Pharmacological modulation of adaptive thermogenesis: new clues for obesity management?

BACKGROUND: Adaptive thermogenesis represents the main mechanism through which the body generates heat in response to external stimuli, a phenomenon that includes shivering and non-shivering thermogenesis. The non-shivering thermogenesis is mainly exploited by adipose tissue characterized by a brown aspect, which specializes in energy dissipation. A decreased amount of brown adipose tissue has been observed in ageing and chronic illnesses such as obesity, a worldwide health problem characterized by dysfunctional adipose tissue expansion and associated cardiometabolic complications. In the last decades, the discovery of a trans-differentiation mechanism ("browning") within white adipose tissue depots, leading to the generation of brown-like cells, allowed to explore new natural and synthetic compounds able to favour this process and thus enhance thermogenesis with the aim of counteracting obesity. Based on recent findings, brown adipose tissue-activating agents could represent another option in addition to appetite inhibitors and inhibitors of nutrient absorption for obesity treatment. PURPOSE: This review investigates the main molecules involved in the physiological (e.g. incretin hormones) and pharmacological (e.g. ß3-adrenergic receptors agonists, thyroid receptor agonists, farnesoid X receptor agonists, glucagon-like peptide-1, and glucagon receptor agonists) modulation of adaptive thermogenesis and the signalling mechanisms involved.

Neuroergonomic and psychometric evaluation of full-face crew oxygen masks respiratory tolerance: a proof-of-concept study.

INTRODUCTION: Preventing in-flight hypoxia in pilots is typically achieved by wearing oxygen masks. These masks must be as comfortable as possible to allow prolonged and repeated use. The consequences of mask-induced facial contact pressure have been extensively studied, but little is known about mask-induced breathing discomfort. Because breathlessness is a strong distractor and engages cerebral resources, it could negatively impact flying performances. METHODS: Seventeen volunteers (age 20-32) rated respiratory discomfort while breathing with no mask and with two models of quick-donning full-face crew oxygen masks with regulators (mask A, mask B). Electroencephalographic recordings were performed to detect a putative respiratory-related cortical activation in response to inspiratory constraint (experiment 1, n=10). Oxygen consumption was measured using indirect calorimetry (experiment 2, n=10). RESULTS: With mask B, mild respiratory discomfort was reported significantly more frequently than with no mask or mask A (experiment 1: median respiratory discomfort on visual analogue scale 0.9 cm (0.5-1.4), experiment 1; experiment 2: 2 cm (1.7-2.9)). Respiratory-related cortical activation was present in 1/10 subjects with no mask, 1/10 with mask A and 6/10 with mask B (significantly more frequently with mask B). Breathing pattern, sigh frequency and oxygen consumption were not different. CONCLUSIONS: In a laboratory setting, breathing through high-end aeronautical full-face crew oxygen masks can induce mild breathing discomfort and activate respiratory-related cortical networks. Whether or not this can occur in real-life conditions and have operational consequences remains to be investigated. Meanwhile, respiratory psychometric and neuroergonomic approaches could be worth integrating to masks development and evaluation processes.

Ultrasound Guided Transversus Thoracic Plane block, Parasternal block and fascial planes hydrodissection for internal mammary post thoracotomy pain syndrome.

INTRODUCTION: Pectoral Nerves Block (PECS) and Serratus Plane Block (SPB) have been used to treat persistent post-surgical pain after breast and thoracic surgery; however, they cannot block the internal mammary region, so a residual pain may occur in that region. Parasternal block (PSB) and Thoracic Transversus Plane Block (TTP) anaesthetize the anterior branches of T2-6 intercostal nerves thus they can provide analgesia to the internal mammary region. METHODS: We describe a 60-year-old man suffering from right post-thoracotomy pain syndrome with residual pain located in the internal mammary region after a successful treatment with PECS and SPB. We performed a PSB and TTP and hydrodissection of fascial planes with triamcinolone and Ropivacaine. RESULTS: Pain disappeared and the result was maintained 3 months later. DISCUSSION: This report suggests that PSB and TTP with local anaesthetic and corticosteroid with hydrodissection of fascial planes might be useful to treat a post thoracotomy pain syndrome located in the internal mammary region. SIGNIFICANCE: The use of Transversus Thoracic Plane and Parasternal Blocks and fascial planes hydrodissection as a novel therapeutic approach to treat a residual post thoracotomy pain syndrome even when already treated with Pectoral Nerves Block and Serratus Plane Block.

Peripheral blood CD8+ T-cell profiles in patients with psoriatic arthritis: a cross-sectional case-control study.

OBJECTIVE: While CD4+ T-cells are traditionally regarded as the main pathogenic T-cell subpopulation in psoriatic arthritis (PsA), the role of circulating CD8+ T-cells remains poorly characterized. We evaluated the differential representation of CD8+ T-cell subpopulations in peripheral blood (PB) of PsA patients. PATIENTS AND METHODS: CD8+IL-17+, CD8+IFNγ+ and CD8+IL-17-IL-22+ T-cells were evaluated by flow-cytometry in 25 consecutive PsA patients, 7 rheumatoid arthritis (RA) patients, 16 patients with psoriasis, and 26 healthy controls (HC). RESULTS: We observed a significant expansion of circulating IFN-γ producing CD8+ T-cells in PsA when compared to psoriasis [21.2 (6.9-55.8)% vs. 3.8 (0.7-11.8)%, p < 0.0001] and HC samples [21.2 (6.9-55.8)% vs. 4.05 (0.44-19.8)%, p < 0.0001]. A frequency of circulating IFN-γ producing CD8+T-cells ≥ 9% distinguished PsA from psoriasis patients with a specificity of 84% and a sensitivity of 87.5% [AUC = 0.9 (0.80-0.99), p < 0.0001]. In addition, we found a significant expansion of circulating IL-17 producing CD8+ T cells in RA patients when compared to PsA, psoriasis and HC samples. By contrast, there were no significant between-group differences in the prevalence of circulating IL-22 producing CD8+ T-cells. In PsA patients there was a significant correlation between number of swollen joints and frequency of circulating IFN-γ producing CD8+ T-cells, and between extent and severity of psoriasis and frequency of circulating IL-17 producing CD8+ T-cells. CONCLUSIONS: Circulating IFNγ-producing CD8+ T-cells are raised in PsA when compared to psoriasis, suggesting a potential pathogenetic involvement of CD8+ T-cells and IFNγ production in chronic joint inflammation and damage. The significant enrichment of circulating IL-17 producing CD8+ T-cells in RA when compared to PsA warrants functional characterization and confirmation in larger studies. We found no significant enrichment of circulating IL-22 producing CD8+ T-cells in PsA, RA and psoriasis.

Vasculitis and infectious diseases.

Vasculitis usually presents without a well-known underline cause (idiopathic vasculitis), nevertheless, it is sometimes possible to find out one or more causative agents (secondary vasculitis). Nowadays, thanks to the increasing amount of precise diagnostic tools, a piece of idiopathic vasculitis is reclassified as associated with probable etiology, which can be set off by several factors, such as infections. Infections are considered to be the most common cause of secondary vasculitis. Virtually, every infectious agent can trigger a vasculitis by different mechanisms which can be divided in two main categories: direct and indirect. In the former, infectious agents destroy directly the vascular wall leading, eventually, to a subsequent inflammatory response. In the latter, indirect form, they stimulate an immune response against blood vessels. Different infectious agents are able to directly damage the vascular wall. Among these, it is possible to recognize Staphylococcus spp, Streptococcus spp, Salmonella spp, Treponema spp, Rickettsia spp, Cytomegalovirus, Herpes Simplex Virus 1 and 2, and many others which have a peculiar tropism for endothelial cells. Conversely, another group of microbial agents, such as Mycobacterium tuberculosis, Mycobacterium leprae, Hepatits B Virus, Human Immunodeficiency Virus and others, trigger vasculitis in the indirect way. This is due to the fact that they can share epitopes with the host or modify self-antigens, thus leading to a cross-self reaction of the immune system. These mechanism, in turn, leads to immunological responses classified as type I-IV by Gell-Coombs. Nevertheless, it is difficult to strictly separate the direct and indirect forms, because most infectious agents can cause vasculitis in both ways (mixed forms). This paper will analyze the link between infectious agents and vasculitis, focusing on direct and indirect secondary vasculitis, and on a group of probable infection-related idiopathic vasculitis, and finally on a group of idiopathic vasculitis with microbiological triggers. Furthermore, a diagnostic and therapeutic approach to vasculitis when an underline infection has been suspected is suggested.

Rapamycin-induced hypophosphatemia and insulin resistance are associated with mTORC2 activation and Klotho expression.

Rapamycin, an immunosuppressive drug used to prevent rejection after kidney transplantation, influences phosphate homeostasis, induces insulin resistance and has been shown to prolong lifespan in animal models. Because Klotho is an aging-suppressor gene controlling phosphate metabolism and insulin sensitivity, we investigated the influence of rapamycin on Klotho expression. A total of 100 kidney transplant recipients, 50 chronically treated with rapamycin and 50 with calcineurin inhibitors, were enrolled; 20 healthy subjects were employed as control. In the rapamycin group, serum phosphate was lower than in the CNI group with an increase in phosphate excretion and a reduction in its reabsorption. In addition, rapamycin increased insulin resistance as shown by HOMA index. Rapamycin treatment of an immortalized proximal tubular cell line induced the expression of Klotho, the phosphorylation of AKT in Ser473, downstream target of mTORC2 and the expression of RICTOR, mTORC2 main component. AKT inhibition reduced the rapamycin-induced expression of Klotho. In vivo rapamycin treatment induced higher degree of RICTOR and AKT Ser(473) expression directly correlating with long-term rapamycin exposure, FE(PO4) and HOMA index. In conclusion, our data would suggest that rapamycin may influence phosphate homeostasis and insulin resistance modulating Klotho expression through mTORC2 activation.

The department of psychology within a pediatric cardiac transplant unit.

In 1979, the department of Psychology started its activity to provide psychological support to patients and their families during the course of treatment and during the follow-up period. Since 1986, a transplantation program was initiated in the cardiology and pediatric cardiac surgery departments, performing 179 cardiac, 3 heart-kidney, 18 heart-lung 14 both lung, 1 heart-lung-liver, and 1 single lung transplantation. From 1993, to September 2010 the kidney transplant program has performed. 218 cases. Since 2008, we performed (32 liver and 1 intestinal transplantations). We examined the quality of life and coping with transplantation attitudes because there is recent evidence of high levels of family anxiety and depression related to a child's poor response to the disease and compliance. Our work associated post-traumatic stress disorder (PTSD) with anxiety and with these clinical variables: gender pathology, rejection, number of drugs frequency of hospital visits, number of hospitalizations, as well as age at and time from transplantation. We examined 56 parents (25 fathers and 31 mothers) of cardiac transplant recipients. Our most relevant data demonstrated the presence of PTSD among 52% of mothers and 40% of fathers. Significant correlations were observed within the trait of anxiety. No correlations were noted between PTSD and other variables. Testing anxiety levels of parents is considered to be basic to provide psychological support to parents, encourage personal skills, and avoid PTSD symptoms.

Correlation between abnormal brain excitability and emotional symptomatology in paediatric migraine.

We investigated a possible correlation between brain excitability in children with migraine and tension-type headache (TTH) and their behavioural symptomatology, assessed by using the Child Behaviour Checklist (CBCL). The mismatch negativity (MMN) and P300 response were recorded in three successive blocks to test the amplitude reduction of each response from the first to the third block (habituation). MMN and P300 habituation was significantly lower in migraineurs and TTH children than in control subjects (two-way ANOVA: P < 0.05). In migraineurs, but not in TTH patients, significant positive correlations between the P300 habituation deficit and the CBCL scores were found (P < 0.05), meaning that the migraineurs with the most reduced habituation showed also the worst behavioural symptomatology. To the best of our knowledge, this is the first study showing a correlation between neurophysiological abnormality and emotional symptomatology in migraine, suggesting a role of the latter in producing the migrainous phenotype.

Veno-occlusive disease of the liver after lung transplantation.

Veno-occlusive disease (VOD) of the liver is mainly described after chemo-irradiation conditioning regimens during haematopoietic stem cell transplantation (SCT) and has been sporadically reported after kidney and liver transplantation. In the latter cases, it is commonly attributed to azathioprine and/or tacrolimus. One case of tacrolimus-induced hepatic VOD developing after lung transplantation (LT) has been recently reported. Here we describe another case of VOD occurring after LT, but in which the causative role was played by azathioprine.

Immunoglobulin enhancer HS1,2 polymorphism: a new powerful anthropogenetic marker.

The human HS1,2 enhancer of the immunoglobulin (Ig) heavy chain 3' enhancer complex plays a central role in the regulation of Ig maturation and production. Four common alleles HS1,2-A*1, *2, *3, *4 are directly implicated with the transcription level and at least one of them, HS1, 2-A*2, seems to be related to immune disorders, such as coeliac disease, herpetiform dermatitis and Berger syndrome. Given their clinical significance it is of interest to know the distribution of HS1,2-A variants in populations from different continents, as well as to determine whether the polymorphism is associated to specific evolutionary factors. In this paper we report the distribution of the HS1,2-A polymorphism in 1098 individuals from various African, Asian and European populations. HS1,2-A*3 and HS1,2-A*4 alleles are at their highest frequencies among Africans, and HS1,2-A*2 is significantly lower in Africans in comparison with both Europeans and, to a lesser extent, Asians. Analysis of molecular variance of the allele frequencies indicates that the HS1,2-A polymorphism can be considered as a reliable anthropogenetic marker.

Gallstone ileus in patient with Crohn's disease: report of a clinical observation.

Gallstone ileus is an uncommon form of bowel obstruction, related in the majority of cases to a cholecystoenteric fistula. In patients with Crohn's disease the stone can obstruct the diseased bowel. We report a case of gallstone ileus in a patient with Crohn's disease. An explorative laparoscopy and a minimally-invasive laparotomy were achieved to resolve the obstruction. Cholecystectomy and closure of the cholecystoduodenal fistula were not performed. The association of gallstone ileus and Crohn's disease is very rare; only few cases are reported in the literature. Laparoscopic approach could identify the extension of the disease and the site of impaction, allowing the differential diagnosis in particular in patients with Crohn's disease. In the cases described, cholecystectomy and the closure of the fistula were not performed considering the absence of any residual stone in the gallbladder and the associated risk of treating the cholecysto-duodenal fistula in an emergency settings.

Intranasal steroid reduces exhaled bronchial cysteinyl leukotrienes in allergic patients.

BACKGROUND: Allergic rhinitis (AR) precedes and is often associated with bronchial asthma. Indeed, local and systemic inflammations in both conditions are very similar. Cysteinyl-leukotrienes (cys-LTs) are generated during early- and late-phase allergic reactions and induce smooth-muscle contraction, microvascular leakage, and mucous hypersecretion. Cys-LTs are detected in exhaled breath condensate (EBC) of asthmatics and regardless of bronchial symptoms, they are also found in EBC of rhinitic patients. OBJECTIVE: To evaluate cys-LTs in EBC of allergic patients and to assess the activity of nasal fluticasone propionate (FP) on EBC cys-LTs levels. METHODS: Cys-LTs coefficient of variation (CV) was evaluated from different EBC in 5 healthy volunteers. Cys-LTs levels from EBCs in 13 healthy controls and 56 allergic rhinitic (n=31) and rhinitic/asthmatic (n=25) patients were also evaluated at baseline. Subsequently patients were randomized to receive either FP 100 microg/day per nostril or placebo for 2 weeks and then re-evaluated for EBC cys-LTs. RESULTS: The CV was 14.12%. EBC cys-LTs in allergic patients were significantly higher than in healthy subjects (70.9 vs. 20.6 pg/mL (median), P<0.05), while it did not differ between asthmatic/rhinitic and purely rhinitic patients. Treatment significantly reduced cys-LTs (from 93.6 to 19.9 pg/mL, P<0.001). This effect was evident both in asthmatic/rhinitic and in rhinitic patients. CONCLUSION: Treatment of AR with FP significantly reduces the levels of cys-LTs, major noninvasive markers of lower airway inflammation, suggesting that upper and lower airway inflammation is present and should be thus treated as a whole in subjects with AR with and without asthma.

Isonymy and the structure of the Provençal-Italian ethnic minority.

Surnames were obtained for the second half of the 20th century from civil and religious marriage registers on fifteen Provençal-Italian and five Italian villages of Cuneo Province, Italy. To insert in the analysis an outward comparison, surnames from two Italian villages of Turin Province, one parish of Turin, one village of Alessandria Province and one village of Asti Province were also collected. Ethnicity does not seem to be the main factor affecting the present genetic structure of the Provençal-Italians. They are an open community, and evidence the end of the genetic isolation of the alpine populations.

Serum levels of interleukin-18 in patients with uncomplicated Plasmodium falciparum malaria.

Interleukin (IL)-18, a newly discovered cytokine produced primarily by macrophages, has been shown to induce gamma interferon (IFN-gamma) production by natural killer cells, to induce the T helper type 1 response. To further elucidate the role of this cytokine in uncomplicated malaria caused by Plasmodium falciparum, serum levels of IL-18, and gamma interferon (IFN-gamma), determined by an immunoenzymatic assay, were analyzed in 40 adult patients, and in 15 healthy control subjects. A significant increase in serum levels of IL-18 was observed in patients with uncomplicated P. falciparum malaria on admission, whereas serum levels of IFN-gamma tended to increase although not significantly. Serum levels of IL-18 decreased three days later, but still remained significantly high, whereas IFN-gamma levels returned to normal levels compared to the controls. No significant correlation was found between parasitemia and serum levels of IL-18 and IFN-gamma. The increase of IL-18 levels during acute and recovery phases of uncomplicated P. falciparum malaria may reflect a proinflammatory role of IL-18 in these patients. An early and effective immune response regulated by proinflammatory Th1 cytokines, including tumor necrosis factor (TNF), interleukin (IL)-12, and possibly IFN-gamma may limit the progression from uncomplicated malaria to severe and life-threatening complications.

The ethnic minorities of southern Italy and Sicily: relationships through surnames.

Surnames of grandparents were collected from children in the primary schools of the Albanian-Italian, Croat-Italian and Greek-Italian villages of southern Italy and Sicily. The coefficients of relationships by isonymy show almost no relationship with ethnicity. Ethnolinguistic minorities of southern Italy and Sicily are geographically subdivided into two main clusters: the first cluster comprises the Albanian, Croat and Greek communities of the Adriatic area; and the second cluster comprises the Albanian and Greek communities of the Ionian, Thirrenian and Sicilian areas.

Migration through surnames in Campobasso Province, Italy.

Data on grandparental surnames were obtained from school-children in 22 communes from Campobasso Province, Italy (Molise Region). The distribution of surnames was shown to be almost exactly linear by a log2-log2 transformation, which justified the fitting of the data to Fisher's logarithmic distribution. The values for v were higher among women. When v was standardized to minimize bias due to sample size, the value was one-third the estimate of migration from exogamy data. The higher values of v for females indicate that there is greater mobility of female marriage partners than males.

Detection of IgG in cerebrospinal fluid for diagnosis of neurocysticercosis: evaluation of saline and SDS extracts from Taenia solium and Taenia crassiceps metacestodes by ELISA and immunoblot assay.

We compared saline (S) and sodium dodecyl sulphate (SDS) extracts from Taenia solium (homologous species - HO) and Taenia crassiceps (heterologous species - HE) metacestodes in order to detect IgG by ELISA and immunoblot assay (IBA) in cerebrospinal fluid (CSF) for the diagnosis of human neurocysticercosis (NC). CSF samples were obtained from 93 patients. Of these, 40 had NC, five had a diagnosis of probable NC, nine had central nervous system schistosomiasis or strongyloidiasis and 39 had other neurological alterations. Samples were analysed by ELISA and the results were compared with IBA in all samples with confirmed and probable NC diagnosis, in all samples with other central nervous system parasitic infection, and in 10 of those with another neurological alterations. ELISA sensitivity was 100%, 85%, 95% and 87.5% for the S-HO, S-HE, SDS-HO and SDS-HE extracts, respectively, and ELISA specificity was 100% for S-HO, S-HE, SDS-HO extracts and 97.9% for SDS-HE antigen. Immunodominant peptides detected by IBA were, by decreasing percentage of recognition: 64-68 and 45 kDa for S-HO; 108-114, 92-95, 64-68, 83 and 88 kDa for S-HE; 64-68, 108-114, 77 and 86 kDa for SDS-HO; and 108-114, 88 and 92-95 kDa for SDS-HE. Overall the homologous antigenic extracts showed higher sensitivity than the heterologous extracts in the diagnosis of NC in CSF samples. The heterologous extracts contained most of the immunodominant peptides presented in the homologous extracts, which are recognized by IgG antibodies in CSF samples.

Culture and biology: surnames in evaluating genetic relationships among the ethnic minorities of Southern Italy and Sicily.

Surnames of grandparents were collected from children in the primary schools of the Albanian-Italian, Croat-Italian, and Greek-Italian villages. The coefficients of relationships by isonymy show almost no relationship with ethnicity. Ethnolinguistic minorities of Southern Italy and Sicily are geographically subdivided in two main clusters: the first cluster comprises the Albanian, Croat, and Greek communities of the Adriatic area; and the second cluster comprises the Albanian communities of the Ionian, Thirrenian and Sicilian area. The Greeks of Reggio Calabria Province are completely separated from the other communities.

Genetic structure through surnames in Campobasso Province, Italy.

The population of Campobasso Province shows a level of inbreeding that is distinct from most Italian rural populations, regardless of their geographic location (Fr=0.0040; Fn=0.0102; Ft=0.0142). The genetic structure of the Italian-Greek communities of Lecce and Reggio Calabria Provinces does not appear to be affected by ethnicity. The level of inbreeding in Italian-Greeks of Reggio Calabria Province is similar to other Italians of Campobasso Province (Fr=0.0041; Fn=0.0127; Ft=0.0168). The Italian-Greeks of Lecce Province show random mating, and their inbreeding is in fact very low (Fr=0.0038; Fn=0.0024; Ft=0.0062).