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)

Vanilloid receptor subunit 1 (VR1) appears to play a critical role in the transduction of noxious chemical and thermal stimuli by sensory nerve endings in peripheral tissues. Thus, VR1 antagonists are useful compounds to unravel the contribution of this receptor to pain perception, as well as to induce analgesia. We have used a combinatorial approach to identify new, nonpeptidic channel blockers of VR1. Screening of a library of trimers of N-alkylglycines resulted in the identification of two molecules referred to as DD161515 [N-[2-(2-(N-methylpyrrolidinyl)ethyl]glycyl]-[N-[2,4-dichlorophenethyl]glycyl]-N-(2,4-dichlorophenethyl)glycinamide] and DD191515 [[N-[3-(N,N-diethylamino)propyl]glycyl]-[N-[2,4-dichlorophenethyl]glycyl]-N-(2,4-dichlorophenethyl)glycinamide] that selectively block VR1 channel activity with micromolar efficacy, rivaling that characteristic of vanilloid-related inhibitors. These compounds appear to be noncompetitive VR1 antagonists that recognize a receptor site distinct from that of capsaicin. Intraperitoneal administration of both trialkylglycines into mice significantly attenuated thermal nociception as measured in the hot plate test. It is noteworthy that these compounds eliminated pain and neurogenic inflammation evoked by intradermal injection of capsaicin into the animal hindpaw, as well as the thermal hyperalgesia induced by tissue irritation with nitrogen mustard. In contrast, responses to mechanical stimuli were not modified by either compound. Modulation of sensory nerve fibers excitability appears to underlie the peptoid analgesic activity. Collectively, these results indicate that blockade of VR1 activity attenuates chemical and thermal nociception and hyperalgesia, supporting the tenet that this ionotropic receptor contributes to chemical and thermal sensitivity and pain perception in vivo. These trialkylglycine-based, noncompetitive VR1 antagonists may likely be developed into analgesics to treat inflammatory pain.
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PMID:Attenuation of thermal nociception and hyperalgesia by VR1 blockers. 1185 30

A multicentric retrospective study of giant cell tumor of bone was conducted among Canadian surgeons. The hypothesis was that no differences would be found in health status, function, or recurrence rate irrespective to the nature of filling material or adjuvant used in patients treated with curettage. One hundred eighty-six cases were collected. There were 96 females and 90 males. The mean age of the patients was 36 years (range, 14-72 years), the minimum followup was 24 months, and the median followup was 60 months. Sixty-two percent of the tumors involved the knee region. One hundred fifty-eight were primary tumors and 28 were recurrences. Campanacci grading was as follows: Grade 1, seven patients; Grade 2, 100 patients; Grade 3, 76 patients; and unknown in three patients. Fifty-six patients had a pathologic fracture. Resection was done in 38 patients and 148 patients had curettage. The latter was supplemented with high speed burring in 135 patients, cement in 64 patients, various combinations of autograft or allograft bone in 61 patients, phenol in 37 patients, and liquid nitrogen in 10 patients. Structural allografts were used in 25 patients. The overall recurrence rate was 17%, 18% after curettage, and 16% after resection. Patients with primary tumors treated with curettage had a 10% recurrence rate. For recurrent lesions treated by curettage, the recurrence rate was 35%. The nature of the filling material used or the type of adjuvant method used or any combination of both failed to show any statistical impact on the recurrence risk. The results from the Musculoskeletal Tumor Society rating from 1987 were significantly lower in patients who sustained a displaced fracture. Results from the bodily pain section of the Short Form-36 also were found to be lower when a pathologic fracture was present. Results from the Musculoskeletal Tumor Society Rating 1987, the Short Form-36, and the Toronto Extremity Salvage Score did not show differences when either cement or bone graft were used after curettage.
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PMID:Giant cell tumor of long bone: a Canadian Sarcoma Group study. 1195 16

The skeleton is the most common site of metastatic disease in breast cancer and the most common site of first distant relapse. Bone metastases in breast cancer are the source of considerable morbidity, including severe pain, pathological fractures, need for radiotherapy or surgery, and hypercalcemia. Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption, and it is well known that breast cancer cells in bone can stimulate osteoclast formation and activity leading to the release of growth factors and cytokines, which will further stimulate cancer cell growth and their secretion of osteolytic factors. We are thus typically dealing with a vicious cycle, as the bone resorption-induced release of growth factors from the bone matrix will stimulate breast cancer cell growth (probably mainly by IGFs) and the production of the osteolytic factor PTHrP (probably mainly by TGF-beta but also by extracellular calcium). Clodronate, but not the aminobisphosphonates, can be metabolized to an ATP analog that is toxic for osteoclasts. Nitrogen-containing bisphosphonates, such as pamidronate, ibandronate, and zoledronate, interfere with the mevalonate pathway that is crucial to maintain cell membrane integrity. The net result, regardless of the mechanism, is osteoclast apoptosis, notably through the induction of caspase-3. Bisphosphonates are now the standard treatment for cancer hypercalcemia. Repeated bisphosphonate infusions also exert clinically relevant analgesic effects in at least one half of the patients with metastatic bone pain. Most importantly, prolonged administration of bisphosphonates (for at least 1 year) reduces the frequency of morbid skeletal events by 30-40% in breast cancer metastatic to bone and in up to 50% in patients with multiple myeloma. Newer bisphosphonates, such as ibandronate and zoledronate, will simplify the current therapeutic schemes and improve the cost-effectiveness ratio, and they have the potential to improve the therapeutic efficacy, at least in patients with aggressive osteolytic disease or in the adjuvant setting.
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PMID:Bisphosphonates in the treatment of metastatic breast cancer. 1201 36

The aim of this study was to evaluate the tolerability and the possible clinical benefit of intraoperative hyperthermia combined with multischedule chemotherapy and bypass surgery for the palliative treatment of inoperable pancreatic cancer. Ten patients with unresectable adenocarcinoma of the pancreas received preoperative chemotherapy [5-fluorouracil (5-FU)], bypass surgery and postoperative chemotherapy (5-FU, doxorubicin and cisplatin) plus sandostatin and radiotherapy (45 Gy, 25 fractions, 5 days a week). A single session of intraoperative hyperthermia was performed, by using a waveguide-type applicator (433 MHz). The tumour region was heated to 43-45 degrees C for up to 60 min, while 500 mg 5-FU was infused simultaneously through the gastroduodenal into the splenic artery. Postoperative recovery was uneventful for all patients. A brief instrument was developed for evaluating patients' quality of life. Chemotherapy-related toxicity included myelosuppression, vomiting, alopecia and increase in blood urea nitrogen (BUN), creatinine, SGOT and SGPT. Glucose and amylase determinations remained within normal limits throughout the whole treatment. There was a significant improvement before and 1 month after combined treatment in Eastern Cooperative Oncology Group (ECOG) status (1.8 +/- 0.4), Scott-Huskinsson pain scale (3.2 +/- 0.8) and quality of life score (30.5 +/- 6.7). No progressive disease was noticed and the median overall survival was 11 (SE = 2.4) months. There was also a significant (P = 0.002, Wilcoxon test) decrease in values of both serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9), from 7.6 +/- 1.3 ng/mL and 875.7 +/- 104.8 U/mL to 3.5 +/- 0.7 ng/mL and 65.3 +/- 14.1 U/mL respectively. The first clinical results suggest a potential advantage of using combined intraoperative hyperthermia, chemotherapy and postoperative radiotherapy in the palliative treatment of the adenocarcinoma of the pancreas. The whole procedure seems to be free of perioperative morbidity, while the chemotherapy toxicity was rather moderate. However, the preliminary nature limits the general applicability of our results.
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PMID:Intraoperative hyperthermia and chemoradiotherapy for inoperable pancreatic carcinoma. 1209 45

This study was performed to determine the structure-activity relationships (SAR) of L-cysteine based N-type calcium channel blockers. Basic nitrogen was introduced into the C-terminal lipophilic moiety of L-cysteine with a view toward improvement of its physicochemical properties. L-Cysteine derivative 9 was found to be a potent and selective N-type calcium channel blocker with IC(50) of 0.33 microM in calcium influx assay using IMR-32 cells and was 15-fold selective for N-type calcium channels over L-type channels. Compound 9 showed improved oral analgesic efficacy in the rat formalin induced pain model and the rat chronic constriction injury (CCI) model, which is one of the most reliable models of chronic neuropathic pain, without any significant effect on blood pressure or neurological behavior.
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PMID:L-Cysteine based N-type calcium channel blockers: structure-activity relationships of the C-terminal lipophilic moiety, and oral analgesic efficacy in rat pain models. 1216 Nov 13

Calendula officinalis (marigold) has many pharmacological properties. It is used for the treatment of skin disorders, pain and also as a bactericide, antiseptic and anti-inflammatory. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are known to participate in the pathogenesis of various human diseases and may be involved in the conditions which C. officinalis is used to treat. The aim of this study was to investigate the relationship between the beneficial properties of this plant and its antioxidant action. The butanolic fraction (BF) was studied because it is non-cytotoxic and is rich in a variety of bioactive metabolites including flavonoids and terpenoids. Superoxide radicals (O(2)(*-)) and hydroxyl radicals (HO(*)) are observed in decreasing concentrations in the presence of increasing concentrations of BF with IC(50) values of 1.0 +/- 0.09 mg/ml and 0.5 +/- 0.02 mg/ml, respectively, suggesting a possible free radical scavenging effect. Lipid peroxidation in liver microsomes induced by Fe(2+)/ascorbate was 100% inhibited by 0.5 mg/ml of BF (IC(50) = 0.15 mg/ml). Its total reactive antioxidant potential (TRAP) (in microM Trolox equivalents) was 368.14 +/- 23.03 and its total antioxidant reactivity (TAR) was calculated to be 249.19 +/- 14.5 microM. The results obtained suggest that the butanolic fraction of C. officinalis possesses a significant free radical scavenging and antioxidant activity and that the proposed therapeutic efficacy of this plant could be due, in part, to these properties.
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PMID:Protective properties of butanolic extract of the Calendula officinalis L. (marigold) against lipid peroxidation of rat liver microsomes and action as free radical scavenger. 1218 55

Although therapeutic management of hypertrophic scars and keloids using contact or spray cryosurgery has yielded significant improvement or complete regression of hypertrophic scars and keloids, it requires one to 20 treatment sessions. This study was designed to assess the clinical safety and efficacy of an intralesional needle cryoprobe method in the treatment of hypertrophic scars and keloids. Ten patients, ranging in age from 3 to 54 years, with a total of 12 hypertrophic scars and keloids of more than 6 months duration and of diverse causes, were included in this study. The 18-month trial evaluated volume reduction of the hypertrophic scars and keloids after a single session of intralesional cryotherapy. Objective (hardness and color) and subjective (pain/tenderness and itchiness/discomfort) parameters were examined on a scale of 0 to 3 (low score was better). Pretreatment and posttreatment histomorphometric studies of the collagen fibers included spectral picrosirius red polarization and fast Fourier transformation orientation index. A specially designed cryo-needle was inserted into the long axis of the hypertrophic scars and keloids so as to maximize the volume of the hypertrophic scars and keloids to be frozen. The cryo-needle was connected by an adaptor to a cryogun filled with liquid nitrogen, which was introduced into the cryoprobe, thereby freezing the hypertrophic scars and keloids. After the hypertrophic scars and keloids were completely frozen, the cryoprobe defrosted and was withdrawn. An average of 51.4 percent of scar volume reduction was achieved after one session of intralesional cryosurgery treatment (average preoperative hypertrophic scars and keloids volume, 1.82 +/- 0.33; average posttreatment volume, 0.95 +/- 0.21; p < 0.0022). Significant alleviation of objective and subjective clinical symptoms was documented. Mild pain or discomfort during and after the procedure was easily managed. Only mild local edema and epidermolysis, followed by a short reepithelialization period, were evident. During the 18-month follow-up period, there was no evidence of bleeding, infection, adverse effects, recurrence, or permanent depigmentation. The histomorphometric analysis demonstrated rejuvenation of the treated scars (i.e., parallelization) and a more organized architecture of the collagen fibers compared with the pretreated scars. This study demonstrated the increased efficacy of this method as a result of increased freezing area of deep scar material compared with that obtained with contact/spray probes. As a result, fewer treatment cycles are needed. Because the reepithelialization period is short, treatment intervals, if any, can be shortened to 2 to 3 weeks. This intralesional cryoneedle method is simple to operate and safe to use, it necessitates less postoperative care of the wound, and it can easily be added to any preexisting cryosurgical unit.
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PMID:Intralesional cryotherapy for enhancing the involution of hypertrophic scars and keloids. 1271 43

Seventy-six digital and periungual warts in 40 patients were treated topically with cantharidin, a potent blistering agent. The material, dissolved in equal parts of acetone and collodion, was applied directly to the warts. Occlusion facilitated blistering. No pretreatment was required. The warts were re-treated at weekly intervals until clinically cured.Fifty-six per cent of digital warts and 33 per cent of periungual warts cleared after a single application of cantharidin. Few required more than three treatments. Observation was continued for more than six months in more than half of the cases. Cure was lasting in about 70 per cent of the cases in which the long term result was known. Cantharidin ranks with liquid nitrogen in effectiveness, but it is painless to apply and does not cause scarring. For these reasons it is especially useful in children.The main disadvantage is pain and tenderness at the treated site for two to four days in some patients. This can be avoided by careful application of the drug. Occasionally new warts appear at the edge of the cantharidin blister. They are best treated by curettage and desiccation.
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PMID:Cantharidin treatment of digital and periungual warts. 1382 Apr 98

Since it has been recognized as a separate disease during the Korean war, hemorrhagic fever with renal syndrome (HFRS) has often been discovered among the members of different armies in various countries, military personnel being the highest risk group for the disease. In the period from March to May 1999 we treated 6 soldiers coming from the military formation stationed at Kosovo and Metohia. The reaction of indirect hemagglutination test proved the presence of antibodies against Hantavira in each of them. They were infected during the stay in a dugout in the area with great population of field rodents. Only one patient was slightly ill, on the admission to the hospital. The others had severe clinical and laboratory findings: several days lasting fever, strong abdominal pain, as well as the pain in the loins, dyspeptical discomfort, manifold increased blood urea nitrogen and serum creatinine values, thrombocytopenia, etc. Oliguria occurred in 4 patients. Hemorrhagic manifestations were slight (epistaxis, petechial rash, conjunctival injection), or absent. Because of the aggravation of the acute renal failure, hemodialysis was performed in 3 patients, while other 3 underwent conservative treatment. Two of the patients had severe anemia because of which transfusions of erythrocytes and plasma were performed. Complications occurred in 2 patients (convulsive crises and lung infections). All patients recovered completely.
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PMID:[Manifestations of hemorrhagic fever with renal syndrome in a military unit stationed in a combat zone]. 1460 40

Successful clinical small-bowel transplantation is still difficult to achieve. Two features render the small intestine unique among vascularised solid organ grafts. First, the bowel contains a large amount of lymphoid tissue within the Peyer's patches, mesenteric lymph nodes, and intraepithelial lymphocytes, which are thought to mediate graft-versus-host disease and provide a major stimulus for the recipient's immune system. Unfortunately, mere surgical reduction of these tissues, by using segmental allografts, does not furnish any immunological advantage. Second, the small bowel lacks specific serum markers such as blood urea nitrogen (BUN) in the kidney or bilirubin in liver transplantation. Clinical signs such as fever, pain, or tenderness of the abdomen may indicate an already advanced destruction of the graft. Therefore, very potent immunosuppressive regimens are necessary to avoid small-bowel allograft rejection or even to reverse an ongoing rejection process. Cyclosporin was shown in small and large animal models to control rejection reactions sufficiently. However, there are two even more promising immunosuppressive agents currently under investigation. FK506, a macrolide lactone isolated from Streptomyces tsukubaensis, leads to long-term survival of small-bowel allografts in a rodent model and has already been used in a few clinical small-bowel transplantations. RS61443, a mycophenolic acid morpholinoethylester, selectively inhibits T- and B-cell proliferation. We have investigated the use of FK506 and RS61443 for the reversal of small-bowel allograft rejection in a small animal model.
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PMID:The use of FK506 and RS61443 for reversal of small-bowel rejection. 1462


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