001, 0.36) but not with TAC. Interestingly, in women with endometriosis, higher TAC levels and higher ROS-TAC scores were associated with a higher likelihood of finding normal oocytes (P = 0.005 and P = 0.002, respectively).Conclusion. Higher FF TAC, higher FF ROS-TAC scores and lower FF ROS levels are associated with pregnancy after ICSI. Oxidative stress parameters may be markers of metabolic activity within the follicle.

TH-D-201B-04: Optimization of Scanning Protocol for Combined FDG and NaF PET Kinetic Analysis - a Simulation Study

Objective 18F‐Fluorodeoxyglucose (FDG) is a metabolic activity marker with limited use for skeletal lesions. Sodium18F‐flouride (NaF) is a bone imaging agent that complements the FDG limitations for skeletal lesions. The kinetic analysis of combined NaF/FDG PET scan promises concurrent determination of both tumor metabolism and vasculature parameters as well as successful separation of each tracer uptake. The aim of this work is to optimize the combined NaF/FDG PET scanning protocol in order to maximize accuracy in kinetic model estimation of the tumor's parameters. Materials and Methods Simulations assessed the feasibility and accuracy of kinetic analysis of combined NaF/FDG PETimages. Tissue time activity curves (tTAC) were generated with randomized parameters and PET voxel‐wise noise level. Various time delays between NaF and FDG injection times were simulated while keeping the total scan duration at 60 minutes. Parameters were estimated with two simplified versions of the model used for tTAC's generation. Estimated parameters were compared against the simulated parameters. The optimized sequence was tested on canine NaF/FDG PET data.Results Parameter estimation accuracy was maximized if the NaF was injected first followed by the FDG injection of at least 40 minutes later. The estimation accuracy for k1 parameters ranged from 15% to 20% for FDG and 25% to 30% for NaF. Ki estimation accuracy ranged from 40% to 55% for FDG and 10% to 25% for NaF. Vasculature fraction estimation accuracy ranged from 20% to 40%. Results of clinical data kinetic analysis shows that both k1 parameters are highly correlated which implies that it might be common for both radiopharmaceuticals in our model._Conclusions This study has shown that kinetic analysis of combined NaF/FDG PETimages is feasible using an optimized injection and scanning protocol. For the given cases we found the optimal scanning protocol and quantified parameter estimation accuracy.

Alterations in Adipose Tissue during Critical Illness

Critical illness is characterized by lean tissue wasting, whereas adipose tissue is preserved. Overweight and obese critically ill patients may have a lower risk of death than lean patients, suggestive of a protective role for adipose tissue during illness. To investigate whether adipose tissue could protectively respond to critical illness by storing potentially toxic metabolites, such as excess circulating glucose and triglycerides. We studied adipose tissue morphology and metabolic activity markers in postmortem biopsies of 61 critically ill patients and 20 matched control subjects. Adipose morphology was also studied in in vivo biopsies of 27 patients and in a rabbit model of critical illness (n = 22). Adipose tissue from critically ill patients revealed a higher number and a smaller size of adipocytes and increased preadipocyte marker levels as compared with control subjects. Virtually all adipose biopsies from critically ill patients displayed positive macrophage staining. The animal model demonstrated similar changes. Glucose transporter levels and glucose content were increased. Glucokinase expression was up-regulated, whereas glycogen and glucose-6-phosphate levels were low. Acetyl CoA carboxylase protein and fatty acid synthase activity were increased. Hormone-sensitive lipase activity was not altered, whereas lipoprotein lipase activity was increased. A substantially increased AMP-activated protein kinase activity may play a crucial role. Postmortem adipose tissue biopsies from critically ill patients displayed a larger number of small adipocytes in response to critical illness, revealing an increased ability to take up circulating glucose and triglycerides. Similar morphologic changes were present in vivo. Such changes may render adipose tissue biologically active as a functional storage depot for potentially toxic metabolites, thereby contributing to survival.

Bilateral high frequency stimulation of the subthalamic nucleus normalizes COX activity in the substantia nigra of Parkinsonian rats

Part of the mechanism underlying the therapeutic effect of subthalamic nucleus (STN) high frequency stimulation (HFS) involves the activity of the basal ganglia output structures. The general idea is that STN's burst activity leads to an increased activity of the basal ganglia output nuclei and that HFS reverses this. However, the published data sets conflict. Here, we addressed the question which effect STN HFS had on the overall substantia nigra pars reticulata (SNr; one of the basal ganglia output nuclei) activity, in rats rendered Parkinsonian by 6-hydroxydopamine (6-OHDA) injections in the striatum. We used a marker for metabolic activity, cytochrome C oxidase (COX). The expression of COX in the SNr of Parkinsonian rats was significantly higher as compared to sham-operated rats. However, in Parkinsonian rats with STN HFS, expression of COX was significantly lower as compared to non-stimulated Parkinsonian rats, and was comparable to the level of expression in sham-operated rats. These results show that STN HFS decreased the overall activity of the basal ganglia output nucleus in dopamine-depleted rats.

Effect of lactobacillus fermented beetroot juice on composition and activity of cecal microflora of rats

This study aimed at determination of the effect caused by ingestion of beetroot juice fermented by Lactobacillus casei 0920 and Lactobacillus brevis 0944 strains on the state of cecal ecosystem of experimental rats. The intake of fermented beetroot juice containing 3.5–4.0 × 109 CFU/mL live Lactobacillus sp. cells positively modulated the cecal microflora of the rats and its metabolic activity. The counts of Lactobacillus sp., Bifidobacterium sp., Bacteriodes sp., and Enterococcus sp. were maintained at the level of 8.2–8.6, 6.2–7.5, 8.0–8.3, and 7.3–7.7 log units, respectively, while the number of Clostridium sp. cells was increased by 1.1–1.6 log units and Enterobacteriaceae bacteria were reduced by 0.8–2.1 log units. In this study, the selected cecal enzymes such as β-glucosidase, β-glucuronidase, and β-galactosidase as well as the profile and concentration of short chain fatty acids (SCFA) were the biochemical markers of metabolic activity of the intestinal ecosystem. The considerable decrease in activities of β-glucosidase and β-glucuronidase was observed in all three experimental groups fed with the fermented beetroot juice. Total concentration of SCFA was the highest (78.1 μmol/100 g BW vs. 59.2 μmol/100 g BW in control group) in intestines of rats fed with 6 mL of fermented beetroot juice daily. These results prove that the fermented beetroot juice benefits cecal microbial activity.

Ontogeny in terminal buds of Abies nordmanniana (Pinaceae) characterized by ubiquitin

Meristematic activity in the bud meristem of Abies nordmanniana was visualized by ubiquitin immunohistochemical localization from before bud break and throughout shoot expansion. Ubiquitin was detected in meristematic cells either in the cytosol or nucleus, or both, depending on tissue type and developmental stage. During winter dormancy, ubiquitin was only observed in the protodermal/hypodermal layers, but at bud break in mid May, the signal expanded to the entire shoot tip. At the end of May, a clear zonation in ubiquitin localization appeared that lasted about one month. Throughout this period, ubiquitin was barely detectable in a central group of cells that might indicate an organizing center with stem cells. At the end of June, coinciding with the transition from scale leaf to needle primordia production, ubiquitin again was more prevalent in the peripheral cell layers. During shoot expansion, a strong ubiquitin signal developed in the axil of all needles. Most of these signals later disappeared, except for those few axils where buds actually developed. A strong ubiquitin signal was also observed in cells lining the young resin ducts. Our data showed that ubiquitin may be used as a marker for metabolic activity associated with seasonal development in the apical meristem.

Response to the comment by B. Schöne et al. (2006) on “Stable carbon isotopes in freshwater mussel shells: Environmental record or marker for metabolic activity?”

Response to the comment by B. Schöne et al. (2006) on “Stable carbon isotopes in freshwater mussel shells: Environmental record or marker for metabolic activity?”