Cyclooxygenase (COX)-1 Activity Precedes the COX-2 Induction in Aβ-Induced Neuroinflammation

Two different isoforms of cyclooxygenases, COX-1 and COX-2, are constitutively expressed under normal physiological conditions of the central nervous system, and accumulating data indicate that both isoforms may be involved in different pathological conditions. However, the distinct role of COX-1 and COX-2 and the probable interaction between them in neuroinflammatory conditions associated with Alzheimer’s disease are conflicting issues. The aim of this study was to elucidate the comparable role of each COX isoform in neuroinflammatory response induced by β-amyloid peptide (Aβ). Using histological and biochemical methods, 13 days after stereotaxic injection of Aβ into the rat prefrontal cortex, hippocampal neuroinflammation and neuronal injury were confirmed by increased expression of tumor necrosis factor-alpha (TNF-α) and COX-2, elevated levels of prostaglandin E2 (PGE2), astrogliosis, activation of caspase-3, and neuronal cell loss. Selective COX-1 or COX-2 inhibitors, SC560 and NS398, respectively, were chronically used to explore the role of COX-1 and COX-2. Treatment with either COX-1 or COX-2 selective inhibitor or their combination equally decreased the level of TNF-α, PGE2, and cleaved caspase-3 and attenuated astrogliosis and neuronal cell loss. Interestingly, treatment with COX-1 selective inhibitor or the combined COX inhibitors prevented the induction of COX-2. These results indicate that the activity of both isoforms is detrimental in neuroinflammatory conditions associated with Aβ, but COX-1 activity is necessary for COX-2 induction and COX-2 activity seems to be the main source of PGE2 increment.     

The carbohydrate CT1 is expressed in topographically fixed glomeruli in the mouse olfactory bulb

To establish and maintain their polarized morphology, neurons employ active transport driven by cytoskeletal motor proteins to sort cargo between axons and dendrites. These motors can move in a specific direction over either microtubules (kinesins, dynein) or actin filaments (myosins). The basic traffic rules governing polarized transport on the neuronal cytoskeleton have long remained unclear, but recent work has revealed several fundamental sorting principles based on differences in the cytoskeletal organization in axons versus dendrites. We will highlight the basic characteristics of the neuronal cytoskeleton and review existing evidence for microtubule and actin based traffic rules in polarized neuronal transport. We will propose a model in which polarized sorting of cargo is established by recruiting or activating the proper subset of motor proteins, which are subsequently guided to specific directions by the polarized organization of the neuronal cytoskeleton.     

The efficacy of a 1-week triple therapy for eradication of Helicobacter pylori infection in children

Background and study aimsPoor compliance to therapy and antibiotic resistance are the main causes for failure of anti-Helicobacter pylori (H. pylori) therapy. The purpose of this study was to assess the effectiveness of omeprazole-based triple therapy in Iranian children.Patients and methodsFifty-seven children with H. pylori-related gastroduodenal disease received 1-week triple therapy with a combination of omeprazole, amoxicillin and clarithromycin (according to the susceptibility test). Success of eradication was assessed by ¹³C-urea breath test and endoscopy.ResultsSixty-four patients (mean age 11.3 years; range 2.7–16 years) were included. Eradication was successful in 84.2% (95% confidence interval, 72.8% intention to treat).ConclusionOne-week triple therapy was effective for the eradication of H. pylori infection in children.     

Expression of IL-17 and COX2 gene in peripheral blood leukocytes of vitiligo patients

Vitiligo is a pigmentation disorder in which inflammatory mediators such as cytokines have a pivotal role in disease's pathogenesis. Interleukin 17 (IL-17A) is a proinflammatory cytokine which is involved in the induction of several proinflamatory mediators such as cyclooxygenase 2 (COX2). The aim of this study was to investigate the gene expression of IL-17 and COX2 in peripheral blood leukocytes of vitiligo's patients.Peripheral blood leukocytes from 15 patients with vitiligo and 15 healthy controls were separated using a gradient density centrifugation method. After total RNA isolation and cDNA synthesis, IL-17 and COX2 gene expression were quantified by real-time polymerase chain reaction (PCR). There were no significant differences in IL-17 and COX2 gene expression in lymphocytes of patients with vitiligo compared with control group (p<0.05). However there was an increased IL-17 and COX2 gene expression in neutrophils of patients compared to controls, but it did not reach statistical significance (p=0.05). We could not find any differences in IL-17 and Cox2 gene expression between clinical diseases subtypes, sex and age. There was a significant correlation between IL-17 and COX2 genes expression in the neutrophils of patients (p=0.00, r=0.80). Our results showed an increased expression in IL-17 and Cox-2 genes in neurophils of patients with vitiligo. This suggested that these two factors are involved in the inflammatory process. Further studies with a larger sample size might help to establish the role of these factors in the pathogenesis of diseases.     

Phlebotomus papatasi and Meriones libycus as the vector and reservoir host of cutaneous leishmaniasis in Qomrood District, Qom Province, central Iran

ObjectiveTo determine the sand flies species responsible for most transmission of Leishmania major (L. major) to human, as well as to determine the main reservoir hosts of the disease.MethodsSand flies were collected using sticky papers and mounted in Puri's medium for species identification. Rodents were trapped by live Sherman traps. Both sand flies and rodents were subjected to molecular methods for detection of leishmanial parasite.ResultsPhlebotomus papatasi (P. papatasi) was the common species in outdoor and indoor resting places. Employing PCR technique only three specimens of 150 P. papatasi (2%) were found naturally infected by parasites with a band of 350 bp which is equal to the L. major parasite. Forty six rodents were captured by Sherman traps and identified. Microscopic investigation on blood smear of the animals for amastigote parasites revealed 1 (3.22%) infected Meriones libycus (M. libycus). Infection of this animal to L. major was confirmed by PCR against rDNA loci of the parasite.ConclusionsThis is the first molecular report of parasite infection of both vector (P. papatasi) and reservoir (M. libycus) to L. major in the region. The results indicated that P. papatasi was the primary vector of the disease and circulating the parasite between human and reservoirs and M. libycus was the most important host reservoir for maintenance of the parasite source in the area.     

The ultrasonographic correlates of carpal tunnel syndrome in patients with normal electrodiagnostic tests

Purpose

The diagnosis of carpal tunnel syndrome (CTS) is established by electrodiagnostic testing (EDT). Nonetheless, in a portion of patients complaining of the typical signs and symptoms of CTS, the EDT is negative, and yet no paraclinical tool has been acknowledged for confirming the diagnosis. The aim of this study was to investigate the value of ultrasound imaging in diagnosing clinically suspicious patients with normal EDT findings.

Materials and methods

Thirty-four patients, with clinical evidence of CTS but without abnormal findings on electromyography, and 41 healthy controls were enrolled. Ultrasonography was performed in all participants, and cross-sectional area (CSA), hypoechogenicity and hypervascularity of the median nerve were evaluated. Multivariate logistic regression analysis was used to formulate a prediction model for CTS.

Results

CSA of the median nerve in the wrist and wrist-to-forearm ratio were significantly higher in patients compared with controls. Patients had significantly higher hypoechogenicity [odds ratio (OR) 4.317; 95% confidence interval (CI) 1.23?C15.11) and hypervascularity (OR 5.004,; 95% CI 1.02?C21.15) in the median nerve. Clinical evidence of CTS was predicted using a model comprising three ultrasonographic determinant factors, including hypoechogenicity, hypervascularity and wrist CSA of the median nerve. The probability of clinical evidence of CTS in a person with one, two, or three ultrasonographic signs of CTS was estimated to be 35%, 70%, and 90%, respectively.

Conclusions

Ultrasound imaging is a useful technique in diagnosing CTS patients when EDT results are not confirmatory and the patient is suspected of having neuropathy.     

Juvenile-onset mixed connective tissue disease associated with macrophage activation syndrome: A case with refractory Raynaud’s phenomenon

IntroductionMixed connective tissue disease (MCTD) is an autoimmune disease that is rare in children. The disease is presented with complex clinical features, so early diagnosis is challenging. Herein we describe the management and outcome of a girl with MCTD associated with macrophage activation syndrome (MAS) and refractory Raynauds’ phenomenon.Case reportA 13-year-old girl was admitted to the pediatric rheumatology ward with mild fever, reduced appetite, 6 kg weight loss (body mass index 15.8), digital ulcers, sclerodactyly, scleroderma, dysphagia, gastroesophageal reflux and arthralgia. She also had photosensitivity, Raynaud’s phenomenon, painless oral ulcers, and malar rash. She developed arthritis of the knees and ankles with limited range of motion. Spirometry showed a restrictive pattern. There was speckled antinuclear antibodies (ANA; 1/1260) and positive β-2-glycoprotein, U1-ribonucleoprotein (U1-RNP), anti-Scl-70 and anti-Ro52 antibodies. Anti-double stranded deoxyribonucleic acid and anti-cyclic citrullinated protein antibodies were negative. Based on clinical and laboratory findings, MCTD was confirmed. The child was treated with steroid, vasodilators, and immunosuppressives. She had an attack of salmon pink rashes, spiky fevers, Koebner phenomenon, serositis, and organomegaly and the diagnosis of associated MAS was held. The patient was treated with pentoxifylline, prednisolone, methotrexate, low dose aspirin, nifedipine, and hydroxychloroquine. On follow up there was refractory digital ulcers and Raynaud’s phenomenon; transthoracic endoscopic sympathectomy was performed and digital ulcers and coldness resolved.ConclusionMCTD may present with a myriad of rheumatic manifestations and in association with MAS the diagnosis and management may be challenging. Refractory Raynauds’ phenomenon may remarkably improve on transthoracic sympathectomy.