Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We characterized anticancer effects of opioid analgesics that are clinically used for cancer patients for pain relief. Treatment with 100 microM buprenorphine, a representative analgesic, induced cell death of human carcinomas, such as A549 (squamous epithelial cell of lung cancer), MCF-7 (breast cancer) and N417 (small cell of lung cancer), but not in KATO III (gastric cancer) cells as evaluated by alamar blue assay. Among 18 clinically utilized and related analgesics, buprenorphine and loperamide showed potent inhibition of cell viability. However, these anti-cancer effects were not affected by opioid receptor antagonists nor by pertussis toxin. Buprenorphine-induced cell death occurred as early as 1 h after the addition, and its T1/2 of cell viability inhibition was 3 h. The cell death manifested the characteristics of apoptosis, such as DNA-laddering and nuclear fragmentation, which were sensitive to a caspase inhibitor, Z-Asp-CH2-DCB. The nuclear fragmentation was independent of cell cycle phase specificity. The activity of caspase-3-like protease which is known to be closely related to apoptotic DNA laddering was markedly enhanced by buprenorphine. However, the inhibition of cell viability by buprenorphine was not affected by the caspase inhibitor. These findings suggest that some opioid analgesics induce typical apoptotic features sensitive to the caspase inhibitor, while also inhibition of cell viability insensitive to the inhibitor.
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PMID:Opioid analgesic-induced apoptosis and caspase-independent cell death in human lung carcinoma A549 cells. 1093 99

The intrathecal administration of pertussis toxin (PTX) not only blocks the antinociceptive effects of the muscarinic cholinergic receptor agonist oxotremorine administered systemically, but also produces a long-lasting thermal allodynia in mice. The purpose of the present studies was to determine both the antinociceptive effects in normal mice and the antiallodynic effects in PTX-treated mice of systemically administered muscarinic cholinergic receptor agonists and cholinesterase inhibitors. In normal mice, antinociceptive effects were tested using a 55 degrees C water-bath tail-flick test. In mice treated 7 days previously with PTX (0.3 microg i.t.), antiallodynic effects were tested using a 45 degrees C water-bath tail-flick test. The nonselective high-efficacy muscarinic agonists oxotremorine, H-TZTP (3-(1,2, 5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine oxalate), and methylthio[2.2.1], (exo (+)3-(3-methylthio-1,2, 5-thiadiazol-4-yl)-1-azabicyclo[2.2.1]heptane oxalate), as well as vedaclidine, a mixed M(2)/M(4) muscarinic receptor partial agonist and M(1)/M(3)/M(5) muscarinic receptor antagonist, the nonselective partial agonists RS86 and pilocarpine, and the cholinesterase inhibitors physostigmine and tacrine all produced dose-related antinociception. Oxotremorine, H-TZTP and methylthio[2.2.1] produced dose-related reversals of PTX-induced thermal allodynia whereas vedaclidine produced a partial reversal and RS86 and pilocarpine, as well as physostigmine and tacrine, failed to reverse the allodynia. The present results provide further evidence that decrements in PTX-sensitive G(i/o)-protein functioning may be involved in initiating and/or maintaining some persistent or neuropathic pain states. Moreover, the present results suggest that muscarinic receptor agonists such as vedaclidine may be useful in the treatment of persistent pain states that are due at least in part to dysfunction of inhibitory second messenger systems.
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PMID:Reversal of pertussis toxin-induced thermal allodynia by muscarinic cholinergic agonists in mice. 1097 34

We report the first described case of a first rib fracture secondary to pertussis infection. An 11-year-old boy presented with sudden onset of severe right-sided pleuritic chest pain on a background of a 6 week history of a coughing illness and considerable weight loss. Pertussis was clinically suspected and proven on serology. A cause for the severe pain was initially difficult to confirm, causing some concern regarding possible underlying pathology, but was later demonstrated to be due to a first rib fracture. The anatomy of the first rib, and the biomechanical forces placed upon it that are exacerbated during a coughing illness are described.
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PMID:Fracture of the first rib as a consequence of pertussis infection. 1116 80

To assess whether the combination of a diphtheria, tetanus and pertussis vaccine with a Haemophilus influenzae type b conjugate vaccine (PRP-T) had any effect on immunogenicity or safety compared with separate administration of the vaccines, 158 infants were randomized to receive the vaccines either in association or as a combination at 2, 4, and 6 months of age. A total of 126 infants (59 associated, 67 combination) completed the three-dose regimen and were analysed for immunogenicity and safety. With respect to safety, there were no significant differences between the two groups. The combination vaccine was well tolerated with adverse reactions consisting mainly of transient pain, redness, induration and some low-grade fever. With respect to immunogenicity, response to PRP-T vaccine was good. Following just two doses, all infants achieved anti-PRP titers >0.15 microg/ml, regardless of whether the vaccine was given in combination or association. Following three doses, 98.5 per cent of infants in the combination group and 98.3 per cent in the association group had titers higher than 1.0 microg/ml.
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PMID:Safety and immunogenicity of combined or associated administration of PRP-T vaccine with diphtheria, tetanus and pertussis vaccine in Thai children. 1124 47

The adverse effects of vaccines include local reactions and systemic symptoms or illnesses. Local reactions are frequent, most often presenting as transient pain, redness, edema and/or nodule. Fever of short duration is the main systemic symptom, generally occurring within 24-48 hours following vaccination. Some vaccines have recognized specific adverse effects such as thrombocytopenic purpura for the measles-mumps-rubella vaccine, and febrile convulsions for the pertussis vaccine. Hepatitis B vaccine and Haemophilus influenzae type b vaccine have been respectively suspected to be responsible for neurological demyelinating disease and insulin-dependent diabetes mellitus, but large-scale epidemiological studies have failed to confirm these allegations.
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PMID:[Secondary effects of vaccinations]. 1127 Feb 59

Opiates, such as morphine, have been used extensively in the clinical management of pain due to their potent analgesic effect. Astrocytes, representing a major non-neuronal cell population in the CNS, contain opioid receptors that are actively involved in several brain functions. This study was designed to evaluate the effects by which morphine, a preferential mu-opioid receptor agonist, contributes to cytotoxicity of nitric oxide (NO) species, including NO and peroxynitrite (ONOO-), in primary rat neonatal astrocytes. Primary astrocytes isolated from the cerebral cortex of 1- to 2-day-old Sprague-Dawley rats were treated with morphine, naloxone, and 3-morpholinosydnonimine (SIN-1), a donor of peroxynitrite. Morphine significantly protected primary rat astrocytes from apoptosis mediated by sodium nitroprusside, an NO donor, and SIN-1 in a dose-dependent manner, whereas it did not in other types of cells including C6 glioma, RAW 264.7, and HL-60 cells. Moreover, naloxone antagonized the protective effects of morphine on SIN-1-induced apoptosis. Morphine also inhibited the nuclear condensation and fragmentation of SIN-1-treated cells that was antagonized by naloxone pretreatment. The protective role of morphine in SIN-1-induced apoptosis was dependent on an intracellular antioxidant system such as GSH. Furthermore, the effects of morphine on SIN-1-induced cytotoxicity were prohibited by pretreatment with the G(i) protein inhibitor, pertussis toxin, and the phosphatidylinositol 3-kinase (PI3 kinase) inhibitors, wortmannin and LY294002. Taken together, these results suggest that morphine may protect primary rat astrocytes from apoptosis by NO species via the signaling cascades that involve both G protein and PI3 kinase.
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PMID:Protective effects of morphine in peroxynitrite-induced apoptosis of primary rat neonatal astrocytes: potential involvement of G protein and phosphatidylinositol 3-kinase (PI3 kinase). 1127 62

1. Neuropeptides FF (NPFF) and AF (NPAF) are involved in pain modulation and opioid tolerance. These peptides were known to act through uncharacterized G protein-coupled receptors (GPCR). We describe here, using an aequorin-based assay as screening tool, that an orphan GPCR, previously designated HLWAR77, is a functional high affinity receptor for NPFF and related peptides. This receptor is further designated as NPFFR. 2. Binding experiments were performed with a new radioiodinated probe, [(125)I]-EYF, derived from the EFW-NPSF sequence of the rat NPFF precursor. Chinese hamster ovary (CHO) cell membranes expressing NPFFR bound [(125)I]-EYF with a K(d) of 0.06 nM. Various NPFF analogues and related peptides inhibited [(125)I]-EYF specific binding with the following rank order (K(i)): human NPAF (0.22 nM), SQA-NPFF (0.29 nM), NPFF (0.30 nM), 1DMe (0.31 nM), EYW-NPSF (0.32 nM), QFW-NPSF (0.35 nM), 3D (1.12 nM), Met-enk-RF-NH(2) (3.25 nM), FMRF-NH(2) (10.5 nM) and NPSF (12.1 nM). 3. The stimulatory activity of the same set of peptides was measured by a functional assay based on the co-expression of NPFFR, G(alpha 16) and apoaequorin. The rank order of potency was consistent with the results of the binding assay. 4. Membranes from NPFFR expressing CHO cells bound GTP gamma[(35)S] in the presence of SQA-NPFF. This functional response was prevented by pertussis toxin treatment, demonstrating the involvement of G(i) family members. 5. SQA-NPFF inhibited forskolin induced cyclic AMP accumulation in recombinant CHO cells in a dose dependent manner. This response was abolished as well by pertussis toxin pre-treatment. 6. RT -- PCR analysis of human tissues mRNA revealed that expression of NPFFR was mainly detected in placenta, thymus and at lower levels in pituitary gland, spleen and testis.
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PMID:Functional characterization of a human receptor for neuropeptide FF and related peptides. 1132 3

Local anesthetics, commonly used for treating cardiac arrhythmias, pain, and seizures, are best known for their inhibitory effects on voltage-gated Na(+) channels. Cardiovascular and central nervous system toxicity are unwanted side-effects from local anesthetics that cannot be attributed to the inhibition of only Na(+) channels. Here, we report that extracellular application of the membrane-permeant local anesthetic bupivacaine selectively inhibited G protein-gated inwardly rectifying K(+) channels (GIRK:Kir3) but not other families of inwardly rectifying K(+) channels (ROMK:Kir1 and IRK:Kir2). Bupivacaine inhibited GIRK channels within seconds of application, regardless of whether channels were activated through the muscarinic receptor or directly via coexpressed G protein G(beta)gamma subunits. Bupivacaine also inhibited alcohol-induced GIRK currents in the absence of functional pertussis toxin-sensitive G proteins. The mutated GIRK1 and GIRK2 (GIRK1/2) channels containing the high-affinity phosphatidylinositol 4,5-bisphosphate (PIP(2)) domain from IRK1, on the other hand, showed dramatically less inhibition with bupivacaine. Surprisingly, GIRK1/2 channels with high affinity for PIP(2) were inhibited by ethanol, like IRK1 channels. We propose that membrane-permeant local anesthetics inhibit GIRK channels by antagonizing the interaction of PIP(2) with the channel, which is essential for G(beta)gamma and ethanol activation of GIRK channels.
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PMID:Mechanism underlying bupivacaine inhibition of G protein-gated inwardly rectifying K+ channels. 1135 68

A randomised placebo controlled double-blind cross-over trial was performed on twenty healthy adults to assess the effect of osmolality (300,600,850 and 1100 mOsm) on local tolerance of an intramuscular injection (0.5 ml) of five suspensions containing the same components as the excipients of a combined Diphtheria-Tetanus-acellular Pertussis-inactivated Poliomyelitis-Haemophilus influenzae type b paediatric vaccine (DtacP-IPV-Hib, PENTAVAC). The results did not show any dose-effect relationship between burning or pain sensations and the different osmolalities tested. Although mild and not clinically relevant, these sensations seemed to occur more frequently following injection of an isotonic saline solution (P<0.05). Thus, the osmolality of vaccine like suspensions does not appear to be a potential cause of local pain or burning sensation after their administration.
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PMID:Impact of osmolality on burning sensations during and immediately after intramuscular injection of 0.5 ml of vaccine suspensions in healthy adults. 1139 98

An open, randomised, multicentre trial was performed to assess the reactogenicity and safety profile of the administration of a candidate Haemophilus influenzae type b (Hib) conjugate vaccine with a quadrivalent diphtheria-tetanus-acellular pertussis-hepatitis B (DTPa-HBV) vaccine as a single injection (Group 1) versus the simultaneous administration of the latter vaccine (DTPa-HBV) and an available Hib conjugate vaccine (Group 2) in opposite thighs, as a primary vaccination course to healthy infants at 2, 4 and 6 months of age. Eight hundred and eighty five infants (9.3+/-1.4 weeks old) were randomly allocated to Group 1 (n=665) and Group 2 (n=221). Oral polio vaccine was given concomitantly to all subjects. Blood samples (pre-vaccination and 1 month after the third dose) were obtained from a subset of infants (Group 1, 73; Group 2, 22) for serological determinations. Local and general symptoms were recorded by parents on diary cards. 2614 diary cards (Group 1, 1966; Group 2, 648) were collected. There were no statistically significant differences in the incidence of local and general symptoms between groups. Pain such that the infant cried when limb was moved was reported in 0.6 and 0.2% in groups 1 and 2, respectively. Redness and swelling (>20 mm in diameter) were recorded between 2.1 and 3% in both groups. Fussiness preventing normal activities was the most frequently reported general symptom in both groups (1.6 and 1.9% in groups 1 and 2, respectively). Fever (rectal temperature >39.5 degrees C) was reported in 0.4% (Group 1) and 0.3% (Group 2). All subjects included in the immunogenicity analysis had seroprotective or seropositive titres to the diphtheria, tetanus, hepatitis B and pertussis components of the vaccines. About 99 and 100% of infants had anti-PRP titres > or =0.15 mcg/ml in groups 1 and 2, respectively. This study indicates that DTPa-HBV vaccine given in a single injection with a candidate Hib conjugate vaccine has a similar reactogenicity profile to that of two commercially available vaccines (DTPa-HBV, Hib) given in two simultaneous injections to infants 2, 4 and 6 months of age.
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PMID:Reactogenicity of DTPa-HBV/Hib vaccine administered as a single injection vs DTPa-HBV and Hib vaccines administered simultaneously at separate sites, to infants at 2, 4 and 6 months of age. 1145 53


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