Serum Inflammatory and Oxidative Stress Markers in Patients with Vitiligo.

BACKGROUND: Vitiligo is a common chronic hypomelanotic skin disorder. An intricate pool of markers associated with a complex combination of biological and environmental factors is thought to be implicated in etiology. This study aims to investigate the most important markers associated with vitiligo pathogenesis, including redox status, inflammation, and immune profile, in patients with vitiligo. MATERIALS AND METHODS: The study included a total of 96 subjects: 30 patients with active non-segmental vitiligo, 30 patients with stable non-segmental vitiligo, and 36 controls. The vitiligo area severity index (VASI) and vitiligo disease activity score (VIDA) were determined. The following serum parameters were assessed: antioxidant status (TAS), superoxide dismutase activity (SOD), catalase activity (CAT), glutathione peroxidase activity (GPx), glutathione-S-transferase activity (GST), malondialdehyde (MDA), advanced oxidation protein products (AOPP), C reactive protein (CRP), interleukin-15 (IL-15), and chemokines (CXCL9, CXCL10). RESULTS: The VASI score was not significantly different between active and stable vitiligo patients, as it was approximately 0.1. TAS, CAT, GPx, and GST were significantly lower in vitiligo patients compared to controls (p < 0.05). They were also significantly lower in active vitiligo when compared to stable vitiligo (p < 0.05). However, SOD levels were significantly higher in vitiligo patients than in controls and in the active vitiligo group than in the stable vitiligo group (p < 0.05). MDA and AOPP levels were significantly higher in patients with active and stable vitiligo compared to controls (p < 0.05). However, they did not significantly differ between active and stable vitiligo patients (p < 0.05). In both active and stable vitiligo, CRP and IL-15 were significantly higher than controls (p < 0.05). Whereas CRP was significantly higher in active (range = 2.0-7.2, mean = 4.46 ± 1.09) than in stable vitiligo (range = 1.6-6.7, mean = 3.75 ± 1.08) (p < 0.05). There was no significant difference in IL-15 levels between active and stable vitiligo. In both active and stable vitiligo, CXCL9 and CXCL10 were significantly higher than controls (p < 0.05), and they were significantly higher in active than stable vitiligo (p < 0.05). CONCLUSIONS: In vitiligo, oxidative damage induces an increase in pro-inflammatory IL-15, which in turn promotes IFN-γ-inducible chemokines such as CXCL9 and CXCL10. Further, there seems to be a link between the VASI score and IL-15 levels. These data imply that inhibiting IL-15 could be a promising method for developing a potentially targeted treatment that suppresses the early interplay between oxidant stress and IL-15 keratinocyte production, as well as between resident and recirculating memory T cells.

Adjunctive systemic antibiotic effect on periodontal state, salivary enzyme activity, and glycemia imbalance in type-2 diabetics after non-surgical periodontal management.

AIM: The current study aimed at analyzing the effect of non-surgical periodontal treatment accompanied by systemic antibiotics on salivary enzyme activities, periodontal parameters, and glycemic control in type-2 diabetic (T2D) patients with chronic periodontitis. METHODS: The study included 125 type-2 diabetic patients with chronic periodontitis who had good glycemic control (T2Dc), 125 type-2 diabetics who had bad glycemic control (T2Dpc). The 125 T2Dpc were divided randomly into two groups. The first one enrolled 63 T2Dpc and received a non-surgical periodontal treatment (T2Dpc + NST). The second group enrolled 62 T2Dpc and received the non-surgical treatment accompanied by systemic antibiotics (T2Dpc+NST+A). HbA1c, periodontal indices, and salivary enzyme activities were assessed for all groups. The Glycated hemoglobin (HbA1c) was assessed. The Salivary alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransaminase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) activities were measured. RESULTS: The T2Dpc were characterized by the highest probing depth (PPD) and clinical attachment loss (CAL) periodontal scores, as well as ALP, AST, and ALT enzymatic activities. However, BOP did not differ significantly between T2Dc and T2Dpc. Whereas the rest of clinical parameters PI, GI, and OHI-S did not significantly differ between groups. The Pearson's analysis revealed three correlations between ALP-PPD, ALP-CAL, and ALP-BOP (bleeding on probing) in both T2Dc and T2Dpc (P < 0.05). Interestingly, a significant decrease in periodontal indices, salivary enzyme activities, and HbA1c was recorded in T2Dpc+NST+A group. CONCLUSION: The increase in ALP, AST, and ALT activities reflects the impact of uncontrolled T2D on periodontal tissue alteration. The ALP activity increase was associated with the severity of periodontal status in diabetic patients. In comparison to non-surgical treatment alone, the adjunct use of systemic antibiotics improves periodontal state, enzyme activity, and glycemic control.

Perspective of dental medicine students learning in remote biochemistry laboratories during COVID-19.

Students at the Monastir Faculty of Dental Medicine were required to remain inside during the COVID-19 pandemic for their own safety and in accordance with official directives. It is evident that learners' perceptions are a recognized indicator of the efficiency of any teaching approach. Therefore, we focused on students' input on the validity of online biochemistry laboratories to assure their preferences with the finest teaching approaches. The study included 116 undergraduate dental students from the Faculty of Dental Medicine of Monastir. The survey has 40 questions. This investigation covered (i) information technology tool accessibility, (ii) course presentation, interactions in a virtual classroom, teachers' availability, and (iii) preferred learning styles. The percentages were then determined for each item and assessed. Our results showed that almost students were equipped with computers, smartphones and tablets but have encountered some connectivity issues. Moreover, participants find courses well presented, approved class interactions, and were satisfied with teachers' availability. Nevertheless, students were not already prepared for entirely online learning. Despite, the overall positive perception among students toward remote education during the COVID-19 outbreak; they preferred considering shared learning between face-to-face and online once the pandemic is over.

Desloratadine Efficacy in Relation to GSTM1 and GSTT1 Polymorphic Genes in Chronic Spontaneous Urticaria.

Background: The etiopathogeny of chronic spontaneous urticaria (CSU) is not well defined. Allelism in glutathione S-transferase GSTM1 and GSTT1 has been suggested as a risk factor. Desloratadine is the first-line treatment for this disease. Objective: This study aimed to investigate the efficacy of a first-line treatment: desloratadine 5 mg/day on antioxidant status and clinical assessment in Tunisian patients with CSU and to identify possible associations between GSTT1 and GSTM1 genotypes and susceptibility to CSU. Methods: Sixty patients with CSU and 60 age- and gender-matched healthy controls were included in the study. We calculated the urticaria activity score (UAS) and assessed the antioxidant parameters (total antioxidant status [TAS], glutathione S-transferase [GST], SOD, CAT, GPx]). Multiplex PCR was performed to find the relationship between GSTM1 and GSTT1 polymorphisms with CSU susceptibility. Results: At baseline, GST, GPx, CAT, SOD activities, and TAS were significantly lower in CSU patients compared to healthy controls (P < 0.05). After treatment, GST, GPx, CAT, SOD activities and TAS were significantly increased in patients compared to those before treatment (P < 0.001). We observed a significant association in null alleles of GSTM1. Before treatment, GST activity was significantly lower in patients having GSTM1+ genotype than those having GSTM1- genotype (P = 0.001). After treatment, TAS and antioxidant enzymes GST, GPx, SOD, and CAT were significantly elevated in patients having GSTM1- genotype than those having GSTM1+ genotype (P < 0.05). Conclusion: These results suggest the impact of GSTM1 and GSTT1 on CSU susceptibility and desloratadine efficacy in Tunisian patients.

Glycated hemoglobin influence on periodontal status, pathogens and salivary interleukins in type II diabetic Tunisian subjects with chronic periodontitis.

BACKGROUND/PURPOSE: Studies have shown that there is a possible correlation between the amount of glycated hemoglobin and the periodontal status. The goal of this study was to investigate the relationship between glycated hemoglobin (HbA1c) and the prevalence of gingival pathogens and circulating interleukin levels in type II diabetic Tunisian subjects. MATERIAL AND METHODS: The research included four groups; 30 healthy subjects (H group), 30 non-diabetic subjects suffering from chronic periodontitis (CP group). Type-II diabetic patients were divided according to HbA1c level into 30 adequately-controlled type-II diabetes subjects (HbA1c ≤ 7 percent (ATIID&CP group)) and 30 inadequately-controlled type-II diabetes subjects and HbA1c > 7 percent (ITIID&CP group). Clinical periodontal condition parameters and assessment of salivary interleukin IL-1beta, IL-6 and IL-10 were assessed. Quantitative Polymerase Chain Reaction used for detection of Subgingival biofilm of periodontal pathogens. RESULTS: Clinical parameters analyzed were positively associated with HbA1c levels (p < 0.05). A. Actinomycetemcomitans were found in 80 percent of ITIID&CP, 65 percent of CP and almost absent in H group. Porphyromonas gingivalis was present in 100 percent of CP, 85 percent of ITIID&CP, 50 percent of ATIID&CP and 3 percent of H group. T. Denticola had an equivalent occurrence. While Tannerella forsythia was scarce in ITIID&CP groups, but abundant in the H group. ITIID&CP had the highest IL-6 and IL-1beta/IL-10 ratios. CONCLUSION: HBA1c levels affect periodontal status, pathogens and salivary interleukins in Type-II diabetic Tunisians with chronic periodontitis, compared with stable and chronic periodontitis groups and can interact with periodontal infections and increase the inflammatory state.

Saliva diagnostic utility in patients with type 2 diabetes: Future standard method.

BACKGROUND: The purpose of the present study was to assess saliva reliability in diagnosis and monitoring type 2 diabetes instead of blood. METHODS: Blood and unstimulated whole saliva were collected from 300 type 2 diabetic subjects and 300 healthy controls in fasting. Then, the salivary flow rate was calculated. All parameters including glucose, urea, amylase, total protein, albumin, C-reactive protein (CRP), immunoglobulin A (IgA), potassium, calcium and chloride were assessed in the supernatant, using an autoanalyzer. Oral exam was conducted by a single examiner on full mouth excluding third molars. Statistical analysis was performed by the SPSS 20.0 version. RESULTS: Saliva screening showed that glucose, urea, amylase, total protein, potassium, calcium and chloride were significantly higher in patients compared to controls (p < 0.05). Whereas, the IgA level and salivary flow rate were significantly reduced in patients (p < 0.05). No significant difference was found in albumin and CRP levels (p > 0.05). There was a significant positive correlation between salivary and plasma glucose levels (r = 0.887, and r = 0.900, p < 0.001), as well as, salivary and blood urea (r = 0.586, and r = 0.688, p < 0.001) in patients and controls, respectively. CONCLUSIONS: From this study, saliva could be suggested as a useful diagnostic tool for type 2 diabetes.

Investigation of carbonic anhydrase 6 gene polymorphism rs2274327 in relation to the oral health status and salivary composition in type 2 diabetic patients.

OBJECTIVE: The aim of the present study was to investigate the oral manifestations and salivary composition in type 2 diabetics with periodontitis and to evaluate their association with CA6 gene polymorphism rs2274327. METHODS: Oral examination was performed by a single periodontist for 300 type 2 diabetics. Whole unstimulated saliva and blood were collected. The salivary pH, buffer capacity and flow rate were later measured. Immunoglobulin A and electrolytes were assessed using an autoanalyzer. CA6 gene polymorphism rs2274327 was screened by PCR-RFLP assay. The statistical analysis was performed using the SPSS 20.0 version. RESULTS: The salivary pH, buffer capacity and flow rate were significantly lower in the patients carrying TT genotype compared to CC and CT genotype carriers (p < .05). Furthermore, the DMFT index, OHI-s, PI, PPD and CAL were significantly higher in the subjects with TT genotype (p < .05). Carrying at least one T allele seemed to increase the risk of dental caries (OR = 2.59, p < .001), xerostomia (OR = 2.11, p=.003) and taste impairment (OR = 1.97, p < .05). CONCLUSION: CA6 gene polymorphism rs2274327 seemed to increase the risk of developing, dental caries, periodontitis, xerostomia and taste impairment in type 2 diabetics.

Impact of adhesive system generation and light curing units on orthodontic bonding: In vitro study.

OBJECTIVE: We aimed to compare adhesive performance of fourth, fifth and seventh generation adhesive systems (GASs) and the effect of two different light curing units on shear bond strength (SBS). MATERIALS AND METHODS: One hundred and twenty extracted human upper premolars were divided in four groups. Bonds were assessed as following: group 1 using 4th GAS, group 2 using 5th GAS, group 3 and 4 using 7th GAS with two different light curing units (1500 and 800mw/cm2). Adhesive remnant index (ARI) scores were counted. RESULTS: Group 1 and 2 showed similar SBSs (P=0.7) which were significantly higher than group 3 (P=0.0002). Group 4 exhibited significantly the weakest SBS with mean=2.15±0.25. Applying shear forces less than 15MPa on group 3 bonds led to the release of almost all of the of brackets. Whereas, applying the same forces on group 2 bonds leads to the release of 66.7% of brackets. Notably, only 40% of brackets in group 1 were debonded. Group 4 brackets were totally debonded when applying shear forces less than 10MPa. While ARI=0 was the most frequent in group 1, ARI=3 was the most frequent in group 3. CONCLUSION: Fourth and fifth GASs showed similar SBS higher than seventh GAS. Fourth GAS bonds were able to resist longer against traction forces than those set up by fifth generation. Seventh GAS bonds offered the least efficient resistance. ARI=0 was the highest in group 1. However, Group 4 showed the highest ARI=1 and ARI=2 revealing cohesive failure. We also found that the adhesive power is proportional to the power of the lamp used. In fact, we concluded that 1500 mw/cm2 units light curing during 30seconds generated an ideal energy to enhance orthodontic bracket adhesion.

Polymorphisms of glutathione-S-transferases M1, T1, P1 and susceptibility to colorectal cancer in a sample of the Tunisian population.

In this study, we investigated the associations of polymorphisms in glutathione-S-transferases (GSTs) genes that are GSTM1, GSTT1, and GSTP1, with sporadic colorectal cancer (CRC). Hundred and fifty patients with CRC and 128 healthy controls were genotyped. DNA was isolated from blood samples. Polymorphisms were assessed by polymerase chain reaction-restriction fragment length polymorphism-based methods and polymerase chain reaction multiplex. Logistic regression analyses showed significant risk for CRC associated with GSTP1 homozygotes for Val-105 (OR 4.82; 95 % CI 1.97-11.80) or for individuals who possessed at least one Val-105 allele (OR 2.54; 95 % CI 1.751-3.703). There were no statistically significant differences in the frequency of GSTM1- and GSTT1-null genotypes (p > 0.05). The GSTM1-null was found in 70.47 % of all cases and 70.07 % of controls (OR 0.61; 95 % CI 0.33-1.12). The GSTT1-null genotype was found in 38.77 % of cases and 49.22 % of controls (OR 1.53; 95 % CI 0.94-2.47). No effect of any genotype for GSTM1 and GSTT1 on CRC was detected. But then an association between the polymorphism of the GSTP1 and the CRC susceptibility was detected.

Cell oxidant stress delivery and cell dysfunction onset in type 2 diabetes.

Most known pathways of diabetic complications involve oxidative stress. The mitochondria electron transport chain is a significant source of reactive oxygen species (ROS) in insulin secretory cells, insulin peripheral sensitive cells and endothelial cells. Elevated intracellular glucose level induces tricarboxylic acid cycle electron donor overproduction and mitochondrial proton gradient increase leading to an increase in electron transporter lifetime. Subsequently, the electrons leaked combine with respiratory oxygen (O(2)) resulting in superoxide anion ((•)O(2)(-)) production. Advanced glycation end products derive ROS via interaction with their receptors. Elevated diacylglycerol and ROS activate the protein kinase C pathway which, in turn, activates NADPH oxidases. A vicious circle of pathway derived ROS installs. Pathologic pathways induced ROS are activated and persistent though glycemia returns to normal due to hyperglycemia memory. Endothelial nitric oxide synthase may produce both superoxide anion ((•)O(2)(-)) and nitric oxide (NO) leading to peroxynitrite ((•)ONOO(-)) generation. Homocysteine is also implicated in oxidative stress pathogenesis. In this paper we have highlighted the pathologic mechanisms of ROS on atherosclerosis, renal dysfunction, retina dysfunction and nerve dysfunction in type 2 diabetes. Cell oxidant stress delivery have pivotal role in cell dysfunction onset and progression of angiopathies but an early introduction of good glycemic control may protect cells more efficiently than antioxidants.

Update in chronic obstructive pulmonary disease: role of antioxidant and metabolizing gene polymorphisms.

Chronic obstructive pulmonary disease (COPD) is characterized by systemic and local chronic inflammation and oxidative stress. The sources of the increased oxidative stress in COPD patients derive from the increased burden of inhaled oxidants such as cigarette smoke and other forms of particulate or gaseous air pollution and from the increase in reactive oxygen species (ROS) generated by several inflammatory, immune, and structural airways cells. There is increasing evidence that genetic factors may also contribute to the pathogenesis if COPD, particularly antioxidant genes, which may confer a susceptibility to environmental insults such as cigarette smoke and thereafter development of COPD. Consequently, heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), microsomal epoxide hydrolase (EPHX1), and cytochrome P450 (CYP) genetic polymorphisms may have an important role in COPD pathogenesis. In this review the authors summarized the most recent findings dealing with these antioxidant genes contributing to the free radical neutralization and xenobiotic enzymes playing a role in different phases of cell detoxification reactions related to the redox status imbalance in COPD, with an emphasis on their possible roles in disease progression.

Molecular analysis of mucopolysaccharidosis type I in Tunisia: identification of novel mutation and eight Novel polymorphisms.

UNLABELLED: Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder caused by a genetic defect in alpha-L-iduronidase (IDUA) which is involved in the degradation of dermatan and heparan sulfates. The disease has severe and milder phenotypic subtypes. The aim of this study was the detection of mutations in the IDUA gene from 12 additional MPS I patients with various clinical phenotypes (severe, 8 cases; intermediate, 3 cases; mild, 1 case). PATIENTS AND METHODS: In this study, the IDUA mutations in eight unrelated Tunisian families were performed by amplifying and sequencing the IDUA exons and intron-exon jonctions. RESULTS: Five IDUA mutations were detected: one is the L578Q, a novel mutation found, in milder patient. The others were the previously described: P533R, Y581X, F602X and R628X that produce a severe and intermediate phenotype. In addition, eighteen variants, including eight previously unreported polymorphisms (IVS6+21c>a, IVS7+79c>t, IVS7-45 g>c, IVS9+36t>c, IVS10+140c>a, IVS11+33c>t, IVS12+13c>t and IVS12-31c>g), were detected. CONCLUSION: This paper, showed a heterogeneous pattern of mutations and polymorphisms among Tunisian patients.

Homocysteine enhances LDL fatty acid peroxidation, promoting microalbuminuria in type 2 diabetes.

BACKGROUND: We aimed to establish the relationship between glycated haemoglobin (HbA(1c)), hypertension and microalbuminuria onset in type 2 diabetes. We also intended to ascertain the metabolic action of homocysteine on LDL fatty acids and on renal function. METHODS: The study was carried out on 200 patients with type 2 diabetes and 200 healthy subjects. HbA(1c), apolipoprotein B (apo B) and microalbuminuria were measured using immunoturbidimetric methods. Cholesterol, peroxide, urea and uric acid were assayed using colorimetric methods. Creatinine clearance was calculated using the Cockroft-Gault equation. Homocysteine was measured by immunological fluorescence polarization. LDL fatty acids were quantified by gas chromatography. RESULTS: Creatinine and microalbuminuria significantly increased in type 2 diabetes when compared with controls. Microalbuminuria was significantly correlated with HbA(1c) and with the presence of high blood pressure. Homocysteinaemia significantly correlated with creatinine clearance in diabetes. Linoleic acid (C18:2omega6) did not differ between groups. C18:2omega6/C18:3omega3 ratio was three times higher in diabetics than in controls. Total saturated fatty acids, homocysteine, H(2)O(2) and LDL-thiobarbituric reactive substances significantly increased in microalbuminuric when compared with normoalbuminuric diabetes. Total polyunsaturated fatty acids, arachidonic acid (C20:4omega6), LDL-cholesterol, apo B and creatinine clearance significantly decreased in microalbuminuric when compared with normoalbuminuric diabetes. CONCLUSION: Microalbuminuria onset is associated with renal protein oxidation that is preceded by LDL fatty acid oxidation. The latter is initiated by H(2)O(2) produced from an auto-oxidation of homocysteine and increased metabolism of arachidonic acid towards its pro-inflammatory eicosanoids. An oxidative stress state is the common ground of diffused vasculopathy.