Ghrelin does not mediate the somatotroph and corticotroph responses to the stimulatory effect of glucagon or insulin-induced hypoglycaemia in humans

OBJECTIVE: Acylated ghrelin, a gastric peptide, possesses a potent GH- but also significant ACTH/cortisol-releasing activity mediated by the activation of GH secretagogue receptors (GHS-R) at the hypothalamus-pituitary level. The physiological role of ghrelin in the control of somatotroph and corticotroph function is, however, largely unclear. Glucagon is known to induce a clear increase of GH, ACTH and cortisol levels in humans, at least after intramuscular administration. In fact, glucagon is considered to be a classical alternative to insulin-induced hypoglycaemia (ITT) for the combined evaluation of the function of GH and the hypothalamus-pituitary-adrenal (HPA) axis. We aimed to clarify whether ghrelin mediate the GH and corticotroph responses to intramuscular glucagon or ITT, which has recently been reported able to induce a surprising ghrelin decrease. SUBJECTS: To this aim we enrolled six normal young male subjects [age (mean +/- SD): 29.0 +/- 8.0 years, body mass index (BMI) 21.9 +/- 2.5 kg/m(2)]. DESIGN AND MEASUREMENTS: In all the subjects we studied ghrelin, GH, ACTH, cortisol and glucose levels after glucagon (GLU; 0.017 mg/kg intramuscularly), ITT (0.1 IU/kg insulin intravenously) or saline administration. RESULTS: Saline infusion was not followed by any significant variation in ghrelin, GH and glucose levels while ACTH and cortisol showed the expected spontaneous morning trend toward a decrease. GLU administration increased (P < 0.01) circulating GH, ACTH and cortisol as well as insulin and glucose levels. ITT induced an obvious increase (P < 0.01) of GH, ACTH and cortisol levels. The ITT-induced increases in GH and ACTH, but not cortisol, levels were higher (P < 0.01) than those after GLU. Circulating ghrelin levels were not modified by GLU. On the other hand, ghrelin levels underwent a transient reduction (P < 0.01) after insulin-induced hypoglycaemia. CONCLUSIONS: Ghrelin does not mediate the GH and ACTH responses to glucagon or to the ITT. In fact, ghrelin levels are not modified at all by glucagon and transiently decrease during the ITT. These findings support the assumption that ghrelin does not play a major role in the physiological control of somatotroph and corticotroph function.     

Effect of Iron Supplementation on Oxidative Stress and Intestinal Inflammation in Rats with Acute Colitis

In this study, we investigated the effect of intraperitoneal iron dextran (100mg/100 g body weight) on oxidative stress and intestinal inflammation in rats with acute colitis induced by 5% dextran sulfate sodium. In both colitis and healthy animals, disease activity index, crypt and inflammatory scores, colon length, plasma and colonic lipid peroxides, and plasma vitamins E, C, and retinol were assessed. The results showed that iron-supplemented groups had moderate iron deposition in the colonic submucosa and lamina propria. In the colitis group supplemented with iron, colon length was significantly shorter; disease activity index, crypt, and inflammatory scores and colonic lipid peroxides were significantly higher; and plasma -tocopherol was significantly lower compared to the colitis group without iron supplementation. There was no intestinal inflammation and no significant increase in colonic lipid peroxides in healthy rats supplemented with iron. In conclusion, iron injection resulted in an increased oxidative stress and intestinal inflammation in rats with colitis but not in healthy rats.     

The Brazilian Back Complaints in the Elders (Brazilian BACE) study: characteristics of Brazilian older adults with a new episode of low back pain

Objective

Low back pain (LBP) is little explored in the aging population especially when considering age-relevant and culturally dependent outcomes. We aimed to describe socio-demographic and clinical characteristics of Brazilian older people with a new episode of LBP presenting to primary care.

Gardening in greenhouses as a risk factor for silicosis

Silicosis is a typical occupational disease, although some cases caused by non-industrial exposure have also been reported. We saw a 53-year-old male gardener with recurrent non-productive cough. A routine radiograph of the chest showed bilateral pulmonary nodules and subsequent computed tomography suggested that the infiltrates could be metastases. Open lung biopsy revealed nodules consisting of fibrotic tissue while the presence of birefringent silica particles was observed by polarised light microscopy. Mineralogical analysis of the substrata from the patient's workplace revealed an SiO(2) concentration of 31%. This case indicates that the inhalation of siliceous particles in a closed environment such as a greenhouse is a risk factor for silicosis.     

Mast cell recruitment after subcutaneous injection of RANTES in the sole of the rat paw

Granulocyte colony-stimulating factor (G-CSF)-induced alteration of phosphoprotein during differentiation of HL-60 cells was studied. From the two-dimensional gel electrophoresis analysis of phosphoproteins, a 45 kD phosphoprotein in the cytosolic fraction of DMSO-pretreated HL-60 cells was rapidly dephosphorylated by the addition of G-CSF. This 45 kD phosphoprotein migrated into four or five spots between 4.5 and 5.5 pI. The dephosphorylation of 45 kD protein was observed within at least 10 min and reached a maximum at 60 min. Phosphoamino acid analysis showed that only serine residue of 45 kD phosphoprotein was phosphorylated, suggesting that G-CSF induced an activation of serine phosphatase. Furthermore, Staurosporine and calphostin C inhibited the phosphorylation of 45 kD protein, suggesting that protein kinase C or its downstream kinase(s) is involved in the phosphorylation of 45 kD protein. These results indicate that G-CSF causes dephosphorylation of a 45 kD cytosolic phosphoprotein which may play a role in signal transduction of G-CSF.     

Animals recover but plant life knowledge is still impaired 10 years after herpetic encephalitis: the long-term follow-up of a patient

In this study we report the long-term follow-up of EA, a patient originally affected by a disproportionate semantic impairment of biological categories due to herpetic encephalitis. After 10 years, EA still presented a biological categories semantic impairment, but his deficit had become minimal for animals while it remained considerably severe for fruit and vegetables, without any evolution from the original level of impairment. The eventual discrepancy between the two subsets of biological categories was statistically significant at word–picture matching and verbal semantic probes (and could not be explained by nuisance variables), but not significant at picture naming due to an associated lexical impairment that, besides plant life items, also affected animals and artefact stimuli.

Our recovery data corroborate the notion that biological categories should be further fractionated, and we comment on the suitability of different accounts of category specificity to accommodate such findings. We discuss our case against the background of other cases reported in the literature and the current models of organisation of the semantic system, bringing to light some interesting consistencies concerning patients whose semantic impairment disproportionately affects the categories of fruit and vegetables.     

The nonsense mutation stop+4 model correlates with motor changes in Duchenne muscular dystrophy

The aim was to assess 3-year longitudinal data using 6MWT in 26 ambulant boys affected by DMD carrying nonsense mutations and to compare their results to other small mutations. We also wished to establish, within the nonsense mutations group, patterns of change according to several variables. Patients with nonsense mutations were categorized according to the stop codon type newly created by the mutation and also including the adjacent 5′ (upstream) and 3′ (downstream) nucleotides. No significant difference was found between nonsense mutations and other small mutations (p > 0.05) on the 6MWT. Within the nonsense mutations group, there was no difference in 6MWT when the patients were subdivided according to: Type of stop codon, frame status of exons involved, protein domain affected. In contrast, there was a difference when the stop codon together with the 3′ adjacent nucleotide (“stop+4 model”) was considered (p < 0.05) with patients with stop codon TGA and 3′ adjacent nucleotide G (TGAG) having a more rapid decline. Our finding suggest that the stop+4 model may help in predicting functional changes. This data will be useful at the time of interpreting the long term follow up of patients treated with Ataluren that are becoming increasingly available.     

Low levels of frailty in HIV-positive older adults on antiretroviral therapy in northern Tanzania

Journal of NeuroVirology - There are over 3 million people in sub-Saharan Africa (SSA) aged 50 and over living with HIV. HIV and combined antiretroviral therapy (cART) exposure may accelerate the...