The shell effect on the room temperature photoluminescence from ZnO/MgO core/shell nanowires: exciton-phonon coupling and strain.

The room temperature photoluminescence from ZnO/MgO core/shell nanowires (NWs) grown by a simple two-step vapor transport method was studied for various MgO shell widths (w). Two distinct effects induced by the MgO shell were clearly identified. The first one, related to the ZnO/MgO interface formation, is evidenced by strong enhancements of the zero-phonon and first phonon replica of the excitonic emission, which are accompanied by a total suppression of its second phonon replica. This effect can be explained by the reduction of the band bending within the ZnO NW core that follows the removal of atmospheric adsorbates and associated surface traps during the MgO growth process on one hand, and a reduced exciton-phonon coupling as a result of the mechanical stabilization of the outermost ZnO NW monolayers by the MgO shell on the other hand. The second effect is the gradual increase of the excitonic emission and decrease in the defect related emission by up to two and one orders of magnitude, respectively, when w is increased in the ∼3-17 nm range. Uniaxial strain build-up within the ZnO NW core with increasing w, as detected by x-ray diffraction measurements, and photocarrier tunneling escape from the ZnO core through the MgO shell enabled by defect-states are proposed as possible mechanisms involved in this effect. These findings are expected to be of key significance for the efficient design and fabrication of ZnO/MgO NW heterostructures and devices.

Clinical and color Doppler ultrasound evaluation of polyacrylamide injection in HIV patients with severe facial lipoatrophy secondary to antiretroviral therapy.

BACKGROUND/PURPOSE: Facial lipoatrophy in HIV patients, secondary to antiretroviral therapy (ART) with thymidine analogs, has been related to important psychosocial alterations and poor adherence to treatment. Polyacrylamide gel (PAAG) is a filler that has been used for treating facial lipoatrophy in HIV patients. The aim was to assess the clinical and sonographic anatomical changes after injection of PAAG in HIV patients with facial lipoatrophy secondary to ART. METHODS: HIV patients receiving ART and suffering from severe facial lipoatrophy were recruited and underwent clinical and color Doppler ultrasound evaluation prior to PAAG application (AQUAMID® ) and sonographically monitored at 18 months and clinically followed up for 36 months after the procedure. Adverse effects were recorded based on occurrence and complexity. RESULTS: A total of 33 patients were evaluated, 30 men (91%) and 3 women (9%) with an average age of 49.6 years (±8.4). Clinical improvement assessed by a dermatologist had an average score of 5.9 (±0.7) on a scale of 1-7. On color Doppler ultrasound there was a significant increase of the thickness of the subcutaneous tissue (SCT) in both nasofold lines when comparing before and after PAAG injection (P < 0.01) and no signs of inflammation (hypervascularity). User satisfaction was qualified as excellent or good in all cases. Only two patients experienced adverse effects (hematoma and puncture site infection), which was successfully managed without consequences. CONCLUSION: Treatment of facial lipoatrophy with PAAG seems to be effective in HIV patients and no signs of complications were observed in the monitoring at 36 months after injection. Color Doppler ultrasound can identify the filler deposits and the anatomical changes of the SCT non-invasively.

Proportions of several types of plasma and urine microparticles are increased in patients with rheumatoid arthritis with active disease.

We analysed the proportions of different microparticles (MPs) in plasma from patients with rheumatoid arthritis (RA), and assessed their relationship with disease activity/therapy and their in-vitro effect on proinflammatory cytokine release. Blood and urine samples were obtained from 55 patients with RA (24 untreated and 31 under conventional therapy) and 20 healthy subjects. Fourteen patients with systemic lupus erythematosus (SLE) were also studied. The proportions of CD3(+) , CD14(+) , CD19(+) , CD41(+) and CD62E(+) MPs were determined by flow cytometry analysis. The in-vitro effect of plasma MPs on the release of interleukin (IL)-1, IL-6, IL-17 and tumour necrosis factor (TNF)-α was also analysed. We detected that the proportions of different types of annexin-V(+) MPs were enhanced in plasma (CD3(+) , CD14(+) , CD19(+) , CD41(+) and CD62E(+) MPs) and urine (CD14(+) , CD3(+) and CD19(+) MPs) from RA patients with high disease activity (DAS28 index > 5·1). Accordingly, a significant positive correlation was observed between the levels of MPs and DAS28 score, and these levels diminished significantly at week 4 of immunosuppressive therapy. Finally, MPs isolated from patients with high disease activity induced, in vitro, an enhanced release of IL-1, IL-17 and TNF-α. In SLE, enhanced levels of different types of plasma MPs were also detected, with a tight correlation with disease activity. Our data further support that MPs have a relevant role in the pathogenesis of RA and suggest that the analysis of the proportions of these microvesicles in plasma could be useful to monitor disease activity and therapy response in patients with RA.

ZnO nanowire co-growth on SiO2 and C by carbothermal reduction and vapour advection.

Vertically aligned ZnO nanowires (NWs) were grown on Au-nanocluster-seeded amorphous SiO(2) films by the advective transport and deposition of Zn vapours obtained from the carbothermal reaction of graphite and ZnO powders. Both the NW volume and visible-to-UV photoluminescence ratio were found to be strong functions of, and hence could be tailored by, the (ZnO+C) source-SiO(2) substrate distance. We observe C flakes on the ZnO NWs/SiO(2) substrates which exhibit short NWs that developed on both sides. The SiO(2) and C substrates/NW interfaces were studied in detail to determine growth mechanisms. NWs on Au-seeded SiO(2) were promoted by a rough ZnO seed layer whose formation was catalysed by the Au clusters. In contrast, NWs grew without any seed on C. A correlation comprising three orders of magnitude between the visible-to-UV photoluminescence intensity ratio and the NW volume is found, which results from a characteristic Zn partial pressure profile that fixes both O deficiency defect concentration and growth rate.

EXPRESSION OF CHEMOKINE (C-C MOTIF) RECEPTOR 7 IN PROSTATE CANCER TISSUE OF YOUNG PATIENTS AND IN METASTATIC CANCER CELLS.

BACKGROUND: Chemokine (C-C motif) receptor 7 (CCR7) is a chemokine receptor involved in the carcinogenesis of several types of tumors due to its promoting action in epithelial-mesenchymal transition events, invasion, angiogenesis and metastasis. However, its role in prostate cancer (PCa) remains unclear. AIM: To evaluate CCR7 expression by immunohistochemistry in prostate tumors from young patients and to determine the possible relationship with the clinicopathological characteristics. MATERIALS AND METHODS: We analyzed retrospectively paraffin-embedded tissue sections from 23 young PCa (≤ 55 years old) patients and evaluated the transcriptomic expression in the TCGA database. RESULTS: Expression of CCR7 was observed in 15 cases (65%). The tissue samples from younger patients (≤ 50 years) were mostly positive in 72.7% (8/11) of cases. High grade GS (≥ 3) tumors were CCR7-positive in 71% cases. The malignant cells present in lymph nodes were CCR7 positive in 100% cases. The bioinformatic analysis showed a high CCR7 expression associated with the presence of metastasis (FC = 2.6, p = 0.03) in the Cancer Genome Atlas (TCGA) PCa cohort (PRAD). CONCLUSION: We showed that CCR7 expression in tumors from young patients is associated with the early onset of the disease and could also be related to lymph node metastasis.

Host Immunity Alters Community Ecology and Stability of the Microbiome in a Caenorhabditis elegans Model.

A growing body of data suggests that the microbiome of a species can vary considerably from individual to individual, but the reasons for this variation-and the consequences for the ecology of these communities-remain only partially explained. In mammals, the emerging picture is that the metabolic state and immune system status of the host affect the composition of the microbiome, but quantitative ecological microbiome studies are challenging to perform in higher organisms. Here, we show that these phenomena can be quantitatively analyzed in the tractable nematode host Caenorhabditis elegans Mutants in innate immunity, in particular the DAF-2/insulin growth factor (IGF) pathway, are shown to contain a microbiome that differs from that of wild-type nematodes. We analyzed the underlying basis of these differences from the perspective of community ecology by comparing experimental observations to the predictions of a neutral sampling model and concluded that fundamental differences in microbiome ecology underlie the observed differences in microbiome composition. We tested this hypothesis by introducing a minor perturbation into the colonization conditions, allowing us to assess stability of communities in different host strains. Our results show that altering host immunity changes the importance of interspecies interactions within the microbiome, resulting in differences in community composition and stability that emerge from these differences in host-microbe ecology.IMPORTANCE Here, we used a Caenorhabditis elegans microbiome model to demonstrate how genetic differences in innate immunity alter microbiome composition, diversity, and stability by changing the ecological processes that shape these communities. These results provide insight into the role of host genetics in controlling the ecology of the host-associated microbiota, resulting in differences in community composition, successional trajectories, and response to perturbation.

Anti-CD43 and anti-galectin-1 autoantibodies in patients with systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) is characterized by the production of multiple autoantibodies and also by T-cell dysfunction. CD43 is expressed by most immune cells, is involved in lymphocyte adhesion and activation, and interacts with galectin-1 (Gal-1). The aim of this work was to evaluate the plasma levels of autoantibodies against CD43 and Gal-1 as well as the levels of soluble Gal-1 in SLE Mexican mestizo patients, with the aim of establishing a correlation between these parameters and the clinical profile. METHODS: Serum levels of immunoglobulin (Ig)G autoantibodies against CD43 and Gal-1 and levels of soluble Gal-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 55 patients with SLE and 71 healthy controls. RESULTS: We found significantly enhanced titres of anti-CD43 and anti-Gal-1 antibodies in sera from SLE patients compared to controls. In addition, the serum levels of Gal-1 were significantly higher in SLE patients than in healthy individuals. However, we could detect no correlation of these parameters with disease activity [using the Mexican Systemic Lupus Erythematosus Disease Activity Index (MEX-SLEDAI)], age, or a variety of different clinical or laboratory features. Similarly, no significant correlation with immunosuppressive or glucocorticoid therapy was observed. By contrast, a significant association was found between anti-CD43 titres and time of disease evolution, complement levels, and the presence of anti-Gal-1 antibodies. CONCLUSIONS: As CD43 and Gal-1 participate in modulating the immune system, we suggest that the presence of autoantibodies against these molecules may contribute to the immune deregulation observed in SLE.

Male urethritis. A review of the ideal diagnostic method. / Uretritis masculina. Una revisión del método ideal de diagnóstico.

Male urethritis is an inflammation of the urethra and the periurethral glands; it is widely classified as gonococcal or non-gonococcal. The most frequent microorganisms responsible are Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum. In the last three decades, the diagnosis of sexually transmitted diseases depended almost exclusively on traditional methods, such as culture, enzyme immunoassay, fluorescent antibody staining, and hybridization, until the appearance of molecular techniques. Clinical syndromes such as urethritis are rarely specific for a single microorganism, so screening strategies should allow multiple agents to be considered. Multiplex PCR is the fastest and most sensitive technique for the diagnosis of gonococcal and non-gonococcal urethritis. Male urethritis without treatment is one of the main health problems related to reproductive and sexual function, constituting one of the main causes of infertility. The objective of this mini-review was to analyze the epidemiology, causes, diagnosis, and complications of male urethritis.

Transcription factor TAFII250 promotes Mdm2-dependent turnover of p53.

The p53 tumour suppressor is regulated mainly by Mdm2, an E3 ubiquitin ligase that promotes the ubiquitylation and proteasome-mediated degradation of p53. Many agents that induce p53 are inhibitors of transcription, suggesting that the p53 pathway can detect a signal(s) arising from transcriptional malfunction. Mdm2 associates with TAFII250, a component of the general transcription factor TFIID. Inactivation of TAFII250 in ts13 cells, which express a temperature-sensitive mutant of TAFII250, leads to the induction of p53 and cell cycle arrest. In the present study, we show that TAFII250 stimulates the ubiquitylation and degradation of p53 in a manner that is dependent upon Mdm2 and requires its acidic domain. Mechanistically, TAFII250 downregulates Mdm2 auto-ubiquitylation, leading to Mdm2 stabilization, and promotes p53-Mdm2 association through a recently defined second binding site in the acidic domain of Mdm2. These data provide a novel route through which TAFII250 can directly influence p53 levels and are consistent with the idea that the maintenance of p53 turnover is coupled to the integrity of RNA polymerase II transcription.

Nocturnal ultrafiltration profiles in patients on APD: impact on fluid and solute transport.

In order to prevent morbidity and mortality in peritoneal dialysis (PD), sodium and water balance as well as a minimal level of small-solute clearances are needed. The impact of three nocturnal peritoneal ultrafiltration (UF) profiles on UF and small solute clearance in patients on automated PD (APD) was studied: constant glucose concentration of 1.36% (flat) or modifying the glucose concentration of the heater bag (descendant: 3.86-1.36%; ascendant: 1.36-3.86%). Sixty-two patients were enrolled in the study and received each profile within a four-month period, thus serving as their own controls. UF was lower with the flat profile (367+/-420ml; P<0.01), but no difference was seen between the two higher glucose concentration profiles. Peritoneal Kt/V (pKt/V) and peritoneal creatinine clearance (CrpC) showed statistically higher values from the descendant vs ascendant vs flat profiles (pKt/V: 1.54+/-0.30 vs 1.45+/-0.30 vs 1.38+/-0.27, and CrpC: 36.9+/-7.9 vs 33.5+/-7.48 vs 29.92+/-7.5 mlmin(-1)). Multivariate analysis showed statistical significance for the following: in the intrasubject comparisons, the profile for pKt/V (F=9.109, P<0.001) and CrpC (F=11.697, P<0.001), and in the intersubjects comparisons, the effects of both gender (F=14.334, P<0.01) for pKt/V and peritoneal permeability for both parameters (pKt/V: F=4.37, P<0.05; CrpC: F=11.697, P<0.001). In conclusion, the application of ascendant and descendant UF profiles in automated PD is feasible and results in better UF and small solute clearances, thus preventing inadequate dialysis and volume overload..

Conversion to rapamycin in a renal transplant patient with von Hippel-Lindau disease: encouraging results-a case report.

von Hippel-Lindau (VHL) disease is a genetic syndrome based on an abnormality of the VHL gene located on the short arm of chromosome 3. Clinically, it presents as multiple tumors at several levels. The VHL gene product (pVHL) acts as a tumor-suppressing protein. In conditions of hypoxia it leads to an increase in several growth factor levels. mTOR inhibitors have proved to have dual properties: immunosuppressive and antitumor effects. Herein we have presented a case in which conversion to sirolimus improved graft function and also caused regression of retinal angioblastomas.

Acute regulation by insulin of phosphatidylinositol-3-kinase, Rad, Glut 4, and lipoprotein lipase mRNA levels in human muscle.

We have investigated the acute regulation by insulin of the mRNA levels of nine genes involved in insulin action, in muscle biopsies obtained before and at the end of a 3-h euglycemic hyperinsulinemic clamp. Using reverse transcription-competitive PCR, we have measured the mRNAs encoding the two insulin receptor variants, the insulin receptor substrate-1, the p85alpha subunit of phosphatidylinositol-3-kinase, Ras associated to diabetes (Rad), the glucose transporter Glut 4, glycogen synthase, 6-phosphofructo-l-kinase, lipoprotein lipase, and the hormone-sensitive lipase. Insulin infusion induced a significant increase in the mRNA level of Glut 4 (+56 +/- 13%), Rad (+96 +/- 25%), the p85alpha subunit of phosphatidylinositol-3-kinase (+92 +/- 18%) and a decrease in the lipoprotein lipase mRNA level (-49 +/- 5%), while the abundance of the other mRNAs was unaffected. The relative expression of the two insulin receptor variants was not modified. These results demonstrate an acute coordinated regulation by insulin of the expression of genes coding key proteins involved in its action in human skeletal muscle and suggest that Rad and the p85alpha regulatory subunit of phosphatidylinositol-3-kinase can be added to the list of the genes controlled by insulin.

Steroids and bone density in patients with functioning kidney allografts.

INTRODUCTION: Osteopenia and osteoporosis after renal transplantation have been associated with factors related to the cause of end-stage renal disease, as well as to clinical events and therapeutic factors in the posttransplant period. We studied the prevalence of low bone density (LBD) according to WHO criteria. METHODS: A cross-sectional study was performed in a cohort of 106 patients (54 men and 52 women) with functioning renal allografts, who underwent bone densitometry (DEXA) of the lumbar spine and femoral neck. Patients were grouped according to DEXA into those with normal bone density (NBD) or LBD. We studied clinical, analytical, and therapeutic variables. RESULTS: Thirtysix patients (34%) had NBD and 70 patients (66%) LBD. Weight was the only parameter showing a significant difference (P = .034), namely, among NBD it was 80.44+/-15.13 versus LBD 73.94 +/- 14.54 kg, respectively. Creatinine clearance (CCr) tended to be lower among patients with LBD 59.62 +/- 22.73 versus 69.59 +/- 28.15 mL/min in patients with NBD (P = .052). PTHi levels were higher in patients with LBD (149.39 +/- 110.75) than those with NBD (110.94 +/- 82.61) (P = .069). In the multivariate analysis the important determinants were weight Exp(ss) = 0.967 [CI = 0.939 to 0.996] (P = .036); CCr Exp(ss) = 0.982 [CI = 0.965 to 1.000] (P = .055); and PTHi levels Exp(ss) = 1.003 [CI = 0.932 to 0.994] (P = .059). CONCLUSIONS: Osteopenia and osteoporosis are frequent among kidney transplant patients (66%), with a similar distribution between the lumbar spine and femoral neck. Excess weight and possibly better renal function may be protective factors. The cumulative steroid dose showed a significant effect on bone density. As expected, secondary hyperparathyroidism in patients with renal impairment seemed to be a risk factor for LBD.

[Guidelines of the Spanish Society of Nephrology. Clinical practice guidelines for peritoneal dialysis]. / Guías Sociedad Española de Nefrología. Guías de práctica clínica en diálisis peritoneal.

In Spain and in each of its autonomous communities, the dialysis treatment of chronic renal disease stage 5 is totally covered by public health. Peritoneal dialysis, in any of its modalities, is established as the preferred home dialysis technique and is chosen by high percentage of patients as their choice in dialysis treatment. The Spanish Society of Nephrology has promoted a project of creation of performance guides in the field of peritoneal dialysis, entrusting a work group composed of members of the Spanish Society of Nephrology a with the development of these guides. The information offered is based on levels of evidence, opinion and clinical experience of the most relevant publications of the topic. In these guides, after defining the concept of << peritoneal dialysis>>, the obligations and responsibilities of the sanitation team of the peritoneal dialysis unit are determined, and protocols and performance procedures that try to include all the aspects that concern the patient with chronic renal disease in substitute treatment with this technique are developed. They propose prescription objectives based on available clinical evidence and, lacking this, on the consensus of the experts' opinions. The final aim is to improve the care and quality of the of the patient in peritoneal dialysis, optimizing in this way the survival of the patient and of the technique. In Spain, as in other neighbouring countries, peritoneal dialysis has an incidence and prevalence that is much lower than that of hemodialysis, ranging in the last evaluation by the Spanish Society of Nephrology between 5 and 24% in the different autonomous communities. The great majority of peritoneal dialysis units form part of the public network of the Spanish state, with special representation as a Satellite Unit or Concerted Center related to the public hospital of reference, on which it must depend.

Regulation by insulin of gene expression in human skeletal muscle and adipose tissue. Evidence for specific defects in type 2 diabetes.

Defective regulation of gene expression may be involved in the pathogenesis of type 2 diabetes. We have characterized the concerted regulation by insulin (3-h hyperinsulinemic clamp) of the expression of 10 genes related to insulin action in skeletal muscle and in subcutaneous adipose tissue, and we have verified whether a defective regulation of some of them could be specifically encountered in tissues of type 2 diabetic patients. Basal mRNA levels (determined by reverse transcriptase-competitive polymerase chain reaction) of insulin receptor, insulin receptor substrate-1, p85alpha phosphatidylinositol 3-kinase (PI3K), p110alphaPI3K, p110betaPI3K, GLUT4, glycogen synthase, and sterol regulatory-element-binding protein-1c (SREBP-1c) were similar in muscle of control (n = 17), type 2 diabetic (n = 9), type 1 diabetic (n = 9), and nondiabetic obese (n = 9) subjects. In muscle, the expression of hexokinase II was decreased in type 2 diabetic patients (P < 0.01). In adipose tissue, SREBP-1c (P < 0.01) mRNA expression was reduced in obese (nondiabetic and type 2 diabetic) subjects and was negatively correlated with the BMI of the subjects (r = -0.63, P = 0.02). Insulin (+/-1,000 pmol/l) induced a two- to threefold increase (P < 0.05) in hexokinase II, p85alphaPI3K, and SREBP-1c mRNA levels in muscle and in adipose tissue in control subjects, in insulin-resistant nondiabetic obese patients, and in hyperglycemic type 1 diabetic subjects. Upregulation of these genes was completely blunted in type 2 diabetic patients. This study thus provides evidence for a specific defect in the regulation of a group of important genes in response to insulin in peripheral tissues of type 2 diabetic patients.

Depot-specific differences in adipose tissue gene expression in lean and obese subjects.

Intra-abdominal and subcutaneous adipose tissue display important metabolic differences that underlie the association of visceral, but not subcutaneous, fat with obesity-related cardiovascular and metabolic problems. Because the molecular mechanisms contributing to these differences are not yet defined, we compared by reverse transcription-polymerase chain reaction the expression of 15 mRNAs that encode proteins of known importance in adipocyte function in paired omental and subcutaneous abdominal biopsies. No difference in mRNA expression between omental and subcutaneous adipose tissue was observed for hormone sensitive lipase, lipoprotein lipase, 6-phosphofructo-1-kinase, insulin receptor substrate 1, p85alpha regulatory subunit of phosphatidylinositol-3-kinase, and Rad. Total amount of insulin receptor expression was significantly higher in omental adipose tissue. Most of this increase was accounted for by expression of the differentially spliced insulin receptor lacking exon 11, which is considered to transmit the insulin signal less efficiently than the insulin receptor with exon 11. Perhaps consistent with a less efficient insulin signaling, a twofold reduction in GLUT4, glycogen synthase, and leptin mRNA expression was observed in omental adipose tissue. Finally peroxisome proliferator activated receptor-gamma (PPAR-gamma) mRNA levels were significantly lower in visceral adipose tissue in subjects with a BMI <30 kg/m2, but not in obese subjects, indicating that relative PPAR-gamma expression is increased in omental fat in obesity. This suggests that altered expression of PPAR-gamma might play a role in adipose tissue distribution and expansion.

Age-related differences in messenger ribonucleic acid expression of key proteins involved in adipose cell differentiation and metabolism.

This study was performed to compare the expression of key proteins [lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), complement 3 (C3), and peroxisome proliferator-stimulated receptor-gamma (PPAR gamma)] involved in sc abdominal adipose tissue (AT) metabolism of young (n = 13) vs. middle-aged (n = 16) men. The sc abdominal AT-LPL activity as well as fat cell lipolysis were also measured in both groups of men. Young and middle-aged men displayed similar body weight and sc abdominal fat accumulation, measured by computed tomography. However, middle-aged men were characterized by a higher percent body fat (28 +/- 5% vs. 22 +/- 7%; P < 0.05) than young subjects. No difference between groups was observed in sc abdominal adipose tissue LPL activity. On the other hand, maximal lipolytic responses of sc abdominal adipocytes to isoproterenol (beta-adrenergic agonist) or to postadrenoceptor agents such as dibutyryl cAMP, forskolin, and theophylline were lower in middle-aged than in young men (P < 0.05). AT-LPL messenger ribonucleic acid (mRNA) levels were similar regardless of the subject's age. However, HSL, C3, and PPAR gamma mRNA levels were higher in middle-aged than in young individuals (P < 0.01-0.05). After correction for percent body fat, only HSL and C3 mRNA levels remained significantly different between groups (P < 0.05). Taken together, these results suggest that aging has an effect on the up-regulation of HSL and C3 mRNA levels, whereas PPAR gamma expression seems to be related mainly to increased adiposity.

Intramyocitic lipid accumulation and SREBP-1c expression are related to insulin resistance and cardiovascular risk in morbid obesity.

The aim of this study was to investigate the sterol regulatory element-binding protein 1c (SREBP1c) mRNA muscle expression in morbid obese subjects before and after massive lipid malabsorption due to bariatric surgery (bilio-pancreatic diversion, BPD). We studied 11 obese subjects (BMI 49+/-2 kg/m2) before and 24 months after BPD. Skeletal muscle SREBP1c mRNA expression was determined using RT-competitive PCR. Intramyocytic triglycerides were quantified by HPLC. Insulin sensitivity (M/I) was assessed by euglycemic-hyperinsulinemic clamp. Energy expenditure and respiratory quotient (RQ) were measured over 24 h in a calorimetric chamber. Total cardiovascular risk dropped from 2 before to -2.5 after BPD (P<0.0001). The M/I value was normalized after surgery (0.036+/-0.0148 to 0.095+/-0.0147 micromol kgFFM(-1) min(-1) pmoles(-1) P<0.001). SREBP-1c mRNA levels were decreased (from 4.12+/-2.43 to 2.69+/-1.83% of cyclophilin mRNA, P=0.02) after BPD. In a multiple regression analysis, M/I values (P<0.0001) as well as the intramyocytic triglyceride levels (P=0.039) were the most powerful independent variables for predicting cardiovascular risk. Our results show that the reduction of cardiovascular risk after bariatric massive weight loss is strongly related to the reversion of insulin resistance and to the lowering of intramyocytic triglyceride depots. These two parameters are associated with a significant reduction in SREBP-1c mRNA expression in skeletal muscle, suggesting that this transcription factor might be involved in the accumulation of triglycerides in muscle cells of morbidly obese subjects.

Expression of insulin target genes in skeletal muscle and adipose tissue in adult patients with growth hormone deficiency: effect of one year recombinant human growth hormone therapy.

Our aim was to investigate the effects of one year recombinant human growth hormone (rhGH) therapy on the regulation by insulin of gene expression in muscle and adipose tissue in adults with secondary GH deficiency (GHD). Six GHD subjects without upper-body obesity were submitted to a 3-h euglycemic hyperinsulinemic clamp before and after one year of rhGH therapy. Muscle and abdominal subcutaneous adipose tissue biopsies were taken before and at the end of each clamp. The mRNA levels of insulin receptor, p85 alpha-phosphatidylinositol-3 kinase (p85 alpha PI-3K), insulin dependent glucose transporter (Glut4), hexokinase II, glycogen synthase, lipoprotein lipase (LPL) in muscle and in adipose tissue, hormone sensitive lipase and peroxisome proliferator-activated receptor gamma (PPAR gamma) in adipose tissue were quantified by RT-competitive PCR. One year treatment with rhGH (1.25 IU/day) increased plasma IGF-I concentrations (54+/-7 vs 154+/-11 ng/ml, P<0.01) but did not affect insulin-stimulated glucose disposal rate measured during the hyperinsulinemic clamp (74+/-9 vs 85+/-5 micromol/kg free fat mass/min). Insulin significantly increased p85 alpha PI-3K, hexokinase II and Glut4 mRNA levels in muscle both before and after rhGH treatment. One year of GH therapy increased LPL mRNA levels in muscle (38+/-2 vs 70+/-7 amol/microg total RNA, P<0.05) and in adipose tissue (2490+/-260 vs 4860+/-880 amol/microg total RNA, P<0.05), but did not change the expression of the other mRNAs. We conclude from this study that GH therapy did not alter whole body insulin sensitivity and the response of gene expression to insulin in skeletal muscle of adult GHD patients, but it did increase LPL expression in muscle and adipose tissue. This result could be related to the documented beneficial effect of GH therapy on lipid metabolism.