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Open access

Sarah J Hall, Brad Aisbett, Samuel J Robertson, Sally A Ferguson, and Anne I Turner

The effect of working on-call from home on the sympatho-adrenal medullary system activity is currently unknown. This study had two aims, Aim 1: examine salivary alpha amylase awakening response (AAR) and diurnal salivary alpha amylase (sAA) profile in fire and emergency service workers who operate on-call from home following a night on-call with a call (NIGHT-CALL), a night on-call without a call (NO-CALL) and an off-call night (OFF-CALL), and Aim 2: explore whether there was an anticipatory effect of working on-call from home (ON) compared to when there was an off-call (OFF) on the diurnal sAA profile. Participants wore activity monitors, completed sleep and work diaries and collected seven saliva samples a day for one week. AAR area under the curve with respect to ground (AUCG), AAR area under the curve with respect to increase (AUCI), AAR reactivity, diurnal sAA slope, diurnal sAA AUCG and mean 12-h sAA concentrations were calculated. Separate generalised estimating equation models were constructed for each variable of interest for each aim. For Aim 1, there were no differences between NIGHT-CALL or NO-CALL and OFF-CALL for any response variable. For Aim 2, there was no difference between any response variable of interest when ON the following night compared to when OFF the following night (n = 14). These findings suggest that there is no effect of working on-call from home on sAA, but should be interpreted with caution, as overnight data were not collected. Future research, using overnight heart rate monitoring, could help confirm these findings.

Open access

Flavia Letícia Martins Peçanha, Reinaldo Sousa dos Santos, and Wagner Seixas da-Silva

The thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), are very important in organism metabolism and regulate glucose utilization. Hexokinase (HK) is responsible for the first step of glycolysis, catalyzing the conversion of glucose to glucose 6-phosphate. HK has been found in different cellular compartments, and new functions have been attributed to this enzyme. The effects of hyperthyroidism on subcellular glucose phosphorylation in mouse tissues were examined. Tissues were removed, subcellular fractions were isolated from eu- and hyperthyroid (T3, 0.25 µg/g, i.p. during 21 days) mice and HK activity was assayed. Glucose phosphorylation was increased in the particulate fraction in soleus (312.4% ± 67.1, n = 10), gastrocnemius (369.2% ± 112.4, n = 10) and heart (142.2% ± 13.6, n = 10) muscle in the hyperthyroid group compared to the control group. Hexokinase activity was not affected in brain or liver. No relevant changes were observed in HK activity in the soluble fraction for all tissues investigated. Acute T3 administration (single dose of T3, 1.25 µg/g, i.p.) did not modulate HK activity. Interestingly, HK mRNA levels remained unchanged and HK bound to mitochondria was increased by T3 treatment, suggesting a posttranscriptional mechanism. Analysis of the AKT pathway showed a 2.5-fold increase in AKT and GSK3B phosphorylation in the gastrocnemius muscle in the hyperthyroid group compared to the euthyroid group. Taken together, we show for the first time that THs modulate HK activity specifically in particulate fractions and that this action seems to be under the control of the AKT and GSK3B pathways.

Open access

Robert A Hart, Robin C Dobos, Linda L Agnew, Neil A Smart, and James R McFarlane

Pharmacokinetics of leptin in mammals has not been studied in detail and only one study has examined more than one time point in non-mutant mice and this was in a female mice. This is the first study to describe leptin distribution over a detailed time course in normal male mice. A physiologic dose (12 ng) of radiolabelled leptin was injected into adult male mice via the lateral tail vein and tissues were dissected out and measured for radioactivity over a time course of up to two hours. Major targets were the digestive tract, kidneys, skin and lungs. The brain was not a major target, and 0.15% of the total dose was recovered from the brain 5 min after administration. Major differences appear to exist in the distribution of leptin between the male and female mice, indicating a high degree of sexual dimorphism. Although the half-lives were similar between male and female mice, almost twice the proportion of leptin was recovered from the digestive tract of male mice in comparison to that reported previously for females. This would seem to indicate a major difference in leptin distribution and possibly function between males and females.

Open access

Henri Honka, Jukka Koffert, Saila Kauhanen, Nobuyuki Kudomi, Saija Hurme, Andrea Mari, Andreas Lindqvist, Nils Wierup, Riitta Parkkola, Leif Groop, and Pirjo Nuutila


The mechanisms for improved glycemic control after bariatric surgery in subjects with type 2 diabetes (T2D) are not fully known. We hypothesized that dynamic hepatic blood responses to a mixed-meal are changed after bariatric surgery in parallel with an improvement in glucose tolerance.


A total of ten morbidly obese subjects with T2D were recruited to receive a mixed-meal and a glucose-dependent insulinotropic polypeptide (GIP) infusion before and early after (within a median of less than three months) bariatric surgery, and hepatic blood flow and volume (HBV) were measured repeatedly with combined positron emission tomography/MRI. Ten lean non-diabetic individuals served as controls.


Bariatric surgery leads to a significant decrease in weight, accompanied with an improved β-cell function and glucagon-like peptide 1 (GLP-1) secretion, and a reduction in liver volume. Blood flow in portal vein (PV) was increased by 1.65-fold (P = 0.026) in response to a mixed-meal in subjects after surgery, while HBV decreased in all groups (P < 0.001). When the effect of GIP infusion was tested separately, no change in hepatic arterial and PV flow was observed, but HBV decreased as seen during the mixed-meal test.


Early after bariatric surgery, PV flow response to a mixed-meal is augmented, improving digestion and nutrient absorption. GIP influences the post-prandial reduction in HBV thereby diverting blood to the extrahepatic sites.

Open access

Kristin Viste, Marianne A Grytaas, Melissa D Jørstad, Dag E Jøssang, Eivind N Høyden, Solveig S Fotland, Dag K Jensen, Kristian Løvås, Hrafnkell Thordarson, Bjørg Almås, and Gunnar Mellgren

Primary aldosteronism (PA) is a common cause of secondary hypertension and is caused by unilateral or bilateral adrenal disease. Treatment options depend on whether the disease is lateralized or not, which is preferably evaluated with selective adrenal venous sampling (AVS). This procedure is technically challenging, and obtaining representative samples from the adrenal veins can prove difficult. Unsuccessful AVS procedures often require reexamination. Analysis of cortisol during the procedure may enhance the success rate. We invited 21 consecutive patients to participate in a study with intra-procedural point of care cortisol analysis. When this assay showed nonrepresentative sampling, new samples were drawn after redirection of the catheter. The study patients were compared using the 21 previous procedures. The intra-procedural cortisol assay increased the success rate from 10/21 patients in the historical cohort to 17/21 patients in the study group. In four of the 17 successful procedures, repeated samples needed to be drawn. Successful sampling at first attempt improved from the first seven to the last seven study patients. Point of care cortisol analysis during AVS improves success rate and reduces the need for reexaminations, in accordance with previous studies. Successful AVS is crucial when deciding which patients with PA will benefit from surgical treatment.

Open access

Maxime Duval, Kalyane Bach-Ngohou, Damien Masson, Camille Guimard, Philippe Le Conte, and David Trewick


Severe hypocalcemia (Ca <1.9 mmol/L) is often considered an emergency because of a potential risk of cardiac arrest or seizures. However, there is little evidence to support this. The aim of our study was to assess whether severe hypocalcemia was associated with immediately life-threatening cardiac arrhythmias or neurological complications.


A retrospective observational study was carried out over a 2-year period in the Adult Emergency Department (ED) of Nantes University Hospital. All patients who had a protein-corrected calcium concentration measure were eligible for inclusion. Patients with multiple myeloma were excluded. The primary outcome was the number of life-threatening cardiac arrhythmias and/or neurological complications during the stay in the ED.


A total of 41,823 patients had protein-corrected calcium (pcCa) concentrations measured, 155 had severe hypocalcemia, 22 were excluded because of myeloma leaving 133 for analysis. Median pcCa concentration was 1.73 mmol/L (1.57–1.84). Seventeen (12.8%) patients presented a life-threatening condition, 14 (10.5%) neurological and 3 (2.2%) cardiac during ED stay. However, these complications could be explained by the presence of underlying co-morbidities and or electrolyte disturbances other than hypocalcemia. Overall, 24 (18%) patients died in hospital. Vitamin D deficiency, chronic kidney disease and hypoparathyroidism were the most frequently found causes of hypocalcemia.


Thirteen percent of patients with severe hypocalcemia presented a life-threatening cardiac or neurological complication on the ED. However, a perfectly valid alternative cause could account for these complications. Further research is warranted to define the precise role of hypocalcemia.

Open access

Zhou-Qing Kang, Jia-Ling Huo, and Xiao-Jie Zhai


The optimal glycemic target during the perioperative period is still controversial. We aimed to explore the effects of tight glycemic control (TGC) on surgical mortality and morbidity.


PubMed, EMBASE and CENTRAL were searched from January 1, 1946 to February 28, 2018. Appropriate trails comparing the postoperative outcomes (mortality, hypoglycemic events, acute kidney injury, etc.) between different levels of TGC and liberal glycemic control were identified. Quality assessments were performed with the Jadad scale combined with the allocation concealment evaluation. Pooled relative risk (RR) and 95% CI were calculated using random effects models. Heterogeneity was detected by the I 2 test.


Twenty-six trials involving a total of 9315 patients were included in the final analysis. The overall mortality did not differ between tight and liberal glycemic control (RR, 0.92; 95% CI, 0.78–1.07; I 2 = 20.1%). Among subgroup analyses, obvious decreased risks of mortality were found in the short-term mortality, non-diabetic conditions, cardiac surgery conditions and compared to the very liberal glycemic target. Furthermore, TGC was associated with decreased risks for acute kidney injury, sepsis, surgical site infection, atrial fibrillation and increased risks of hypoglycemia and severe hypoglycemia.


Compared to liberal control, perioperative TGC (the upper level of glucose goal ≤150 mg/dL) was associated with significant reduction of short-term mortality, cardic surgery mortality, non-diabetic patients mortality and some postoperative complications. In spite of increased risks of hypoglycemic events, perioperative TGC will benefits patients when it is done carefully.

Open access

Rossella Cannarella, Teresa Mattina, Rosita A Condorelli, Laura M Mongioì, Giuseppe Pandini, Sandro La Vignera, and Aldo E Calogero

Insulin-like growth factor 1 receptor (IGF1R), mapping on the 15q26.3 chromosome, is required for normal embryonic and postnatal growth. The aim of the present study was to evaluate the IGF1R gene expression and function in three unrelated patients with chromosome 15 structural abnormalities. We report two male patients with the smallest 15q26.3 chromosome duplication described so far, and a female patient with ring chromosome 15 syndrome. Patient one, with a 568 kb pure duplication, had overgrowth, developmental delay, mental and psychomotor retardation, obesity, cryptorchidism, borderline low testis volume, severe oligoasthenoteratozoospermia and gynecomastia. We found a 1.8-fold increase in the IGF1R mRNA and a 1.3-fold increase in the IGF1R protein expression (P < 0.05). Patient two, with a 650 kb impure duplication, showed overgrowth, developmental delay, mild mental retardation, precocious puberty, low testicular volume and severe oligoasthenoteratozoospermia. The IGF1R mRNA and protein expression was similar to that of the control. Patient three, with a 46,XX r(15) (p10q26.2) karyotype, displayed intrauterine growth retardation, developmental delay, mental and psychomotor retardation. We found a <0.5-fold decrease in the IGF1R mRNA expression and an undetectable IGF1R activity. After reviewing the previously 96 published cases of chromosome 15q duplication, we found that neurological disorders, congenital cardiac defects, typical facial traits and gonadal abnormalities are the prominent features in patients with chromosome 15q duplication. Interestingly, patients with 15q deletion syndrome display similar features. We speculate that both the increased and decreased IGF1R gene expression may play a role in the etiology of neurological and gonadal disorders.

Open access

Caishun Zhang, Junhua Yuan, Qian Lin, Manwen Li, Liuxin Wang, Rui Wang, Xi Chen, Zhengyao Jiang, Kun Zhu, Xiaoli Chang, Bin Wang, and Jing Dong

Ghrelin plays a pivotal role in the regulation of food intake, body weight and energy metabolism. However, these effects of ghrelin in the lateral parabrachial nucleus (LPBN) are unexplored. C57BL/6J mice and GHSR−/− mice were implanted with cannula above the right LPBN and ghrelin was microinjected via the cannula to investigate effect of ghrelin in the LPBN. In vivo electrophysiological technique was used to record LPBN glucose-sensitive neurons to explore potential udnderlying mechanisms. Microinjection of ghrelin in LPBN significantly increased food intake in the first 3 h, while such effect was blocked by [D-Lys3]-GHRP-6 and abolished in GHSR−/− mice. LPBN ghrelin microinjection also significantly increased the firing rate of glucose-excited (GE) neurons and decreased the firing rate of glucose-inhibited (GI) neurons. Additionally, LPBN ghrelin microinjection also significantly increased c-fos expression. Chronic ghrelin administration in the LPBN resulted in significantly increased body weight gain. Meanwhile, no significant changes were observed in both mRNA and protein expression levels of UCP-1 in BAT. These results demonstrated that microinjection of ghrelin in LPBN could increase food intake through the interaction with growth hormone secretagogue receptor (GHSR) in C57BL/6J mice, and its chronic administration could also increase body weight gain. These effects might be associated with altered firing rate in the GE and GI neurons.

Open access

Yang Lv, Xu Han, Chunyan Zhang, Yuan Fang, Ning Pu, Yuan Ji, Dansong Wang, Xu Xuefeng, and Wenhui Lou


Chromogranin A (CgA) and neuron-specific enolase (NSE) are important markers for neuroendocrine tumors; however, the clinical value of combining these markers has not been well studied. In this study, we investigated the utility of each marker individually and in combination for patients with nonfunctional pancreatic neuroendocrine tumors (NF-pNETs).

Patients and Methods

In this study, NF-pNET patients and controls were recruited from December 2011 to March 2016; 784 serum samples from peripheral vein were collected. The clinical characteristics and biomarker values of all the individuals were recorded and analyzed. Tumor burdens were calculated by CT/MRI scan. Receiver-operating characteristic curves were constructed to assess the diagnostic predictive values; sensitivity and specificity were calculated to determine the cut-off value. Therapeutic responses reflected on the changes of the biomarkers’ concentration were assessed by the RECIST criterion. Clinical relations between the prognosis and the biomarker values were also analyzed. Statistical significance was defined as P value less than 0.05.


Among the 167 NF-pNETs patients, 82 were males (49.1%) and the mean age was 50.0 (17.4). The mean CgA values of G1, G2 and G3 NF-pNENs were 75, 121 and 134 μg/L (P < 0.05), respectively. In NF-pNETs, CgA correlated with the WHO tumor grade (WHO G1 vs G2, P < 0.05); the linear regression relationships were found between the tumor burdens (both in pancreas and liver) and CgA concentration (P < 0.001); changes in CgA and NSE concentrations also reflect treatment response (P < 0.001).


CgA and NSE are important diagnostic and follow-up markers in patients with NF-pNETs. The combined monitoring of CgA and NSE possesses more accuracy than individual values of CgA and NSE at predicting prognosis and disease progression.