Suplementação com Vitamina D atenua a resposta inflamatória aguda / Vitamin D supplementation attenuates acute inflammatory response

Este estudo avaliou os efeitos da suplementação diária de vitamina D na resposta inflamatória aguda em modelo experimental por diferentes agentes flogísticos: carragenina, prostaglandina e dextrana. Os animais (ratos) receberam por via oral (gavagem), dose única de vitamina D ou suplementação diária durante 7, 15 ou 30 dias antes da indução do edema de pata. A suplementação com vitamina D por 15 e 30 dias reduziu significativamente o processo inflamatório induzido por carragenina, o que poderia ser explicado, pelo menos parcialmente, pela redução dos níveis de fator de necrose tumoral α (TNFα). Os resultados indicam que a suplementação de vitamina D pode ser um útil adjuvante terapêutico para o controle do processo inflamatório agudo.

This study evaluated the effects of daily vitamin D supplementation on the acute inflammatory response in experimental model by different phlogistic agents: carrageenan, prostaglandin and dextran. Animals (rats) orally received (gavage) a single dose of vitamin D or daily supplementation for 7, 15 or 30 days prior to paw edema induced. Vitamin D supplementation for 15 and 30 days significantly reduced the carrageenan-induced inflammatory process, which could be at least partially explained by the reduction of tumor necrosis factor α levels (TNFα). Results indicate that vitamin D supplementation may be a useful therapeutic adjuvant for controlling the acute inflammatory process.

Antifungal activity of two oxadiazole compounds for the paracoccidioidomycosis treatment.

Paracoccidioidomycosis (PCM) is a neglected disease present in Latin America with difficulty in treatment and occurrence of serious sequelae. Thus, the development of alternative therapies is imperative. In the current work, two oxadiazole compounds (LMM5 and LMM11) presented fungicidal activity against Paracoccidioides spp. The minimum inhibitory and fungicidal concentration values ranged from 1 to 32 µg/mL, and a synergic effect was observed for both compounds when combined with Amphotericin B. LMM5 and LMM11 were able to reduce CFU counts (≥2 log10) on the 5th and 7th days of time-kill curve, respectively. The fungicide effect was confirmed by fluorescence microscopy (FUN-1/FUN-2). The hippocratic screening and biochemical analysis were performed in Balb/c male mice that received a high dose of each compound, and the compounds showed no in vivo toxicity. The treatment of experimental PCM with the new oxadiazoles led to significant reduction in CFU (≥1 log10). Histopathological analysis of the groups treated exhibited control of inflammation, as well as preserved lung areas. These findings suggest that LMM5 and LMM11 are promising hits structures, opening the door for implementing new PCM therapies.

Different formulations of vancomycin: In vitro antimicrobial activity against clinical isolates of methicillin-resistant Staphylococcus aureus.

We compared in vitro antimicrobial activity of four vancomycin formulations used clinically against clinical isolates of Staphylococcus aureus, including methicillin-resistant and -susceptible (MRSA and MSSA, respectively), using different susceptibility assays. The minimal inhibitory concentrations (MICs) against MRSA clinical isolates were significantly different for some vancomycin formulations by the broth microdilution and agar dilution methods. However, these variations would not compromise their clinical use, since the MICs were within the range recommended by the Clinical and Laboratory Standards Institute. Furthermore, 26.9% of MRSA clinical isolates showed a vancomycin MIC ≥1.5 µg/mL according to the Etest® method but none by broth microdilution. Regarding quality, all formulations were in accordance with United States Pharmacopeia criteria. Our results showed that all vancomycin formulations tested showed similar in vitro antimicrobial activity, making them suitable for clinical use, and that the evaluation method chosen to determine sensitivity to this antimicrobial should be carefully performed, particularly for MRSA.

Anethole reduces inflammation and joint damage in rats with adjuvant-induced arthritis.

AIM: This study evaluated whether anethole attenuates the inflammatory response and joint damage in a model of adjuvant-induced arthritis (AIA) in rats. METHODS: The animals were treated with 62.5-, 125-, or 250-mg/kg anethole daily for 21 days after AIA and necropsied on days 14 and 21 to evaluate the number of serum and synovial leukocytes (total and differential), serum cytokines (IL-2, IL-6, IL-12, IL-17, and TNF-α), and nitric oxide concentrations. Morphologic changes in the cartilage and bone of the femorotibial articulation in both left paw and right paw were studied in hematoxylin/eosin and Sirius Red-hematoxylin sections. RESULTS: Different doses of anethole suppressed paw swelling and the number of serum and synovial leukocytes. However, 250 mg/kg of anethole more effectively controlled local and systemic inflammation. Histological evaluation revealed significant prevention of cartilage damage and inflammatory infiltrate scores. Morphometric analysis showed pannus formation, the thickness of the articular cartilage, and bone resorption lower in the anethole-treated AIA group compared to untreated AIA group on both days 14 and 21. These significant anti-inflammatory effects in the anethole-treated AIA group were associated with downregulation of cytokines and nitric oxide levels. CONCLUSION: Therefore, anethole may be a useful intervention to treat inflammatory arthritis.

Liver Fatty Acid Composition and Inflammation in Mice Fed with High-Carbohydrate Diet or High-Fat Diet.

Both high-carbohydrate diet (HCD) and high-fat diet (HFD) modulate liver fat accumulation and inflammation, however, there is a lack of data on the potential contribution of carbohydrates and lipids separately. For this reason, the changes in liver fatty acid (FA) composition in male Swiss mice fed with HCD or HFD were compared, at the time points 0 (before starting the diets), and after 7, 14, 28 or 56 days. Activities of stearoyl-CoA desaturase-1 (SCD-1), ∆-6 desaturase (D6D), elongases and de novo lipogenesis (DNL) were estimated. Liver mRNA expression of acetyl-CoA carboxylase 1 (ACC1) was evaluated as an additional indicator of the de novo lipogenesis. Myeloperoxidase activity, nitric oxide (NO) production, and mRNA expressions of F4/80, type I collagen, interleukin (IL)-6, IL-1ß, IL-10, and tumor necrosis factor-α (TNF-α) were measured as indication of the liver inflammatory state. The HCD group had more intense lipid deposition, particularly of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). This group also showed higher DNL, SCD-1, and D6D activities associated with increased NO concentration, as well as myeloperoxidase activity. Livers from the HFD group showed higher elongase activity, stored more polyunsaturated fatty acids (PUFAs) and had a lower omega-6/omega-3 fatty acid (n-6/n-3) ratio. In conclusion, liver lipid accumulation, fatty acids (FA) composition and inflammation were modulated by the dietary composition of lipids and carbohydrates. The HCD group had more potent lipogenic and inflammatory effects in comparison with HFD.

Hydroethanolic extract of Smallanthus sonchifolius leaves improves hyperglycemia of streptozotocin induced neonatal diabetic rats.

OBJECTIVE: To evaluate the effect of hydroethanolic extract of yacon on the hyperglycemia induced by streptozotocin (STZ) in neonatal rats. METHODS: Wistar rats aged two days old received an intraperitoneal injection of STZ (160 mg/kg); after seven weeks, glycosuria was determined and animals with glucose levels above 250 mg/dL were included in the study. Groups of diabetic and non-diabetic rats were treated orally with yacon extract at a dose of 400 mg/kg/d for 14 d. Tests were made for phytochemical characterization, glucose tolerance and toxicity. RESULTS: The results showed that treatment with the extract reduced the glucose levels of fed diabetic rats and did not change the glucose levels of fasting diabetic and normal rats. Additionally, also it was observed that treatment with the extract reduced blood glucose levels of diabetic rats during the oral and intravenous glucose tolerance tests. There was no change in body weight, liver enzymes or mortality with yacon extract treatment. The phytochemical screening revealed the presence of caffeic acid, chlorogenic acid, ferulic acid and gallic acid. CONCLUSIONS: The data suggest that yacon extract reduces hyperglycemia, possibly by improving insulin sensibility through its phytochemicals constituents (phenolic compounds).

Pharmacodynamic Evaluation of the Potential Clinical Utility of Fosfomycin and Meropenem in Combination Therapy against KPC-2-Producing Klebsiella pneumoniae.

KPC-producing Klebsiella pneumoniae causes serious infections associated with high death rates worldwide. Combination therapy consisting of fosfomycin and a carbapenem is better than monotherapy to combat multidrug-resistant microorganisms, but no dosages for the combination have been defined. The MICs of meropenem and fosfomycin were evaluated against 18 clinical isolates of KPC-2-producing K. pneumoniae The activities of combination antimicrobials were also determined by the checkerboard method. The MIC50 and MIC90 of each agent alone and in combination were challenged against short (1.5-h) or prolonged (3-h) infusion regimens of meropenem (1 g every 8 h [q8h], 1.5 g q6h, 2 g q8h) and fosfomycin (4 g q8h, 6 g q6h, 8 g q8h) by Monte Carlo simulation to evaluate the time above the MIC of the free drug concentration as a percentage of the dosing interval (fT>MIC). The monotherapy MIC50s and MIC90s were 32 and 256 mg/liter for meropenem and 64 and 512 mg/liter for fosfomycin, respectively. Antimicrobial combination increased bacterial susceptibility to 1/4 the MIC50s and to 1/8 to 1/16 the MIC90s of monotherapy. The antimicrobial combination demonstrated a synergistic effect for at least two-thirds of the isolates. In combination therapy, fosfomycin regimens of 6 g q6h and 8 g q8h as a 3-h infusion against the MIC50 and MIC90 had better chances of achieving ≥90% probability of target attainment (PTA) of 70% fT>MIC. Meropenem regimens of 1.5 g q6h and 2 g q8h in prolonged infusion can achieve close to 90% PTA of 40% fT>MIC for MIC50 but not MIC90 The significant reduction in the MIC values and the achievement of appropriate PTA demonstrated that regimens containing fosfomycin with meropenem can be effective against KPC-2-producing K. pneumoniae.

Treating Staphylococcus aureus infections in an intensive care unit at a University Hospital in Brazil.

BACKGROUND: Optimizing antimicrobial therapy is important for treating patients who are critically ill with Staphylococcus aureus infection, and susceptibility tests are necessary. OBJECTIVE: The aim of the present study was to evaluate antibacterial therapy after susceptibility testing of S. aureus infections. Setting The setting was an intensive care unit at a University Hospital in Brazil. METHODS: An observational and retrospective study was conducted over 6 years. The antimicrobials that were used for S. aureus infection treatment were calculated as the defined daily dose per 1000 patient-days (DDD1000). Antimicrobial susceptibility data were obtained by reviewing bacteriological tests. Patient profiles and treatment were determined by analyzing patient charts. RESULTS: Methicillin-resistant S. aureus (MRSA) was prevalent in this study (76.13 %). Patients who were infected with MRSA had total antimicrobial consumption that was three-times higher (9567.2 DDD1000) than patients who were infected with methicillin-susceptible S. aureus (MSSA; 3101.1 DDD1000). The average length of stay in the intensive care unit was 19 days (interquartile range 17 days) for MSSA and 20 days (interquartile range 20 days) for MRSA. Mortality in patients who were infected with MSSA was higher (52.17 %) than in patients who were infected with MRSA (33.80 %), and de-escalation was not identified in 73.90 % of MSSA patients.

Effect of the Combination of Ezetimibe and Simvastatin on Gluconeogenesis and Oxygen Consumption in the Rat Liver.

The aim of this work was to investigate the effects of chronic treatment with the combination of ezetimibe and simvastatin on gluconeogenesis in rat liver. Rats were treated daily for 28 days with the combination of ezetimibe and simvastatin (10/40 mg/kg) by oral gavage. To measure gluconeogenesis and the associated pathways, isolated perfused rat liver was used. In addition, subcellular fractions, such as microsomes and mitochondria, were used for complementary measures of enzymatic activities. Treatment with the combination of simvastatin and ezetimibe resulted in a decrease in gluconeogenesis from pyruvate (-62%). Basal oxygen consumption of the treated animals was higher (+22%) than that of the control rats, but the resulting oxygen consumption that occurred after pyruvate infusion was 43% lower in animals treated with the combination of simvastatin and ezetimibe. Oxygen consumption in the livers from treated animals was completely inhibited by cyanide (electron transport chain inhibitor), but not by proadifen (cytochrome P450 inhibitor). Chronic treatment with ezetimibe/simvastatin decreased the activity of the key enzymes glucose-6-phosphatase and fructose-1,6-bisphosphatase by 59% and 45%, respectively, which is probably the major reason for the decreased gluconeogenesis seen in ezetimibe-/simvastatin-treated rats. It is also possible that part of the effect of this combination on gluconeogenesis and on the oxygen consumption is related to the impairment of mitochondrial energy transduction.

Hepatoprotective Effect of Silymarin (Silybum marianum) on Hepatotoxicity Induced by Acetaminophen in Spontaneously Hypertensive Rats.

This study was aimed to investigate the effect of Silymarin (SLM) on the hypertension state and the liver function changes induced by acetaminophen (APAP) in spontaneously hypertensive rat (SHR). Animals normotensive (N) or hypertensive (SHR) were treated or not with APAP (3 g/kg, oral) or previously treated with SLM. Twelve hours after APAP administration, plasmatic levels of liver function markers: alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose (GLU), gamma glutamyl transferase (γ-GT), and alkaline phosphatase (ALP) of all groups, were determined. Liver injury was assessed using histological studies. Samples of their livers were then used to determine the myeloperoxidase (MPO) activity and nitric oxide (NO) production and were also sectioned for histological analysis. No differences were observed for ALT, γ-GT, and GLU levels between SHR and normotensive rats groups. However, AST and ALP levels were increased in hypertensive animals. APAP treatment promoted an increase in ALT and AST in both SHR and N. However, only for SHR, γ-GT levels were increased. The inflammatory response evaluated by MPO activity and NO production showed that SHR was more susceptible to APAP effect, by increasing leucocyte infiltration. Silymarin treatment (Legalon) restored the hepatocyte functional and histopathological alterations induced by APAP in normotensive and hypertensive animals.

Problems related to antifungal prescription: a qualitative study of the views of intensivists.

RATIONALE AND OBJECTIVE: The choice of the appropriate antifungal medication is essential for therapeutic success. Although guidelines are available in the literature that regulate the consistent use of antifungal, no previous qualitative studies have addressed the difficulties related to the use of antifungal medication, especially in the intensive care unit (ICU). Our objective was to qualitatively investigate how intensivists consider antifungal prescriptions in an adult ICU. METHODS: The Grounded Theory analytical method was used for the data analysis. Physicians who worked in the adult ICU and prescribed antifungal medications were individually interviewed. A semi-structured interview was used to ask core questions, followed by follow-up questions at the discretion of the interviewer. RESULTS: Our analysis generated eight main emerging themes that were classified into three related groups. The main insights were that various interconnected reasons were given for the lack of conformity with regard to prescription patterns for antifungals. A negative cycle was perceived based on issues related to prescriptions and the search for knowledge. If problems related to individual actions and multidisciplinary team integration are resolved and local protocols are implemented based on local epidemiology, then barriers to proper prescriptions can be overcome when intensivists are faced with the unusual practice of prescribing antifungals. CONCLUSIONS: Our investigation indicates the need for prescription assistance with support from a well-trained multidisciplinary team and consensus among its members and the importance of well-designed protocols.

Utilization of fluconazole in an intensive care unit at a university hospital in Brazil.

BACKGROUND: Fungi have been developing resistance and merit greater attention because these microorganisms are among the major causes of hospital infection. OBJECTIVE: The aim of the present study was to characterize the pattern of fluconazole use in an adult intensive care unit. SETTING: The setting was an intensive care unit at a university hospital in Brazil. METHOD: An observational retrospective study was performed between 2007 and 2010. The use of antifungal drugs was calculated as the defined daily dose per 1,000 patient-days. The pattern of fluconazole use was determined by analyzing patient charts. RESULTS: Fluconazole accounted an average of 66.6 % of the antifungal agents prescribed. All of the patients exhibited important risk factors for the development of fungal infection. Treatment was empirical in 45.2 % of the cases and therapeutic in 54.8 % of the cases. The dose interval was inadequate in 51.1 % of the treatments. Fluconazole at doses ≥400 mg/day was related to a greater likelihood of survival. C. albicans was the most prevalent species (31.3 %). Urine was the biological material with the greatest number of positive mycological exams (71.9 %). CONCLUSION: This study found a high utilization of fluconazole and, in most cases, its administration at intervals that were different from the recommended intervals.

Inhibitory effect of anethole in nonimmune acute inflammation.

Anethole [1-methoxy-4-(1-propenyl)benzene] occurs naturally as a major component of the essential oil of star anise (Illicium verum Hook.f., family Illiciaceae), comprising more than 90 % of its volatile components. Studies showed that this substance has antioxidant, antibacterial, antifungal, and anesthetic properties. In this study, the anti-inflammatory properties of anethole in animal models of nonimmune acute inflammation such as croton oil-induced ear edema and carrageenan-induced pleurisy were investigated. The investigated parameters were edema formation, leukocyte migration, and inflammatory mediators involved. Oral administration of anethole at a dose of 250 and 500 mg/kg reduced both the volume of pleural exudates and the number of migrated leukocytes. Levels of nitric oxide (NO) and prostaglandins (PGE2) in the inflammatory exudate were reduced by treatment with anethole, but levels of tumor necrosis factor-α and interleukin-1ß were not significantly altered. In ear edema, the oral treatment with anethole inhibited the formation of exudate and the activity of myeloperoxidase, but not after topical administration. These results suggest that the anethole may be effective in controlling some nonimmune acute inflammation-related disease, probably by an inhibitory action on production and/or release of PGE2 and NO.

Effects of simvastatin, atorvastatin, ezetimibe, and ezetimibe + simvastatin combination on the inflammatory process and on the liver metabolic changes of arthritic rats.

In this study, simvastatin, atorvastatin, ezetimibe, and ezetimibe + simvastatin combination were administered to arthritic rats, first to determine their effects on the inflammatory response, employing a low-dose adjuvant-induced arthritis model in rats. Arthritis was induced by the subcutaneous injection of a suspension of Mycobacterium tuberculosis (100 µg) in mineral oil [complete Freund's adjuvant used (CFA)] into the plantar surface of the hind paws. Simvastatin(40 mg/kg), atorvastatin(10 mg/kg), ezetimibe(10 mg/kg), ezetimibe(10 mg/kg) + simvastatin(20 mg/kg or 40 mg/kg) were given intragastrically and the treatment began on the day of CFA injection and continued daily up to the 28th day after arthritis induction. The ezetimibe + simvastatin combination was more effective in reducing the inflammatory response in arthritic rats than in atorvastatin, simvastatin, or ezetimibe monotherapy. The observed effect seems to be cholesterol-independent as there were no changes in plasma cholesterol levels. In spite of the benefits on joint lesions, treatment with ezetimibe + simvastatin combination caused a marked increment in liver, kidneys, spleen size, and plasma transaminases activities. Therefore, animals treated with the ezetimibe(10 mg/kg) + simvastatin(40 mg/kg) combination were also submitted to liver perfusion experiments. In this regard, ezetimibe + simvastatin did not improve the liver metabolic alterations seen in control arthritic rats, on the contrary, a worsening was observed in liver production of glucose from alanine, as well as in oxygen uptake. All of these metabolic changes appear to be induced by treatment with ezetimibe + simvastatin combination, as the same metabolic effects were observed in normal and treated arthritic animals.

Inhibitory Effect of Helicteres gardneriana Ethanol Extract on Acute Inflammation.

The anti-inflammatory effect of an ethanol extract of Helicteres gardneriana (Nees) Castiglioni was assayed in experimental models of pleurisy and microcirculation in situ. Treatment of animals with 500 mg/kg body weight reduced the exudate volume (35% reduction) induced by intrapleural injection of carrageenan and the migration of polymorphonuclear cells into the inflamed pleural cavity of rats (40%). Additionally, rolling and adhesion of leukocytes and the number of leukocytes that migrated toward the perivascular space in response to the carrageenan injection were decreased by the extract (500 mg/kg). These data demonstrate the anti-inflammatory effect of the ethanol extract of Helicteres gardneriana and imply that inhibition of leukocyte-endothelial interactions is important in the extract's mechanism of action.

Topical anti-inflammatory effect of hypocholesterolaemic drugs.

OBJECTIVES: The topical anti-inflammatory effect of simvastatin, atorvastatin, pravastatin, ezetimibe and combined ezetimibe + simvastatin was investigated, using the croton oil model of ear oedema in mice. METHODS: Simvastatin, atorvastatin, pravastatin, ezetimibe and ezetimibe + simvastatin combination (dissolved in 20 µl of 70% acetone) were topically applied simultaneously with croton oil (200 µg/ear, dissolved in 20 µl of 70% acetone) at the inner surface of each ear. Ear oedema and myeloperoxidase activity, indicative of polymorphonuclear cell migration, were assessed 6 h after inflammatory stimuli. KEY FINDINGS: It was found that statins can act as topical anti-inflammatories, but the pharmacological effect is dependent on statin polarity. At 0.3 mg/ear inhibition of ear oedema was 79%, 67% and 40% for simvastatin, atorvastatin and pravastatin, respectively. Simvastatin and atorvastatin also remarkably diminished myeloperoxidase activity, even at low concentrations (0.03 mg/ear). Pravastatin, the most polar statin, however, did not cause any reduction in ear oedema or myeloperoxidase activity at low doses. The order of topical anti-inflammatory activity was pravastatin < < < atorvastatin ≤ simvastatin. Ezetimibe, another hypocholesterolaemic drug, also presented anti-inflammatory effects, inhibiting ear oedema by 64% at 0.3 mg/ear. However, when used in combination with simvastatin, no further beneficial effect was observed. CONCLUSIONS: These results consistently support current evidence showing that statins can be used for treatment of dermatological disorders. Polarity of the molecule, however, is a factor that should be considered before recommending use.

Protective effects of indomethacin and cyclophosphamide but not of infliximab on liver metabolic changes caused by adjuvant-induced arthritis.

In the study, indomethacin, cyclophosphamide, and infliximab were administered to adjuvant-induced arthritic rats to determine if they were able to prevent the abnormalities caused by arthritis on hepatic metabolism. The drugs were administered to arthritic rats, and at the clinical onset of arthritis (day 14 after adjuvant injection), the livers were perfused to evaluate gluconeogenesis, ureagenesis, oxygen uptake, L: -lactate, pyruvate, and ammonia release from L: -alanine. The effects of the drugs on body weight gain and the signs of arthritis (paw edema, appearance of secondary lesions, and weights of lymphoid tissues) were also evaluated. Cyclophosphamide could completely prevent liver metabolic changes and the inflammatory response. Indomethacin restored ureagenesis, minimized the decrease in gluconeogenesis, and exerted a partially beneficial effect on inflammatory reactions. Infliximab did not improve arthritis-induced liver metabolic alterations or inflammatory responses. These results suggest the participation of prostaglandins, but not TNF-α, on arthritis-induced liver metabolic alterations.

Immunomodulatory activity of Zingiber officinale Roscoe, Salvia officinalis L. and Syzygium aromaticum L. essential oils: evidence for humor- and cell-mediated responses.

OBJECTIVES: The immunomodulatory effect of ginger, Zingiber officinale (Zingiberaceae), sage, Salvia officinalis (Lamiaceae) and clove, Syzygium aromaticum (Myrtaceae), essential oils were evaluated by studying humor- and cell-mediated immune responses. METHODS: Essential oils were administered to mice (once a day, orally, for a week) previously immunized with sheep red blood cells (SRBCs). KEY FINDINGS: Clove essential oil increased the total white blood cell (WBC) count and enhanced the delayed-type hypersensitivity (DTH) response in mice. Moreover, it restored cellular and humoral immune responses in cyclophosphamide-immunosuppressed mice in a dose-dependent manner. Ginger essential oil recovered the humoral immune response in immunosuppressed mice. Contrary to the ginger essential oil response, sage essential oil did not show any immunomodulatory activity. CONCLUSIONS: Our findings establish that the immunostimulatory activity found in mice treated with clove essential oil is due to improvement in humor- and cell-mediated immune response mechanisms.

Principais aspectos do tratamento das infecções no idoso / Specific aspects of infection treatment in elderly patients

Os idosos fazem parte da população que mais consome medicamentos e os antimicrobianos estão entre as classes medicamentosas mais freqüentemente prescritas para estes pacientes. Existem aspectos específicosdo idoso que complicam a prescrição e o monitoramento do uso do antimicrobiano. As modificações fisiológicas decorrentes da idade resultam em alterações na farmacodinâmica e na farmacocinética, que podem alterar o decurso da infecção e a resposta a um determinado antimicrobiano. Em função da alta prevalência de doenças crônicas, os idosos fazem uso simultâneo de muitos medicamentos, o que resulta emmaior risco de reações adversas ou interações medicamentosas. Todos estes aspectos justificam atenção especial na condução do tratamento da infecção no idoso.

Elderly people are great consumers of medicines, and antimicrobial medicines are among those most frequently prescribed to patients. There are specific aspects related to the elderly that make the prescription, use and monitoring of antimicrobials highly complicated. Age-caused physiological changes result in alterations in their pharmacodynamic and pharmacokinetic traits, which may modify the development of the infection and there sponse to certain antimicrobial medicines. Due to the prevalence of chronic diseases, the elderly simultaneously consume many types of medicines, which may be the cause of adverse reactions or drug-drug interactions. Since the aspects mentioned above must be taken into account, special attention in infection treatment of the elderly is justified.

Los ancianos hacen parte de la población que más consume medicamentos, y los antimicrobianos están entrelas clases de medicamentosas más frecuentemente prescritas para estos pacientes. Existen aspectos específicos del anciano que complican la prescripción y el control del uso del antimicrobiano. Las modificaciones fisiológicas decurrentes de la edad resultan en alteraciones en la farmacodinámica y en la farmacocinética, que pueden alterar el decurso de la infección y la respuesta a un determinado antimicrobiano. En función de la gran prevalencia de enfermedades crónicas, los ancianos hacen uso simultáneo de muchos medicamentos, lo que resulta en mayor riego de reacciones adversas o interacciones medicamentosas. Todos estos aspectos justifican atención especial en la conducción del tratamiento de la infección en el anciano.

Anti-inflammatory activity of crude extract and fractions of Nectandra falcifolia leaves.

The present study evaluated the effect of the crude extract of the leaves of Nectandra falcifolia (NEES) Castiglioni and its fractions in different experimental models of inflammation (paw edema, pleurisy, and ear edema). Carrageenan-induced edema of the paw and pleurisy were evaluated in Wistar rats (180-220 g), which were treated with different doses of the total extract (250, 500 mg.kg-1). Edema of the ear, induced by croton oil, and determination of myeloperoxidase activity were evaluated in Swiss mice (25-35 g). In this experiment, the crude extract of Nectandra falcifolia (Nf) (1.25, 2.5, 5.0, 7.5 mg) and the hexane, chloroform, ethyl-acetate and hydromethanol fractions (5.0 mg) were applied topically, immediately after application of the oil. The crude extract of Nf (500 mg.kg-1) significantly reduced edema of the paw compared to the control group. Similarly, at doses of 250 and 500 mg.kg-1 it significantly reduced the volume of pleural inflammatory exudate compared to the control animals. However, it did not change the number of migrated cells. At doses of 2.5, 5.0 and 7.5 mg, the crude extract significantly inhibited edema of the ear and the influx of neutrophils. The fractions from Nectandra falcifolia (hexane, chloroform, ethyl acetate and hydromethanol) also inhibited edema of the ear. Taken together, the results demonstrated that the crude extract and its fractions administered to animals orally or topically showed an anti-inflammatory effect.