Characterization and pharmacological evaluation of febrile response on zymosan-induced arthritis in rats

Kanashiro A, Pessini AC, Machado RR, Malvar DC, Aguiar FA, Soares DM, Vale ML, Souza GEP. Characterization and pharmacological evaluation of febrile response on zymosan-induced arthritis in rats. Am J Physiol Regul Integr Comp Physiol 296: R1631-R1640, 2009. First published February 25, 2009; doi:10.1152/ajpregu.90527.2008.-The present study investigated the febrile response in zymosan-induced arthritis, as well as the increase in PGE(2) concentration in the cerebrospinal fluid (CSF), along with the effects of antipyretic drugs on these responses in rats. Zymosan intra-articularly injected at the dose of 0.5 mg did not affect the body core temperature (Tc) compared with saline (control), whereas at doses of 1 and 2 mg, zymosan promoted a flattened increase in Tc and declined thereafter. The dose of 4 mg of zymosan was selected for further experiments because it elicited a marked and long-lasting Tc elevation starting at 3 1/2 h, peaking at 5 1/2 h, and remaining until 10 h. This temperature increase was preceded by a decrease in the tail skin temperature, as well as hyperalgesia and edema in the knee joint. No febrile response was observed in the following days. In addition, zymosan-induced fever was not modified by the sciatic nerve excision. Zymosan increased PGE2 concentration in the CSF but not in the plasma. Oral pretreatment with ibuprofen (5-20 mg/kg), celecoxib (1-10 mg/kg), dipyrone (60-240 mg/kg), and paracetamol (100-200 mg/kg) or subcutaneous injection of dexamethasone (0.25-1.0 mg/kg) dose-dependently reduced or prevented the fever during the zymosan-induced arthritis. Celecoxib (5 mg/kg), paracetamol (150 mg/kg), and dipyrone (120 mg/kg) decreased CSF PGE2 concentration and fever during zymosan-induced arthritis, suggesting the involvement of PGE2 in this response.

Pédiatrie 4. Comment traiter la fièvre de l'enfant en 2013 avec un peu d'évidence [How to treat pediatric fever in 2013 with little evidence-based?].

Treatment of pediatric fever is based on two main molecules, paracetamol and ibuprofen. Fever should be treated when associated with discomfort. The two molecules have almost similar efficacy and safety. Monotherapy should be preferred to a combined or alternating treatment. Antipyretics do not seem to prevent febrile seizures.

Induced normothermia attenuates cerebral metabolic distress in patients with aneurysmal subarachnoid hemorrhage and refractory Fever.

BACKGROUND AND PURPOSE: The purpose of this study was to analyze whether fever control attenuates cerebral metabolic distress after aneurysmal subarachnoid hemorrhage (SAH). METHODS: Eighteen SAH patients, who underwent intracranial pressure (ICP) and cerebral microdialysis monitoring and were treated with induced normothermia for refractory fever (body temperature >or=38.3 degrees C, despite antipyretics), were studied. Levels of microdialysate lactate/pyruvate ratio (LPR) and episodes of cerebral metabolic crisis (LPR >40) were analyzed during fever and induced normothermia, at normal and high ICP (>20 mm Hg). RESULTS: Compared to fever, induced normothermia resulted in lower LPR (40+/-24 versus 32+/-9, P<0.01) and a reduced incidence of cerebral metabolic crisis (13% versus 5%, P<0.05) at normal ICP. During episodes of high ICP, induced normothermia was associated with a similar reduction of LPR, fewer episodes of cerebral metabolic crisis (37% versus 8%, P<0.01), and lower ICP (32+/-11 versus 28+/-12 mm Hg, P<0.05). CONCLUSIONS: Fever control is associated with reduced cerebral metabolic distress in patients with SAH, irrespective of ICP.

European Stroke Organisation (ESO) guidelines for the management of temperature in patients with acute ischemic stroke.

BACKGROUND: Hyperthermia is a frequent complication in patients with acute ischemic stroke. On the other hand, therapeutically induced hypothermia has shown promising potential in animal models of focal cerebral ischemia. This Guideline Document presents the European Stroke Organisation guidelines for the management of temperature in patients with acute ischemic stroke. METHODS: A multidisciplinary group identified related questions and developed its recommendations based on evidence from randomized controlled trials elaborating the Grading of Recommendations Assessment, Development, and Evaluation approach. This Guideline Document was reviewed within the European Stroke Organisation and externally and was approved by the European Stroke Organisation Guidelines Committee and the European Stroke Organisation Executive Committee. RESULTS: We found low-quality evidence, and therefore, we cannot make any recommendation for treating hyperthermia as a means to improve functional outcome and/or survival in patients with acute ischemic stroke and hyperthermia; moderate evidence to suggest against routine prevention of hyperthermia with antipyretics as a means to improve functional outcome and/or survival in patients with acute ischemic stroke and normothermia; very low-quality evidence to suggest against routine induction of hypothermia as a means to improve functional outcome and/or survival in patients with acute ischemic stroke. CONCLUSIONS: The currently available data about the management of temperature in patients with acute ischemic stroke are limited, and the strengths of the recommendations are therefore weak. We call for new randomized controlled trials as well as recruitment of eligible patients to ongoing randomized controlled trials to allow for better-informed recommendations in the future.

Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles in rats

The objective of this study was to determine the effect of eight 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-carboxyamidepyrazoles (TFDPs) on rat body temperature and baker’s yeast-induced fever. TFDPs or vehicle (5% Tween 80 in 0.9% NaCl, 5 mL/kg) were injected subcutaneously and rectal temperature was measured as a function of time in 28-day-old male Wistar rats (N = 5-12 per group). Antipyretic activity was determined in feverish animals injected with baker’s yeast (Saccharomyces cerevisiae suspension, 0.135 mg/kg, 10 mL/kg, ip). 3-Ethyl- and 3-propyl-TFDP (140 and 200 μmol/kg, respectively, 4 h after yeast injection) attenuated baker’s yeast-induced fever by 61 and 82%, respectively. These two effective antipyretics were selected for subsequent analysis of putative mechanisms of action. We then determined the effects on cyclooxygenase-1 and -2 (COX-1 and COX-2) activities on 1,1-diphenyl-2-picrylhydrazyl (DPPH) oxidation in vitro, on tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels and on leukocyte counts in the washes of peritoneal cavities of rats injected with baker’s yeast. While 3-ethyl- and 3-propyl-TFDP did not reduce baker’s yeast-induced increases of IL-1β or TNF-α levels, 3-ethyl-TFDP caused a 42% reduction in peritoneal leukocyte count. 3-Ethyl- and 3-propyl-TFDP did not alter COX-1 or COX-2 activities in vitro, but presented antioxidant activity in the DPPH assay with an IC50 of 39 mM (25-62) and 163 mM (136-196), respectively. The data indicate that mechanisms of action of these two novel antipyretic pyrazole derivatives do not involve the classic inhibition of the COX pathway or pyrogenic cytokine release.

Automedicação e guarda de medicamentos por universitários das áreas de saúde e tecnologia

This study aimed to compare self-medication and domestic drug storage among undergraduate students in the areas of health and technology. This is a descriptive study of cross-sectional type and quantitative approach, conducted in a Public University of Natal, Rio Grande do Norte, Brazil. The sample consisted of 300 students of the third year of undergraduate courses at the Center for Health Sciences and Technology Center, selected through a simple random sample. The project was authorized by the Ethics Committee of Federal University of Rio Grande do Norte (CAAE 0137.0.051.000-10). Data collection lasted twelve months and was conducted during the period of study participants, in the university environment. The instrument for data collection was a structured questionnaire consisting of open and closed questions. For data analysis, we used descriptive statistics and applied Fisher s exact test and Chi-square test with adopted level of significance α=5% and 10%. For the variables that correlated with self-medication (p<0.05), we subsequently calculated the odds ratios and confidence intervals. The prevalence of undergraduate students who performed self-medication in the 15 days prior to the collection accounted for 33.7% and, by analyzing each knowledge area, we verified was a higher prevalence of self-medication among students in the technological area (37.3%). The analysis of the socio-demographic characteristics of the participants in this practice revealed a significant difference between the knowledge areas in the income and self-medication variables (p=0.005). General analgesics and antipyretics (N02) represent the therapy group most used in self-medication (57.4%), especially acetaminophen (28.7%), and the main health situations that motivated this practice related to pain, especially headaches (48.5%). Regarding the indication of the drugs used, the majority of students self-medicated themselves on their own (71.3%). As regards to the in-home drug storage, most of the participants had a home pharmacy (88%). By analyzing the socioeconomic characteristics, the variables medical service and home medicine presented a significant difference (p=0.002). General 10 analgesics and antipyretics constituted the medicinal products most found in the home pharmacies, especially acetaminophen. The main room used for the drug storage was the kitchen (36.4%), most students kept these products in boxes of different materials (38.6%) and the medicines stored at home of most of the participants were not easily accessible to children (75%). The results reinforce the need to develop strategies, from the reality found, aiming to encourage and implement educational and preventive activities with undergraduate students on the importance of proper self-medication and in-home drug storage. Despite the sample in our study is relatively small, not representative for the whole country, we believe that, at national level, the panorama of the subject does not present major differences

Involvement of PGE(2) and RANTES in Staphylococcus aureus-induced fever in rats

Martins JM, Longhi-Balbinot DT, Soares DM, Figueiredo MJ, Malvar D do C, de Melo MC, Rae GA, Souza GE. Involvement of PGE(2) and RANTES in Staphylococcus aureus-induced fever in rats. J Appl Physiol 113: 1456-1465, 2012. First published August 30, 2012; doi:10.1152/japplphysiol.00936.2011.-This study investigated the involvement of prostaglandins and regulated on activation, normal T cell expressed and secreted (RANTES), in fever induced by live Staphylococcus aureus (no. 25923, American Type Culture Collection) injection in rats. S. aureus was injected intraperitoneally at 10(9), 10(10), and 2 x 10(10) colony-forming units (CFU)/cavity, and body temperature (T-b) was measured by radiotelemetry. The lowest dose of S. aureus induced a modest transient increase in T-b, whereas the two higher doses promoted similar long-lasting and sustained T-b increases. Thus, the 10(10) CFU/cavity dose was chosen for the remaining experiments. The T-b increase induced by S. aureus was accompanied by significant decreases in tail skin temperature and increases in PGE(2) levels in the cerebrospinal fluid (CSF) and hypothalamus but not in the venous plasma. Celecoxib (selective cyclooxygenase-2 inhibitor, 2.5 mg/kg po) inhibited the fever and the increases in PGE(2) concentration in the CSF and hypothalamus induced by S. aureus. Dipyrone (120 mg/kg ip) reduced the fever from 2.5 to 4 h and the PGE(2) increase in the CSF but not in the hypothalamus. S. aureus increased RANTES in the peritoneal exudate but not in the CSF or hypothalamus. Met-RANTES (100 mu g/kg iv), a chemokine (C-C motif) receptor (CCR)1/CCR5 antagonist, reduced the first 6 h of fever induced by S. aureus. This study suggests that peripheral (local) RANTES and central PGE(2) production are key events in the febrile response to live S. aureus injection. As dipyrone does not reduce PGE(2) synthesis in the hypothalamus, it is plausible that S. aureus induces fever, in part, via a dipyrone-sensitive PGE(2)-independent pathway.

A febre em pediatria : perspectiva de pais, médicos e enfermeiros

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Paracetamol [acetaminophen]-induced gastrotoxicity: Revealed by induced hyperacidity in combination with acute or chronic inflammation

Paracetamol is regarded as a relatively safe drug in the gastro-duodenal region of humans but recent epidemiological investigations have suggested that at high doses there may be an increased risk of ulcers and bleeding. To investigate the possibility that inflammatory conditions and gastric acidity may play a role in potentiating development of gastric mucosal injury from paracetamol in rats (as noted previously with various non-steroidal anti-inflammatory drugs) we studied the gastric irritant effects of paracetamol and some phenolic and non-phenolic analgesics and antipyretics in rats with adjuvant or collagen II induced arthritis or zymosan-induced paw inflammation and given 1.0 ml hydrochloric acid (HCl) 0.1 M and/or an i. p. injection of the cholinomimetic, acetyl-β-methyl choline chloride 5.0 mg/kg. Gastric lesions were determined 2 h after oral administration of 100 or 250 mg/kg paracetamol or at therapeutically effective doses of the phenolic or non-phenolic analgesics/antipyretics. The results showed that gastric mucosal injury occurred with all these agents when given to animals that received all treatments so indicating there is an adverse synergy of these three factors, namely: (i) intrinsic disease; (ii) hyperacidity; and (iii) vagal stimulation for rapidly promoting gastric damage, both in the fundic as well as the antral mucosa, for producing gastric damage by paracetamol, as well as the other agents. Removing one of these three predisposing factors effectively blunts/abolishes expression of this paracetamol-induced gastrotoxity in rats. These three factors, without paracetamol, did not cause significant acute gastropathy.

Effects of nursing interventions for fever in acutely ill adults

Fever has both beneficial and detrimental effects. There is evidence that antipyretics and physical cooling methods, when used in combination, are more effective than antipyretics alone. This randomized controlled study examined 45 acutely ill adults with fever ${\ge}102.5\sp\circ\rm F$ where three nursing interventions were used. Group I received acetaminophen 650 mgs., Group II received acetaminophen 650 mgs. and tepid sponging, and Group III received acetaminophen 650 mgs. and hypothermia blanket. The purpose of this study was to evaluate which nursing intervention reduced temperature most effectively with respect to eight biobehavioral variables. Research hypotheses were tested statistically using the chi-square test and repeated measures analysis of variance. The study found statistically significant results for fever reduction overall, but no difference for the groups. Therefore, we suggest that acetaminophen alone be used in the treatment of fever in order to decrease cost, nursing time, and increase patient comfort. ^

Self-medication on the students of the school of health from Polytechnic Institute of Bragança

The self-medicatíon is a phenomenon more and more frequent and used for several years already, and tts incidence and dlstribution are related wtth the organizatíon and health system of each country. Following Medeiros thoughts (2011), this practíce conststs in the consumptíon of a medicine with the purpose of treating or relieving the symptoms and diseases or even promote self health, without using a professional prescription. Methods: With thts study, we intend to find the self-medication practice incidence on the students in the School of Health of Polytechnic Institute of Bragança (ESSa), identify the motives that lead these students to resort to this methods and identify the most used medicatíons. lt's a transversal descriptive, observational and quantítative study. To obtain the best results it was applied a questíonnaire built for that purpose. The statístícs analyses was made using Excel program. Our sample hás 219 students of the School of Health from Polytechntc Instítute of Bragança. Results: The studied sample includes 194 female and 25 male students distributed as follows: 36 frequenting Biomedical Laboratory Sdences, 26 Dietetics and Nutrition, 99 Nursing, 33 Gerontology and 22 studying Pharmacy. The self-medicatíon prevalence was 98%. The most used medicines was the analgesics and antipyretics with 86%. The most prevalent reason for the use of self-medicatíon was the thought that the disease was a "minor health issue". It was also considered a risky practice by 77% of the students. Conclusions: The self-medication is an evident practíce on the ESSa students. This results reveal some contradiction stnce the most consider 1t as a risky practíce, however it is, stíll, practíced.