Neutrophils: are they hyperalgesic or anti-hyperalgesic?
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Animals↗
Biomedical subjects
T M Cunha
Publications and source records attributed to T M Cunha.
Atorvastatin inhibits inflammatory hypernociception.
BACKGROUND AND PURPOSE: Atorvastatin is an inhibitor of the enzyme 3-hydroxyl-3-methylglutaryl coenzyme A reductase used to prevent coronary heart disease. We have studied the analgesic effect of atorvastatin in inflammatory models in which a sequential release of mediators (bradykinin, (BK), tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and the chemokine, KC/CXCL) links the stimulus with release of directly acting hypernociceptive mediators such as prostaglandin E(2) (PGE(2)). EXPERIMENTAL APPROACH: The effects of orally administered atorvastatin on inflammatory mechanical hypernociception in mouse paws were evaluated with an electronic pressure-meter. Cytokines and PGE(2) were measured by ELISA and RIA. KEY RESULTS: Treatment with atorvastatin for 3 days dose-dependently reduced hypernociception induced by lipopolysaccharide (LPS) or that following antigen challenge in sensitized animals. Atorvastatin pre-treatment reduced hypernociception induced by bradykinin and cytokines (TNF-alpha, IL-1beta and KC), and the release of IL-1beta and PGE(2) in paw skin, induced by lipopolysaccharide. The antinociceptive effect of atorvastatin on LPS-induced hypernociception was prevented by mevalonate co-treatment without affecting serum cholesterol levels. Hypernociception induced by PGE(2) was inhibited by atorvastatin, suggesting intracellular antinociceptive mechanisms for atorvastatin. The antinociceptive effect of atorvastatin upon LPS- or PGE(2)-induced hypernociception was prevented by non-selective inhibitors of nitric oxide synthase (NOS) but not by selective inhibition of inducible NOS or in mice lacking this enzyme. CONCLUSIONS AND IMPLICATIONS: Antinociceptive effects of atorvastatin depend on inhibition of cytokines and prostanoid production and on stimulation of NO production by constitutive NOS. Our study suggests that statins may constitute a novel class of analgesic drugs.
Animals↗
A cascade of cytokines mediates mechanical inflammatory hypernociception in mice.
The hypernociceptive effects of cytokines [TNF-alpha, keratinocyte-derived chemokine (KC), and IL-1beta] and their participation in carrageenan (Cg)-induced inflammatory hypernociception in mice were investigated. Nociceptor sensitization (hypernociception) was quantified with an electronic version of the von Frey filament test in WT and TNF receptor type 1 knockout mice (TNF-R1-/-). TNF-alpha-induced hypernociception was abolished in TNF-R1-/- mice, partially inhibited by pretreatment with IL-1 receptor antagonist (IL-1ra) or indomethacin and unaffected by Ab against KC (AbKC) or guanethidine. IL-1ra and indomethacin pretreatment strongly inhibited the hypernociception induced by IL-1beta, which was not altered by AbKC or guanethidine or by knocking out TNF-R1. KC-induced hypernociception was abolished by AbKC, inhibited by pretreatment with indomethacin plus guanethidine, and partially inhibited by IL-1ra, indomethacin, or guanethidine. In contrast, KC-induced hypernociception was not altered by knocking out TNF-R1. Cg-induced hypernociception was abolished by administration of indomethacin plus guanethidine, diminished in TNF-R1-/- mice, and partially inhibited in WT mice pretreated with AbKC, IL-1ra, indomethacin, or guanethidine. TNF-alpha, KC, and IL-1beta concentrations were elevated in the skin of Cg-injected paws. The TNF-alpha and KC concentrations rose concomitantly and peaked before that of IL-1beta. In mice, the cytokine cascade begins with the release of TNF-alpha (acting on TNF-R1 receptor) and KC, which stimulate the release of IL-1beta. As in rats, the final mediators of this cascade were prostaglandins released by IL-1beta and sympathetic amines released by KC. These results extend to mice the concept that the release of primary mediators responsible for hypernociception is preceded by a cascade of cytokines.
Animals↗
An electronic pressure-meter nociception paw test for rats.
The objective of the present investigation was to compare the sensitivity of an electronic nociceptive mechanical paw test with classical mechanical tests to quantify the intensity variation of inflammatory nociception. The electronic pressure-meter test consists of inducing the hindpaw flexion reflex by poking the plantar region with a polypropylene pipette tip adapted to a hand-held force transducer. This method was compared with the classical von Frey filaments test and with the rat paw constant pressure test, a modification of the Randall and Selitto test developed by our group. When comparing the three methods, the electronic pressure-meter and the rat paw constant pressure test, but not the von Frey filaments test, detected time vs treatment interactions in prostaglandin E2 (PGE2)-induced hypernociception. Both methods also detected the PGE2-induced hypernociception in dose- (50-400 ng/paw) and time- (1-4 h) dependent manners, and time vs treatment interactions induced by carrageenin (25-400 microg/paw). Furthermore, the electronic pressure-meter test was more sensitive at early times, whereas the constant pressure test was more sensitive at later times. Moreover, the electronic pressure-meter test detected the dose-dependent antinociceptive effect of local indomethacin (30-300 microg/paw) and dipyrone (80-320 microg/paw) on carrageenin- (200 microg/paw) and PGE2- (100 ng/paw) induced hypernociception, respectively, and also detected the ineffectiveness of indomethacin (300 microg) on the effect of PGE2. Our results show that the electronic pressure-meter provides a sensitive, objective and quantitative mechanical nociceptive test that could be useful to characterize new nociceptive inflammatory mediators and also to evaluate new peripheral analgesic substances.
Analysis of Variance↗
An electronic pressure-meter nociception paw test for mice.
The aim of the present investigation was to describe and validate an electronic mechanical test for quantification of the intensity of inflammatory nociception in mice. The electronic pressure-meter test consists of inducing the animal hindpaw flexion reflex by poking the plantar region with a polypropylene pipette tip adapted to a hand-held force transducer. This method was compared to the classical von Frey filaments test in which pressure intensity is automatically recorded after the nociceptive hindpaw flexion reflex. The electronic pressure-meter and the von Frey filaments were used to detect time versus treatment interactions of carrageenin-induced hypernociception. In two separate experiments, the electronic pressure-meter was more sensitive than the von Frey filaments for the detection of the increase in nociception (hypernociception) induced by small doses of carrageenin (30 microg). The electronic pressure-meter detected the antinociceptive effect of non-steroidal drugs in a dose-dependent manner. Indomethacin administered intraperitoneally (1.8-15 mg/kg) or intraplantarly (30-300 microg/paw) prevented the hypersensitive effect of carrageenin (100 microg/paw). The electronic pressure-meter also detected the hypernociceptive effect of prostaglandin E2 (PGE2; 10-100 ng) in a dose-dependent manner. The hypernociceptive effect of PGE2 (100 ng) was blocked by dipyrone (160 and 320 microg/paw) but not by intraplantar administration of indomethacin (300 microg/paw). The present results validate the use of the electronic pressure-meter as more sensitive than the von Frey filaments in mice. Furthermore, it is an objective and quantitative nociceptive test for the evaluation of the peripheral antinociceptive effect of anti-inflammatory analgesic drugs, which inhibit prostaglandin synthesis (indomethacin) or directly block the ongoing hypernociception (dipyrone).
Analysis of Variance↗
Schwannoma of the esophagus: computed tomography and endosonographic findings of a special type of schwannoma.
Schwannomas of the digestive tract are uncommon benign tumors seldom located in the esophagus. We present a case of intramural esophageal schwannoma with histopathological correlation evaluated by computed tomography and endoscopic ultrasonography. The imaging findings are described and other relevant features of schwannomas of the esophagus are discussed.
Endosonography↗
Case report: sacrococcygeal teratoma with malignant transformation in an adult female: CT and MRI findings.
This report describes a case of sacrococcygeal teratoma with adenocarcinomatous transformation in a 45-year-old woman. This is an infrequent location for teratoma in adults and malignant transformation has rarely been described. Prognosis depends on complete excision. Clinical manifestations, imaging aspects and histological findings of this case are presented. CT and MRI adequately document the mixed cystic and solid nature of the tumour, its extension and relations with adjacent structures, allowing accurate pre-operative planning.
Adenocarcinoma↗
Ticks (Acari: Ixodidae) associated with domestic dogs in Franca region, São Paulo, Brazil.
Ticks on 140 domestic dogs from both urban and rural areas of Franca region in São Paulo state were identified with 102 dogs from urban areas and 38 from rural areas. Of urban dogs, 27.5% were infested exclusively by Rhipicephalus sanguineus ticks. Of the rural dogs, 36.8% were infested with the following tick species: R. sanguineus, Boophilus microplus, Amblyomma ovale and A. cajennense. Mixed infestations included a dog hosting A. cajennense and A. ovale and another with B. microplus and R. sanguineus. The most intense infestations were detected on urban dogs. Hemolymph tests of these ticks performed to detect rickettsial or Borrelia bacteria yielded negative results.
Animals↗
Determinants of preterm delivery and intrauterine growth retardation in north-east Brazil.
A case-control study was conducted in Natal, north-east Brazil to determine the risk factors for low birthweight (LBW). Cases were 429 preterm and 422 intrauterine growth retarded (IUGR) singleton infants. Controls were 2555 infants of normal birthweight and gestational age. The prevalence of LBW was 10% (5.1% preterm and 4.9% IUGR). Logistic regression was used to estimate the adjusted odds ratios of LBW, and attributable risk per cent (AR%) was used to estimate the proportion of LBW that might be prevented. The preventable determinants of preterm delivery were births to women less than 20, (AR = 7.1%), low maternal weight less than 50 kg (AR = 20.5%), smoking during pregnancy (AR = 14.6%) and infrequent antenatal visits (AR = 28.1%). Other important determinants of preterm delivery were prior LBW births, gestational illness and vaginal bleeding. The main preventable causes of IUGR were low maternal weight (AR = 17.8%), low maternal education (AR = 11.6%), smoking (AR = 14.8%), and inadequate antenatal care (AR = 11.6%). Other risk factors for IUGR include primiparity, prior LBW births, and illness during gestation. In this population, the focus of short-term preventive programme should be improvement in maternal nutrition, cessation of smoking, reduction of births to women under 20, and improved antenatal care.
Body Weight↗
Preoperative assessment of deep myometrial and cervical invasion in endometrial carcinoma: comparison of magnetic resonance imaging and gross visual inspection.
This study aimed to evaluate the accuracy of magnetic resonance imaging (MRI) in the detection of deep myometrial invasion and cervical extension by endometrial carcinoma. We also aimed to compare MRI results to surgical staging of endometrial carcinoma. Forty women with a histologic diagnosis of endometrial carcinoma underwent a preoperative pelvic MRI. In 33 cases intraoperative gross visual inspection (GVI) of the surgical specimen was also evaluated. The results obtained were compared with the histologic diagnosis. Pathologic evaluation of the myometrium determined that superficial invasion was present in 25 patients and deep invasion in 15. The uterine cervix was found to be involved in 12 cases. The accuracy, sensitivity, and specificity of MRI and GVI were 93%/91%, 80%/77%, and 100%/100%, respectively, in detecting deep myometrial invasion and 80%/79%, 33%/36% and 100%/100%, respectively, in determining cervical invasion. When the Kappa statistical measurement was applied, the results from each technique, MRI and GVI, showed an agreement on the evaluation of myometrial and cervical invasion by endometrial carcinoma. In conclusion, MRI, in this series, was demonstrated to be a reliable method for preoperative endometrial carcinoma "imagiological staging". The high accuracy achieved by MRI and GVI suggests that they may be used interchangeably.
Aged↗