Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Maintaining skin integrity can be challenging but it is vital to overall health, particularly in elderly patients. In this population, skin integrity is frequently compromised as a result of under- or over-hydration, which may cause serious complications. Plans of care must include preventive efforts such as the use of barriers and protectants including zinc oxide preparations, petrolatum- and silicone-based ointments and creams, liquid-forming products, adhesive dressings, fluid managers, skin cleansers, and moisturizers. A team approach that includes the patient, caregivers, and healthcare professionals is needed to address patient concerns regarding independence/dependence, utilization of support systems and services, pain, and control of body fluids. The healthcare provider's role in this team should emphasize continuity of care, patient satisfaction, and product selection - all vital to protecting skin integrity.
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PMID:Intact skin--an integrity not to be lost. 1287 82

Fibrosis following breast radiotherapy for mammary cancer is a frequent undesired effect with objective (esthetic) and subjective (pain) consequences. Forty-four patients with clinical radiofibrosis following conservative treatment of breast cancer were evaluated for the local antifibrosis effect of copper zinc superoxide dismutase [SOD(Cu/Zn)]. Extracted SOD(Cu/Zn) in a concentration of 3,600 units/mg was applied as ointment to the fibrotic affected area, b.i.d. for 90 days, in a total dose of 40 mg. The radiofibrosis intensity was scored on the basis of clinical criteria (pain and the fibrosis area) before and after SOD(Cu/Zn) treatment. SOD(Cu/Zn) was found to be effective in reducing radiation induced fibrosis by a lowering pain score in 36/39 patients and a decrease of the fibrotic area size in half cases, after 6 months. The intensity and changes of breast fibrosis were assessed also by mammography and, for the topographical distribution of subcutaneous temperature, by infrared thermography. Mammography density suggested decreased fibrosis in one third of patients. Thermography showed that fibrosis was accompanied by two zones clinically indistinctive: a central area with maximum thermal activity, called "Maximal Thermic zone" (MTZ) and a peripheral area with less thermal activity but higher than in the surrounding normal tissue, "Transitional Thermic Zone" (TTZ). Both MTZ and TTZ were significantly decreased in 36/44 patients after SOD(Cu/Zn) treatment. Clinical changes persisted all along the study. Treatment was well tolerated except for one case of local allergic reaction, and no important side effects. Molecular mechanisms involved are discussed. Further studies are running to confirm and explain these results.
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PMID:Topical superoxide dismutase reduces post-irradiation breast cancer fibrosis. 1509 Feb 66

Increased oxidative stress has been postulated to be an important mechanism in the pathophysiology of chronic pancreatitis (CP). Micronutrient deficiency may increase the oxidative stress as they assist in free radical clearance. The present study was undertaken to assess the intake of micronutrients, i.e. vitamins E and C, carotene, selenium, copper, zinc, manganese, magnesium, sulphur, riboflavin, methionine and choline in patients with CP. All consecutive patients with CP attending the Pancreas Clinic at the All India Institute of Medical Sciences were enrolled in the study. The usual dietary intake was estimated by the 24-hour dietary recall method and food frequency questionnaire. Dietary restrictions, if any, were also noted. The micronutrient intake of patients not on any nutritional supplements (n=75, 65 males and 10 females, mean age 31.06 +/- 10.64 years) was compared with age- and sex- matched healthy controls (n=75). The micronutrients were calculated as per the Nutritive value of Indian Foods given by the National Institute of Nutrition, Indian Council of Medical Research, India and the US dietary intake guidelines as applicable. It was found that the Body Mass Index (BMI) of patients was significantly lower than that of healthy controls. The total intake in terms of calorie was lower in patients when compared to controls. The dietary intake of vitamin E, riboflavin, choline, magnesium, copper manganese and sulfur was significantly lower than that of controls as well as the Recommended Dietary Allowance (RDA). Dietary intake of selenium and vitamin C was within the limits of the RDA but was lower than that of controls, while the intake of carotene was similar in both the groups and met the RDA. We conclude that patients with CP had significantly decreased micronutrient intake owing to diet modification due to pain. Micronutrient deficiency might contribute to increased oxidative stress in these patients.
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PMID:Micronutrient antioxidant intake in patients with chronic pancreatitis. 1547 19

Matrix metalloproteinases (MMPs) are a family of zinc-containing enzymes involved in the degradation and remodeling of extracellular matrix proteins. Under normal physiological conditions, the activities of these enzymes are well-regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs). Chronic stimulation of MMP activities due to an imbalance in the levels of MMPs and TIMPs has been implicated in the pathogenesis of a variety of diseases such as cancer, osteoarthritis, and rheumatoid arthritis. Thus, MMP inhibitors are expected to be useful for the treatment of these disorders. Because of their importance in a variety of pathological conditions, a number of small molecular weight MMP inhibitors have entered clinical trials in humans. However, the results of these trials have been extremely disappointing and have led many investigators to conclude that MMP inhibitors have no therapeutic benefit in human cancer. To date, the first generation MMP inhibitors exhibited poor bioavailability while second-generation compounds revealed that prolonged treatment caused musculoskeletal pain and inflammation or had a lack of efficacy. This article describes the design of small molecular weight MMP inhibitors, a brief description of available three-dimensional MMP structures, a review of the proposed therapeutic utility of MMP inhibitors, and a clinical update of compounds that have entered clinical trials in humans. The experimentally determined structures used in the structure-based design of MMP inhibitors are thoroughly covered. Major emphasis is on recently published and/or patented potent MMP inhibitors, from approximately January 2000 to April 2003, and their pharmacological properties. Protein inhibitors of these proteolytic enzymes, i.e. TIMPs, will not be discussed.
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PMID:The design, structure, and clinical update of small molecular weight matrix metalloproteinase inhibitors. 1554 83

Neurocutaneous syndrome, a newly discovered toxicity disorder, is characterized by neurological sensations, pain, depleted energy, and memory loss as well as itchy cutaneous lesions that may invite various opportunistic infections. Components in the calcium hydroxide dental sealants Dycal, Life and Sealapex have been identified as sources of the observed symptoms. Sulfonamide and neurological toxicity issues are discussed, and three case histories are presented. Additional notes on zinc oxide, Fynal, IRM, and Sultan U/P sealers are also included. Diagnostic and management protocols at the Parasitology Center, Inc., are proposed.
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PMID:On the diagnosis and management of neurocutaneous syndrome, a toxicity disorder from dental sealants. 1592 52

Combining nutritional supplements to achieve synergistic benefit is a common practice in the nutraceutical industry. However, establishing added health benefit from a combination of natural ingredients is often assumed, untested and without regard to the principle of metabolic competition between the active components. Here, we report on the combination of a cat's claw water extract (C-Med-100, carboxy alkyl esters = active ingredients) + medicinal mushroom extracts (Cordyceps sinensis, Grifola blazei, Grifolafrondosa, Trametes versicolor and Ganoderma lucidum, polysaccharides = active ingredients) + nicotinamide + zinc into a formulation designed to optimize different modes of immunostimulatory action, and yet that would avoid metabolic antioxidant competition yielding less than expected efficacious effects. Isobole curve analyses of these two active classes of ingredients determined by growth inhibition of HL-60 human leukemic cells in vitro confirmed they were indeed synergistic when in combination, and not metabolically competitive. Furthermore, an in vivo study showed significant health benefit for 14 subjects treated for 4 weeks with the unique C-Med-100/mushroom extract formulation in that they had reduced pain, reduced fatigue, weight loss and a reduced presence of DNA damage in peripheral blood assessed by (8-OH) guanine DNA adducts and elevation in serum protein thiols. Because this broad-based panel of clinical parameters indicating clinical efficacy has never been demonstrated before for either of the active ingredients evaluated alone in humans, these data were taken as strong evidence that the combination of C-Med-100 + mushroom extracts + nicotinamide + zinc gave additive or synergistic effects to health benefit, and thus supported no efficacious limits from metabolic competition regarding this particular formulation.
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PMID:Formulation and in vitro/in vivo evaluation of combining DNA repair and immune enhancing nutritional supplements. 1589 2

Tertiapin, a short peptide from honey bee venom, has been reported to specifically block the inwardly rectifying K(+) (Kir) channels, including G protein-coupled inwardly rectifying potassium channel (GIRK) 1+GIRK4 heteromultimers and ROMK1 homomultimers. In the present study, the effects of a stable and functionally similar derivative of tertiapin, tertiapin-Q, were examined on recombinant human voltage-dependent Ca(2+)-activated large conductance K(+) channel (BK or MaxiK; alpha-subunit or hSlo1 homomultimers) and mouse inwardly rectifying GIRK1+GIRK2 (i.e., Kir3.1 and Kir3.2) heteromultimeric K(+) channels expressed in Xenopus oocytes and in cultured newborn mouse dorsal root ganglion (DRG) neurons. In two-electrode voltage-clamped oocytes, tertiapin-Q (1-100 nM) inhibited BK-type K(+) channels in a use- and concentration-dependent manner. We also confirmed the inhibition of recombinant GIRK1+GIRK2 heteromultimers by tertiapin-Q, which had no effect on endogenous depolarization- and hyperpolarization-activated currents sensitive to extracellular divalent cations (Ca(2+), Mg(2+), Zn(2+), and Ba(2+)) in defolliculated oocytes. In voltage-clamped DRG neurons, tertiapin-Q voltage- and use-dependently inhibited outwardly rectifying K(+) currents, but Cs(+)-blocked hyperpolarization-activated inward currents including I(H) were insensitive to tertiapin-Q, baclofen, barium, and zinc, suggesting absence of functional GIRK channels in the newborn. Under current-clamp conditions, tertiapin-Q blocked the action potential after hyperpolarization (AHP) and increased action potential duration in DRG neurons. Taken together, these results demonstrate that the blocking actions of tertiapin-Q are not specific to Kir channels and that the blockade of recombinant BK channels and native neuronal AHP currents is use-dependent. Inhibition of specific types of Kir and voltage-dependent Ca(2+)-activated K(+) channels by tertiapin-Q at nanomolar range via different mechanisms may have implications in pain physiology and therapy.
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PMID:Tertiapin-Q blocks recombinant and native large conductance K+ channels in a use-dependent manner. 1594 38

Cyclooxygenase-2 (COX-2) is up-regulated in stromal and inflammatory cells. The inducible COX-2 isoform is expressed during inflammation, in some cancers, and in brain tissue after global and focal ischemia. Tissue acidosis is a dominant factor in inflammation, and contributes to pain and hyperalgesia. Recently, compelling epidemiological and clinical evidence has documented the COX-independent effects of some COX-2 inhibitors (i.e., celecoxib, valdecoxib, and rofecoxib); among these effects are carbonic anhydrase (CA) inhibition. Carbonic anhydrases are zinc metalloenzymes expressed in various cell types, including those of the kidney, where they act as general acid-base catalysts. The kidneys are also known to express the highest concentration of COX-2 messenger ribonucleic acid. Celecoxib, like the prototypic CA inhibitor acetazolamide, is structurally characterized by an unsubstituted sulfonamide moiety. In the present study, we report that celecoxib exhibits the characteristics of a potent CA inhibitor, showing inhibitory human carbonic anhydrase II (hCAII) activity in the nanomolar range. Valdecoxib was relatively less potent. Rofecoxib, which lacks the unsubstituted sulfonamide moiety characteristic of CA inhibitors, showed no significant hCAII inhibitory activity. The current study corroborates our earlier report of structure-activity relationships as predictors of such metabolic events as hyperchloremia, acidosis, and changes in calcium and phosphate disposition; and clinical manifestations associated with CA inhibition reported with celecoxib. These data showing inhibition of hCAII by the unsubstituted sulfonamides celecoxib and valdecoxib, but not by rofecoxib, may have important implications for the elucidation of the mechanisms of action as well as the side effects associated with COX-2 inhibitors.
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PMID:The cyclooxygenase-2 inhibitor celecoxib is a potent inhibitor of human carbonic anhydrase II. 1613 2

The severe deformities of the fingers seen in poorly treated or late presenting cases of paronychia stimulated this prospective study. The aim was to make early diagnosis and to find a simple method of draining the pus in the paronychia. This was a prospective hospital based study at the Wesley Guild Hospital (WGH) Ilesa for 9 months. Using simple materials like 23G or 21G needle, cotton wool, chlorohexidine solution, methlylated spirit and zinc oxide plaster, abscess in acute paronychia was drained by lifting the nail fold with the tip of the needle. Ten cases of paronychia in 8 patients were drained with the method. Combination of the early drainage and antibiotics showed that all the patients were relieved of pain and could use their fingers normally within 2 days. There was no need of anesthesia and daily dressing. The drainage technique is simple and effective. The early drainage prevents the occurrence of any form of complication.
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PMID:DAREJD simple technique of draining acute paronychia. 1620 Dec 54

A 55-year-old woman, suffered from severe pain in her mandibular jaw for several years. A metallic artifact of about 2(3) mm was detected by a panorama radiography in an edentulous region with a surrounding inflammation in close contact to the canal of the mandibular nerve. Inflammated tissue with the central metallic inclusion was removed from the bone under local anesthesia and operation. Postoperatively, pain and missensitivity disappeared within 1 week. Although the patient had no macroscopically visible so-called amalgam tattoo, the metallic cube was identified as amalgam by the detection of mercury, silver, tin, copper, and zinc using energy dispersive X-ray analysis (EDX) in a scanning electron microscope (SEM). Nevertheless, brown to black pigments in the connective tissue matrix and inside histiocytes, fibroblasts, and multinucleated foreign giant cells of the surrounding inflammatory tissue were observed by light and electron microscopy. However, the elemental analysis by EDX in SEM or by electron energy loss spectroscopy in transmission electron microscope detected only silver, tin, and sulfur but no mercury in these precipitates and in the residual bodies of phagocytes. The presented case demonstrates a seldom complication of amalgam deposition in the tissue. The authors assume that the chronic pain results from a forgotten amalgam filling inside an alveole after extraction of a molar tooth, causing a chronic inflammation by resolving mercury and other toxic elements out of the metallic artifact.
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PMID:Chronic inflammation and pain inside the mandibular jaw and a 10-year forgotten amalgam filling in an alveolar cavity of an extracted molar tooth. 1625 67


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