Conceptualizing and measuring potentially inappropriate drug therapy.

WHAT IS KNOWN AND OBJECTIVE: Elderly people are the principal consumers of prescription drugs. The more the medication used by the patient, the greater the likelihood there is of the patient being subjected to potentially inappropriate drug therapy (PIDT). PIDT has been measured in the literature with both implicit and explicit tools. The purpose of this review was to assess the use of tools to detect PIDT in various studies and to determine which terms are used to refer to PIDT in practice. METHODS: A systematic review was conducted according to the following steps: the first was identification. In this step, studies were selected from different combinations of the descriptors 'aged', 'elderly', 'inappropriate prescribing' and 'drug utilization' in three different languages, using the Embase, Medline, Scielo, Scopus and Web of Science databases. Second, the papers that satisfied the inclusion criteria for data extraction were carefully examined by three evaluators to determine the tools used and terms that referred to PIDT. RESULTS AND DISCUSSION: From the combinations of keywords, 8610 articles were found. At the end of the selection process, 119 of the articles complied with the specified criteria. The degree of agreement among evaluators was moderate for the study titles (κ1  = 0·479) and substantial for abstracts (κ2  = 0·647). With respect to the PIDT evaluation criteria used by the studies, 27·7% used two criteria. Of the 27 evaluation criteria identified, the Beers criteria were used by 82·3% of the studies. More than 50 different terms to identify PIDT were found in the literature. WHAT IS NEW AND CONCLUSION: This review is the first study to conceptualize and discuss terms that refer to PIDT. At present, there is no consensus regarding terms used to refer to PIDT, with over 50 different terms currently in use. This review shows an increase in the number of articles aimed at evaluating PIDT using implicit and explicit tools.

Evaluation of the analgesic and anti-inflammatory effects of the essential oil of Lippia gracilis leaves.

AIM OF THE STUDY: The aim of the present study is to investigate the antinociceptive, anti-inflammatory, and antioxidant activities of essential oil (EO) of Lippia gracilis Schauer (Verbenaceae) leaves to support the medicinal uses claimed by folklore practitioners in the caatinga region (semi-arid) of Northeastern Brazil. MATERIALS AND METHODS: The chemical composition and antinociceptive and anti-inflammatory activities of the EO of Lippia gracilis leaves (50-200 mg/kg) were investigated. Antinociceptive activity of the EO was evaluated by writhing test. Anti-inflammatory activity of the EO was evaluated using paw oedema and peritonitis methods. RESULTS: Oral treatment with the EO of Lippia gracilis leaves elicited inhibitory activity on acetic acid effect at 50, 100, and 200 mg/kg (30.33+/-2.36, 25.20+/-1.48, and 21.00+/-1.54 abdominal writhes, respectively, P<0.05), as compared with the control group (36.73+/-1.92 writhes). The compound acetylsalicylic acid (ASA, 300 mg/kg) inhibited the acetic acid-induced writhing (12.67+/-0.50 abdominal writhes, P<0.001). Carrageenan-induced oedema formation was reduced with the EO of Lippia gracilis leaves at 200 mg/kg (0.72+/-0.06 mL h, P<0.001) and by the reference compound ASA (300 mg/kg, 0.85+/-0.04 mL h, P<0.001), as compared with the control group (1.76+/-0.06 mL h). Leukocyte migration into the peritoneal cavity induced by carrageenan was reduced with the EO of Lippia gracilis leaves at 50, 100, and 200 mg/kg (13.81+/-0.61, 11.77+/-0.91, and 10.30+/-0.60 leukocytes x 10(6)/mL, respectively, P<0.01), and by the compound dexamethasone (2 mg/kg, 5.34+/-0.33 leukocytes x 10(6)/mL, P<0.001), as compared with the control group (16.71+/-0.54 leukocytes x 10(6)/mL). The analyses of the essential oil allowed the identification of Lippia gracilis as a thymol-p-cymene chemotype (32.68% and 17.82%, respectively). CONCLUSIONS: The EO of Lippia gracilis leaves shows antinociceptive and anti-inflammatory activities.

Phythochemical screening and anticonvulsant activity of Cymbopogon winterianus Jowitt (Poaceae) leaf essential oil in rodents.

Cymbopogon winterianus (Poaceae) is used for its analgesic, anxiolytic and anticonvulsant properties in Brazilian folk medicine. This report aimed to perform phythochemical screening and to investigate the possible anticonvulsant effects of the essential oil (EO) from fresh leaves of C. winterianus in different models of epilepsy. The phytochemical analysis of EO showed presence of geraniol (40.06%), citronellal (27.44%) and citronellol (10.45%) as the main compounds. A behavioral screening demonstrated that EO (100, 200 and 400mg/kg; ip) caused depressant activity on CNS. When administered concurrently, EO (200 and 400mg/kg, ip) significantly reduced the number of animals that exhibited PTZ- and PIC-induced seizures in 50% of the experimental animals (p<0.05). Additionally, EO (100, 200 and 400mg/kg, ip) significantly increased (p<0.05) the latencies of clonic seizures induced by STR. Our results demonstrated a possible activity anticonvulsant of the EO.

Cardiovascular effects of Hyptis fruticosa essential oil in rats.

In non-anesthetized normotensive rats, Hyptis fruticosa essential oil (HFEO, 5, 10, 20 and 40 mg/kg; i.v.) induced hypotension associated with tachycardia. In intact and isolated rings of rat superior mesenteric artery (control), HFEO (1-1000 microg/ml, n=6, cumulatively) induced concentration-dependent relaxations of tonus induced by 10 microM phenylephrine (Phe) (pD(2)=2.6+/-0.27; E(max)=64+/-8.3%). In denuded endothelium pre-contracted rings with Phe or K(+)-depolarizing solution (80 mM), the concentration-response curves to HFEO were not shifted (pD(2)=2.3+/-0.25 and 2.3+/-0.28, respectively), but their maximal responses were significantly (P<0.05 vs control) increased (E(max)=122.3+/-18.2% and 92+/-3.6%, respectively). HFEO was also capable of antagonizing the concentration-response curves to CaCl(2) (3 microM-30 mM) in a dose-dependent manner.

Morphological, agronomical and pharmacological characterization of Hyptis pectinata (L.) Poit germplasm

Several species of the genus Hyptis have presented medicinal characteristics and are frequently indicated to treat gastro intestinal infections, gramps and pain, as well as for skin infections. Three harvests were carried out using six H. pectinata accessions, and the following characteristics were evaluated: plant height, canopy diameter, leave length (L) and width (W), L/W relation and dry weight of leaves and stem. The accession SAM006 have presented highest leave dry matter yield when the three harvests were summed. The aqueous leaf extracts of the same six H. pectinata accessions were tested for anti-edematogenic effect using the carrageenin-induced rat paw edema at doses of 200, 400 and 600 mg/kg. The extracts administered orally had a significant anti-edematogenic effect. The dose of 200 mg/kg of accessions SAM004 and SAM005 had a stronger effect reducing the edema by 19.6 percent and 15.4 percent, respectively. Similar results were obtained using higher dosages of the aqueous extract of the accessions SAM002, SAM003 and SAM006. It can be concluded that the accessions SAM004, SAM005 and SAM006 are promising genotypes for a plant breeding program that aims the development of a cultivar with highest leave yielding and anti-edematogenic effect.

Antinociceptive and antiedematogenic properties and acute toxicity of Tabebuia avellanedae Lor. ex Griseb. inner bark aqueous extract.

BACKGROUND: Tabebuia avellanedae is a tree from the Bignoniaceae family. Commonly know as "pau d'arco" in Brazil, its inner bark is used as analgesic, anti-inflammatory, antineoplasic and diuretic at the Brazilian northeast. A validation of the plant usage has not been previously performed. RESULTS: Antinociceptive and antiedematogenic effects of Tabebuia avellanedae Lor. ex Griseb. inner bark were measured by nociceptive experimental models in mice. A rat paw edema test induced by carrageenan (1%) was also performed in rats to access the plant's antiedematogenic effect. The inner bark aqueous extract, administered via oral in three different concentration, namely 100, 200 and 400 mg/Kg, reduced the nociception produced by acetic acid (0.6% in water, i.p.) by 49.9%, 63.7% and 43.8%, respectively. The aqueous extract (200 and 400 mg/Kg, p.o.) reduced formalin (1%) effects only at the second phase of the experiment by 49.3% and 53.7%, respectively. Naloxone (5 mg/Kg, i.p.) was not able to revert the extract effect, however caffeine (10 mg/Kg, i.p.) reverted its effect by 19.8% at the second phase of the formalin test. The aqueous extract (200 mg/Kg, p.o.) inhibited edema by 12.9% when we used the rat paw edema model. The acute toxicity was low in mice. CONCLUSION: The T. avellanedae inner bark aqueous extract presented antinociceptive and antiedematogenic activities at the used models, with a possible antinociceptive effect associated to the adenosine system.

Differential effects of lead and zinc on inhibitory avoidance learning in mice

We studied the effects of chronic intoxication with the heavy metals lead (Pb2+) and zinc (Zn2+) on memory formation in mice. Animals were intoxicated through drinking water during the pre- and postnatal periods and then tested in the step-through inhibitory avoidance memory task. Chronic postnatal intoxication with Pb2+ did not change the step-through latency values recorded during the 4 weeks of the test (ANOVA, P>0.05). In contrast, mice intoxicated during the prenatal period showed significantly reduced latency values when compared to the control group (day 1: q = 4.62, P<0.05; day 7: q = 4.42, P<0.05; day 14: q = 5.65, P<0.05; day 21: q = 3.96, P<0.05, and day 28: q = 6.09, P<0.05). Although chronic postnatal intoxication with Zn2+ did not alter a memory retention test performed 24 h after training, we noticed a gradual decrease in latency at subsequent 4-week intervals (F = 3.07, P<0.05), an effect that was not observed in the control or in the Pb2+-treated groups. These results suggest an impairment of memory formation by Pb2+ when the animals are exposed during the critical period of neurogenesis, while Zn2+ appears to facilitate learning extinction

Efeitos do extrato aquoso da hyptis pectinata sobre a regeneraçäo hepática após hepatectomia parcial de 70 por cento: resultados preliminares / Effects of the aqueous extract of hyptis pectinata on liver regeneration after 70 percent partial hepatectomy: preliminary results

O uso de plantas medicinais tem aumentado bastante na populaçäo mundial. O objetivo desta pesquisa é avaliar os efeitos do extrato aquoso das folhas da Hyptis pectinata, popularmente conhecida como "sambacaitá" ou "canudinho", sobre a regeneraçäo hepática após hepatectomia parcial de 70 por cento. Foram utilizados 24 ratos, divididos em 4 grupos: grupo OS, em que se realizou operaçäo simulada e aplicaçäo oral de água destilada por 4 dias; grupo OSD200, também submetido à laparotomia com manipulaçäo do fígado e aplicaçäo de 200 mg de extrato/Kg de animal durante o mesmo período; grupo HP, hepatectomizado a 70 por cento após 4 dias de aplicaçäo por via oral de água destilada; e grupo HPD200, hepatectomizado a 70 por cento após 4 dias de administraçäo de 200 mg extrato/Kg de animal. Foram dosadas fosfatase alcalina, bilirrubina total e as aminotransferases e estudou-se o estado III da funçäo mitocondrial. O grupo OSD200, quando comparado ao OS, apresentou reduçäo significativa da fosfatase alcalina. O grupo HPD200, em comparaçäo ao HP, teve reduçäo estatisticamente significativa no nível da AST e do estado III da funçäo mitocondrial.

Evidence for the involvement of nitric oxide in the electrically induced relaxations of human lower esophageal sphincter and distal pylorus

The aim of the present study was to investigate in vitro the effect of Ng-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, on neurogenic relaxation of human lower esophageal sphincter (LES) and distal pylorus (DP) circular muscle strips induced by electr4ical field stimulation (EFS). Muscle strips obtained from 5 patients who underwent total gastrectomy were suspended in 10-ml organ baths containing Krebs solution for recording isometric tension. L-NAME(30 uM) reduced the amplitude of the EFS-induced relaxation by 85 ñ 9% (N=3) in the LES and by 52 ñ 16% (N=3) in the DP but did not affect sodium nitroprusside-induced relaxation. L-Arginine (300 uM) partially reversed the L-NAME inhibition in the LES and totally in the DP. These findings suggest a role for L-arginine-derived NO in the nerve-mediated NANC relaxation of the human LES and DP