Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study assessed the possible local nociceptive and hyperalgesic properties of endothelin-1 (ET-1) in the rat knee-joint incapacitation test, in which animals are placed for 1 min/h on a revolving (3 rpm) metal cylinder and nociception is measured as the time the hindpaw of the injected limb was off the cylinder (i.e., paw elevation time, PET). Carrageenan (Cg; 150 micrograms/joint), E. coli LPS (1 microgram/joint), and ET-1 (120 or 240 pmol/joint) each increased PET persistently, unlike sarafotoxin S6c (120-240 pmol/joint) or PBS. ET-1 (15 and 30 pmol/joint, 30 min before) did not cause incapacitation per se but potentiated PET induced by Cg, increasing the area under the curve (AUC in arbitrary units, 0-6 h) from 105 +/- 9 to 165 +/- 10 and 169 +/- 25, respectively. Prior Cg injection (300 micrograms/joint, 72 h before) sensitized the joint to incapacitation triggered by restimulation with either Cg (300 micrograms/joint), LPS (1 microgram/joint), or ET-1 (30 pmol/joint). Treatment with bosentan (10 mg/kg i.v., 15 min before joint stimulation) did not affect PET values in naive animals to Cg or LPS, but significantly reduced the upregulated response evoked by restimulation with LPS (but not Cg), from 465 +/- 24 to 290 +/- 49 (AUC 0-12 h). Therefore, ET-1 triggers nociception and hyperalgesia in the naive knee joint of the rat, perhaps via ETA receptors. Although local endogenous ETs may not have a role in inflammatory nociception in the naive joint, they may participate in articular incapacitation induced by restimulation with LPS. This latter finding could be relevant to the etiology of pain associated with chronic arthritic diseases.
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PMID:Effects of endothelin-1 on inflammatory incapacitation of the rat knee joint. 959 30

The present study tested the effects of in vivo administration of brain-derived neurotrophic factor (BDNF) and of its antibody (anti-BDNF) in a Morris Water Maze (MWM) task. Adult male rats were trained for three days in a MWM. At the end of the last training trial, subjects were injected intracerebroventricularly with one of the following: (i) BDNF (24 microg); (ii) anti-BDNF (25 microg); or (iii) vehicle (PBS, injection volume 10 microl). On day 5, subjects were tested for memory retention, pain sensitivity and locomotor behaviour. No differences emerged in the MWM as a function of treatment, even with a reduced number of acquisition trials. Nonetheless, BDNF affected both pain threshold in the hot-plate test, as well as exploratory behaviour in the open field test.
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PMID:Intracerebroventricular administration of brain-derived neurotrophic factor in adult rats affects analgesia and spontaneous behaviour but not memory retention in a Morris Water Maze task. 1086 31

The antibody-stimulating activities and side effects of commercially available adjuvants were compared in BALB/c mice immunised with the immunosuppressive (ISU) peptide of HIV I. Clinical and pathological-histological parameters as well as behavioural changes, were used to assess the distress and pain caused to the animals. Complete Freund's Adjuvant (FAk) was used as the positive control and PBS as the negative control. The oil-based adjuvants Montanide ISA 51(R) (M 51), Specol(R), and Hunter's TiterMax Gold(R) (HTMG) were used with the ISU-peptide conjugated to KLH. The water-soluble Gerbu Adjuvant(R) was administered together with the antigen KLH conjugate and also with the ISU-peptide conjugated to cholera toxin B subunit (ChTxB). The Dutch "Code of Practice" was used as a guideline for all immunisations. No changes in animal activity or behaviour was observed in any of the groups. All the oil-based adjuvants gave rise to swellings and encapsulations, which were most pronounced in the HTMG-group. Although body weight increased throughout the study, no increase was seen in any adjuvant group for a short period after each booster immunisation, nor after the first immunisation in the HTMG group. FAk induced a light fever after all immunisations. FAk, Specol and M 51 as well as Gerbu-ChTxB induced antibody titres which were detectable in the ELISA, but no detectable antibody the water-soluble adjuvants or following administration of HTMG applied with the ISU-peptide-KLH conjugate.
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PMID:[: A comparison of commercially available adjuvants in BALB/c-mice immunised with a weekly immunogenic peptide] 1117 51

The effects of the adjuvant QS-21 in various formulations on immediate pain on injection after intramuscular injection were evaluated in three Phase I clinical trials in healthy adults. Each trial was designed as a double-blind, randomized, four-way or five-way cross-over study with each subject acting as his/her own control. In the first trial, four formulations designed to evaluate the effect of QS-21 or pH (over a range of 6--7.2) were evaluated: phosphate-buffered saline at pH 6.0 or 7.2, and 50 microg of QS-21 in phosphate-buffered saline at pH 6.0 or 7.2. Thirty-three volunteers received each of the four intramuscular injections in random order separated by approximately 1 week. The volunteers assessed the immediate injection pain from 0 to 10 (none to most pain). The data indicate that the presence of QS-21, but not pH, is associated with transient injection site pain. The second trial, which utilized the same design as the first trial, evaluated formulations of QS-21 in various excipients. Fifteen volunteers received phosphate-buffered saline, QS-21/PBS, QS-21/aluminum hydroxide, and QS-21/4 mg/ml of polysorbate 80. Polysorbate 80, but not aluminum hydroxide, reduced the mean pain score compared to QS-21/PBS. The third trial evaluated formulations of QS-21 in additional excipients. Fifteen volunteers received aluminum hydroxide (without QS-21), QS-21/PBS, QS-21/0.72% benzyl alcohol, QS-21/30 mg/ml of hydroxypropyl-beta-cyclodextrin, and QS-21/8-mg/ml of polysorbate 80. Benzyl alcohol, cyclodextrin, and the higher concentration of polysorbate 80 reduced the pain scores associated with QS-21. Hence, QS-21 is associated with injection pain in simple buffer formulations, but it is possible to improve the acceptability of QS-21-containing formulations through reformulation with certain excipients.
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PMID:Three double-blind, randomized trials evaluating the safety and tolerance of different formulations of the saponin adjuvant QS-21. 1142 71

Therapeutic angiogenesis using vascular endothelial growth factor (VEGF) is considered a promising new therapy for patients with arterial obstructive disease. Clinical improvements observed consist of improved muscle function and regression of rest pain or angina. However, direct evidence for improved vascularization, as evaluated by angiography, is weak. In this study, we report an angiogenesis-independent effect of VEGF on ischemic skeletal muscle, ie, upregulation of myoglobin after VEGF treatment. Mice received intramuscular injection with adenoviral VEGF-A or either adenoviral LacZ or PBS as control, followed by surgical induction of acute hindlimb ischemia at day 3. At day 6, capillary density was increased in calf muscle of Ad.VEGF-treated versus control mice (P<0.01). However, angiographic score of collateral arteries was unchanged between Ad.VEGF-treated and control mice. More interestingly, an increase in myoglobin was observed in Ad.VEGF-treated mice. Active myoglobin was 1.5-fold increased in calf muscle of Ad.VEGF-treated mice (P< or =0.01). In addition, the number of myoglobin-stained myofibers was 2.6-fold increased in Ad.VEGF-treated mice (P=0.001). Furthermore, in ischemic muscle of 15 limb amputation patients, VEGF and myoglobin were coexpressed. Finally, in cultured C2C12 myotubes treated with rhVEGF, myoglobin mRNA was 2.8-fold raised as compared with PBS-treated cells (P=0.02). This effect could be blocked with the VEGF receptor tyrosine kinase inhibitor SU5416. In conclusion, we show that VEGF upregulates myoglobin in ischemic muscle both in vitro and in vivo. Increased myoglobin expression in VEGF-treated muscle implies an improved muscle oxygenation, which may, at least partly, explain observed clinical improvements in VEGF-treated patients, in the absence of improved vascularization.
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PMID:Vascular endothelial growth factor overexpression in ischemic skeletal muscle enhances myoglobin expression in vivo. 1524 80

Using a rat formalin-induced conditioned place avoidance (F-CPA) model and Fos immunohistochemistry, the present study observed the effect of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-isoxozole propionic acid/kainite (AMPA/KA) receptors on pain-related aversion. Adult Sprague-Dawley rats were implanted with cannula in the anterior cingulate cortex (ACC) or the lateral ventricle. Before (10 min) the injection of formalin into a hindpaw on days 2 and 4 of place-conditioning trials, vehicle (0.01 M PBS), the NMDA receptors antagonist, 2-amino-5-phosphonovalerate (AP5), or the AMPA/KA receptors antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX), was injected through the cannula. F-CPA was effectively eliminated by both intracerebroventricular (icv) and intra-ACC microinjection of AP5. In contrast, the intra-ACC or icv injection of DNQX failed to alter the conditioning scores of F-CPA compared with vehicle control group (P >0.05). Intra-ACC or icv injection of AP5 or DNQX had no effect on formalin-induced acute nociceptive behaviors. Fos immunoreactivity in the ACC was activated by retrieval of pain-related aversion, and this activation was significantly suppressed by preadministration of AP5, but not DNQX (P <0.001). These results suggest that NMDA receptors in the ACC are preferentially involved in the processing of the affective dimension of pain.
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PMID:NMDA receptors in the anterior cingulate cortex mediate pain-related aversion. 1538 Apr 91

Painful bladder syndrome/interstitial cystitis (PBS/IC) is a severely debilitating condition. Its cause is poorly understood; therapy is symptomatic and often unsuccessful. To study urothelial involvement, we characterized the keratin phenotype of bladder urothelium in 18 patients with PBS/IC using a panel of 11 keratin antibodies recognizing simple keratins found in columnar epithelia (keratins 7, 8, 18, and 20) and keratins associated with basal cell compartments of squamous epithelia (keratins 5, 13, 14, and 17). We also tested 2 antibodies recognizing more than 1 keratin also directed against basal cell compartments of squamous epithelia (D5/16 B4 and 34betaE12). Bladder urothelium in PBS/IC showed distinct differences in the profiles of keratins 7, 8, 14, 17, 18, and 20 compared with literature reports for normal bladder urothelium. These were characterized by a shift from the normal bladder urothelial keratin phenotype to a more squamous keratin profile, despite the lack of morphologic evidence of squamous epithelial differentiation and a loss of compartmentalization of keratin expression. The severity of these changes varied between biopsy specimens. Whether these changes are primary or secondary to another underlying condition remains to be determined.
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PMID:Keratin expression profiling of transitional epithelium in the painful bladder syndrome/interstitial cystitis. 1648 98

PBS/IC, which was traditionally thought to be a rare condition, is increasingly thought to be a frequent cause of CPP. Failure to consider the bladder as a component of this pain is common, primarily because of the similarity in symptoms to other urogynecologic conditions. The diagnosis of PBS/IC has been one of exclusion; as a result, PBS/IC is frequently misdiagnosed as urogenital infection, OAB or endometriosis, among other conditions with similar symptomatology. Such misdiagnosis results in unnecessary and ineffective pharmacologic or even surgical interventions. Diagnosis of PBS/IC and appropriate management early in the disease process afford women a better outcome and a better quality of life. Making PBS/IC a diagnosis of inclusion is necessary to attain this goal. Two additions to the diagnostic armamentarium, the PUF Patient Symptom Scale and the PST, can help to identify women whose presenting complaints of CPP might have a bladder component. The high correlation between these 2 tools allows clinicians to administer the noninvasive PUF questionnaire as an initial screening device to identify women suspected of having IC. If PBS/IC is diagnosed early in the disease process, it can be treated successfully in most patients.
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PMID:Current issues in the diagnosis of painful bladder syndrome/interstitial cystitis. 1667 19

This study described a modified rat model of bone cancer pain. Syngeneic Walker 256 mammary gland carcinoma cells were injected into the tibia medullary cavity via intercondylar eminence. Series of tests were carried out including bone radiology, bone histology, ambulatory pain, thermal hyperalgesia, mechanical allodynia, weight bearing ability, and electrophysiological recording from primary afferent fibers. The rats inoculated with carcinoma cells showed significant ambulatory pain, mechanical allodynia, and reduction in weight bearing, as well as increased incidence of spontaneous activity in Abeta fibers in affected limb, whereas PBS (vehicle) or heat-killed cells (sham) injected rats showed no significant difference in comparison to normal rats. The pain hypersensitive behaviors were aggravated with time and destruction of bone. Interestingly, mechanical allodynia was also observed in the contralateral limb, indicating the involvement of 'mirror image' pain in bone cancer pain. In summary, the present study provided a useful and easily established rat model of bone cancer pain which will contribute to further study of the mechanisms underlying cancer pain.
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PMID:A rat model of bone cancer pain induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells. 1672 12

Painful bladder syndrome/interstitial cystitis (PBS/IC) is a disease of unknown aetiology, characterised by severe pressure and pain in the bladder area or lower pelvis that is frequently or typically relieved by voiding, along with urgency or frequency of urination in the absence of urinary tract infections. PBS/IC occurs primarily in women, is increasingly recognised in young adults, and may affect as many as 0.1-1% of adult women. PBS/IC is often comorbid with allergies, endometriosis, fibromyalgia, irritable bowel syndrome and panic syndrome, all of which are worsened by stress. As a result, patients may visit as many as five physicians, including family practitioners, internists, gynaecologists, urologists and pain specialists, leading to confusion and frustration. There is no curative treatment; intravesical dimethyl sulfoxide, as well as oral amitriptyline, pentosan polysulfate and hydroxyzine have variable results, with success more likely when these drugs are given together. Pilot clinical trials suggest that the flavonoid quercetin may be helpful. Lack of early diagnosis and treatment can affect outcomes and leads to the development of hyperalgesia/allodynia.
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PMID:Treatment approaches for painful bladder syndrome/interstitial cystitis. 1728 85


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