This study investigated the short-term effects of the intensity level of physical exercise on bone metabolism and related hormones. The responses of calciotropic hormones and bone biochemical markers ...were evaluated in seven male cyclists (mean age 24.4 years, range 20-39) during two 50-min cycling tests performed 15% below (-VT) and 15% above (+VT) the ventilatory threshold. In each test, venous blood samples were drawn at rest, at the 30th and 50th min of exercise, and after 15 min of recovery. For both intensity levels, no significant variation in calcium, 25-hydroxyvitamin D, 1.25-dihydroxyvitamin D, or cortisol level was observed. Intact parathyroid hormone (iPTH) level increased significantly after the last minute of the test (41%, p < 0.05) and peaked during the recovery (80%, p < 0.05) only in response to exercise performed at +VT. Serum phosphorus concentration rose during both tests, while albumin levels increased only at +VT. Concerning bone cell activity, osteocalcin, and type I-C telopeptide breakdown products transiently increased only in response to exercise performed at +VT (11% and 16.8%, respectively; p < 0.05). Bone alkaline phosphatase increased similarly for both intensity levels after 30 min (12%, p < 0.05) and 50 min (12% for -VT vs. 14% for +VT, p < 0.05). All markers of bone turnover returned to initial values during the recovery. In conclusion, a no-impact but intense and sustained exercise performed at +VT transiently stimulated bone turnover and iPTH secretion, suggesting the existence of a bone stimulation threshold. In addition to the well known effect of mechanical constraints, both the duration and intensity of exercise may induce changes in bone turnover.
We have used homologous recombination in human embryonic stem cells (hESCs) to insert sequences encoding green fluorescent protein (GFP) into the NKX2.1 locus, a gene required for normal development ...of the basal forebrain. Generation of NKX2.1‐GFP+ cells was dependent on the concentration, timing, and duration of retinoic acid treatment during differentiation. NKX2.1‐GFP+ progenitors expressed genes characteristic of the basal forebrain, including SHH, DLX1, LHX6, and OLIG2. Time course analysis revealed that NKX2.1‐GFP+ cells could upregulate FOXG1 expression, implying the existence of a novel pathway for the generation of telencephalic neural derivatives. Further maturation of NKX2.1‐GFP+ cells gave rise to γ‐aminobutyric acid‐, tyrosine hydroxylase‐, and somatostatin‐expressing neurons as well as to platelet‐derived growth factor receptor α‐positive oligodendrocyte precursors. These studies highlight the diversity of cell types that can be generated from human NKX2.1+ progenitors and demonstrate the utility of NKX2.1GFP/w hESCs for investigating human forebrain development and neuronal differentiation. STEM CELLS 2011;29:462–473
Abstract Introduction Prescription drug abuse is a major concern in several countries. France appears to be particularly prone to the abuse of opiate maintenance treatment (OMT) opioids and ...benzodiazepines (BZD), whereas the abuse of opioid analgesics (OA) is less commonly reported. To estimate the extent of psychoactive drug abuse, the French drug agency relies on different methods measuring various diversion indicators used as proxies for the detection of abuse/misuse: suspicion of abuse/dependence, illegal acquisition by patients seen in specialized care centers, prescription forgery and doctor shopping. The main objectives of the present study are to analyse the abuse and diversion of opioids (both OA and OMT), in comparison with those of BZDs, through the concurrent use of three different data sources. Methods Diversion and abuse of opioids were analysed using indicators of abuse and diversion derived from three data sources over the period 2006–2008. Then, opioids were compared to BZDs for the year 2008 using the same indicators. Results The analysis suggests that BZDs are more commonly dispensed than OAs and OMTs but that abuse and diversion are related mainly to OMT (particularly to buprenorphine), morphine and BZDs and less to OAs (except for morphine). Conclusion This study presents an original approach, based on the use of multiple data sources, to evaluate and compare the estimated abuse and diversion of opioids and benzodiazepines. It provides health authorities with a global, comparative and summarized overall view of the importance of different patterns of diversion and abuse for different prescription drugs.
Mitochondrial pyruvate dehydrogenase (mtPDH) is a key respiratory enzyme that links glycolysis and the tricarboxylic acid cycle, and it is negatively regulated by mtPDH kinase (mtPDHK). Arabidopsis ...lines carrying either a constitutive or seed-specific antisense construct for mtPDHK were used to test the hypothesis that alteration of mtPDH activity in a tissue- and dosage-dependent manner will enhance reproductive growth particularly at elevated CO2 (EC) through a combined enhancement of source and sink activities. Constitutive transgenic lines showed increased mtPDH activity in rosette leaves at ambient CO2 (AC) and EC, and in immature seeds at EC. Seed-specific transgenic lines showed enhanced mtPDH activity in immature seeds. A strong relationship existed between seed mtPDH activity and inflorescence initiation at AC, and at EC inflorescence stem growth, silique number and seed harvest index were strongly related to seed mtPDH activity. Leaf photosynthetic rates showed an increase in rosette leaves of transgenic lines at AC and EC that correlated with enhanced inflorescence initiation. Collectively, the data show that mtPDHK plays a key role in regulating sink and source activities in Arabidopsis particularly during the reproductive phase.
Thrombocytopenia (TCP) is a haematological condition known to occur in chronically infected hepatitis C (HCV) patients and may interfere with diagnostic procedures, such as liver biopsy, because of ...risk of bleeding. It may also exclude patients from effective antiviral treatment. We conducted a systematic literature review of articles and conference s, to assess the prevalence of TCP among those with HCV and to describe demographics, liver disease stage and treatment characteristics of these patients. Studies of individuals with confirmed chronic HCV infection were included in the review if the study had a clear definition of thrombocytopenia and a sample size of at least 50 subjects. The final selection included 27 studies (21 articles and six s). The definitions of thrombocytopenia varied between studies and were based either on platelet counts, with threshold levels ranging between ≤100 × 109 and ≤180 × 109/L, or on criteria set in haematological guidelines. The prevalence of TCP ranged from 0.16% to 45.4% and more than half of the studies reported a TCP prevalence of 24% or more. Because of the different TCP definitions, heterogeneity in study design and insufficient data on study characteristics such as age, gender, HCV treatment rates and disease severity an overall summary estimate of TCP prevalence among patients with HCV was not feasible. However, the relatively large prevalence in the majority of the studies suggests that there may be a substantial number of HCV patients at risk of bleeding complications and reduced likelihood of successful HCV antiviral treatment.
Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare, autosomal recessive inborn error of metabolism in which several neurotransmitters including serotonin, dopamine, norepinephrine and ...epinephrine are deficient. Symptoms typically appear in the first year of life and include oculogyric crises and dystonia, hypotonia, and global developmental delay. Dystonia is of particular concern as a dystonic storm can ensue leading to rhabdomyolysis. Rhabdomyolysis can become life-threating and therefore its recognition and prompt management is of significant importance. Here we present two cases of patients with AADC deficiency and a history of dystonic crisis causing rhabdomyolysis. We hypothesize that in addition to the hypodopaminergic, a hypercholinergic state is contributing to the pathophysiology of dystonia in AADC deficiency, as well as to the associated rhabdomyolysis. We were able to prevent rhabdomyolysis in both patients with using Dantrolene and we suggest using a trial of this medication in cases of sustained dystonic crisis in AADC deficiency patients.
Retinoic Acid Induces Pdx1 -Positive Endoderm in Differentiating Mouse Embryonic Stem Cells
Suzanne J. Micallef 1 ,
Mary E. Janes 1 ,
Kathy Knezevic 2 ,
Richard P. Davis 1 ,
Andrew G. Elefanty 1 and
...Edouard G. Stanley 1
1 Centre for Early Human Development, Monash Institute of Reproduction and Development, Monash University, Clayton, Victoria,
Australia
2 Department of Hematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K
Address correspondence and reprint requests to Edouard G. Stanley, Centre for Early Human Development, Monash Institute of
Reproduction and Development, 27-31 Wright St., Clayton, Victoria 3168, Australia. E-mail: ed.stanley{at}med.monash.edu.au
Abstract
We have generated an embryonic stem (ES) cell line in which sequences encoding green fluorescent protein (GFP) were targeted
to the locus of the pancreatic-duodenal homeobox gene ( Pdx1 ). Analysis of chimeric embryos derived from blastocyst injection of Pdx1 GFP/w ES cells demonstrated that the pattern of GFP expression was consistent with that reported for the endogenous Pdx1 gene. By monitoring GFP expression during the course of ES cell differentiation, we have shown that retinoic acid (RA) can
regulate the commitment of ES cells to form Pdx1 + pancreatic endoderm. RA was most effective at inducing Pdx1 expression when added to cultures at day 4 of ES differentiation, a period corresponding to the end of gastrulation in the
embryo. RT-PCR analysis showed that Pdx1 -positive cells from day 8 cultures expressed the early endoderm markers Ptf1a , Foxa2 , Hnf4α , Hnf1β , and Hnf6 , consistent with the notion that they corresponded to the early pancreatic endoderm present in the embryonic day 9.5 mouse
embryo. These results demonstrate the utility of Pdx1 GFP/w ES cells as a tool for monitoring the effects of factors that influence pancreatic differentiation from ES cells.
EB, embryoid body
E-cad, E-cadherin
ES, embryonic stem
GFP, green fluorescent protein
RA, retinoic acid
Footnotes
Posted on the World Wide Web at http://diabetes.diabetesjournals.org on 7 December 2004.
Accepted November 16, 2004.
Received September 28, 2004.
DIABETES
Patient data monitoring is a key issue for health and disease management. The use of wireless sensors within a body area network (BAN) makes this task seamless and easy. A BAN system is presented, ...which allows the connectivity of a wide range of heterogeneous body sensors to a portable hub device that is connectable to external networks. This BAN is based on the use of Zigbee/IEEE 802.15.4 standard technology and off-the-shelf modules. It is currently being used at the European level for the detection and the prediction of the human physiological state in relation to wakefulness, fatigue, and stress applications in which users carrying out daily activities are monitored in an unobtrusive and comfortable way. Characterised by its low power consumption, low cost, and ability to connect a wide range of heterogeneous sensors, this system can substantially improve the performance of different services, especially those that are health related.
Background : : Cellulite is a complex aesthetic problem caused by a complex interplay of dermal-fascial septae, lipodystrophy, and inadequate skin elasticity, but reliable solutions for this ...condition remain elusive.Objective: To evaluate a novel radiofrequency-based body contouring device cleared by the FDA for the temporary improvement in the appearance of cellulite in the thighs and abdomen (NuEra; Lumenis, Ltd., Yokneam, Israel).Methods : : A prospective cohort trial was designed to first collect subjective patient and provider reported outcome measures of safety, comfort, and efficacy of the NuEra system in treatment of thigh cellulite in 9 participants. Following review of this data, the second portion of the trial was conducted using the NuEra system to treat the abdominal area in the same patients, collecting anthropometric measurements using a 3-dimensional imaging system (Vectra M3; Canfield, Parsippany, NJ, USA). Treatment protocol specified 5 treatments at approximately 1 week intervals with a final treatment after a 6 week delay. Results : were assessed at the time of the treatments and at two month following the last treatment. Likert scales were used to evaluate subjective provider and patient experience and a standardized cellulite assessment scale was used to rate the pre and post treatment photographs.Results : : Patients rated the overall level of comfort at 4.3 and satisfaction as 3.3 on a 5-point scale. Pain scale scores during treatment averaged 1.4 on a 5-point scale. Providers reported very high levels of satisfaction with the ease of the treatment (4.3 on a 5-point scale). Evaluation of standardized photographs showed an average improvement of 0.53 (standard deviation SD=0.53), with the average pre-treatment score of 2.2 (SD=0.62) and post-treatment score of 1.64 (SD=0.68). The average reduction in waist and hip circumference measurements was 0.99 cm (SD=2.68 cm) and 0.71 cm (SD=1.44 cm).Conclusion : : Radiofrequency based body contouring is a safe, effective, and well tolerated treatment for thigh cellulite.
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