The incidence of endocrine autoimmunity is increasing worldwide. Complex molecular and cellular mechanisms underline the pathogenesis of autoimmune diseases with the contribution of putative environmental factors and the requisite allele(s) responsible for antigen presentation by antigen-presenting cells for T cell recognition. Although genetic factors have been well dissected, the environmental agents, including putative viruses, which may be causative of disease, are still under investigation. The long preclinical period of autoimmune disorders is characterised by an enhanced challenge over time of autoreactive T cells by an increased number of autoantigenic peptides and autoantibodies production. It is of considerable importance to establish predictive, preventive strategies of the disease onset. It is also relevant to project novel immunotherapeutic interventions aiming to halt the disease progression before and after the clinical manifestations become evident. In this article, we review the most recent and important patents related to autoimmune endocrine disorders with special reference to insulin-dependent diabetes mellitus, Addisons disease, Graves disease and Hashimotos thyroiditis. Engineered bioactive compounds aim to interfere with T cell activation and differentiation, to modulate other inflammatory effectors cells and cytokine production. We discuss the importance of the novel therapeutic targets in treating the immunopathological process in these categories of disorders.
Experimental and clinical data provide evidence for the lifelong reciprocal influence of mammalian neuroendocrine and immune systems. The functions of these systems change during ontogeny. In the perinatal period, the neuroendocrine system has both regulatory and morphogenetic functions: during early ontogeny, neurohormones stimulate the growth and differentiation of fetal tissues, including the lymphoid tissue. In postnatal life, effects of many hormones on the immune system are apparently unspecific: their function is mainly to maintain its homeostasis in the changing environment. Thymic peptides regulate the production of hormones, neuropeptides, and cytokines both in the thymus and in the hypothalamus, pituitary, and gonads. The perinatal period is critical for the complete structural and functional development of these systems. Disturbances in neuroendocrine-immune interactions at this stage result in longlasting predisposition to various pathologies in adulthood. The plasticity of physiological systems in the perinatal period allows the environmental factors acting on the mother and fetus to alter the functions of certain organs and tissues, providing for fetal adaptation to adverse conditions. Exposure to stress, adverse environmental factors, etc., as well as mothers improper diet and behavior during pregnancy and breast feeding put the young at risk for autoimmune, allergic, metabolic, psychic, and nervous disorders during adult life. The possibility of using neurohormones for treating immunodeficiencies caused by various adverse factors is discussed. The review also includes recent patents relevant to the problem at issue.
Modifications in the structure of native LDL that are capable of inducing aggregation and/or fusion of the particles are currently recognized to be a prerequisite for the initiation of lipid accumulation in arterial intima. Modified forms of LDL can play an important role on atherogenesis and atherosclerosis progression, inducing atherosclerosis through complex inflammatory and immunological mechanisms. LDL can be modified by oxidation, glycation, alkylation and nitration, among other reactions. All modifications of LDL can generate neoepitopes, which become LDL immunogenic. Since modified forms of LDL are associated with several pathological states, monitoring their levels in human plasma would be very useful for studying atherogenesis. Monoclonal antibodies are powerful tools in identifying specific structures on heterogeneously modified LDL particles. Monoclonal antibodies specific for epitopes on modified lipoproteins have been obtained and used for developing diagnosis kits to evaluate the concentrations of modified lipoproteins in blood plasma and other biological fluids. Most of the tests concerning to the assay of modified LDL are ELISAs. More recently, immunosensor systems, based on the biosensor technologies, begin to be developed. In this review, the recent advances on the assessment of these modified LDL particles and related patents will be discussed.
The immune system is a complex defense mechanism, able to protect the body against pathogens. It consists of a network of cells, tissues, and organs that work together to protect the body. Leukocytes are key operatives of the immune system. Cells destined to become immune cells, like all blood cells, arise in your bodys bone marrow from stem cells (HSC). A large body of evidence show the transcription factors play critical roles in the homeostasis of T cells, B cells, neutrophils and other non-lymphoid leneages. This review discusses the role of the Smek (Suppressor of mek null) gene, that acts in the stress response pathway of animals by binding to and enhancing the transcription of FoxO transcription factors. Furthermore, the review deals with tachykinins, involved in neurotransmission and immune/hematopoietic modulation. Both molecules, objects of recent patents, may have real therapeutic potential.
Osteoporosis characterized by low bone mass and structural deterioration of bone tissue; has a huge impact on public health through high morbidity, mortality and economic costs associated with resultant fractures. The prevention and treatment of fragility fractures in the osteoporosis patients worldwide becomes an important issue in the current clinical practice. Women often have an accelerated bone loss after menopause and result in a lower bone mass than men. Since the bone loss is irreversible, early prevention and treatment of osteoporosis is important in the early postmenopausal period. The goal of prevention needs to be not only effective, but also safe, to diminish the risk of vertebral, hip and other nonvertebral fractures. Non-pharmacological treatments, such as calcium, vitamin D, exercise and reduction of risk factors may diminish the impact of menopause and age-mediated bone loss. Current pharmacological options available include bisphosphonates, calcitonin, hormone replacement therapy, selective estrogen receptor modulators, teriparatide, and strontium ranelate, etc. Lots of natural products including dietary components and herbal products have also been demonstrated to be capable of modifying bone metabolism, particularly of inhibiting bone resorption. These natural products may provide as an alternative treatment for osteoporosis. More than 150 patents have recently been issued for the prevention and treatment of postmenopausal osteoporosis. The development of other new medications also sheds light on either prevention or treatment of osteoporosis, such as human monoclonal anti-RANKL antibody, cathepsin K inhibitors, and cannabinoid-based drugs.
To better understand the pathogenesis of Type 1 diabetes, we have developed a new classification of Type 1 diabetes based on islet autoantibodies, mode of disease onset and insulin deficiency. The first marker is mode of disease onset and insulin deficiency, i.e. fulminant-onset (F), acute-onset (A), slow-onset and insulin-deficient (S), and slow-onset and non-insulin-deficient (N). The second marker is islet autoantibodies- a) positive (autoimmune) or b) negative (idiopathic). The combination of the four uppercase (F, A, S, and N) and two lowercase (a and b) letters indicates the clinical type of diabetes. Therefore, Type 1 diabetes is the sum of Fa, Fb, Aa, Ab, Sa and Na types of diabetes, while Type 2 diabetes is the sum of Sb and Nb types of diabetes. For example, fulminant Type 1 diabetes is the sum of Fa and Fb types of diabetes. Classic Type 1 diabetes is the sum of Fa and Aa types of diabetes. Latent autoimmune diabetes in adults (LADA) is the sum of Sa and Na types of diabetes, in which disease onset was in adulthood. An appropriate classification would improve our understanding of the pathogenesis of Type 1 diabetes and allow for easier discrimination of Type 1 diabetes from Type 2 diabetes. This review article also discusses some recent patent related to the field.
Melatonin (N-acetyl-5- methoxytryptamine) is a pineal gland hormone, synthesized from amino acid Ltryptophan. Other tissues including retina, skin, and gastrointestinal tract also synthesize it. It is secreted into the cerebrospinal fluid and circulatory system in a circadian pattern. Its production is light:dark dependent and its levels are low during the day and maximal during the hours of darkness. It plays an important role in different physiological and pathophysiological processes in the brain, which includes regulation of biological rhythms and seasonal reproduction. Its biological activity is associated with its action on melatonin receptors - ML-1 and ML-2. It has antioxidant and neuroprotective propertities and potential therapeutic role in different neurological disorders. Melatonin has been used as a sleep-promoting agent; more recently it has also been used in headache, movement disorders, neuropathic pain, and seizure disorders. In this review, some recent patents also discussed.
Women with type 1 diabetes frequently report problems with blood glucose control around the time of menstruation. Although this issue has been extensively studied, the correlation between the phases of the menstrual cycle and blood glucose control remains to be established. This present study discusses the controversy that exists in the current literature regarding the effect of the menstrual cycle on metabolic control in women with type 1 diabetes. A search was made in the PubMed database in March 2008 of papers published in the last fifteen years that included the terms “menstrual cycle” and “type 1 diabetes”. Six articles were selected. In some women with type 1 diabetes, premenstrual hyperglycemia has been reported as being detrimental to adequate blood glucose control. Many factors have been attributed to this phenomenon. Some studies have reported elevated progesterone levels during premenstrual hyperglycemia. Other studies have suggested that premenstrual symptoms may explain the unsatisfactory blood glucose control found during this period. Despite conflicting reports in the literature, it would appear that premenstrual hyperglycemia does occur in some diabetic women. More studies with larger sample sizes and reliable methodology have been recommended. This review also took into consideration the registration of some recent patents.
Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are two chronic intestinal diseases having a mutual pathophysiological pathways with different manifestations. Generally, inflammatory mediators and cytokines orchestrate the scenario that amongst them, tumor necrosis factor-alpha (TNF-α) is a cornerstone. Nowadays different medications and drug classes are administered for treatment of IBD and IBS but there is no full cure and side effects of drugs limit their usage. Concerning the novel suggestion of ATP in the treatment of bowel diseases, we were invited to conduct a systematic review. MeSh keywords of IBD, IBS, TNF-α, IL-12, and ATP were searched in search engines like Pubmed, Scopus, Web of sciences, Embase, and Google scholar. Comparing the common medications with ATP in terms of side effects, efficacy, and other limitations lead us to the conclusion that ATP could be a reasonable alternative that may replace all other medications in this field in the near future. ATP is prepared as lyophilized form that is stable at room temperature for at least 1-3 years and can be used as intravenous infusion in the setting of private homes without direct medical supervision. Other routes of administration include intraperitoneal, subcutaneous, oral, topical, nasal, and sublingual. Also, it can be mixed with parenteral and enteral nutrition cocktails. The review also discussed some recent patents relevant to the field.