Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Numerous factors may be involved in the development of chronic recurrent otitis externa: altered pH of the cerumen, increased susceptibility to contact allergens (e.g. nickel ear-rings) in atopic patients, the use of instruments for cleaning out the auditory canal, the presence of a foreign body, congential narowing of the auditory canal, or systemic diseases (in particular diabetes mellitus). For diagnostic purposes, the use of the otoscope is mandatory, and swabs to determine the presence of bacteria or fungi are to be recommended. Treatment is dictated by the clinical picture presenting, and may comprise the local application of antibiotic cortisone containing or antimycotic preparations and temponade of the auditory canal (acute inflammatory phase) or pH-stabilizing lotions (chronic dry inflammatory phase) with the aim of ameliorating the frequently highly troublesome pruritus.
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PMID:[Chronic recurrent otitis externa. Excessive ear hygienic care can have sequelae]. 1465 37

It is known that certain inorganic trace elements such as vanadium, zinc, chromium, copper, iron, potassium, sodium, and nickel play an important role in the maintenance of normoglycemia by activating the beta-cells of the pancreas. In the present study, the elemental composition in the leaves of four traditional medicinal plants (Murraya koenigii, Mentha piperitae, Ocimum sanctum, and Aegle marmelos) widely used in the treatment of diabetes-related metabolic disorders has been studied using atomic absorption spectroscopy. The levels of Cu, Ni, Zn, K, and Na were found to be in trace amounts, whereas Fe, Cr, and V levels were found in marginal levels. The importance of these elements in disorders related to diabetes is also briefly discussed.
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PMID:Mineral content of some medicinal plants used in the treatment of diabetes mellitus. 1577 35

Metal-induced toxicity and carcinogenicity, with an emphasis on the generation and role of reactive oxygen and nitrogen species, is reviewed. Metal-mediated formation of free radicals causes various modifications to DNA bases, enhanced lipid peroxidation, and altered calcium and sulfhydryl homeostasis. Lipid peroxides, formed by the attack of radicals on polyunsaturated fatty acid residues of phospholipids, can further react with redox metals finally producing mutagenic and carcinogenic malondialdehyde, 4-hydroxynonenal and other exocyclic DNA adducts (etheno and/or propano adducts). Whilst iron (Fe), copper (Cu), chromium (Cr), vanadium (V) and cobalt (Co) undergo redox-cycling reactions, for a second group of metals, mercury (Hg), cadmium (Cd) and nickel (Ni), the primary route for their toxicity is depletion of glutathione and bonding to sulfhydryl groups of proteins. Arsenic (As) is thought to bind directly to critical thiols, however, other mechanisms, involving formation of hydrogen peroxide under physiological conditions, have been proposed. The unifying factor in determining toxicity and carcinogenicity for all these metals is the generation of reactive oxygen and nitrogen species. Common mechanisms involving the Fenton reaction, generation of the superoxide radical and the hydroxyl radical appear to be involved for iron, copper, chromium, vanadium and cobalt primarily associated with mitochondria, microsomes and peroxisomes. However, a recent discovery that the upper limit of "free pools" of copper is far less than a single atom per cell casts serious doubt on the in vivo role of copper in Fenton-like generation of free radicals. Nitric oxide (NO) seems to be involved in arsenite-induced DNA damage and pyrimidine excision inhibition. Various studies have confirmed that metals activate signalling pathways and the carcinogenic effect of metals has been related to activation of mainly redox-sensitive transcription factors, involving NF-kappaB, AP-1 and p53. Antioxidants (both enzymatic and non-enzymatic) provide protection against deleterious metal-mediated free radical attacks. Vitamin E and melatonin can prevent the majority of metal-mediated (iron, copper, cadmium) damage both in vitro systems and in metal-loaded animals. Toxicity studies involving chromium have shown that the protective effect of vitamin E against lipid peroxidation may be associated rather with the level of non-enzymatic antioxidants than the activity of enzymatic antioxidants. However, a very recent epidemiological study has shown that a daily intake of vitamin E of more than 400 IU increases the risk of death and should be avoided. While previous studies have proposed a deleterious pro-oxidant effect of vitamin C (ascorbate) in the presence of iron (or copper), recent results have shown that even in the presence of redox-active iron (or copper) and hydrogen peroxide, ascorbate acts as an antioxidant that prevents lipid peroxidation and does not promote protein oxidation in humans in vitro. Experimental results have also shown a link between vanadium and oxidative stress in the etiology of diabetes. The impact of zinc (Zn) on the immune system, the ability of zinc to act as an antioxidant in order to reduce oxidative stress and the neuroprotective and neurodegenerative role of zinc (and copper) in the etiology of Alzheimer's disease is also discussed. This review summarizes recent findings in the metal-induced formation of free radicals and the role of oxidative stress in the carcinogenicity and toxicity of metals.
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PMID:Metals, toxicity and oxidative stress. 1589 31

Multiple mechanisms of tolerance are induced by oral antigen. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral antigen induces T-helper 2 [interleukin (IL)-4/IL-10] and Th3 [transforming growth factor (TGF)-beta] T cells plus CD4+CD25+ regulatory cells and latency-associated peptide+ T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-beta, cholera toxin B subunit, Flt-3 ligand, and anti-CD40 ligand. Oral (and nasal) antigen administration suppresses animal models of autoimmune diseases including experimental autoimmune encephalitis, uveitis, thyroiditis, myasthenia, arthritis, and diabetes in the non-obese diabetic (NOD) mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, graft rejection, allergy, colitis, stroke, and models of Alzheimer's disease. Oral tolerance has been tested in human autoimmune diseases including multiple sclerosis (MS), arthritis, uveitis, and diabetes and in allergy, contact sensitivity to dinitrochlorobenzene (DNCB), and nickel allergy. Although positive results have been observed in phase II trials, no effect was observed in phase III trials of CII in rheumatoid arthritis or oral myelin and glatiramer acetate (GA) in MS. Large placebo effects were observed, and new trials of oral GA are underway. Oral insulin has recently been shown to delay onset of diabetes in at-risk populations, and confirmatory trials of oral insulin are being planned. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time, and antigen-specific mechanisms of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral), formulation, mucosal adjuvants, combination therapy, and early therapy.
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PMID:Oral tolerance. 1604 53

Seven kinds of Chinese traditional medicines, including laoniankechuan tablet, fufangbanxia tablet, weitongning tablet, quanshen tablet, shengshijiangtang capsule, xiasangju particle, and American yangshen tablet, were digested with HNO3-HClO4 mixed acid. The fourteen trace elements, including calcium, magnesium, iron, zinc, potassium, sodium, manganese, copper, chromium, cobalt, strontium, nickel, cadmium and lead in the drugs were determined by atomic absorption spectrometry. The effects of the type of mixed acid, the ratio of HNO3 to HClO4 in mixed acid, the volume of digesting solution, and the digesting time were also investigated in detail. The results obtained show that the concentrations of Ca, Mg, Fe, K and Na in seven kinds of Chinese traditional medicines are higher than those of other elements. Moreover, shengshijiangtang capsule for the treatment of diabetes contains plenty of Mn, and weitongning tablet for the treatment of stomach disease contains plenty of Sr, Mn and Cu.
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PMID:[Determination of fourteen trace elements in chinese traditional medicines by atomic absorption spectrometry]. 1637 4

Specific elements are bioconcentrated in human hair and nails, which have unique advantages of application in population monitoring studies thereby, recognized as biological tools for disease diagnosis and prevention. However, investigations are meager for relative element profile in hair and nails of same subjects. In this study, hair and nails were analyzed to find effects of age, sex, smoking habit, diet, urban and rural exposure gradients, occupation, and health on element levels. Scalp hair and fingernails were sampled along with a questionnaire from urban and rural subjects of New Delhi; patients of hypertension, coronary heart disease, and diabetes were identified clinically. Cadmium, chromium, copper, nickel, lead and zinc concentrations were determined by AAS in both the samples; CRM (human hair powder) analysis showed acceptable precision and accuracy in element measurement. In comparison to controls, Cr-H and Zn-H levels were lower respectively in female hypertensive and total hypertensive subjects, whereas, Zn-N and Cu-N were lower respectively in total CHD and diabetic subjects, and hypertensive and CHD urban subjects. Cd concentrations were higher in both the samples of tobacco smoking rural subjects than that of non-smokers. Farmers had lower Pb-H than rural businessmen did. Cr, Cu, Ni, and Zn concentrations were different due to rural and urban gradient but not to the influence of age, sex, and diet. Pb value was alone correlated between the paired samples. Thus, higher Cd levels in the smokers and lower Cr, Cu and Zn levels in the patients were observed.
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PMID:Relative element levels in the paired samples of scalp hair and fingernails of patients from New Delhi. 1714 Jun 38

Cardiovascular diseases are the major cause of morbidity and mortality in diabetic patients. Contractile function of the heart is frequently compromised in the clinical setting and in experimental models of diabetes mellitus (DM). This article investigated the effect of streptozotocin (STZ)-induced type 1 DM on contraction, L-type calcium (Ca2+) current (I(Ca(2+)L)), and on cytosolic calcium concentrations [Ca2+]i in ventricular myocytes of the rat heart. After 4-10 weeks of STZ treatment, blood glucose levels in diabetic animals were significantly (P < 0.05) higher compared to age-matched controls. Diabetic rats have significantly (P < 0.05) reduced body, reduced heart weight, and reduced viability of ventricular myocytes compared to controls. The amplitude of I(Ca(2+)L) and amplitude of contraction were significantly reduced (P < 0.05) at test potentials in the range -10 mV to +20 mV and -30 mV to +40 mV, respectively, in myocytes from diabetic animals compared to age-matched controls. Moreover, there was a significant (P < 0.05) delay in electrically stimulated and caffeine-evoked time to half relaxation of the Ca2+ transient in myocytes from diabetic animals compared to controls. A similar effect was obtained in myocytes treated with a combination of caffeine and nickel chloride (NiCl2). It is concluded that the diabetes-induced voltage-dependent decrease in contraction is associated with reduced Ca2+ channel activities and prolonged diastolic cytosolic Ca2+ compared to age-matched control. Taken together, the results suggest that Ca2+ homeostasis is deranged during DM and this may be expressed at the level of the Na+/Ca2+ exchanger.
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PMID:Effects of streptozotocin-induced diabetes on contraction and calcium transport in rat ventricular cardiomyocytes. 1715 3

Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag) that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10) and Th3 (TGF-beta) regulatory T cells (Tregs) plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-beta, cholera toxin B subunit (CTB), Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE), uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD) mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral), formulation, mucosal adjuvants, combination therapy and early therapy.
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PMID:Oral tolerance: therapeutic implications for autoimmune diseases. 1716 57

Recent data indicate that T-type Ca2+ channels are amplifiers of peripheral pain signals, but their involvement in disorders of sensory neurons such as those associated with diabetes is poorly understood. To address this issue, we used a combination of behavioral, immunohistological, molecular, and electrophysiological studies in rats with streptozotocin (N-[methylnitrosocarbamoil]-D-glucosamine)-induced early diabetic neuropathy. We found that, in parallel with the development of diabetes-induced pain, T-type current density increased by twofold in medium-size cells from L4-L5 dorsal root ganglia (DRG) with a depolarizing shift in steady-state inactivation. This not only correlated closely with more prominent afterdepolarizing potentials (ADPs) but also increased cellular excitability manifested as a lower threshold for burst firing in diabetic than in control cells. T-type currents and ADPs were potently inhibited by nickel and enhanced by L-cysteine, suggesting that the Ca(V)3.2 T-type channel isoform was upregulated. Both control and diabetic DRG cells with ADPs stained positively for isolectin B4, but only diabetic cells responded robustly to capsaicin, suggesting enhanced nociceptive function. Because increased excitability of sensory neurons may result in such pathological perceptions of pain as hyperalgesia and allodynia, upregulation of T-type Ca2+ currents and enhanced Ca2+ entry into these cells could contribute to the development of symptoms in diabetic neuropathy.
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PMID:Cell-specific alterations of T-type calcium current in painful diabetic neuropathy enhance excitability of sensory neurons. 1737 91

Magnetic nanoparticles with appropriate surface coatings are increasingly being used clinically for various biomedical applications, such as magnetic resonance imaging, hyperthermia, drug delivery, tissue repair, cell and tissue targeting and transfection. This is because of the nontoxicity and biocompatibility demand that mainly iron oxide-based materials are predominantly used, despite some attempts to develop 'more magnetic nanomaterials' based on cobalt, nickel, gadolinium and other compounds. For all these applications, the material used for surface coating of the magnetic particles must not only be nontoxic and biocompatible but also allow a targetable delivery with particle localization in a specific area. Magnetic nanoparticles can bind to drugs and an external magnetic field can be applied to trap them in the target site. By attaching the targeting molecules, such as proteins or antibodies, at particles surfaces, the latter may be directed to any cell, tissue or tumor in the body. In this review, different polymers/molecules that can be used for nanoparticle coating to stabilize the suspensions of magnetic nanoparticles under in vitro and in vivo situations are discussed. Some selected proteins/targeting ligands that could be used for derivatizing magnetic nanoparticles are also explored. We have reviewed the various biomedical applications with some of the most recent uses of magnetic nanoparticles for early detection of cancer, diabetes and atherosclerosis.
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PMID:Recent advances on surface engineering of magnetic iron oxide nanoparticles and their biomedical applications. 1771 88


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