CC chemokine ligand 3 and receptors 1 and 5 gene expression in recurrent aphthous stomatitis

Objective. The aim of this study was to investigate the local and systemic expression of CC-chemokine ligand 3 (CCL3) and its receptors (CCR1 and CCR5) in tissue samples and peripheral blood mononuclear cells of recurrent aphthous stomatitis (RAS) patients. Study Design. This case-control study enrolled 29 patients presenting severe RAS manifestations and 20 non-RAS patients proportionally matched by sex and age. Total RNA was extracted from biopsy specimens and peripheral blood mononuclear cells for quatitative reverse-transcription polymerase chain reaction. The data obtained by relative quantification were evaluated by the 2(-Delta Delta Ct) method, normalized by the expression of an endogenous control, and analyzed by Student t test. Results. The results demonstrated overexpression in RAS tissue samples of all of the chemokines evaluated compared with healthy oral mucosa, whereas the blood samples showed only CCR1 overexpression in RAS patients. Conclusions. These findings suggest that the increased expression of CCL3, CCR1, and CCR5 may influence the immune response in RAS by T(H)1 cytokine polarization. (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:93-98)

Theoretical luminescence spectra in p-type superlattices based on InGaAsN

In this work, we present a theoretical photoluminescence (PL) for p-doped GaAs/InGaAsN nanostructures arrays. We apply a self-consistent method in the framework of the effective mass theory. Solving a full 8 x 8 Kane's Hamiltonian, generalized to treat different materials in conjunction with the Poisson equation, we calculate the optical properties of these systems. The trends in the calculated PL spectra, due to many-body effects within the quasi-two-dimensional hole gas, are analyzed as a function of the acceptor doping concentration and the well width. Effects of temperature in the PL spectra are also investigated. This is the first attempt to show theoretical luminescence spectra for GaAs/InGaAsN nanostructures and can be used as a guide for the design of nanostructured devices such as optoelectronic devices, solar cells, and others.

Gene expression profiles displayed by peripheral blood mononuclear cells from patients with type 2 diabetes mellitus focusing on biological processes implicated on the pathogenesis of the disease

Patients with type 2 diabetes mellitus (T2DM) exhibit insulin resistance associated with obesity and inflammatory response, besides an increased level of oxidative DNA damage as a consequence of the hyperglycemic condition and the generation of reactive oxygen species (ROS). In order to provide information on the mechanisms involved in the pathophysiology of T2DM, we analyzed the transcriptional expression patterns exhibited by peripheral blood mononuclear cells (PBMCs) from patients with T2DM compared to non-diabetic subjects, by investigating several biological processes: inflammatory and immune responses, responses to oxidative stress and hypoxia, fatty acid processing, and DNA repair. PBMCs were obtained from 20 T2DM patients and eight non-diabetic subjects. Total RNA was hybridized to Agilent whole human genome 4x44K one-color oligo-microarray. Microarray data were analyzed using the GeneSpring GX 11.0 software (Agilent). We used BRB-ArrayTools software (gene set analysis - GSA) to investigate significant gene sets and the Genomica tool to study a possible influence of clinical features on gene expression profiles. We showed that PBMCs from T2DM patients presented significant changes in gene expression, exhibiting 1320 differentially expressed genes compared to the control group. A great number of genes were involved in biological processes implicated in the pathogenesis of T2DM. Among the genes with high fold-change values, the up-regulated ones were associated with fatty acid metabolism and protection against lipid-induced oxidative stress, while the down-regulated ones were implicated in the suppression of pro-inflammatory cytokines production and DNA repair. Moreover, we identified two significant signaling pathways: adipocytokine, related to insulin resistance; and ceramide, related to oxidative stress and induction of apoptosis. In addition, expression profiles were not influenced by patient features, such as age, gender, obesity, pre/post-menopause age, neuropathy, glycemia, and HbA(1c) percentage. Hence, by studying expression profiles of PBMCs, we provided quantitative and qualitative differences and similarities between T2DM patients and non-diabetic individuals, contributing with new perspectives for a better understanding of the disease. (C) 2012 Elsevier B.V. All rights reserved.

Prevalence of adults with type 1 diabetes who meet the goals of care in daily clinical practice: A nationwide multicenter study in Brazil

Objective: To determine the prevalence of patients with type 1 diabetes mellitus who meet the glycemic and cardiovascular (CV) risk factors goals and the frequency of screening for diabetic complications in Brazil according to the American Diabetes Association guidelines. Research design and methods: This was a cross-sectional, multicenter study conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 1774 adult patients (56.8% females, 57.2% Caucasians) aged 30.3 +/- 9.8 years with diabetes duration of 14.3 +/- 8.8 years. Results: Systolic blood pressure was at goal in 40.3% and diastolic blood pressure was at goal in 26.6% of hypertensive patients. LDL cholesterol and HbA1c were at the goal in 45.2% and 13.2% of the patients, respectively. Overweight was presented in 25.6% and obesity in 6.9%. Among those with more than 5 years of disease, screening for retinopathy was performed in the preceding year in 70.1%. Nephropathy and feet complications were screened in 63.1% and 65.1%, respectively. Conclusions: The majority of patients did not meet metabolic control goals and a substantial proportion was not screened for diabetic complications. These issues may increase the risk of chronic complications and negatively impact public health. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Detection of human T-cell lymphotropic virus type 1 in plasma samples

Human T-cell lymphotropic virus type 1 (HTLV-1) is-an RNA virus responsible for diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATL). Cell-to-cell contact and Tax-induced clonal expansion of infected cells are the main modes of virus replication, making virus detection during the viremic stage difficult. Consequently, the proviral load is the current virologic marker for disease monitoring, but the mechanisms of progression have not been established yet. Thus, this study investigated the presence of virus in plasma from asymptomatic HTLV-1 carriers and from HAM/TSP patients. Real-time PCR was performed on DNA from 150 plasma samples; 12(8%) had detectable DNA amplification, including 6(4%) asymptomatic HTLV-1 carriers and 14(26%) HAM/TSP patients (p < 0.005). Of the 33 samples submitted for nested PCR, six (18%, p = 0.02) were positive for HTLV-1 RNA in the plasma. Additionally, 26 plasma samples were treated with DNAse enzyme to eliminate any DNA contamination before RNA extraction. Two of them (8%) showed amplification for HTLV-1 (p = 0.5). Therefore, this study described for the first time the detection of free HTLV-1 RNA in plasma from HTLV-1-infected subjects, regardless of their clinical status. Thus, HTLV-1 viral replication does occur in plasma, and other transmission pathways for HTLV-1 should be investigated further. (C) 2011 Elsevier B.V. All rights reserved.

Complete Sequence of Broad-Host-Range Plasmid pRIO-5 Harboring the Extended-Spectrum-beta-Lactamase Gene bla(BES-1)

Broad-host-range plasmid pRIO-5, harboring the extended-spectrum beta-lactamase bla(BES-1) gene in Serratia marcescens, was fully sequenced. Analysis of the 12,957-bp sequence of this IncP6-type plasmid revealed that the bla(BES-1) gene was associated with two copies of the insertion sequence IS26. The promoter responsible for the bla(BES-1) expression was hybrid, made of a - 35 box located inside the inverted repeat of IS26 and a - 10 box inside a remnant of an insertion sequence.

Creatine-induced glucose uptake in type 2 diabetes: a role for AMPK-alpha?

This study focused on understanding the signaling mechanisms leading to GLUT-4 translocation and increased skeletal-muscle glucose uptake that follow creatine (Cr) supplementation in type 2 diabetes (n = 10). AMPK-alpha protein content presented a tendency to be higher (p = 0.06) after Cr supplementation (5 g/d for 12w). The changes in AMPK-alpha protein content significantly related (p < 0.001) to the changes in GLUT-4 translocation (r = 0.78) and Hb1Ac levels (r = -0.68), suggesting that AMPK signaling may be implicated in the effects of supplementation on glucose uptake in type 2 diabetes.

Effects of Gastric Bypass Surgery in Patients With Type 2 Diabetes and Only Mild Obesity

OBJECTIVE-Roux-en-Y gastric bypass (RYGB) ameliorates type 2 diabetes in severely obese patients through mechanisms beyond just weight loss, and it may benefit less obese diabetic patients. We determined the long-term impact of RYGB on patients with diabetes and only class 1 obesity. RESEARCH DESIGN AND METHODS-Sixty-six consecutively selected diabetic patients with BMI 30-35 kg/m(2) underwent RYGB in a tertiary-care hospital and were prospectively studied for up to 6 years (median 5 years [range 1-6]), with 100% follow-up. Main outcome measures were safety and the percentage of patients experiencing diabetes remission (HbA(1c) <6.5% without diabetes medication). RESULTS-Participants had severe, longstanding diabetes, with disease duration 12.5 +/- 7.4 years and HbA(1c) 9.7 +/- 1.5%, despite insulin and/or oral diabetes medication usage in everyone. For up to 6 years following RYGB, durable diabetes remission occurred in 88% of cases, with glycemic improvement in 11%. Mean HbA(1c) fell from 9.7 +/- 1.5 to 5.9 +/- 0.1% (P < 0.001), despite diabetes medication cessation in the majority. Weight loss failed to correlate with several measures of improved glucose homeostasis, consistent with weight-independent antidiabetes mechanisms of RYGB. C-peptide responses to glucose increased substantially, suggesting improved beta-cell function. There was no mortality, major surgical morbidity, or excessive weight loss. Hypertension and dyslipidemia also improved, yielding 50-84% reductions in predicted 10-year cardiovascular disease risks of fatal and nonfatal coronary heart disease and stroke. CONCLUSIONS-This is the largest, longest-term study examining RYGB for diabetic patients without severe obesity. RYGB safely and effectively ameliorated diabetes and associated comorbidities, reducing cardiovascular risk, in patients with a BMI of only 30-35 kg/m(2).

Tax Gene Characterization of Human T-Lymphotropic Virus Type 1 Strains from Brazilian HIV-Coinfected Patients

The tax gene of human T-lymphotropic virus type 1 (HTLV-1) diverges among isolates according to geographic regions and has been classified into two genotypes: taxA and taxB. In Brazil, taxA is the most prevalent genotype in symptomatic and asymptomatic carriers. Few studies have been conducted in HIV-infected patients. The present study characterized the tax gene (1059 bp) in 13 Brazilian HIV-1/HTLV-1-coinfected patients from the south and southeast regions. The results confirmed the transcontinental HTLV-1 subgroup A of the Cosmopolitan subtype and showed high nucleotide similarity both among Brazilian sequences and in relation to the ATK prototype (99.5% and 99.2%, respectively). Six nucleotide substitutions were highly conserved among isolates, ranging from 76.9% to 100%: C7401T, T7914C, C7920T, C7982T, G8231A, and A8367C. The presence of the Brazilian molecular signature of genotype taxA was confirmed in all of the isolates, and they clustered into two Latin American clusters, which confirms the double introduction of HTLV-1 in Brazil.

Increased TLR2 expression in patients with type 1 diabetes: evidenced risk of microalbuminuria

Objective: To study the activation of an inflammatory cascade through leukocyte mRNA expression of TLR2, TLR4, MyD88, and pro-inflammatory cytokines in individuals with childhood onset type 1 diabetes. Design and methods: Seventy-six type 1 diabetic patients and 100 normoglycemic subjects (NG) 6 to 20 years old were recruited. Type 1 diabetic patients (DM1) were considered to have good (DM1G) or poor (DM1P) glycemic control according to the values of glycated hemoglobin. TLR2, TLR4, MyD88, interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) mRNA expressions were measured in peripheral blood leukocytes (PBL) by real-time polymerase chain reaction (PCR). Urea, creatinine, albumin, and total protein serum levels were determined. Urinary albumin-to-creatinine ratio (ACR) was calculated. Results: DM1 and DM1P patients showed higher glycated hemoglobin (10 and 11%, respectively) and serum glucose concentrations (208 and 226 mg/ dL, respectively) compared to NG (Glycated hemoglobin: 7% and glucose: 76 mg/ dL) (p < 0.05). PBL mRNA expressions of TLR2, MyD88, IL-1 beta, IL-6, and TNF-alpha were higher in DM1 and TLR2, IL-1 beta, and IL-6 expressions were higher in DMP1 compared to NG (p < 0.05). In DM1, serum albumin and total protein were lower, while serum urea and ACR were higher in comparison to NG (p < 0.05). However, these differences compared to NG were more pronounced in DM1P, which included nine individuals with microalbuminuria. Conclusions: Increased mRNA expression of TLR2, MyD88, and pro-inflammatory cytokines in leukocytes of patients with childhood onset type 1 diabetes indicates the development of a TLR2-mediated pro-inflammatory process, which may also be associated with an early inflammatory process in the kidney and the occurrence of microalbuminuria.

Surgical Treatment of Type 2 Diabetes in Patients with BMI Below 35: Mid-term Outcomes of the Laparoscopic Ileal Interposition Associated with a Sleeve Gastrectomy in 202 Consecutive Cases

The objective of this study was to evaluate the mid-term outcomes of the laparoscopic ileal interposition into the jejunum (JII-SG) or into the duodenum (DII-SG) associated with sleeve gastrectomy for type 2 diabetes mellitus (T2DM) patients with BMI below 35. The procedures were performed on 202 consecutive patients. Mean age was 52.2 +/- 7.5. Mean duration of T2DM was 9.8 +/- 5.2 years. Insulin therapy was used by 41.1%. Dyslipidemia was observed in 78.2%, hypertension in 67.3%, nephropathy in 49.5%, retinopathy in 31.2%, coronary heart disease in 11.9%, and other cardiovascular events in 12.9%. Mean follow-up was 39.1 months (range, 25-61). Early and late mortality was 0.99% and 1.0%, respectively. Early reoperation was performed in 2.5%. Early and late major complications were 8.4% and 3.5%. Early most frequent complications were pneumonia and ileus. Intestinal obstruction was diagnosed in 1.5%. Mean BMI decreased from 29.7 to 23.5 kg/m(2), mean fasting glucose from 202.1 to 112.2 mg/dl, and mean postprandial glucose from 263.3 to 130 mg/dl. Triglycerides diminished from a mean of 273.4 to 110.3 mg/dl and cholesterol from a mean of 204.7 to 160.1 mg/dl. Hypertension was resolved in 87.5%. Mean hemoglobin A(1c) (HbA(1c)) decreased from 8.7 to 6.2% after the JII-SG and to 5.9% following the DII-SG. HbA(1c) below 7% was seen in 89.9% of the patients and below 6.5% in 78.3%. Overall, 86.4% of patients were off antidiabetic medications. Both JII-SG and DII-SG demonstrated to be safe, effective, and long-lasting alternatives for the treatment of T2DM patients with BMI < 35. Beyond glycemic control, other benefits were achieved.

The inactive form of glycogen synthase kinase-3 beta is associated with the development of carcinomas in galectin-3 wild-type mice, but not in galectin-3-deficient mice

Galectin-3 has been implicated in the tumor development via its mediation of the Wnt signaling pathway. Likewise, glycogen synthase kinase-3beta (GSK3 beta) also plays a role in the Wnt signaling pathway by controlling the levels of cytoplasmic beta-catenin. Altered GSK3 beta expression has been described in various tumors, but to date, there are no studies evaluating its expression in models of oral carcinogenesis. Additionally, it is unknown whether the absence of galectin-3 regulates the expression of GSK3 beta. To this end, Gal3-deficient (Gal3(-/-)) and wild-type (Gal3(+/+)) male mice were treated with 4NQO for 16 weeks and sacrificed at week 16 and 32. The tongues were removed, processed, and stained with H&E to detect dysplasias and carcinomas. An immunohistochemical assay was performed to determine the level of P-GSK3 beta-Ser9 expression in both groups. Carcinomas were more prevalent in Gal3(+/+) than Gal3(-/-) mice (55.5% vs. 28.5%), but no statistical difference was reached. In the dysplasias, the proportion of cells positive for P-GSK3 beta-Ser9 was slightly higher in Gal3(+/+) than Gal3(-/-) mice (63% vs. 61%). In the carcinomas, a significant difference between Gal3(+/+) and Gal3(-/-) mice was found (74% vs. 59%; p=0.02). P-GSK3 beta-Ser9-positive cells slightly decreased from the progression of dysplasias to carcinomas in Gal3(-/-) mice (61% vs. 59%; p>0.05). However, a significant increase in P-GSK3 beta-Ser9 expression was observed from dysplasias to carcinomas in Gal3(+/+) mice (63% vs. 74%; p=0.01). In conclusion, these findings suggest that fully malignant transformation of the tongue epithelium is associated with increased P-GSK3 beta-Ser9 expression in Gal3(+/+) mice, but not in Gal3(-/-) mice.

Host-guest interactions between xanthones and water: the role of O-H center dot center dot center dot O, C-H center dot center dot center dot O, and pi center dot center dot center dot pi contacts in the channel- and cage-type frameworks

In this article were studied two xanthone derivatives known as 1,5-dihydroxy-8-methoxyxanthone (I) and 1,3,7-trihydroxy-8-methoxyxanthone (II), which show one water molecule into their crystal structures. In xanthone I, there are water wires contributing to build up channel-like cavities along the c axis, whereas in xanthone II the water is surrounded by three xanthone molecules forming a cage-type structure. The geometries of I and II were optimized using the density functional theory method with B3LYP functional, and the results were compared with crystal structure. Both theoretical and experimental investigations reveal a concordance between structural parameters, with the xanthone core presenting an almost flat conformation and substituents adopting the more stable orientations. In the two compounds, the hydroxyl group linked at position 1 is involved in a resonance-assisted hydrogen bond with the carbonyl group. Besides, the supramolecular arrangement of the host/guest systems are stabilized mainly by classical intermolecular hydrogen bonds (O-H center dot center dot center dot O) involving xanthone-to-water and xanthone-to-xanthone. In addition, C-H center dot center dot center dot O weak hydrogen bonds, as well as pi-pi interactions play an important role to stabilize the crystal self-assembly of xanthones I and II. The results reported here underline the role of inclusion of water molecules and their different arrangement into the crystal structure of two xanthone host/guest systems.

Opposing Roles for Cannabinoid Receptor Type-1 (CB1) and Transient Receptor Potential Vanilloid Type-1 Channel (TRPV1) on the Modulation of Panic-Like Responses in Rats

The midbrain dorsal periaqueductal gray (dPAG) has an important role in orchestrating anxiety-and panic-related responses. Given the cellular and behavioral evidence suggesting opposite functions for cannabinoid type 1 receptor (CB1) and transient receptor potential vanilloid type-1 channel (TRPV1), we hypothesized that they could differentially influence panic-like reactions induced by electrical stimulation of the dPAG. Drugs were injected locally and the expression of CB1 and TRPV1 in this structure was assessed by immunofluorescence and confocal microscopy. The CB1-selective agonist, ACEA (0.01, 0.05 and 0.5 pmol) increased the threshold for the induction of panic-like responses solely at the intermediary dose, an effect prevented by the CB1-selective antagonist, AM251 (75 pmol). Panicolytic-like effects of ACEA at the higher dose were unmasked by pre-treatment with the TRPV1 antagonist capsazepine (0.1 nmol). Similarly to ACEA, capsazepine (1 and 10 nmol) raised the threshold for triggering panic-like reactions, an effect mimicked by another TRPV1 antagonist, SB366791 (1 nmol). Remarkably, the effects of both capsazepine and SB366791 were prevented by AM251 (75 pmol). These pharmacological data suggest that a common endogenous agonist may have opposite functions at a given synapse. Supporting this view, we observed that several neurons in the dPAG co-expressed CB1 and TRPV1. Thus, the present work provides evidence that an endogenous substance, possibly anandamide, may exert both panicolytic and panicogenic effects via its actions at CB1 receptors and TRPV1 channels, respectively. This tripartite set-point system might be exploited for the pharmacotherapy of panic attacks and anxiety-related disorders. Neuropsychopharmacology (2012) 37, 478-486; doi:10.1038/npp.2011.207; published online 21 September 2011

Reduced muscle carnosine content in type 2, but not in type 1 diabetic patients

Carnosine is present in high concentrations in skeletal muscle where it contributes to acid buffering and functions also as a natural protector against oxidative and carbonyl stress. Animal studies have shown an anti-diabetic effect of carnosine supplementation. High carnosinase activity, the carnosine degrading enzyme in serum, is a risk factor for diabetic complications in humans. The aim of the present study was to compare the muscle carnosine concentration in diabetic subjects to the level in non-diabetics. Type 1 and 2 diabetic patients and matched healthy controls (total n = 58) were included in the study. Muscle carnosine content was evaluated by proton magnetic resonance spectroscopy (3 Tesla) in soleus and gastrocnemius. Significantly lower carnosine content (-45%) in gastrocnemius muscle, but not in soleus, was shown in type 2 diabetic patients compared with controls. No differences were observed in type 1 diabetic patients. Type II diabetic patients display a reduced muscular carnosine content. A reduction in muscle carnosine concentration may be partially associated with defective mechanisms against oxidative, glycative and carbonyl stress in muscle.