Correlation between serum cardiac troponin I level and PDAI score in patients with pemphigus vulgaris.

Pemphigus vulgaris (PV) is a rare, yet serious autoimmune disorder primarily affecting the skin and mucous membranes. While the dermatological and mucosal aspects of PV are well-documented, the potential for systemic involvement, particularly cardiac complications, remains under-explored. This study aimed to investigate the serum cardiac troponin I (cTnI) level in patients with PV versus healthy controls. The relationship between serum cardiac troponin I (cTnI) levels and various demograpgics, clinical and laboratory characteristics in patients with PV was also dealt with. This cross-sectional study was conducted on 59 patients with pemphigus vulgaris and 59 age- and sex- matched healthy controls, visited at a tertiary care hospital from August 2021 to May 2023. After thorough history taking and physical examination, troponin level was measured by the ECL (Electrochemiluminescence) method. The correlation between serum cTnI level and various variables was evaluated using Pearson's correlation coefficient. The mean serum cardiac troponin I (cTnI) level in patient group was 0.104 ± 0.05 ng/mL, with a range of 0.01 to 0.25 ng/mL. Despite mean cTnI level in patients was greater than controls, this difference was not reach to the significance level (P value: 0.058). The analysis revealed a significant positive correlation (r = 0.52, p = 0.005310), suggesting that higher PDAI scores were associated with elevated cTnI level. The correlation between serum cardiac troponin I (cTnI) level and PDAI score, even without any clinical sign or risk factor for cardiovascular disease suggests a potential link between the severity of PV and subtle cardiac involvement, highlighting the importance of cardiac monitoring in these patients.

Boosting wound healing in diabetic rats: The role of nicotinamide riboside and resveratrol in UPR modulation and pyroptosis inhibition.

BACKGROUND: Diabetes-related skin ulcers provide a substantial therapeutic issue, sometimes leading to amputation, needing immediate practical treatments for efficient wound care. While the exact mechanisms are unknown, pyroptosis and deregulation of the unfolded protein response (UPR) are known to exacerbate inflammation. Nicotinamide Riboside (NR) and Resveratrol (RV), which are known for their Nicotinamide adenine dinucleotide (NAD+) boosting and anti-inflammatory properties, are being studied as potential treatments. The purpose of this study was to shed light on the underlying molecular mechanisms and explore the medical application of NR and RV in diabetic wound healing. METHODS: 54 male Sprague-Dawley rats divided into control, diabetic (DM), Gel Base, DM-NR, DM-RV, and DM-NR + RV. Rats were orally administered 50 mg/kg/day of RV and 300 mg/kg/day of NR for 5 weeks. Following diabetes induction, their wounds were topically treated with 5 % NR and RV gel for 15 days. The wound closure rate, body weight, and serum lipid profiles were examined. Gene expression study evaluated UPR and pyroptosis-related genes (BIP, PERK, ATF6, IRE1α, sXBP1, CHOP, NLRP3, caspase-1, NFκB, and IL1-ß) in wound tissues, alongside histological assessment of cellular changes. RESULTS: NR and RV treatments greatly enhanced wound healing. Molecular investigation demonstrated UPR and pyroptosis marker modifications, suggesting UPR balance and anti-inflammatory effects. Histological investigation demonstrated decreased inflammation and increased re-epithelialization. The combination of NR and RV therapy had better results than either treatment alone. CONCLUSION: This study shows that NR and RV have therapeutic promise in treating diabetic wounds by addressing UPR dysregulation, and pyroptosis. The combination therapy is a viable strategy to improving the healing process, providing a multimodal intervention for diabetic skin ulcers. These findings pave the way for additional investigation and possible therapeutic applications, giving hope for better outcomes in diabetic wound care.

Serologic Biomarkers in Pemphigus Monitoring: C-reactive Protein, Macrophage Migration Inhibitory Factor, and Prolactin Levels Versus Autoantibody Assays.

Evaluation and monitoring of pemphigus vulgaris (PV) typically involve autoantibody detection by enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF). We aimed to determine the levels of antipemphigus immunoglobulin (Ig) G autoantibodies using ELISA and IIF (as standard biomarkers), and compare it to prolactin, macrophage migration inhibitory factor (MIF), and C-reactive protein (CRP) (as nonstandard biomarkers) to determine which of these non-standard biomarkers is appropriate for PV monitoring. The experiment was performed before and during therapy. Anti-Dsg immunoglobulin G autoantibodies were measured using ELISA and IIF (as standard biomarkers) versus prolactin, MIF, and CRP (nonstandard), before 1 and 3 months after the treatment. Before beginning the treatment, the severity of the disease was determined using the pemphigus disease area Index (PDAI). We enrolled 60 newly diagnosed patients with PV (32 men and 28 women; mean age=43.8±14.2 years). Before treatment, the levels of anti-Dsg1, anti-Dsg3, and IIF were high and had a significant relationship with PDAI. PDAI also had a connection with the levels of CRP and prolactin. The anti-Dsg1, anti-Dsg3, IIF, and CRP titers decreased in patients treated with conventional (prednisolone plus azathioprine) and rituximab therapy during and after treatment. In conclusion, anti-Dsg1, anti-Dsg3, and IIF autoantibody titers remain standard biomarkers for assessing disease activity, severity, and PV monitoring. The trend of CRP was similar to that of anti-Dsg1, anti-Dsg3, and IIF. Thus, CRP may be used for PV monitoring.

Disaster Risk Assessment Among Iranian Exceptional Schools.

BACKGROUND: Exceptional children, like other children, have the right to be educated in a safe environment. Disasters are considered as serious issues regarding safety and security of educational environments. Following disasters, vulnerable groups, especially children with handicaps and disabilities are more likely to be seriously injured. Thus, the present study aimed to evaluate the safety and disaster risk assessment of exceptional schools in Tehran, Iran. METHOD: The cross-sectional study was conducted in exceptional schools in Tehran, 2018. First, 55 exceptional schools in all grades were selected based on census sampling method and evaluated by using a checklist designed by Tehran Disaster Mitigation and Management Organization (TDMMO) and Ministry of Education in 2015. The data were analyzed using Excel software and statistical descriptive tests. RESULT: Based on the results, school facilities are worn and have unsafe elevators (least safety: 7.69%), yards (least safety: 9.52%), laboratories (least safety: 16.67%), libraries (least safety: 24.24%), fire extinguishing systems (least safety: 28.99%), and storage rooms and kitchens (least safety: 33.33%) which require immediate considerations. In total, the safety of exceptional schools in this study was 70.13%, which suggests medium-risk level. CONCLUSION: The educational settings must be reconsidered, along with identifying the risk and safety at school. In addition, a standard should be established for evaluating safety, especially in exceptional schools.

Rapid Speciation of Lead in Human Blood and Urine Samples Based on MWCNTs@DMP by Dispersive Ionic Liquid-Suspension-Micro-Solid Phase Extraction.

An efficient sorbent based on 2,3-dimercapto-1-propanol immobilized on multi-wall carbon nanotubes (MWCNTs@DMP) was developed for separation/speciation of organic and inorganic lead (alkyl-Pb, Pb2+) in human blood, urine, and water samples by dispersive ionic liquid-suspension-micro-solid phase extraction (DIL-S-µ-SPE). By procedure, the MWCNTs@DMP as solid phase, acetone, and ionic liquid (IL, [HMIM][PF6]) were mixed and injected to 10 mL of the liquid phase at pH = 6.5. After shaking, the Pb(II) was extracted in MWCNTs@DMP and settled down in a conical tube with IL by centrifuging (Pb2+→: SH-SiO2@CNTs). The lead (Pb2+) was back-extracted from sorbent/IL in acidic pH and measured by atom trap atomic absorption spectrometry (AT-AAS). In addition, the organic lead (R-Pb, alkyl lead) converted to Pb(II) and total lead (T-Pb) was determined in the same conditions by UV radiation in 95 °C. Under the optimal conditions, the linear range (9.5-480 µg L-1), LOD (3.2 µg L-1), and enrichment factor (10.4) were obtained (RSD < 5%). The adsorption capacity of the MWCNTs@DMP and MWCNTs was achieved as 191.6 mg g-1 and 25.8 mg g-1, respectively. The method was validated by standard reference materials (SRM 1643d, SRM 955, and SRM 2668), ET-AAS, and ICP-MS analysis in real samples. Graphical abstract.

Evaluation of the effects of metformin administration on morphine tolerance in mice.

Opioids are used in clinical practice to relieve moderate to severe pain. Prolonged use of opioids can lead to a situation of analgesic tolerance and dependence. Several mechanisms are involved in the tolerance to analgesic opioids, including desensitization or internalization of the opioid receptor, elevation of cAMP levels, microglial activation and neuroinflammation, elevation of spinal mTOR activity and change in the expression of some proteins involved in tolerance, such as nNOS. Activation of the AMPK pathway inhibits mTOR and p38 MAPK ameliorating neuroinflammation and tolerance induced by morphine. Metformin, a potent antidiabetic agent, can also activate AMPK. Morphine tolerance was induced in mice by intraperitoneal administration three times daily at 08:00, 11.00 and 16.00 h of 50, 50 and 75 mg/kg morphine, respectively during four days. On the fifth day mice received a single injection of morphine 50 mg/kg. To evaluate the effects of metformin in development of morphine-induced analgesic tolerance a group of mice received metformin (10 mg/kg) 45 min before each morphine administration. Tail flick and hot plate tests were performed to estimate analgesic latency on days 1, 3 and 5. At five days, the animals were sacrificed, the brain dissected and nitrite levels determined. Chronic metformin administration significantly increased the analgesic latency on days 3 and 5 compared to the morphine group in hot plate test and in tail flick test. Chronic and acute metformin administration significantly decreased nitric oxide level compare to morphine group. The present results revealed that metformin attenuated analgesic tolerance induced by repeated intraperitoneal injections of morphine in mice.

TNF-α -308G/A gene polymorphism in bullous pemphigoid and alopecia areata.

BACKGROUND: TNF-α -308G/A polymorphism has been investigated in few studies for an association with susceptibility to bullous pemphigoid (BP) and alopecia areata (AA). Yet, these findings had so far not been independently replicated, and no data on a possible association of TNFα -308G/A polymorphism with these diseases in Iranian population were available. OBJECTIVES: In the present study, a possible effect of TNF-α -308G/A variation on susceptibility to BP or AA disease was evaluated. METHODS: Genomic DNA was extracted from the blood of the patients with BP and AA as well as control subjects which genotyped for the TNF-α -308 G/A polymorphism. TNF-α gene expression levels were analyzed by real-time RT-PCR. RESULTS: No association was observed between the TNF-α -308 G/A variation and susceptibility to BP or AA diseases in our Iranian cohort. In contrast to AA patients, expression of TNF-α gene was significantly higher in BP patients compared to control group. TNF-α gene was found to be similarly expressed in mutant and wild-type genotypes. CONCLUSIONS: TNF-α -308G/A polymorphism is not associated with the risk to develop of BP and AA in our Iranian cohort. Furthermore, this polymorphism is contributed to altering the levels of gene expression in BP disease.

Oxidative stress and age-related changes in T cells: is thalassemia a model of accelerated immune system aging?

Iron overload in ß-thalassemia major occurs mainly due to blood transfusion, an essential treatment for ß-thalassemia major patients, which results in oxidative stress. It has been thought that oxidative stress causes elevation of immune system senescent cells. Under this condition, cells normally enhance in aging, which is referred to as premature immunosenescence. Because there is no animal model for immunosenescence, most knowledge on the immunosenescence pattern is based on induction of immunosenescence. In this review, we describe iron overload and oxidative stress in ß-thalassemia major patients and how they make these patients a suitable human model for immunosenescence. We also consider oxidative stress in some kinds of chronic virus infections, which induce changes in the immune system similar to ß-thalassemia major. In conclusion, a therapeutic approach used to improve the immune system in such chronic virus diseases, may change the immunosenescence state and make life conditions better for ß-thalassemia major patients.

Study of carbon nano-tubes effects on the chondrogenesis of human adipose derived stem cells in alginate scaffold.

BACKGROUND: Osteoarthritis is one of the most common diseases in middle-aged populations in the World and could become the fourth principal cause of disability by the year 2020. One of the critical properties for cartilage tissue engineering (TE) is the ability of scaffolds to closely mimic the extracellular matrix and bond to the host tissue. Therefore, TE has been presented as a technique to introduce the best combination of cells and biomaterial scaffold and to stimulate growth factors to produce a cartilage tissue resembling natural articular cartilage. The aim of study is to improve differentiation of adipose derived stem cells (ADSCs) into chondrocytes in order to provide a safe and modern treatment for patients suffering from cartilage damages. METHODS: After functionalization, dispersions and sterilizing carbon nano-tubes (CNTs), a new type of nanocomposite gel was prepared from water-soluble CNTs and alginate. ADSCs seeded in 1.5% alginate scaffold and cultured in chondrogenic media with and without transforming growth factor-ß1 (TGF-ß1) for 7 and 14 days. The genes expression of sex determining region Y-box 9 (SOX9), types II and X collagens was assessed by real-time polymerase chain reaction and the amount of aggrecan (AGC) and type I collagen was measured by ELISA. RESULTS: Our findings showed that the expression of essential cartilage markers, SOX9, type II collagen and AGC, in differentiated ADSCs at the concentration of 1 µg/ml CNTs in the presence of TGF-ß1 were significantly increased in comparison with the control group (P < 0.001). Meanwhile, type X collagen expression and also type I collagen production were significantly decreased (P < 0.001). CONCLUSIONS: The results showed that utilized three-dimensional scaffold had a brilliant effect in promoting gene expression of chondrogenesis.

Comparison between Chondrogenic Markers of Differentiated Chondrocytes from Adipose Derived Stem Cells and Articular Chondrocytes In Vitro.

OBJECTIVE(S): Osteoarthritis is one of the most common diseases in middle-aged population in the world. Cartilage tissue engineering (TE) has been presented as an effort to introduce the best combination of cells, biomaterial scaffolds and stimulating growth factors to produce a cartilage tissue similar to the natural articular cartilage. In this study, the chondrogenic potential of adipose derived stem cells (ADSCs) was compared with natural articular chondrocytes cultured in alginate scaffold. MATERIALS AND METHODS: Human ADSCs were obtained from subcutaneous adipose tissue and human articular chondrocytes from non-weight bearing areas of knee joints. Cells were seeded in 1.5% alginate and cultured in chondrogenic media for three weeks with and without TGFß3. The genes expression of types II and X collagens was assessed by Real Time PCR and the amount of aggrecan (AGC) and type I collagen measured by ELISA and the content of glycosaminoglycan evaluated by GAG assay. RESULTS: Our findings showed that type II collagen, GAG and AGC were expressed, in differentiated ADSCs. Meanwhile, they produced a lesser amount of types II and X collagens but more AGC, GAG and type I collagen in comparison with natural chondrocytes (NCs). CONCLUSION: Further attempt should be carried out to optimize achieving type II collagen in DCs, as much as, natural articular chondrocytes and decline of the production of type I collagen in order to provide efficient hyaline cartilage after chondrogenic induction, prior to the usage of harvested tissues in clinical trials.

The evaluation of perioperative safety of local anesthesia with lidocaine containing epinephrine in patients with ischemic heart disease.

The use of local anesthesia with lidocaine containing epinephrine in patients with cardiac disease is controversial in the literature. The aim of our study was determining the safety of use the local anesthesia contain epinephrine in patients with ischemic heart disease that undergoing reconstructive surgery. Thirty two patients that had known ischemic heart disease and candidate to undergo reconstructive surgery for skin tumor enrolled in this study.  All patients continued their medication for cardiac disease till morning of the operation. 10 ml lidocaine 2% containing 1:100,000 epinephrine was injected in patients for local anesthesia. The hemodynamic changes and electrocardiographic variables before injection were compared with them after injection, during surgery and till 6 hours postoperation period. A 12 lead electrocardiogram was recorded in all our cases for detection of myocardial ischemic changes. The mean age, weight and height were 58.2±10.4, 74.8.±14.4 kg and 164.5± 8 cm respectively. Twelve patients (37.5%) were diagnosed with systemic hypertension and 10 patients with diabetes (31.2%). The comparison of change of systolic, diastolic and mean blood pressure between baseline, during procedure and after operation defined that our subjects did not have any significant disturbance in blood pressure in perioperative period. The comparison of baseline heart rate with heart rate after injection, during procedure and in postoperation period indicated a significant changes in this variable (P=0.044). The heart rhythm during the perioperative period also failed to exhibit alterations. The ischemic change was not recorded in our patients before injection compared to after injection. None of our patients have any early complications because of infiltration of local anesthetic containing epinephrine in our patients. The use of 10 ml 2% lidocaine with epinephrine 1:100,000 in patients with cardiac disease represent a safe anesthetic procedure. These patients experienced a more profound anesthesia with hemodynamic stability and without myocardial ischemic changes.

The hemodynamic effects of spinal block with low dose of bupivacaine and sufentanil in patients with low myocardial ejection fraction.

The aim of this study was to assess the effect of spinal block with low dose of bupivacaine and sufentanil on patients with low cardiac output who underwent lower limb surgery. Fifteen patients who had ejection fraction less than 40% (group 1) were compared with 65 cases with ejection fraction more than 40% (group 2) in our study. Our subjects underwent spinal block with 7.5 mg hyperbaric bupivacaine 0.5% and 5 µg sufentanil. We recorded early events such as hypotension, bradycardia, vasopressor need and ST segment change in our cases. The average mean arterial pressure decreased 13% (110 mmHg to 95.7 mmHg) in group 1 and 20% (160 mmHg to 128 mmHg) in group 2 (P<0.001). Hypotension due to spinal anesthesia was observed in none of our subjects in both groups and none of our cases need to vasopressor support. All patients remained alert, and no ST segment changes were observed in two groups. In our study none of subjects complained of pain intraoperatively. The subjects were without complaints during the spinal anesthetic in both groups. Spinal block with low dose local anesthetic and sufentanil was a safe and effective method for lower limb surgery in patients with low ejection fraction.

Phenotypic characterizations and comparison of adult dental stem cells with adipose-derived stem cells.

OBJECTIVES: Mesenchymal stem cells or "multipotent stromal cells" are heterogeneous cell population with self-renewal and multilinage differentiation. The aim of this study was to examine and compare the expression of important stem cell surface markers on two populations of mesenchymal stem cells, one derived from human exfoliated deciduous teeth and the other derived from human adipose tissue. These new stem cells will offer a promising avenue for prevention and reversal of many human diseases such as type 1 diabetes and prevention of liver fibrotic process. METHODS: Mesenchymal stem cells were isolated and cultured from human adipose tissue and dental pulp of human exfoliated deciduous teeth. The cultured cells then were harvested and stained by different fluorescent labeled monoclonal antibodies against surface markers and were analyzed using flow cytometry. RESULTS: Both different cell populations expressed CD44, CD90 and CD13 (stem cell markers) with similar intensity. They did not express hematopoietic markers (CD11b, CD19 and CD34), and lymphocyte or leukocyte antigens CD3, CD7, CD20, CD14, CD45, CCR5 (CD195), CD11b and CD10 on their surfaces. Two different cell types demonstrated different levels of expression in CD56 and CD146. Mesenchymal stem cells from human exfoliated deciduous teeth were positive for CD105 and were negative for CCR3 and CCR4 expression. CONCLUSIONS: Both cell populations derived from adipose tissue and dental pulp showed common phenotypic markers of mesenchymal stem cells. In conclusion, mesenchymal stem cells could be isolated and cultured successfully from dental pulp of human exfoliated deciduous teeth, they are very good candidates for treatment and prevention of human diseases.