Gene/Protein Disease Symptom Drug Enzyme Compound
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BACKGROUND: Eosinophilic gastritis is related to eosinophilic gastroenteritis, varying only in regards to the extent of disease and small bowel involvement. Common symptoms reported are similar to our patient's including: abdominal pain, epigastric pain, anorexia, bloating, weight loss, diarrhea, ankle edema, dysphagia, melaena and postprandial nausea and vomiting. Microscopic features of eosinophilic infiltration usually occur in the lamina propria or submucosa with perivascular aggregates. The disease is likely mediated by eosinophils activated by various cytokines and chemokines. Therapy centers around the use of immunosuppressive agents and dietary therapy if food allergy is a factor. CASE PRESENTATION: The patient is a 31 year old Caucasian female with a past medical history significant for ulcerative colitis. She presented with recurrent bouts of vomiting, abdominal pain and chest discomfort of 11 months duration. The bouts of vomiting had been reoccurring every 7-10 days, with each episode lasting for 1-3 days. This was associated with extreme weakness and cachexia. Gastric biopsies revealed intense eosinophilic infiltration. The patient responded to glucocorticoids and azathioprine. The differential diagnosis and molecular pathogenesis of eosinophilic gastritis as well as the molecular effects of glucocorticoids in eosinophilic disorders are discussed. CONCLUSIONS: The patient responded to a combination of glucocorticosteroids and azathioprine with decreased eosinophilia and symptoms. It is likely that eosinophil-active cytokines such as interleukin-3 (IL-3), granulocyte macrophage colony stimulating factor (GM-CSF) and IL-5 play pivotal roles in this disease. Chemokines such as eotaxin may be involved in eosinophil recruitment. These mediators are downregulated or inhibited by the use of immunosuppressive medications.
Clin Mol Allergy 2004 May 14
PMID:Eosinophilia in a patient with cyclical vomiting: a case report. 1514 61

Many forms of liver disease may ultimately lead to fibrosis of the liver, the most advanced state being cirrhosis. Cirrhosis is a morphologic disease that eventually results in a functional change of the liver. It is generally not accompanied by signs or symptoms early in its course, and is often diagnosed late when signs of liver failure become overt. Imaging studies may suggest cirrhosis, but only if there have been gross changes in the appearance of the liver, and this is often not the case. The only way to diagnose cirrhosis reliably has been through direct histologic examination of liver tissue. The drawback to histologic diagnosis has been the risks and discomfort associated with liver biopsy. Hesitation to perform the procedure also exists due to lack of experience of many practitioners and the low reimbursement rates for a procedure that is viewed as time consuming and potentially dangerous. The search for noninvasive modalities to assess fibrosis through biochemical and other means has begun. Several markers are currently under investigation, many of which are combined with clinical assessment and other biochemical parameters, to establish the presence of liver fibrosis. FIBROSpect II is an example of a commercially available assay that employs a combination of three markers to distinguish between no, minimal and advanced fibrosis.
Expert Rev Mol Diagn 2004 Sep
PMID:FIBROSpect II: a potential noninvasive test to assess hepatic fibrosis. 1534 53

Herpes simplex virus induced oral and genital ulcerating lesions will fluoresce brightly yellow and yellow-orange, respectively, if treated with a chlorinated solution of neutral red and exposed to ultraviolet-A light. An orange to red fluorescence is seen with similarly treated and illuminated Herpes zoster virus induced shingles; while treated human papillomavirus induced genital warts display more of a purplish fluorescence. Pain and discomfort commonly disappear soon after the treatment and all lesions undergo expedited healing that is readily observable within 24 h. The mechanism of healing is thought to involve an interaction between neutral red and alternative cellular energy pigments (ACE pigments) present within the viral lesions that enhances responsiveness to ultraviolet light energy. The healing effects are not restricted to the treated lesions and may involve transmission of a biological energy throughout the body. Beyond its obvious clinical and diagnostic utility, this model system may help usher in a new era of energy-based medicine.
Exp Mol Pathol 2005 Apr
PMID:Symptomatic relief of herpetic skin lesions utilizing an energy-based approach to healing. 1571 38

The present study compared the plasma corticosterone concentrations between meat- and layer-type neonatal chicks (Gallus gallus) (1) exposed to isolation-induced stress or (2) injected intracerebroventricularly (ICV) with corticotropin-releasing factor (CRF). Both types of neonatal chicks housed in groups were individually introduced to an open field arena and locomotion and distress-induced vocalizations were monitored for 10 min. The responses of the two strains were remarkably different, with meat-type chicks being less active than layer-type chicks. Distress-induced vocalizations were drastically decreased over time in meat-type chicks while they remained high in layer-type chicks throughout the test. Plasma corticosterone concentrations measured at the end of the test were significantly higher in layer-type chicks than in meat-type ones. Plasma corticosterone concentrations measured 10 min after the ICV injection of CRF were significantly higher in layer- than meat-type chicks. These results indicate that meat-type chicks have either a greater capability to acclimatize to novel environments, or a blunted HPA axis compared with layer-type chicks.
Comp Biochem Physiol A Mol Integr Physiol 2005 Jul
PMID:ICV CRF and isolation stress differentially enhance plasma corticosterone concentrations in layer- and meat-type neonatal chicks. 1597 66

The first reported reference to delayed onset muscle soreness (DOMS) was that by Theodore Hough in 1902. Hough stated that when an untrained skeletal muscle performed exercise, it often resulted in discomfort that did not manifest until 8-10 h post-exercise, and concluded that this could not be solely attributed to fatigue. Since Hough's initial observation there has been a proliferation in research into DOMS, and despite this, the exact aetiology remains unclear. This review explores the concept of DOMS in relation to the likely causative factors and also discusses possible reasons for the equivocal findings in the literature. Free radicals are unquestionably produced during and following various forms of contractile activity and are known to result in skeletal muscle damage. Given the link between DOMS and contraction-induced muscle damage, post-exercise free radical production has been associated with DOMS; however, the precise nature of this relationship remains unsubstantiated. This review will address free radical production during and following exercise, discuss methods of assessing their generation, and critically evaluate their relationship with DOMS. There is increasing literature to suggest that free radicals act as signalling molecules, specifically activating redox sensitive transcription factors, which are necessary for muscle regeneration and adaptation following damage. Consequently free radicals may play a key physiological role in the aetiology of DOMS as opposed to a pathological role. Evidence for and against free radicals causing DOMS will be presented, and finally a suggested role of free radicals in DOMS will be proposed.
Comp Biochem Physiol A Mol Integr Physiol 2005 Nov
PMID:The emerging role of free radicals in delayed onset muscle soreness and contraction-induced muscle injury. 1615 65

Biomaterials are regularly used in various types of artificial tissues and organs, such as oxygenators, plasmapheresis equipment, hemodialysers, catheters, prostheses, stents, vascular grafts, miniature pumps, sensors and heart aids. Although progress has been made regarding bioincompatibility, many materials and procedures are associated with side effects, in particular bioincompatibility-induced inflammation, infections and subsequent loss of function. After cardiopulmonary bypass, coagulopathies can occur and lead to cognitive disturbances, stroke and extended hospitalization. Hemodialysis is associated with anaphylatoid reactions that cause whole-body inflammation and may contribute to accelerated arteriosclerosis. Stents cause restenosis and, in severe cases, thrombotic reactions. This situation indicates that there is still a need to try to understand the mechanisms involved in these incompatibility reactions in order to be able to improve the biomaterials and to develop treatments that attenuate the reactions and thereby reduce patients' discomfort, treatment time and cost. This overview deals with the role of complement in the incompatibility reactions that occur when biomaterials come in contact with blood and other body fluids.
Mol Immunol 2007 Jan
PMID:The role of complement in biomaterial-induced inflammation. 1690 92

One major goal in pain research is to identify novel pain targets. Tissue injury, inflammation, and ischemia are usually accompanied by local tissue acidosis, the degree of associated pain or discomfort well correlated with the magnitude of acidification. Proton-sensing ion channels, transient receptor potential/vanilloid receptor subtype 1, and acid-sensing ion channel 3 are involved in acidosis-linked pain. However, whether recently identified proton-sensing G-protein-coupled receptors (GPCRs) also have some contributions is unclear. Proton-sensing GPCRs, including OGR1, GPR4, G2A, and TDAG8, are fully activated at pH 6.4-6.8 in vitro. To understand whether the proton-sensing GPCRs are expressed in nociceptors, we cloned the four mouse genes and examined their tissue distribution and localization in pain-relevant loci, the dorsal root ganglion (DRG). The OGR1 family members were widely expressed in neuronal and non-neuronal tissues. Their transcripts were expressed in the DRG, and most (75-82%) were present in small-diameter neurons responsible for nociception. Approximately 31-40% of total DRG neurons expressed at least two proton-sensing GPCRs. We have also demonstrated that gene expression of proton-sensing GPCRs is changed in ASIC3 knockout mice. Our finding suggests that proton-sensing GPCRs could have some roles in nociception or in compensation of loss of ASIC3 gene.
Mol Cell Neurosci 2007 Oct
PMID:Nociceptors of dorsal root ganglion express proton-sensing G-protein-coupled receptors. 1772 May 33

Immunotherapy against infectious agents and malignant tumors requires efficient priming of effector cells through direct expression and/or efficient cross-presentation of antigens by antigen-presenting cells. Electroporation is a new procedure aimed at transiently increasing cell membrane permeability and direct delivery of antigen or antigen-encoding nucleic acids inside targeted cells. We evaluated the tolerability including compliance with repeated electroporation treatments using MedPulser DDS in 24 healthy adults. Pain severity was evaluated at time of electroporation treatment, and at 1, 5, 10, and 20 minutes, and 24 hours thereafter, using two clinically validated questionnaires: McGill Pain Questionnaire (MPQ) (Present Pain Intensity) and Brief Pain Inventory (BPI). Electroporation treatments were generally well tolerated. Twenty-two out of 24 subjects returned for the second electroporation treatment 14 days after first treatment. Only two subjects reported a treatment-related systemic adverse experience following either electroporation application. For both pain assessment tools, maximum pain and/or discomfort were mostly reported immediately (within 5 minutes) after electroporation; Furthermore, no difference was observed when comparing peak-pain scores after first and second electroporation treatments. This study supports the clinical application of MedPulser DDS for the improvement of antigen-induced immune responses for prophylactic or therapeutic vaccines, especially in gene-based therapies for cancer.
Mol Ther 2009 May
PMID:Tolerability of two sequential electroporation treatments using MedPulser DNA delivery system (DDS) in healthy adults. 1927 16

The scabies mite (Sarcoptes scabiei) is a parasite responsible for major morbidity in disadvantaged communities and immuno-compromised patients worldwide. In addition to the physical discomfort caused by the disease, scabies infestations facilitate infection by Streptococcal species via skin lesions, resulting in a high prevalence of rheumatic fever/heart disease in affected communities. The scabies mite produces 33 proteins that are closely related to those in the dust mite group 3 allergen and belong to the S1-like protease family (chymotrypsin-like). However, all but one of these molecules contain mutations in the conserved active-site catalytic triad that are predicted to render them catalytically inactive. These molecules are thus termed scabies mite inactivated protease paralogues (SMIPPs). The precise function of SMIPPs is unclear; however, it has been suggested that these proteins might function by binding and protecting target substrates from cleavage by host immune proteases, thus preventing the host from mounting an effective immune challenge. In order to begin to understand the structural basis for SMIPP function, we solved the crystal structures of SMIPP-S-I1 and SMIPP-S-D1 at 1.85 A and 2.0 A resolution, respectively. Both structures adopt the characteristic serine protease fold, albeit with large structural variations over much of the molecule. In both structures, mutations in the catalytic triad together with occlusion of the S1 subsite by a conserved Tyr200 residue is predicted to block substrate ingress. Accordingly, we show that both proteases lack catalytic function. Attempts to restore function (via site-directed mutagenesis of catalytic residues as well as Tyr200) were unsuccessful. Taken together, these data suggest that SMIPPs have lost the ability to bind substrates in a classical "canonical" fashion, and instead have evolved alternative functions in the lifecycle of the scabies mite.
J Mol Biol 2009 Jul 24
PMID:Structural mechanisms of inactivation in scabies mite serine protease paralogues. 1942 18

Probiotics are live microorganisms that promote health benefits upon consumption, while prebiotics are nondigestible food ingredients that selectively stimulate the growth of beneficial microorganisms in the gastrointestinal tract. Probiotics and/or prebiotics could be used as alternative supplements to exert health benefits, including cholesterol-lowering effects on humans. Past in vivo studies showed that the administration of probiotics and/or prebiotics are effective in improving lipid profiles, including the reduction of serum/plasma total cholesterol, LDL-cholesterol and triglycerides or increment of HDL-cholesterol. However, other past studies have also shown that probiotics and prebiotics had insignificant effects on lipid profiles, disputing the hypocholesterolemic claim. Additionally, little information is available on the effective dosage of probiotics and prebiotics needed to exert hypocholesterolemic effects. Probiotics and prebiotics have been suggested to reduce cholesterol via various mechanisms. However, more clinical evidence is needed to strengthen these proposals. Safety issues regarding probiotics and/or prebiotics have also been raised despite their long history of safe use. Although probiotic-mediated infections are rare, several cases of systemic infections caused by probiotics have been reported and the issue of antibiotic resistance has sparked much debate. Prebiotics, classified as food ingredients, are generally considered safe, but overconsumption could cause intestinal discomfort. Conscientious prescription of probiotics and/or prebiotics is crucial, especially when administering to specific high risk groups such as infants, the elderly and the immuno-compromised.
Int J Mol Sci 2010 Jun 17
PMID:Cholesterol-lowering effects of probiotics and prebiotics: a review of in vivo and in vitro findings. 2064 Jan 65


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