The effects of human herpesvirus 8 infection and interferon-gamma response in cutaneous lesions of Kaposi sarcoma differ among human immunodeficiency virus-infected and uninfected individuals

Background Kaposi sarcoma (KS) is associated with human herpesvirus 8 (HHV-8). The cutaneous immune response in this tumour is not well established and a better understanding is necessary. Objectives To evaluate the HHV-8 expression and immune response in cutaneous lesions of classic KS (CKS) and AIDS-associated KS (AIDS-KS). Methods We performed a quantitative immunohistochemical study of cells expressing HHV-8 latency-associated nuclear antigen (LANA), CD4, CD8 and interferon (IFN)-gamma in skin lesions from patients with CKS and AIDS-KS (with or without highly active antiretroviral therapy, HAART). Results CKS showed higher LANA expression compared with AIDS-KS, regardless of HAART. We also found higher LANA expression in nodules compared with patch/plaque lesions. The tissue CD4+ cell proportion was lower in AIDS-KS patients without HAART than in patients with CKS. In CKS lesions, CD4+ and CD8+ cells expressed IFN-gamma, as shown by double immunostaining. AIDS-KS presented low numbers of IFN-gamma-expressing cells. CD8+ cell numbers were similar in all groups, which appeared unrelated to the clinical or epidemiological type of KS. Conclusions. Our quantitative data on the pattern of KS lesions in selected groups of patients, as shown by in situ immune response, demonstrated a CD4+ T-cell involvement associated with IFN-gamma, an environment of immune response-modified human immunodeficiency virus (HIV) infection. In our sample, the promotion of KS in patients without HIV appears to be related to higher HHV-8 load or virulence than in those with AIDS. This higher resistance may be explained by a sustained immune response against this herpesvirus, that is only partially restored but effective after HAART.

Genotype and mating type distribution within clinical Cryptococcus neoformans and Cryptococcus gattii isolates from patients with cryptococcal meningitis in Uberaba, Minas Gerais, Brazil

We molecularly characterized 81 cryptococcal isolates recovered from cerebrospinal fluid samples of 77 patients diagnosed between 1998 and 2007 as having cryptococcal meningitis in Uberaba Minas Gerais, Brazil. Fifty-seven (74%) were male with a mean age 35.6 years. Seventy-two (88.9%) of the isolates were from 68 AIDS patients and cryptococcosis was the first AIDS-defining condition in 38 (55.9%) patients. Cryptococcosis and AIDS were simultaneously diagnosed in 25 (65.8%) of these 38 patients. Genotypes were characterized through the use of URA5 restriction fragment length polymorphisms analysis, the genetic variability was determined using PCR-fingerprinting with the minisatellite-specific primer M13, and the mating type and serotypes were established by PCR. Seventy-six of the 81 isolates were Cryptococcus neoformans (93.8%), while the remaining five were C. gattii (6.1%), but all were mating type a. C. neoformans isolates were genotype VNI (serotype A), while C. gattii isolates were VGII. Four of the latter isolates were identical, but only two were from AIDS patients. Six of the nine isolates from non-AIDS patients were VNI. PCR fingerprints of the isolates from two of the three AIDS patients with clinical relapse were 100% identical. The predominance of VNI and mating type a is in accordance with data from other parts of the world. The occurrence of VGII in Minas Gerais indicates a geographical expansion within Brazil.

Effect of the glycemic control on intracellular cytokine production from peripheral blood mononuclear cells of type 1 and type 2 diabetic patients

Aims: To evaluate the intracellular production of tumor necrosis factor (TNF-alpha), interleukine-6 (IL-6), INF-gamma, IL-8 and IL-10 in peripheral blood lympbomononuclear cells from type 1 and type 2 diabetic patients, stratified according to the glycemic control. Methods: Thirty-five diabetic patients (17 type 1 and 18 type 2) and nine healthy individuals paired to patients in terms of sex and age were studied. Nine patients of each group were on inadequate glycemic controls. Intracellular cytokines were evaluated using flow cytometry. Cell cultures were stimulated with LPS to evaluate TNF-alpha and IL-6 or with PMA and lonomycin to evaluate IFN-gamma, IL-8 and IL-10 intracellular staining. Results: The percentages of CD33(+) cells bearing TNF-alpha and CD3(+) cells bearing IL-10 were increased in type 1 diabetic patients with inadequate glycemic control in relation to those with adequate control. In contrast, the percentage of CD3(+) cells bearing IL-8 was decreased in type 2 patients under inadequate glycemic control. Conclusions: The glycemic control is important for the detection of intracellular cytokines, and may contribute towards the susceptibility to infections in diabetic patients. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Autologous stem cell transplantation for early type 1 diabetes mellitus

Type 1 diabetes mellitus (T1DM) is the result of the autoimmune response against pancreatic insulin producing cells. This autoimmune response begins months or even years before the first presentation of signs and symptoms of hyperglycemia and at the time of clinical diagnosis near 30% of -cell mass still remains. In daily clinical practice, the main therapeutic option for T1DM is multiple subcutaneous insulin injections that are shown to promote tight glucose control and reduce much of diabetic chronic complications, especially microvascular complications. Another important aspect related to long-term complications of diabetes is that patients with initially larger -cell mass suffer less microvascular complications and less hypoglycemic events than those patients with small -cell mass. In face of this, -cell preservation is another important target in the management of type 1 diabetes and its related complications. For many years, various immunomodulatory regimens were tested aiming at blocking autoimmunity against -cell mass and at promoting -cell preservation, mainly in secondary prevention trials. In this review, we summarize some of the most important studies involving -cell preservation by immunomodulation and discuss our preliminary data on autologous nonmyeloablative hematopoietic stem cell transplantation in newly-diagnosed T1DM.

Gene Expression Profiles Stratified according to Type 1 Diabetes Mellitus Susceptibility Regions

The MHC region (6p21) aggregates the major genes that contribute to susceptibility to type 1 diabetes (T1D). Three additional relevant susceptibility regions mapped on chromosomes 1p13 (PTPN22), 2q33 (CTLA-4), and 11p15 (insulin) have also been described by linkage studies. To evaluate the contribution of these susceptibility regions and the chromosomes that house these regions, we performed a large-scale differential gene expression on lymphomononuclear cells of recently diagnosed T1D patients, pinpointing relevant modulated genes clustered in these regions and their respective chromosomes. A total of 4608 cDNAs from the IMAGE library were spotted onto glass slides using robotic technology. Statistical analysis was carried out using the SAM program, and data regarding gene location and biological function were obtained at the SOURCE, NCBI, and FATIGO programs. Three induced genes were observed spanning around the MHC region (6p21-6p23), and seven modulated genes (5 repressed and 2 repressed) were seen spanning around the 6q21-24 region. Additional modulated genes were observed in and around the 1p13, 2q33, and 11p15 regions. Overall, modulated genes in these regions were primarily associated with cellular metabolism, transcription factors and signaling transduction. The differential gene expression characterization may identify new genes potentially involved with diabetes pathogenesis.

Factors involved in the T helper type 1 and type 2 cell commitment and osteoclast regulation in inflammatory apical diseases

Periapical chronic lesion formation involves activation of the immune response and alveolar bone resorption around the tooth apex. However, the overall roles of T helper type 1 (Th1), Th2, and T-regulatory cell (Treg) responses and osteoclast regulatory factors in periapical cysts and granulomas have not been fully determined. This study aimed to investigate whether different forms of apical periodontitis, namely cysts and granulomas, show different balances of Th1, Th2 regulators, Treg markers, and factors involved in osteoclast chemotaxis and activation. Gene expression of these factors was assessed using quantitative real-time polymerase chain reaction, in samples obtained from healthy gingiva (n = 8), periapical granulomas (n = 20), and cysts (n = 10). Periapical cysts exhibited a greater expression of GATA-3, while a greater expression of T-bet, Foxp3, and interleukin-10 (IL-10) was seen in granulomas. The expression of interferon-gamma, IL-4, and transforming growth factor-beta was similar in both lesions. Regarding osteoclastic factors, while the expression of SDF-1 alpha/CXCL12 and CCR1 was higher in cysts, the expression of RANKL was significantly higher in granulomas. Both lesions exhibited similar expression of CXCR4, CK beta 8/CCL23, and osteoprotegerin, which were significantly higher than in control. Our results showed a predominance of osteoclast activity in granulomas that was correlated with the Th1 response. The concomitant expression of Treg cell markers suggests a possible suppression of the Th1 response in granulomas. On the other hand, in cysts the Th2 activity is augmented. The mechanisms of periradicular lesion development are still not fully understood but the imbalance of immune and osteoclastic cell activity in cysts and granulomas seems to be critically regulated by Treg cells.

Role of cytokines in mediating mechanical hypernociception in a model of delayed-type hypersensitivity in mice

In the present study, we used the electronic version of the von Frey test to investigate the role of cytokines (TNF-alpha and IL-1 beta) and chemokines (KC/CXCL-1) in the genesis of mechanical hypernociception during antigen-induced inflammation in mice. The nociceptive test consisted of evoking a hindpaw flexion reflex with a hand-held force transducer (electronic anesthesiometer) adapted with a 0.5 mm(2) polypropylene tip. The intraplantar administration of methylated bovine serum albumin (mBSA) in previously immunized (IM), but not in sham-immunized (SI) mice, induced mechanical hypernociception in a dose-dependant manner. Hypernociception induced by antigen was reduced in animals pretreated with IL-lra and reparixin (a non-competitive allosteric inhibitor of CXCR2), and in TNF receptor type 1 deficient (TNFR1-/-) mice. Consistently, antigen challenge induced a time-dependent release of TNF-alpha, IL-1 beta and KC/CXCL-1 in IM, but not in SI, mice. Consistently, antigen challenge induced a time-dependent release of TNF-alpha, IL-1 beta and KC/CXCL-1 in IM, but not in SI, mice. The increase in TNF-alpha levels preceded the increase in IL-1 beta and KC/CXCL1. Antigen-induced release of IL-1 beta and KC/CXCL1 was reduced in TNFR1-/- mice, and TNF-alpha induced hypernociception was inhibited by IL-lra and reparixin. Hypernociception induced by IL-1 beta in immunized mice was inhibited by indomethacin, whereas KC/CXCL1-induced hypernociception was inhibited by indomethacin and guanethidine, Antigen-induced hypernociception was reduced by indomethacin and guanethidine and abolished by the two drugs combined. Together, these results suggest that inflammation associated with an adaptive immune response induces hypernociception that is mediated by an initial release of TNF-alpha, which triggers that subsequent release of IL-1 beta and KC/CXCL1. The latter cytokines in turn stimulate the release of the direct-acting final mediator, prostanoids and sympathetic amines. (C) 2008 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.

Internal Pudendal Artery from Type 2 Diabetic Female Rats Demonstrate Elevated Endothelin-1-Mediated Constriction

Introduction. Diabetes is a risk factor for female sexual dysfunction (FSD). FSD has several etiologies, including a vasculogenic component that could be exacerbated in diabetes. The internal pudendal artery supplies blood to the vagina and clitoris and diabetes-associated functional abnormalities in this vascular bed may contribute to FSD. Aim. The Goto-Kakizaki (GK) rat is a non-obese model of type 2 diabetes with elevated endothelin-1 (ET-1) activity. We hypothesize that female GK rats have diminished sexual responses and that the internal pudendal arteries demonstrate increased ET-1 constrictor sensitivity. Methods. Female Wistar and GK rats were used. Apomorphine (APO)-mediated genital vasocongestive arousal (GVA) was measured. Functional contraction (ET-1 and phenylephrine) and relaxation (acetylcholine, ACh) in the presence or absence of the ETA receptor antagonist (ET(A)R; atrasentan) or Rho-kinase inhibitor (Y-27632) were assessed in the internal pudendal and mesenteric arteries. Protein expression of ET-1 and RhoA/Rho-kinase signaling pathway was determined in the internal pudendal and mesenteric arteries. Main Outcome Measure. APO-mediated GVAs; contraction and relaxation of internal pudendal and mesenteric arteries; ET-1/RhoA/Rho-kinase protein expression. Results. GK rats demonstrated no APO-induced GVAs. Internal pudendal arteries, but not mesenteric arteries, from GK rats exhibited greater contractile sensitivity to ET-1 compared with Wistar arteries. ETAR blockade reduced ET-1-mediated constriction in GK internal pudendal and mesenteric arteries. Rho-kinase inhibition reduced ET-1-mediated constriction of GK internal pudendal but not mesenteric arteries; however, it had no effect on arteries from Wistar rats. RhoA protein expression was elevated in GK internal pudendal arteries. At the highest concentrations, ACh-mediated relaxation was greater in the GK internal pudendal artery; however, no difference was observed in the mesenteric artery. Conclusions. Female GK rats demonstrate decreased sexual responses that may be because of increased constrictor sensitivity to the ET-1/RhoA/Rho-kinase signaling in the internal pudendal artery. Allahdadi KJ, Hannan JL, Ergul A, Tostes RC, and Webb RC. Internal pudendal artery from type 2 diabetic female rats demonstrate elevated endothelin-1-mediated constriction. J Sex Med 2011;8:2472-2483.

Risk stratification in neonates and infants submitted to cardiac surgery with cardiopulmonary bypass: A multimarker approach combining inflammatory mediators, N-terminal pro-B-type natriuretic peptide and troponin I

Low cardiac output syndrome (LCOS) is a common problem following cardiac surgery with cardiopulmonary bypass (CPB) in neonates and infants, and its early recognition remains a challenging task. We aimed to test whether a multimarker approach combining inflammatory and cardiac markers provides complementary information for prediction of LCOS and death in children submitted to cardiac surgery with CPB. Forty-six children younger than 18 months with congenital heart defects were prospectively enrolled. No intervention was made. Blood samples were collected pre-operatively, during CPB and post-operatively (PO) for measurement of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Clinical data and outcome variables were recorded. Logistic regression was used to identify predictors of LCOS and death. Multivariate logistic regression identified pre-operative NT-proBNP and IL-8 4 h PO as independent predictors of LCOS, while cTnI 4 h PO and CPB length were independent predictors of death. The use of inflammatory and cardiac markers in combination improved sensitivity, negative predictive value and accuracy of the models. In conclusion, the combined assessment of inflammatory and cardiac biochemical markers can be useful for identifying young children at increased risk for LCOS and death after heart surgery with CPB. (C) 2008 Elsevier Ltd. All rights reserved.

C-Peptide Levels and Insulin Independence Following Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in Newly Diagnosed Type 1 Diabetes Mellitus

Context In 2007, the effects of the autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) in 15 patients with type 1 diabetes mellitus (DM) were reported. Most patients became insulin free with normal levels of glycated hemoglobin A(1c) (HbA(1c)) during a mean 18.8-month follow-up. To investigate if this effect was due to preservation of beta-cell mass, continued monitoring was performed of C-peptide levels after stem cell transplantation in the 15 original and 8 additional patients. Objective To determine C-peptide levels after autologous nonmyeloablative HSCT in patients with newly diagnosed type 1 DM during a longer follow-up. Design, Setting, and Participants A prospective phase 1/2 study of 23 patients with type 1 DM(aged 13-31 years) diagnosed in the previous 6 weeks by clinical findings with hyperglycemia and confirmed by measurement of serum levels of anti glutamic acid decarboxylase antibodies. Enrollment was November 2003-April 2008, with follow-up until December 2008 at the Bone Marrow Transplantation Unit of the School of Medicine of Ribeirao Preto, Ribeirao Preto, Brazil. Hematopoietic stem cells were mobilized via the 2007 protocol. Main Outcome Measures C-peptide levels measured during the mixed-meal tolerance test, before, and at different times following HSCT. Secondary end points included morbidity and mortality from transplantation, temporal changes in exogenous insulin requirements, and serum levels of HbA1c. Results During a 7- to 58-month follow-up (mean, 29.8 months; median, 30 months), 20 patients without previous ketoacidosis and not receiving corticosteroids during the preparative regimen became insulin free. Twelve patients maintained this status for a mean 31 months (range, 14-52 months) and 8 patients relapsed and resumed insulin use at low dose (0.1-0.3 IU/kg). In the continuous insulin-independent group, HbA(1c) levels were less than 7.0% and mean (SE) area under the curve (AUC) of C-peptide levels increased significantly from 225.0 (75.2) ng/mL per 2 hours pretransplantation to 785.4 (90.3) ng/mL per 2 hours at 24 months posttransplantation (P<.001) and to 728.1 (144.4) ng/mL per 2 hours at 36 months (P=.001). In the transient insulin-independent group, mean (SE) AUC of C-peptide levels also increased from 148.9 (75.2) ng/mL per 2 hours pretransplantation to 546.8 (96.9) ng/mL per 2 hours at 36 months (P=.001), which was sustained at 48 months. In this group, 2 patients regained insulin independence after treatment with sitagliptin, which was associated with increase in C-peptide levels. Two patients developed bilateral nosocomial pneumonia, 3 patients developed late endocrine dysfunction, and 9 patients developed oligospermia. There was no mortality. Conclusion After a mean follow-up of 29.8 months following autologous nonmyeloablative HSCT in patients with newly diagnosed type 1 DM, C-peptide levels increased significantly and the majority of patients achieved insulin independence with good glycemic control. Trial Registration clinicaltrials.gov Identifier: NCT00315133

A Nationwide Population-Based Study of Tension-Type Headache in Brazil

To estimate the 1-year prevalence of tension-type headache (TTH) and the degree of the association of TTH with some sociodemographic characteristics of a representative sample of the adult population of Brazil. This was an observational, cross-sectional, population-based study. We conducted telephone interviews on 3848 people, aged 18-79 years, randomly selected from the 27 states of Brazil. Trained lay interviewers administered the structured questionnaire. It included questions about the sociodemographic characteristics of the population, as well as questions about headache. The degree of the association was calculated through prevalence ratios, adjusted with Poisson regression by gender, age, years of education, marital status, household income, job status, body mass index (BMI), and physical exercise. The estimated 1-year gender- and-age-adjusted prevalence of TTH was 13.0% (95% CI: 11.8-14.2%); 15.4% in males and 9.5% in females. The prevalence of probable TTH was 22.6% (95% CI: 21.1-24.1%). Most (86.2%) subjects reported episodic TTH; 6.4% had chronic TTH. The prevalence was higher at 18-29 years of age (16.2%). TTH was 1.6 times more prevalent in men, and 1.54 times more in subjects with more than 11 years of education. There was no significant association of TTH with marital or job status, household income, BMI, and physical activity. This is the first nationwide epidemiological study of TTH in Brazil. The overall prevalence of TTH in Brazil is low, at 13%. TTH is significantly more prevalent in males and subjects with higher education level.

Effects of equine chorionic gonadotropin and type of ovulatory stimulus in a timed-AI protocol on reproductive responses in dairy cows

The objectives were to evaluate the effects of equine chorionic gonadotropin (eCG) supplementation (with or without eCG) and type of ovulatory stimulus (GnRH or ECP) on ovarian follicular dynamics, luteal function, and pregnancies per AI (P/AI) in Holstein cows receiving timed artificial insemination (TAI). On Day 0, 742 cows in a total of 782 breedings, received 2 mg of estradiol benzoate (EB) and one intravaginal progesterone (P4) insert (CIDR). On Day 8, the CIDR was removed, and all cows were given PGF2 alpha and assigned to one of four treatments in a 2 x 2 factorial arrangement: (1) CG: GnRH 48 h later; (2) CE: ECP; (3) EG: eCG + GnRH 48 It later; (4) EE: eCG + ECP. There were significant interactions for eCG x ovulatory stimulus and eCG x BCS. Cows in the CG group were less likely (28.9% vs. 33.8%; P < 0.05) to become pregnant compared with those in the EG group (odds ratio [OR] = 0.28). There were no differences in P/AI between CE and EE cows (30.9% vs. 29.1%; OR = 0.85; P = 0.56), respectively. Thinner cows not receiving eCG had lower P/AI than thinner cows receiving eCG (15.2% vs. 38.0%; OR = 0.20; P < 0.01). Treatment with eCG tended to increase serum progestesterone concentrations during the diestrus following synchronized ovulation (P < 0.10). However, the treatment used to induce ovulation did not affect CL volume or serum progesterone concentrations. In conclusion, both ECP and GnRH yielded comparable P/AI. However, eCG treatment at CIDR removal increased pregnancy rate in cows induced to ovulate with GnRH and in cows with lower BCS. (C) 2009 Elsevier Inc. All rights reserved.

Differences in thermoregulatory ability between slick-haired and wild-type lactating Holstein cows in response to acute heat stress

Animals inheriting the slick hair gene have a short, sleek, and sometimes glossy coat. The objective of the present study was to determine whether slick-haired Holstein cows regulate body temperature more effectively than wild-type Holstein cows when exposed to an acute increase in heat stress. Lactating slick cows (n = 10) and wild-type cows (n = 10) were placed for 10 h in an indoor environment with a solid roof, fans, and evaporative cooling or in an outdoor environment with shade cloth and no fans or evaporative cooling. Cows were exposed to both environments in a single reversal design. Vaginal temperature, respiration rate, surface temperature, and sweating rate were measured at 1200, 1500, 1800, and 2100 h (replicate 1) or 1200 and 1500 h (replicate 2), and blood samples were collected for plasma cortisol concentration. Cows in the outdoor environment had higher vaginal and surface temperatures, respiration rates, and sweating rates than cows in the indoor environment. In both environments, slick-haired cows had lower vaginal temperatures (indoor: 39.0 vs. 39.4 degrees C; outdoor 39.6 vs. 40.2 degrees C; SEM = 0.07) and respiration rate (indoor: 67 vs. 79 breaths/min; outdoor 97 vs. 107 breaths/min; SEM = 5.5) than wild-type cows and greater sweating rates in unclipped areas of skin (indoor: 57 vs. 43 g.h(-1)/m(2); outdoor 82 vs. 61 g.h(-1)/m(2); SEM = 8). Clipping the hair at the site of sweating measurement eliminated the difference between slick-haired and wild-type cows. Results indicate that slick-haired Holstein cows can regulate body temperature more effectively than wild-type cows during heat stress. One reason slick-haired animals are better able to regulate body temperature is increased sweating rate.

Cardiovascular responses to different stages of restorative dental treatment unaffected by local anaesthetic type

Background: The aim of this study was to evaluate the cardiovascular effects of maxillary infiltration using 2% lidocaine with 1: 100 000 adrenaline, 4% articaine with 1: 200 000 adrenaline, and 4% articaine with 1: 100 000 adrenaline in different stages during restorative dental procedures. Methods: Twenty healthy patients randomly received 1.8 mL of the three local anaesthetics. Systolic blood pressure, average blood pressure, diastolic blood pressure, and heart rate were evaluated by the oscillometric and photoplethysmograph methods in seven stages during the appointment. Results: Statistical analysis by ANOVA and Tukey tests of cardiovascular parameters did not show significant differences between the anaesthetic associations. There were significant differences for the parameters among different clinical stages. Conclusions: The variation of cardiovascular parameters was similar for lidocaine and articaine with both adrenaline concentrations and showed no advantage of one drug over the other. Cardiovascular parameters were influenced by the stages of the dental procedures, which showed the effect of anxiety during restorative dental treatment.

Salivary Interleukin-6, Matrix Metalloproteinase-8, and Osteoprotegerin in Patients With Periodontitis and Diabetes

Background: Diabetes and periodontitis produce a protein discharge that can be reflected in saliva. This study evaluates the salivary concentrations of interleukin (IL)-6, matrix metalloproteinase (MMP)-8, and osteoprotegerin (OPG) in patients with periodontitis with type 2 diabetes. Methods: Whole saliva samples were obtained from 90 subjects who were divided into four groups: healthy (control; n = 22), untreated periodontitis (UPD; n = 24), diabetes mellitus (DM; n = 20), and UPD + DM (n = 24) groups. Clinical and metabolic data were recorded. Salivary IL-6, MMP-8, and OPG concentrations were determined by a standard enzyme-linked immunosorbent assay. Results: The UPD and UPD + DM groups exhibited higher salivary IL-6 than the control and DM groups (P <0.01). The salivary MMP-8 concentrations in all diseased groups (UPD, DM, and UPD + DM) were higher than in the control group (P <0.01). The salivary OPG concentrations in the DM group were higher than in the UPD and control groups (P<0.05). In the UPD + DM group, salivary IL-6 was correlated with glycated hemoglobin (HbA1c) levels (r = 0.60; P<0.05). The regression analysis indicated that the number of remaining teeth, clinical attachment level, and IL-6 might have influenced the HbA1c levels in patients with diabetes. Conclusions: Salivary 1L-6 concentrations were elevated in patients with periodontitis with or without diabetes. Salivary MMP-8 and OPG concentrations were elevated regardless of periodontal inflammation in patients with diabetes. Therefore, periodontitis and diabetes are conditions that may interfere with protein expression and should be considered when using saliva for diagnoses. J Periodontol 2010;81:384-391.