Differential 3,5,3'-triiodothyronine-mediated regulation of uncoupling protein 3 transcription: role of Fatty acids

T(3) regulates energy metabolism by stimulating metabolic rate and decreasing metabolic efficiency. The discovery of mitochondrial uncoupling protein 3 (UCP3), its homology to UCP1, and regulation by T(3) rendered it a possible molecular determinant of the action of T(3) on energy metabolism, but data are controversial. This controversy may in part be attributable to discrepancies observed between the regulation by T(3) of UCP3 expression in rats, humans, and mice. To clarify this issue, we studied 1) the induction kinetics of the UCP3 gene by T(3) in rat skeletal muscle, 2) the influence of fatty acids, and 3) the structure and regulation of the various UCP3 promoters by T(3). Within 8 h of single-dose T(3) administration, hypothyroid rats showed a rise in serum fatty acid levels concomitant with a rapid increase in UCP3 expression in gastrocnemius muscle, followed by inductions of peroxisome proliferator activated receptor delta (PPARdelta) (within 24 h) and PPAR target gene expression (after 24 h). This T(3)-induced early UCP3 expression depended on fatty acid-PPAR signaling because depleting serum fatty acid levels abolished its expression, restorable by administration of the PPARdelta agonist L165,041 (4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenoxy]acetic acid). In transfected rat L6 myoblasts, only the rat UCP3 promoter positively responded to T(3) and L165,041 together in the presence of MyoD, thyroid hormone receptor beta1 (TRbeta1), PPARdelta, or PPARdelta plus the TR dimerization partner retinoid X receptor alpha. All promoters share a response element common to TR and PPAR (TRE 1), but the observed species differences may be attributable to different localizations of the MyoD response element, which in the rat maps to exon 1.     

Effect of age and cold exposure on morphofunctional characteristics of skeletal muscle in neonatal pigs

Muscular changes accompanying and/or promoting the rapid postnatal improvement of the thermogenic efficiency of shivering were investigated in piglets. Animals were obtained at birth or killed after 5 days at thermoneutrality (34-30 degrees C) or in the cold (24-15 degrees C), to stimulate intense shivering thermogenesis. Fast-twitch-glycolytic (longissimus lumborum) and slow-twitch-oxidative (rhomboid) muscles were prepared for electron microscopic examination and chemical measurements. Muscle-specific changes in energy stores and metabolism were observed after birth, including the switch from glycogen to lipids and variation of the lactate/pyruvate ratio corresponding to the progressive acquisition of the metabolic type of the mature muscles. There was major age-related and/or cold-induced development of the structures involved in excitation-contraction coupling (triadic profiles, +80% in the cold), oxidative metabolism (number of lipid droplets, +81% with age in the cold; number of mitochondria, +29% with age or cold; surface of mitochondrial inner membranes, +18% with age and +32% in the cold) and contraction potential (myofibril volume, +62% with age). In contrast, neither age nor cold affected capillary volume density and capillary-to-fibre ratio. The observed changes reflect the immaturity and remarkable plasticity of piglet skeletal muscle and are likely to underlie its enhanced capacity for shivering thermogenesis after birth.     

Ultrasound-guided reduction of an incarcerated Spigelian hernia

Spigelian hernia is a rare abdominal hernia. We report a case in which its diagnosis proved ultrasonography to be an effective tool, not only to diagnose an incarcerated Spigelian hernia but, moreover, to reduce it by echo-probe palpation. Ultrasound (US) is an aid for therapy of various diseases. In our experience, US-guidance prevented possible damage related to forced and wrongly applied compression during the hernia reduction, and allowed us to perform surgical repair on an elective basis. In conclusion, if an incarcerated Spigelian hernia is suspected, a US examination should be done on an emergency basis to confirm the diagnosis and to attempt US-guided reduction.     

High levels of circulating N‐terminal pro‐brain natriuretic peptide in patients with hepatitis C

Summary. Many patients chronically infected by hepatitis C virus (HCV) experience symptoms like fatigue, dyspnea and reduced physical activity. However, in many patients, these symptoms are not proportional to the liver involvement and could resemble symptoms of chronic heart failure. To our knowledge, no study evaluated serum levels of N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) in a large series of patients with HCV chronic infection (HCV+). Serum NT‐proBNP was assayed in 50 patients HCV+ and in 50 sex‐ and age‐matched controls. HCV+ patients showed significantly higher mean NT‐proBNP level than controls (P = 0.001). By defining high NT‐proBNP level as a value higher than 125 pg/mL (the single cut‐off point for patient under 75 years of age), 34% HCV+ and 6% controls had high NT‐proBNP (Fisher exact test; P < 0.001). With a cut‐off point of 300 pg/mL (used to rule out chronic heart failure in patients under 75 years of age) 10% HCV+ and 0 controls had high NT‐proBNP (Fisher exact test; P = 0.056). With a cut‐off point of 900 pg/mL (used for ruling in chronic heart failure in patients with age 50–75) 8% HCV+ patients and 0 controls had high NT‐proBNP (Fisher exact test; P = 0.12). The study demonstrates high levels of circulating NT‐proBNP in HCV+ patients compared to healthy controls. The increase of NT‐proBNP may indicate the presence of a sub‐clinical cardiac dysfunction. Further prospective studies quantifying these symptoms in correlation with echocardiography are needed to confirm this association.     

Selected treatments for duodenal perforation after ERCP. A report of three cases

Perforation is one of the most serious complications of endoscopic sphincterotomy. In the last decade, the management has shifted towards a more selective approach. Three cases are reported here involving three different treatments. In one case, the patient was submitted to a surgical procedure, while a conservative strategy was preferred in the other two, consisting in a naso-biliary drain and endoscopic clip placement, respectively. In this way, the safety of surgical and nonsurgical management of ERCP-related duodenal perforations was tested.     

Treatment of a pituitary metastasis from a neuroendocrine tumour: case report and literature review

Herein we report a rare case of a pituitary metastasis from a neuroendocrine tumour mimicking an adenoma. Moreover, starting from this unusual case, the relevant literature concerning the diagnosis and management of patients with metastasis at pituitary level is reviewed. A 69-year-old woman was admitted to our Unit for severe headache, diplopia, and critical visual field impairment. MRI showed a large pituitary mass compressing the optic chiasm and infiltrating the cavernous sinus. Trans-sphenoidal biopsy revealed a pituitary metastasis from a neuroendocrine tumour, in line with the multiple liver lesions that were already considered metastases from an ileal primary neuroendocrine tumour. In vitro receptor characterisation of both pituitary and liver tissues by immunohistochemistry showed a heterogeneous somatostatin receptor subtype pattern, with a predominant expression of sst₂ within the pituitary lesion. However, the liver metastasis receptor profile was completely different from the pituitary. Octreotide LAR was administered first, followed by receptor radiometabolic therapy with radiolabelled somatostatin analogues (⁹⁰Y-DOTATOC and ¹⁷⁷Lu-DOTATATE). After 16 months, MRI showed a significant shrinkage of the sellar mass. Moreover, disappearance of diplopia and visual defects, together with a considerable improvement in quality of life were gradually recorded. To our knowledge, this is the first case of combined treatment using “cold” and radiolabelled octreotide in a pituitary metastasis from a neuroendocrine tumour. Umberto Goglia and Diego Ferone contributed equally.