Analysis of 5HT3Ra gene expression by real time PCR in Systemic Lupus Erythematosus (SLE) patients

Systemic lupus erythemathosus is an autoimmune disease that affected many various types of tissues in 10% of world population and over 30 genes has associated with it. Nouroimmunoendocrynology concepts have shown that immune system could be affected by neuron system and vice versa, 5-hydroxytryptamine receptor a (5HT3Ra) was studied as a main receptor in these relations.In this study, peripheral blood sample were collected from (SLE) patient and normal individuals. The total cellular RNAs were extracted and the cDNAs were synthesized. This process was followed by real-time PCR using specific primers for 5HT3Ra gene and beta-actin gene as internal control. Eventually PCR products have been sequenced.Results of this study suggested that this special receptor expressed in polymorpho-nuclear cells. We found over expression of 5HT3Ra in patients in comparison with healthy individuals group. Interestingly, some nucleotide changes have been found in 5HT3Ra gene in patients but not found sequential nucleotide changes in healthy individuals group.This study supposed that over expression of 5HT3Ra gene in SLE patients lead to over activation of immune cells that derived from over stimulation  of them from serotonin blood serum that finally lead to autoimmune reactions that terminated in SLE

Expression of Cholera Toxin B–Proinsulin Fusion Protein in Lettuce and Tobacco Chloroplasts – Oral Administration Protects Against Development of Insulitis in Non-Obese Diabetic Mice

Lettuce and tobacco chloroplast transgenic lines expressing the cholera toxin B subunit–human proinsulin (CTB-Pins) fusion protein were generated. CTB-Pins accumulated up to ~16% of total soluble protein (TSP) in tobacco and up to ~2.5% of TSP in lettuce. Eight milligrams of powdered tobacco leaf material expressing CTB-Pins or, as negative controls, CTB–green fluorescent protein (CTB-GFP) or interferon–GFP (IFN-GFP), or untransformed leaf, were administered orally, each week for 7 weeks, to 5-week-old female non-obese diabetic (NOD) mice. The pancreas of CTB-Pins-treated mice showed decreased infiltration of cells characteristic of lymphocytes (insulitis); insulin-producing β-cells in the pancreatic islets of CTB-Pins-treated mice were significantly preserved, with lower blood or urine glucose levels, by contrast with the few β-cells remaining in the pancreatic islets of the negative controls. Increased expression of immunosuppressive cytokines, such as interleukin-4 and interleukin-10 (IL-4 and IL-10), was observed in the pancreas of CTB-Pins-treated NOD mice. Serum levels of immunoglobulin G1 (IgG1), but not IgG2a, were elevated in CTB-Pins-treated mice. Taken together, T-helper 2 (Th2) lymphocyte-mediated oral tolerance is a likely mechanism for the prevention of pancreatic insulitis and the preservation of insulin-producing β-cells. This is the first report of expression of a therapeutic protein in transgenic chloroplasts of an edible crop. Transplastomic lettuce plants expressing CTB-Pins grew normally and transgenes were maternally inherited in T1 progeny. This opens up the possibility for the low-cost production and delivery of human therapeutic proteins, and a strategy for the treatment of various other autoimmune diseases

Pathophysiology of autism spectrum disorders: Revisiting gastrointestinal involvement and immune imbalance

Autism spectrum disorders (ASD) comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted interests and repetitive behaviors. Several genes have been implicated in the pathogenesis of ASD, most of them are involved in neuronal synaptogenesis. A number of environmental factors and associated conditions such as gastrointestinal (GI) abnormalities and immune imbalance have been linked to the pathophysiology of ASD. According to the March 2012 report released by United States Centers for Disease Control and Prevention, the prevalence of ASD has sharply increased during the recent years and one out of 88 children suffers now from ASD symptoms. Although there is a strong genetic base for the disease, several associated factors could have a direct link to the pathogenesis of ASD or act as modifiers of the genes thus aggravating the initial problem. Many children suffering from ASD have GI problems such as abdominal pain, chronic diarrhea, constipation, vomiting, gastroesophageal reflux, and intestinal infections. A number of studies focusing on the intestinal mucosa, its permeability, abnormal gut development, leaky gut, and other GI problem raised many questions but studies were somehow inconclusive and an expert panel of American Academy of Pediatrics has strongly recommended further investigation in these areas. GI tract has a direct connection with the immune system and an imbalanced immune response is usually seen in ASD children. Maternal infection or autoimmune diseases have been suspected. Activation of the immune system during early development may have deleterious effect on various organs including the nervous system. In this review we revisited briefly the GI and immune system abnormalities and neuropeptide imbalance and their role in the pathophysiology of ASD and discussed some future research directions

Neuropeptides And Other Chemical Mediators, And The Role Of Antiinflammatory Drugs In Primary Headaches

Primary headaches including the migraine, cluster, and tension headaches are common neurological disorders which cause pain and disability to the patients. The pathomechanism of migraine is not very well understood however, current clinical findings indicate a possible primary brain disorder due to activation of the brain and brainstem as triggers for migraine. The headache phase of migraine may be due to activation of the peripheral nerves including the trigeminal nerve and others innervating the cranial blood vessels and release of vasoactive substances including the calcitonin generelated peptides (CGRP), possibly leading to vasodilation and brainstem activation. Several of our studies in an experimental model of pain using electrical stimulation of the trigeminal ganglion in rats focused on various neuropeptides release from the peripheral and central trigeminal nerve terminals, however, clinically only the CGRP in migraine and CGRP and vasoactive intestinal peptide (VIP) in cluster headache were found in patient\u27s blood. Although several drugs are used in the treatment of migraine, the non-steroid anti-inflammatory drugs (NSAIDs) and the triptan family of drugs are the first choice drugs recommended for the treatment of acute migraine headache. Although clinically very few studies detected other vasoactive/inflammatory molecules in the blood of migraine patients, sensitization of peripheral axons can involve many inflammatory mediators affecting the peripheral tissue substrates of pain. Moreover, central sensitization in the trigeminal nucleus can also contribute to additional pain responses. This article reviews neuropeptides and other molecules involved in primary headaches and major drugs proposed for their treatment in recent years. © 2010 Bentham Science Publishers Ltd

Major Neuroanatomical And Neurochemical Substrates Involved In Primary Headaches

Neuroanatomical structures involved in head pain are primarily the sensory distribution of four cranial nerves: the trigeminal-and to a lesser extent, facial, glossopharyngeal, and vagus-as well as the terminations of the upper three cervical nerves.In addition, various pain sensitive cranial structures including the scalp and its blood supply, the head and neck muscles, intracranial and meningeal arteries, and dura mater including the venous sinuses are the major anatomical substrates of various types of headaches. Although brain tumors, different types of hemorrhage, hypertension, and meningitis may present as a headache, the migraine, cluster, and tension headaches are the three major types of primary headaches. Current opinion suggests a primary central nervous system activation may initiate a migraine. Several triggering factors such as disturbances of brain oxygenation and metabolism, alterations in the serotonin levels, low levels of brain tissue magnesium, altered transport of ions across the cell membrane, abnormal mitochondrial energy metabolism, and genetic abnormalities including mutations of the P/Q type calcium channel gene, Na+/K+ pump ATP1A2, or sodium channel Nav1.1 mutations have been linked to the pathogenesis of migraines. Patients with mutations in the calcium channel gene are more sensitive to environmental factors, which results in a wave of cortical spreading depression in the patient after the attack is initiated.Moreover, several recent clinical and diagnostic studies indicate a dysfunction of the brainstem periaqueductal gray matter during migraine, or initiation of migraine by activation of the brainstem including the dorsal rostral and midline pons. Consistent with this, an active locus in the posterior hypothalamus has been implicated in cluster headache (CH). The headache phase involves the activation of the trigeminovascular system and possibly dilatation of the cranial blood vessels presumably mediated by the release of vasoactive substances and neuropeptides including the calcitonin gene-related peptide (CGRP). Increased serum CGRP levels were detected during migraine and CH. In addition, in CH, there is a release of parasympathetic peptide, vasoactive intestinal peptide. Currently, inhibiting the release of vasoactive substances and neuropeptides including the CGRP or nitric oxide, or blocking their receptors in the neuroanatomical substrates of head pain is a major focus in treatment of headaches. © 2010 by Nova Science Publishers, Inc. All rights reserved