Serum Biomarkers for Discrimination between Hepatitis C-Related Arthropathy and Early Rheumatoid Arthritis.

In the present study, we aimed to estimate the concentrations of cytokines (interleukin 6, IL-6, tumor necrosis factor-α, TNF-α) and auto-antibodies (rheumatoid factor IgM isotype, IgM-RF, antinuclear auto-antibodies, ANA, anti-cyclic citrullinated peptide antibodies IgG isotype, IgG anti-CCP3.1, anti-cardiolipin IgG isotype, IgG anti-aCL) in serum of patients with eRA (early rheumatoid arthritis) and HCVrA (hepatitis C virus-related arthropathy) and to assess the utility of IL-6, TNF-α together with IgG anti-CCP and IgM-RF in distinguishing between patients with true eRA and HCVrA, in the idea of using them as differential immunomarkers. Serum samples were collected from 54 patients (30 diagnosed with eRA-subgroup 1 and 24 with HCVrA-subgroup 2) and from 28 healthy control persons. For the evaluation of serum concentrations of studied cytokines and auto-antibodies, we used immunoenzimatique techniques. The serum concentrations of both proinflammatory cytokines were statistically significantly higher in patients of subgroup 1 and subgroup 2, compared to the control group (p < 0.0001). Our study showed statistically significant differences of the mean concentrations only for ANA and IgG anti-CCP between subgroup 1 and subgroup 2. We also observed that IL-6 and TNF-α better correlated with auto-antibodies in subgroup 1 than in subgroup 2. In both subgroups of patients, ROC curves indicated that IL-6 and TNF-α have a higher diagnostic utility as markers of disease. In conclusion, we can say that, due to high sensitivity for diagnostic accuracy, determination of serum concentrations of IL-6 and TNF-α, possibly in combination with auto-antibodies, could be useful in the diagnosis and distinguishing between patients with true eRA and HCV patients with articular manifestation and may prove useful in the monitoring of the disease course.

Determination of VEGFR-2 (KDR) 604A>G Polymorphism in Pancreatic Disorders.

Pancreatic disorders have a high prevalence worldwide. Despite the fact that screening methods became more effective and the knowledge we have nowadays about pancreatic diseases has enhanced, their incidence remains high. Our purpose was to determine whether single nucleotide polymorphism (SNP) of VEGFR-2/KDR (vascular endothelial growth factor receptor 2/kinase insert domain receptor) influences susceptibility to develop pancreatic pathology. Genomic DNA was extracted from blood samples collected from patients diagnosed with acute pancreatitis (n = 110), chronic pancreatitis (n = 25), pancreatic cancer (n = 82) and healthy controls (n = 232). VEGFR-2 (KDR) 604A>G (rs2071559) polymorphism frequency was determined with TaqMan allelic discrimination assays. Statistical assessment was performed by associating genetic polymorphism with clinical and pathological data. In both pancreatic disorders and healthy control groups the polymorphism we studied was in Hardy-Weinberg equilibrium. Association between increased risk for pancreatic disorders and studied polymorphism was statistically significant. KDR 604AG and AG + GG genotypes were more prevalent in acute pancreatitis and pancreatic cancer patients than in controls. These genotypes influence disease development in a low rate. No association was found between chronic pancreatitis and KDR 604AG and AG + GG genotypes. In Romanian cohort, we found an association between the KDR 604A→G polymorphism and acute pancreatitis and pancreatic cancer. Carriers of the -604G variant allele were more frequent among acute pancreatitis and pancreatic cancer than among controls, suggesting that KDR 604G allele may confer an increased risk for these diseases. In the future, more extensive studies on larger groups are necessary, in order to clarify the role of VEGFR2 polymorphisms in pancreatic pathology.

Involvement of TSP1 and MMP9/NGAL in angiogenesis during orthodontic periodontal remodeling.

In the present study the aim was to measure the levels of Thrombospondin-1 (TSP1) and Lipocalin-2/matrix metalloproteinase 9 (MMP9/NGAL) complex in gingival crevicular fluid (GCF) at different time points of orthodontic treatment, to determine the relationship between these values and those of total-matrix metalloproteinase 9 (MMP9) and theirs implication in angiogenesis balance, in the situation of a good control of the bacterial plaque, emphasizing the role of TSP1 and MMP9/NGAL complex. GCF samples were collected from 16 young orthodontic patients requiring upper canine distalization (test tooth) with first premolar extraction. The contralateral canine (control tooth) was free from orthodontic force. For the orthodontic appliance, brackets Roth 0.018 inch with 0.012 inch NiTi archwire and a laceback were used. TSP1, MMP9/NGAL, and MMP9 increased from 1 hour before activation of orthodontic appliance to a maximum at 8 hours for MMP9 and 72 hours for MMP9/NGAL and TSP1. The results show a change in time of TSP1, MMP9/NGAL, and MMP9 levels in GCF of patients with this method of orthodontic treatment. The powerful correlation of MMP9/NGAL with TSP1 suggests their stronger involvement in angiogenesis processes in PDL during orthodontic periodontal remodeling, in the situation of a healthy periodontium and a good control of the bacterial plaque.

Perioperative inflammatory response in natural orifice translumenal endoscopic surgery.

BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) could offer multiple advantages compared with the laparoscopic approach. One such potential advantage, not yet proven, is the inferior inflammatory response, which translates into less significant operative stress. This study aimed to compare the immuno-inflammatory response between transgastric NOTES and laparoscopy for simple surgical procedures (oophorectomy) with reference to the cytokine levels. METHODS: For this study, 20 female pigs were randomly assigned to either NOTES or laparoscopic oophorectomy. Seven animals were used as a control group and received only general anesthesia, with no other procedure performed. Blood samples were obtained before surgery, 1 h after the start of the procedure, and at the end of the intervention. The serum levels of IL1ß and IL6 were determined using a porcine enzyme-linked immunosorbent assay (ELISA) kit. The mean operative time, intraoperative incidents, and postoperative complications were recorded. On postoperative day 14, the animals were killed, and gastric leak tests were performed. RESULTS: Both the NOTES and laparoscopic procedures were successfully completed. No gastric leaks were observed during necropsy. The transgastric oophorectomy required a significantly longer time to perform than the laparoscopic surgery. Compared with the NOTES procedures, laparoscopic oophorectomy resulted in significantly higher levels of interleukin-1ß (IL1ß) (42.34 ± 5.26 ng/ml with NOTES vs 46.93 ± 4.79 ng/ml with laparoscopy; p = 0.028) and IL6 (66.95 ± 7.29 ng/ml with NOTES vs 71.75 ± 4.76 ng/ml with laparoscopy, p = 0.049) during the postoperative phase. No statistical difference was detected between the pre- and postoperative cytokine levels in the NOTES group. CONCLUSION: The study findings suggest that pure transgastric endoscopic surgery is a safe approach resulting in less perioperative inflammatory response than laparoscopy in the early postoperative phase.

Host immune response in chronic hepatitis C infection: involvement of cytokines and inflammasomes.

Chronic liver disease is a major health issue worldwide and chronic hepatitis C (CHC) is associated with an increased risk of cirrhosis and hepatocellular carcinoma (HCC). There is evidence that the hepatitis C virus (HCV) infection is correlated with immune senescence by way of immune activation and chronic inflammation, which lead to increased metabolic and cardiovascular risk, as well as progressive liver damage. Both the innate and adaptive immunity are firmly tied to the prognosis of an infection with HCV and its response to antiviral therapy. HCV is therefore associated with increased pro-inflammatory status, heightened production of cytokines, prolonged systemic inflammation, as well as increased morbidity and mortality, mainly due to the progression of hepatic fibrosis and HCC, but also secondary to cardiovascular diseases. Viral hepatic pathology is increasingly considered a disease that is no longer merely limited to the liver, but one with multiple metabolic consequences. Numerous in vitro studies, using experimental models of acute or chronic inflammation of the liver, has brought new information on immunopathological mechanisms resulting from viral infections and have highlighted the importance of involving complex structures, inflammasomes complex, in these mechanisms, in addition to the involvement of numerous proinflammatory cytokines. Beyond obtaining a sustained viral response and halting the aforementioned hepatic fibrosis, the current therapeutic "treat-to-target" strategies are presently focused on immune-mediated and metabolic disorders, to improve the quality of life and long-term prognosis of CHC patients.

The role of mediating factors involved in angiogenesis during implantation.

Angiogenesis is a critical component of normal implantation and placentation and underlines the importance of vascularization in early pregnancy. Differentiated expression of angiogenesis factors in different decision tissues during different stages of implantation, indicates their involvement in the regulation of vascular remodeling and angiogenesis. Disorders in vascular development may play a role in the pathogenesis of recurrent abortions. The success of implantation, placentation and subsequent pregnancy evolution requires coordination of vascular development and adaptations at both sides of the maternal-fetal interface. The human implantation process is a continuous process, which begins with the apposition and attachment of the blastocyst to the apical surface of the luminal endometrial epithelium and continues throughout the first trimester of pregnancy until the extravillous trophoblast invades and remodels maternal vascularization. Numerous regulatory molecules play functional roles in many processes, including preparation of the endometrial stroma (decidualization), epithelium for implantation, control of trophoblastic adhesion and invasion. These regulatory molecules include cytokines, chemokines, and proteases, many of which are expressed by different cell types, having slightly different functions as the implant progresses.

Evaluation of iNOS -2087A>G polymorphism in recurrent pregnancy loss.

BACKGROUND: Due to its role in angiogenesis, the inducible nitric oxide synthase (iNOS) gene promoter polymorphism may have a presumed role in recurrent spontaneous abortions (RSA). It is an intensely studied protein, a biological mediator, a modulator and an effector molecule by implication in numerous physiological processes: vasodilatation, angiogenesis, immunity, tissue remodeling, smooth muscle activity. AIM: Our study aims to investigate a possible association between iNOS -2087A>G (rs2297518) polymorphism and the occurrence of idiopathic recurrent pregnancy loss (RPL). PATIENTS, MATERIALS AND METHODS: In this study, as in the previously published one, 169 women, diagnosed with RPL, in the Clinics of Obstetrics and Gynecology, "Filantropia" Municipal Hospital, Craiova, Romania, were subjected to the analysis, from October 2009 to October 2016. As a control group, we used 145 women. Subjects from both groups were genotyped using specific probes for TaqMan polymerase chain reaction (PCR), allelic discrimination technique. RESULTS: We evaluated in this study a possible association between iNOS -2087A>G (rs2297518) polymorphism and the occurrence of idiopathic RPL. The chi-square test showed no significant association between the presence of this polymorphism and the increased risk to develop RPL. When we performed a comparative analysis of the frequency of genotypes and our statistical data, it was observed that this polymorphism, iNOS -2087A>G (rs2297518), has not been associated with an increased risk of developing RPL. Also, when one genotype was compared with another, we did not obtain any association that would have statistical significance, between the presence of this polymorphism and the increased risk for patients to develop RPL [in dominant - A allele carriers, iNOS 2087 AG+AA vs. GG: odds ratio (OR) 1.31, 95% confidence interval (CI) 0.83-2.07, p=0.24]. Analyzing the overall risk of developing RPL by iNOS 2087 single-nucleotide polymorphism (SNP) genotype frequencies, between controls and RPL patients (which were stratified by number of consecutive PLs), taking into account the number of consecutive pregnancies, the chi-square test showed no association between the presence of this polymorphism and the increased risk for developing RPL in all three subgroups we analyzed (in a dominant model - A allele carriers, iNOS 2087 AG+AA vs. GG: the first subgroup, OR 1.31, 95% CI 0.83-2.07, p=0.24; the second subgroup, OR 1.26, 95% CI 0.76-2.11, p=0.37; the three subgroup, OR 1.4, 95% CI 0.77-2.53, p=0.272). CONCLUSIONS: The iNOS -2087A>G (rs2297518) gene polymorphism does not influence RPL in the study area of Dolj County, Romania.

Serological and immunohistochemical biomarkers for discrimination between benign and malignant ovarian tumors.

BACKGROUND: Ovarian tumors are difficult to diagnose because symptoms are nonspecific, occurring in late stages when the tumor mass reaches large proportions, when complications arise or when dissemination occurs in neighboring organs. Research over the past decades has been aimed at clarifying the mechanisms of ovarian oncogenesis, to identify ways of transforming normal cells into a neoplastic cell, as well as discovering of tumor markers used in the detection of neoplastic processes, along with the synthesis of therapeutic substances, which would influence its development. AIMS: In our study, we aimed to determine the serum concentrations of cancer antigen 125 (CA125), human epididymis protein 4 (HE4) and the risk of ovarian malignancy algorithm (ROMA) in patients with ovarian tumors, as well as assessing their diagnostic performance. Furthermore, another objective of the study was to identify a concordant relation between serological and immunohistochemical (IHC) biomarkers in supporting and aiding the differentiation between benign and malignant tumors, here including the group of borderline tumors. PATIENTS, MATERIALS AND METHODS: We accomplished a study that included a group of 92 patients diagnosed with ovarian tumors (benign and malignant), who were examined and treated between January 2015 and July 2018. The study was conducted at the Clinics of Obstetrics and Gynecology, "Filantropia" Municipal Hospital of Craiova, Romania. The patients were divided into two groups: the group of patients with benign tumors, subdivided into pre-menopausal (51 cases, 55.43%) and post-menopausal (30 cases, 32.6%) patients, and a group of patients who presented with malignant formation (seven cases with malignant tumors, 7.61% and four cases with borderline tumors, 4.34%, respectively). In parallel, we investigated 35 women as control subjects, who did not have a personal history of ovarian tumors. RESULTS: In our study, we have observed that for the analyzed parameters, CA125, HE4, and the ROMA index, significantly higher serum concentrations were detected in the malignant tumor group, when these have been compared to the values obtained for the pre-menopausal and for the post-menopausal subgroup, respectively. The IHC results also showed different expression patterns for the different markers studied. Corroboration of the results of the serological biomarkers with the IHC data is necessary and useful for differentiating borderline tumors and for their final integration as benign or malignant ovarian tumors. This can only be done for the cases with surgical resections, thus having tissue available. CONCLUSIONS: The serum levels of CA125 and HE4, ROMA index and IHC markers for surgical tissue fragments play a very important role in discriminating and reporting borderline ovarian tumors, as well as benign or malignant ovarian forms. Due to the superior sensitivity and specificity of CA125 and HE4, we can consider these markers as an alternative or additional diagnostic criterion to the ROMA index.

Sepsis and identification of reliable biomarkers for postoperative period prognosis.

Sepsis is currently defined as the presence of organ dysfunction occurring as the result of a disturbed host response to a serious infection. Sepsis is one of the most common diseases, which cause mortality and a considerable absorber of healthcare resources. Despite progress in technology and improving knowledge of pathophysiology, the disease mechanism is still poorly understood. At present, diagnosis is based on non-specific physiological criteria and on the late identification of the pathogen. For these reasons, the diagnosis may be uncertain, treatment delayed or an immunomodulatory therapy cannot be established. An early and reliable diagnosis is essential to achieve better outcomes on disease progression. The host response to infection involves hundreds of many mediators of which have been proposed as biomarkers. There is a need for new diagnostic approaches for sepsis, new sepsis biomarkers that can aid in diagnosis, therapeutic decision and monitoring of the response to therapy. The differentiation of sepsis from non-infectious systemic inflammatory response syndrome is difficult, and the search for a highly accurate biomarker of sepsis has become one important objective of the medicine. The goal of our review is to summarize the recent advances on the most commonly studied serum biomarkers, evaluated in clinical and experimental studies, for early diagnosis of sepsis and their informative value in diagnosis, prognosis, or response to therapy. In this context, we have tracked the clinical utility of measuring serum biomarkers, such as procalcitonin, pro- and anti-inflammatory cytokines, C-reactive protein, leptin and their combinations. Currently, has not been identified an ideal biomarker to aid in the diagnosis of sepsis. It is hoped that the discovery of new serum markers, as well as their combinations, will serve for the diagnosis and prognosis of sepsis.

The association between chronic pancreatitis and the iNOS-2087A>G polymorphism.

INTRODUCTION: Chronic pancreatitis is morphologically characterized by ductal dysplasia, breeding grounds for the proliferation of the ductal cells, the degenerative changes in pancreatic acinar cells and fibrosis, and it is defined on the basis of the clinical, morphological and functional criteria. AIM: The aim of our study is to examine the existence of a possible correlation between the iNOS-2087A>G polymorphism and chronic pancreatitis by means of the genetic analysis. MATERIAL AND METHOD: We have conducted the study at the Gastroenterology Clinic and the Research Center of Gastroenterology and Hepatology of the University of Medicine and Pharmacy, Craiova, between March 2015 - September 2016. The study had a prospective character. Both for the 58 patients diagnosed with chronic pancreatitis and for the 132 patients in the witness group, the biological material was represented by blood, (around 2.5 - 5 milliliters of venous blood) let on EDTA and kept at 4°C up to the separation of the DNA molecule. All the patients were genotyped for the iNOS - 2087A>G polymorphism, by means of the Real Time PCR technique with TaqMan probes. RESULTS: Analysing the prevalence of the iNOS genotypes within the study group and witness group, we have noticed that, statistically speaking, there are no significant differences between the two groups. CONCLUSION: As a conclusion, in the study lot we can sustain that the risk of developing chronic pancreatitis is not increased by the presence of the iNOS-2087A>G polymorphism.

Expression of Pentraxin 3 and Thrombospondin 1 in Gingival Crevicular Fluid during Wound Healing after Gingivectomy in Postorthodontic Patients.

Background. Wound healing is a tissue repair process after an injury, and two of its main components are inflammation and angiogenesis, in which course a cascade of mediators is involved. The aim of this research was to evaluate the involvement of Pentraxin 3 and Thrombospondin 1 in wound healing after periodontal surgery (gingivectomy) for gingival overgrowth during orthodontic treatment with or without magnification devices, by assessing their levels in GCF. Methods. From 19 patients with gingival overgrowth as a result of fixed orthodontic treatment, the overgrown gingiva was removed by gingivectomy, from one half of the mandibular arch without magnification and from the other under magnification. Pentraxin 3 and Thrombospondin 1 were determined from gingival crevicular fluid by ELISA tests. Results. Statistically significant differences (p < 0.05) and correlations between levels of the two biomarkers were analyzed. Statistically significant differences were established between levels of the two biomarkers at different time points, with significant positive correlation at the point of 24 hours. Conclusions. Within the limitations of this study, the results seem to sustain the involvement of Pentraxin 3 and Thrombospondin 1 in the processes of inflammation and angiogenesis in wound healing of patients with postorthodontic gingivectomy. The dynamics of Pentraxin 3 and Thrombospondin 1 levels could suggest a reduced inflammation and a faster angiogenesis using microsurgery.

Lymph node tuberculosis after melanoma treatment - sometimes the patient is lucky.

Tuberculosis (TB) is considered a pulmonary disease that can however disseminate to other organs through hematogenous dissemination following primary TB infection. Evolution of the disease can either be precocious, before healing of the primary infection, or late after primary infection, due to reactivation of initial lesions usually because of simultaneous immunosuppressive factors such as diabetes, renal disease, hepatic disease or different type of immunosuppressing treatments. Rare cases when tuberculosis and cancer are diagnosed at the same time create diagnostic difficulties and therapeutic challenges. We present the case of an asymptomatic 52-year-old female that was diagnosed "by chance, at the right moment" with a form of skin melanoma on the right forearm, for which she received a rather well tolerated cytostatic treatment. At the end of this treatment, she was also investigated for a breast mass that proved to be benign; however, enlarged lymph nodes were discovered in the right armpit were discovered upon further investigation. One of the lymph nodes was surgically removed, as first suspicion was of a metastasis from the skin melanoma. However, it was lymph node tuberculosis therefore anti-tuberculosis treatment was initiated. The patient tolerated the treatment with minor side effects. On few occasions, a patient can be diagnosed with incipient stages of skin melanoma and even more rarely the same patient is diagnosed and treated prematurely for lymph node tuberculosis. Sometimes, a successful outcome needs an organized and well-educated patient and a little luck.

Peritumoral inflammatory reaction in non-melanoma skin cancers - histological and immunohistochemical study.

Non-melanoma skin cancers (NMSCs) are the most frequent types of cancer in white skin populations, all over the world. In the last 40 years, there was observed a rapid increase of their incidence, because of the UV radiations exposure and weather changes. Although its morbidity is a relatively modest one, the direct social costs of NMSCs are quite substantial due to a high incidence. Due to these reasons, numerous studies try to clarify the etiopathogenic mechanisms of NMSCs, to elaborate treatment and prevention measures. In the last years, a special attention was given to the relation between inflammation and skin cancer. In our study, we performed a histological and immunohistological evaluation of the inflammatory reaction on a number of 73 surgical exeresis pieces coming from the patients diagnosed with NMSCs. Of these, 21 were squamous cell carcinomas (SCCs) and 52 basal cell carcinomas (BCCs). The peritumoral inflammatory reaction in NMSCs was an extremely variable one in intensity and distribution, from one case to another and even from one area to another within the same tumor, thus proving the complexity of the relations between tumor cells and the cells of the immune system. By comparing the intensity of the inflammatory reaction between the two main types of NMSCs, there was observed that in SCCs the inflammatory reaction was more intense in comparison to BCCs. Also, in SCC there was highlighted a more abundant inflammatory infiltrate in poorly differentiated carcinomas, in comparison to the well-differentiated ones. The presence of the immune system cells (T-lymphocytes, macrophages, mast cells) among the tumoral cells, in a direct contact with these, makes us believe that between the two categories of cells there may appear mechanisms of intercellular communication, distinct from the mechanisms of paracrine signaling.

The role of autoantibodies in health and disease.

Serum of healthy individuals contains antibodies that react with self and non-self antigens, generated in absence of external antigen stimulation. These antibodies, called natural antibodies, are particularly IgM isotype, are considered natural autoantibodies (NAA), displaying a moderate affinity for self-antigens. Although incidence of NAA in healthy individuals is not reported, it is established that autoreactive antibodies and B-cells, as well as autoreactive T-cells, are present in healthy persons. The functional abilities of NAA are not clear but is well accepted that they may participate in a variety of activities, such as maintenance of immune homeostasis, regulation of the immune response, resistance to infections, transport and functional modulation of biologically active molecules. On the other hand, specific adaptive immune responses through high-affinity, class-switched IgG autoantibodies, which bind self-proteins, can cause tissue damage or malfunctions, inducing autoimmune diseases. The new technology that allows for more autoantibody screening may further enhance the clinical utility of autoantibody tests, making it possible to diagnose autoimmune disease in its early stages and to intervene before installing injuries. The aim of this review paper is to succinctly analyze the progress in the physiological role and regulatory significance of natural autoantibodies in health and disease.

The Relationship of Cytokines IL-13 and IL-17 with Autoantibodies Profile in Early Rheumatoid Arthritis.

Aims. In the present study, we aimed to assess the concentrations of IL-13 and IL-17 in serum of patients with early rheumatoid arthritis (eRA), the investigation of correlation between the concentrations of these cytokines and disease activity score, and the concentration of some autoantibodies and the evaluation of the utility of IL-13 and -17 concentration measurements as markers of disease activity. Materials and Methods. Serum samples were collected from 30 patients and from 28 controls and analysed parameters. Results. The serum concentrations of IL-13, IL-17, anti-CCP, and IgM-RF were statistically significantly higher in patients with eRA, compared to the controls. IL-13 concentrations in the severe and moderate groups with eRA were statistically higher than in the mild and control groups. Also, in the case of IL-17, serum concentrations increased proportionally with the disease activity of eRA. We observe that concentrations of IL-13 and -17 did not correlate with autoantibodies. IL-17 concentration significantly positively correlated with CRP, while IL-13 concentration significantly negatively correlated with CRP. Disease activity score, DAS28, was strongly positively correlated with levels of ESR and weakly positively correlated with concentrations of anti-RA33 autoantibodies. IL-13 has a higher diagnostic utility than IL-17, CRP, ESR, IgM-RF, and anti-CCP as markers of disease activity. Conclusions. The presence of higher IL-13 and IL-17 serum levels in patients, compared with those of controls, confirms that these markers, found with high specificity, might be involved in the pathogenesis of eRA. IL-13 and IL-17 might be of better usefulness in the prediction of eRA activity status than IgM-RF and anti-CCP.

Significance of circulating and crevicular matrix metalloproteinase-9 in rheumatoid arthritis-chronic periodontitis association.

In the recent years, statistically significant associations between rheumatoid arthritis (RA) and periodontal disease have been identified. Emerging as a chronic inflammatory joint disease, RA displays various features and pathogenetic events similar to chronic periodontitis (CP). The purpose of this study was to evaluate the utility of determining systemic and crevicular levels of metalloproteinase-9 (MMP-9) as potential biomarkers for association between RA and CP. A total of fifty-six patients were included in the study. The subjects were categorized into four groups as follows: healthy-control (n = 21), active RA (n = 16), CP (n = 14), and RA-CP association (n = 12). Assessment of serum and crevicular concentrations of total MMP-9 (active and pro-MMP-9) was based on ELISA technique. The results of this study showed statistically significant differences of serum MMP-9 between patients groups and control. Serum levels of MMP-9 were similar in RA and RA-CP associated patients. Gingival crevicular fluid (GCF) recorded increased MMP-9 levels in RA-CP association subjects as compared to CP. Considering that RA-CP association is characterized by a disregulation of the inflammatory response, MMP-9 may play a role in the pathogenesis of RA-CP association. MMP-9 is therefore a sensitive tool in the diagnosis and management of patients affected by this binomial association.

Salivary and serum biomarkers for the study of side effects of aripiprazole coprescribed with mirtazapine in rats.

The aim of this study was to investigate whether the co-administration of aripiprazole and mirtazapine could determine weight gain and lipid metabolism disorders in Wistar rats, compared to the same side effects produced by mirtazapine alone, and the risk of hepatotoxicity due to the combination of the two substances. Tumor necrosis factor alpha (TNF-α), liver fatty acid binding protein (L-FABP/FABP1) and repulsive guidance molecule C/hemojuvelin (RGM-C/HJV) levels were determined in serum and in saliva. Also, serum levels for total cholesterol (TC), low and high-density lipoprotein (LDL, HDL), triglycerides (TG), aspartate aminotransferase (ASAT) and alanine amino transferase (ALAT) were assessed. We found positive and statistically significant correlations between serum and salivary levels of TNF-α, L-FABP/FABP1 and RGM-C/HJV. Mirtazapine determined significantly differences of TNF-α and L-FABP serum levels; final body weight; TC and LDL levels, leading to higher concentrations than its association with aripiprazole. Although not statistically significant, mirtazapine group experienced higher values for salivary levels of TNF-α, TG and ASAT, and lower values for HDL, compared to aripiprazole + mirtazapine group. The results suggest that aripiprazole might improve some of the disturbances caused by mirtazapine, and that the two drugs combination cause no additional alterations in liver function. Also, the findings indicate that TNF-α, L-FABP/FABP1 and RGM-C/HJV levels can be helpful as biomarkers for metabolic disturbances and impaired function of hepatocytes, and that their salivary determination can replace serum determination.

[Immunopathologic mechanism in some ocular diseases]. / Implicatii imunopatologice în unele afectiuni oculare.

OBJECTIVES: The goal of the present study is to elucidate the pathogenic mechanisms that determine the ocular involvement in some systemic diseases. MATERIAL AND METHODS: We have studied 45 patients with ocular diseases and concomitant systemic diseases (systemic lupus erythematosus-SLE, ankylosing spondylitis, Reiter syndrome, juvenile rheumatoid arthritis, Sjögren syndrome). The patients studied have been compared with a control group represented by 20 healthy individuals. In each case we have determined the serum levels of the following humoral markers: the C3 complement fraction, circulating immune complexes, autoantibodies (antinuclear autoantibodies, anti-double stranded DNA autoantibodies, anti-smooth muscle autoantibodies, anti-neutrophilic cytoplasm autoantibodies, anti-cardiolipin autoantibodies, anti-SSA, anti-SSB, rheumatoid factor). RESULTS: The autoantibodies detected in certain cases of uveitis suggest the existence of an autoimmune etiology; the antibody titers have been high in some severe cases of rheumatic uveitis, especially in patients with ankylosing spondylitis. We have found that there is a correlation between the presence and the titer of certain autoantibodies, and the onset and evolution of the disease. Specifically, the antinuclear autoantibodies may be considered a predictive factor for the development of chorio-retinopathy of SLE. Uveitis mediated by immune complexes has been seen in rheumatoid arthritis, ankylosing spondylitis, and SLE, these being the same systemic diseases where there is an important pathogenic role of immune complexes. CONCLUSIONS: The abnormal immunologic function, that was observed in the ocular inflammatory diseases studied, may be synthesized by the association between two immunopathologic phenomena; both of them are finalized by the non-self transformation of the antigens linked to various eye structures. These are represented by autoimmunity (of humoral, cellular, or mixed type), and the immediate type III hypersensitivity reaction. This study provides important data regarding the involvement of autoimmune diseases in the etiology of ocular diseases.

[Humoral and cellular immunity investigation in idiopathic uveitis]. / Investigarea imunitatii umorale si celulare în uveitele idiopatice.

OBJECTIVES: There is an amount of controversy regarding the patho-physiology of uveitis. Due to the fact that the eye (and especially the highly vascular tissues such as the uvea and the conjunctiva) is considered a special "target" for the immunopathologic reactions, the goal of our study is to contribute to the understanding of the causal role of the immune reactions in the development of idiopathic uveitis. MATERIAL AND METHODS: We have studied 48 patients with idiopathic uveitis and 20 control subjects (with no ocular symptomatology) for the following humoral and cellular immune markers: IgM and IgG, the C3 complement fraction, circulating immune complexes, autoantibodies (antinuclear autoantibodies, anti-double stranded DNA autoantibodies, anti-smooth muscle autoantibodies, anti-neutrophilic cytoplasm autoantibodies, anti-cardiolipin autoantibodies, anti-parietal cell autoantibodies), and lymphocyte subtypes. RESULTS: Changes in the serum levels of the immune humoral and cellular markers have been noted in 39 (81.25%) of the patients studied. C3 was decreased in 12 (30%) of all cases; the immune complex level was increased over 50 U/mL in 20 patients (51.28%). The presence of the above-mentioned autoantibodies was seen in 19 patients (48.71%), with different incidence. By flow cytometry the percentage of CD4+ (T helper lymphocytes) has been found to be decreased, and the percentage of CD8+ was found to be increased in 8 cases (20.51%). The opposite, the increase in the percentage of CD4+ lymphocytes, and the decrease in the percentage of CD8+ cells was seen in 25 (64.10%) of the studied patients. Taking into consideration the clinical symptoms and the level of the immune humoral and cellular parameters, the cases included in the study have been included in two groups: anterior uveitis (acute and chronic), and posterior uveitis. CONCLUSIONS: By comparing the results, we conclude that the autoimmunity and the immediate hypersensitivity mediated by immune complexes may be involved in the appearance and the development of the intraocular inflammation in certain cases of idiopathic uveitis.

Peripheral nervous system manifestations in systemic autoimmune diseases.

The peripheral nervous system refers to parts of the nervous system outside the brain and spinal cord. Systemic autoimmune diseases can affect both the central and peripheral nervous systems in a myriad of ways and through a heterogeneous number of mechanisms leading to many different clinical manifestations. As a result, neurological complications of these disorders can result in significant morbidity and mortality. The most common complication of peripheral nervous system (PNS) involvement is peripheral neuropathy, with symptoms of numbness, sensory paresthesias, weakness, or gait imbalance. The neuropathy may be multifocal and asymmetric or, less frequently, distal and symmetric.