Band 26, Heft 4

Background : Levofloxacin, an optically active isomer of ofloxacin, exerts broad spectrum antibacterial activity. Apart from its antibacterial action, experimental studies have documented antinociceptive properties in animal pain models suggesting an analgesic effect. This study was conducted with the aim to evaluate the analgesic activity of levofloxacin in healthy human volunteers. Methods : This was an open label, prospective, non-randomized, interventional study conducted on 12 apparently healthy volunteers at a tertiary care teaching hospital in India. Permission from the Institutional Ethics Committee was obtained. After obtaining informed consent, volunteers fulfilling the inclusion criteria were enrolled. Analgesic activity was assessed by Cola cap and sphygmomanometer, a human experimental pain model. Observation of pain threshold and tolerance was recorded at baseline and at an interval of 2 h and 4 h after administration of levofloxacin (500 mg oral) in all 12 subjects. The results were analysed using repeated measures one way analysis of variance. Results : The mean age of the volunteers was 27.5±3.26 years. A statistically significant increase in the pain threshold and tolerance was found at 2 h and 4 h when compared to baseline. Conclusions : Levofloxacin exhibited significant analgesic activity in a human pain model and can be used in infections associated with pain or for pre-operative prophylaxis. Further investigations are required to understand the precise mechanism and pathway of antinociception exhibited by levofloxacin.

Background: The appropriateness of spirometric reference value depends on all its features matching those of the person being assessed, like ethnicity, environment, nutrition, absence of disease, measurement protocol, as well as equipment used. The present study determines the lung function parameters in normal young healthy Indians and derives reliable prediction formulae for Indian population. Methods: Computerized spirometry was done in 298 nonsmoking medical students of both genders studying in MKCG Medical College, Berhampur. All the data were statistically analyzed, and prediction equations for the young Indian population were derived. Results: All the lung parameters showed significant gender difference. Height showed the greatest effect on the predicted value of FEV 1 and FVC in males and females. Height has the greatest effect on the predicted value of FEV 1 % in females, whereas weight has the least effect. We formulated univariate and multivariate regression models for prediction of lung parameters in the young Indian adults. The predicted values of pulmonary function parameters for men were 4%–17% higher than most studies, except for Kashmiri population where it was 9% lower. For females, lung parameters were 1%–29% higher in comparison to study groups in other Indian studies. The lung parameters for males were found to be lower than Iranian and Caucasian population study, but higher than Pakistani population. For females, lung parameters were 3%–8% lower than Iranian and Caucasian population, but higher in comparison to Pakistani population. Conclusions: The computed regression norms may be used to predict the spirometric values in young Indian population of similar age group as the study population.

Background: The study was designed to evaluate the anti-inflammatory, analgesic and antioxidant properties of Andrographis paniculata leaf extracts in laboratory animals. Methods: The dried and powdered leaves of the plant were subjected to phytochemical and proximate analyses. Its mineral content was also determined. Acute toxicity experiments were first performed to determine a safe dose level. The plant material was extracted using water and ethanol as solvents. These extracts were then used to test for the anti-inflammatory, analgesic and antioxidant properties of the plant. The anti-inflammatory tests included carrageenan-induced and histamine-induced paw oedema. The analgesic tests conducted were formalin paw lick test and acetic acid writhing test. The antioxidant activities of the extracts of A. paniculata were determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), total polyphenol (TP) and 2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) using ascorbic acid as standard for both DPPH and FRAP, and gallic acid as a standard for both TP and ABTS. Results: The acute toxicity experiment demonstrated that the plant is safe at high doses even at 1600 mg/kg. It was observed that the ethanolic extract of A. paniculata had higher antioxidant activity than the aqueous extract. The experiments using both extracts may suggest that the extracts of A. paniculata leaves possess anti-inflammatory, analgesic and antioxidant properties, although the ethanolic extract seemed to have higher biological properties than the aqueous extract. Conclusions: The results from this study may have justified the plant’s folkloric use for medicinal purpose.

Background: Preclinical and clinical studies suggest the use of antioxidants as an effective measure to reduce the progression of oxidative-stress-related disorders. Nuclear factor E2-related factor 2 (Nrf2) is a key component to cellular redox homeostasis in the attenuation of oxidative-stress-associated pathological processes. The objective of the current study was to evaluate the role of geraniol (GOH) in preserving the plasma lipid status, endothelial function, antioxidant status, and inhibition of lipid peroxidation (LPO) in hamsters fed an atherogenic diet (AD). Methods: Male Syrian hamsters were randomly grouped into four groups: group 1 was control animals; group 2 was animals fed GOH alone (100 mg/kg bw po); group 3 was animals fed AD (standard pellet diet+10% coconut oil+0.25% cholesterol+0.25% cholic acid); and group 4 was fed AD+GOH (100 mg/kg bw) for 12 weeks. At the end of the feeding period, the animals were sacrificed and the liver, heart, and aorta from each group were analyzed for antioxidants, LPO markers, and histological changes. Results: AD feeding induced a significant change in lipid profile, endothelial function marker, activities of the antioxidant enzymes, alterations in the LPO markers, Nrf2 expression, and equally significant changes in the organ histology. Conclusions: Supplementation with GOH appreciably prevented the alterations induced by the AD on all the above parameters. Thus, GOH offers marked protection against AD-induced abnormalities.

Background: Despite growing claims of functional health benefits in folkloric medicine, the safety of chronic/elevated intakes of onion and garlic cannot be assumed. Therefore, this study assesses oral administration of varied doses of onion and garlic on some biomarkers of hepatic and renal functions in rats. Methods: Animals were divided into five groups: control group received vehicle and extract-treated groups received varied doses of onion or garlic extract (0.5 mL and 1.0 mL/100 g bwt/day) for 6 weeks. Results: Both doses of onion caused marked (p<0.05) increase in hepatic and renal levels of glutathione (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and marked (p<0.05) decrease in malondialdehyde (MDA). Treatment with low dose of garlic elicited similar trend except in hepatic CAT, renal SOD and GST levels. A high dose of garlic only caused marked (p<0.05) increase in hepatic GST, renal GST, and SOD. Both doses of onion and low dose of garlic significantly (p<0.05) enhanced renal Na + /K + -ATPase activity. Only a high dose of onion caused significant (p<0.05) increase in hepatic aspartate transaminase (AST), alkaline phosphatase (ALP), and decrease in plasma AST activities. Conclusions: These findings suggest antioxidant enhancing capability for both doses of onion and low dose of garlic, while high dose of garlic elicited pro-oxidant conditions.

Background : Silver nanoparticles (AgNPs) are increasingly and extensively being applied for biomedical purposes. However, studies on the safety/toxicity profiles of AgNPs are limited. This necessitates the further studies in this direction. Here, we studied the effect of AgNP administration on rat serum metabolites and tissue morphology. Methods : Rats were randomly distributed into eight groups of five animals each. Oral administration of AgNPs to rats at 100, 1000, and 5000 mg/kg was done daily and carried out for 7, 14, and 21 days alternately. The control received distilled water. Animals were sacrificed under diethyl ether anesthesia 24 h after cessation of last treatments. The blood and vital organs were harvested and prepared for biochemical and histopathology examinations, respectively. Results : Data revealed that AgNP administration at the different dosages caused elevated serum urea and creatinine levels. On the other hand, levels of inorganic phosphate in rat serum following administration of AgNPs were significantly (p<0.05) reduced. Also, administration at 1000 and 5000 mg/kg AgNPs in rats decreased serum levels of sodium. In contrast, AgNP administration in rats caused elevated (p<0.05) serum potassium levels. The histopathological presentations show diverse inimical alterations to cellular architecture in rats administered with AgNPs. Conclusions : We show evidence suggesting that AgNPs may have potential to adversely affect the kidney functions as well as capability to cause myriad of cellular damage.

Background: This study was designed to provide information about the antipyretic and anti-inflammatory effects of Corchorus olitorius root. Methods: Thirty male Wistar rats were divided into six groups of five animals each; the control and reference groups were administered normal saline (10 mL/kg) and indomethacin (5 mg/kg), respectively, whereas the remaining four groups were administered aqueous extract of C. olitorius at doses of 25, 50, 100, or 200 mg/kg, respectively. Pyrexia was induced by injecting 10 mL/kg of 20% (w/v) brewer’s yeast suspension into the dorsum of rats, whereas inflammation was induced through an injection of 0.1% carrageenan into the right hind paw of each rat and through a subcutaneous implantation of a 30-g sterilized cotton pellet into the groin of each rat. Results: The results showed that C. olitorius root extract (p<0.05) decreased the elevated temperature after brewer’s yeast injection compared with the 17 h (pre-drug) temperature. In the inflammatory tests, the paw sizes and granuloma weights in the test groups were significantly (p<0.05) decreased compared with the control group. Conclusions: Corchorus olitorius root is another good source of phytomedicine that can be used effectively to treat inflammation and pyrexia that accompany some diseases.

Background: The importance of inflammatory diseases and side effects of conventional drugs necessitate the finding of new anti-inflammatory agents from natural sources. In this study, for the first time, the anti-inflammatory and analgesic effects of the aqueous extract of Astragalus arbusculinus gum were evaluated in animal models. Methods: Thirty-five male Wistar rats were divided into five groups and pretreated with different doses of A. arbusculinus gum extract before the injection of formalin. Paw edema was measured by a plethysmometer at time 0 and after 8 days and compared to controls. The analgesic effect of the extract was evaluated using the hot-plate test in 42 male albino mice. Results: The extract of A. arbusculinus gum decreased the rat paw edema in a dose-dependent manner. The effect on inflammation of the highest dose of extract was comparable to sodium salicylate. Astragalus arbusculinus gum extract at doses of 300 and 1000 mg/kg showed analgesic effects comparable to sodium salicylate and morphine, respectively. A preliminary phytochemical study and the determination of the total phenolic content of the gum extract were performed for the first time. Conclusions: The aqueous extract of A. arbusculinus gum reduced the inflammation and pain in a dose-dependent manner and is a good candidate for further studies of safety and efficacy. The clarification of active components of the plant is necessary.

Background: The attendant side effects associated with some synthetic drugs used in the management of diseases have led to the search for safer alternative therapies that are relatively cheaper with minimal side effects. Methods: The methanol extract of Calliandra portoricensis root bark (CPRB) was orally administered at the doses of 5, 10, 20, and 25 mg/kg body weight for 14 consecutive days of 5 rats in each group. The control rats were given distilled water. Results: The 95% methanol extract of CPRB significantly (p<0.05) scavenged NO • and OH • radicals compared to vitamin C. The level of lipid peroxidative products (malondialdehyde, MDA) was significantly (p<0.05) attenuated in a dose-dependent manner. Antioxidant enzymes including superoxide dismutase and catalase were significantly (p<0.05) exercabated in both liver and kidney in a dose-dependent manner. Furthermore, serum AST, alanine aminotransaminase and γ-glutamyltransferase (GGT) activity depicted non-significant (p>0.05) increase in the treated animals. The histological examination showed mild vacuolar, portal congestion and cell infiltration by mononuclear of the hepatic tissues. Conclusions: The study then concluded that a therapeutic dose of the methanol extract of CPRB triggered the antioxidant defence systems in male rats. It is, therefore, recommended that the doses should be carefully and clinically chosen because higher doses may cause some health risks.

Background : The hydro-ethanolic extract of Synedrella nodiflora (L.) Gaertn whole plant has demonstrated analgesic effects in acute pain models. The extract has also demonstrated anticonvulsant effects in murine models of experimental epilepsy. The present study illustrates an evaluation of the hydro-ethanolic extract of the plant for possible analgesic properties in hyperalgesia and allodynia associated with vincristine-induced neuropathy in rats. Methods : Neuropathic pain was induced in Sprague-Dawley rats by injecting 100 μg/kg of vincristine sulphate on alternative days for 6 days (days 0, 2, 4, 8, 10 and 12). Vincristine-induced cold allodynia, mechanical hyperalgesia and thermal hyperalgesia were measured pre-vincristine administration and on days 15, 17 and 19 post-vincristine administration. The rats were then treated with S. nodiflora extract (SNE) (100, 300 and 1000 mg/kg), pregabalin (10, 30 and 100 mg/kg) and distilled water as vehicle daily for 5 days and pain thresholds were measured on alternate days for 3 days. Results: SNE and pregabalin produced analgesic properties observed as increased paw withdrawal latencies to mechanical, tactile, cold water stimuli and thermal hyperalgesic tests during the 5 days of treatment. Conclusions : The findings suggest that hydro-ethanolic extract of S. nodiflora possesses anti-hyperalgesic and anti-allodynic effects in vincristine-induced neuropathic pain in rats.

Background: Diplazium esculentum is the most commonly consumed edible fern throughout Asia and Oceania. Several studies have been performed so far to determine different functional properties of this plant, but there have been no reports on the anticholinesterase and nicotinamide adenine dinucleotide (NADH) oxidase inhibitory activities of this plant. Therefore, the present study was conducted to determine the anticholinesterase and NADH oxidase inhibitory activities of 70% methanolic extract of D. esculentum . Methods: The D. esculentum extract was investigated for its acetylcholinesterase and NADH oxidase inhibitory activities as well as its free radical scavenging and total antioxidant activities in the linoleic acid system. The free radical scavenging activity of the extract was determined by the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) method. The total antioxidant activity of the extract was evaluated by ferric thiocyanate (FTC) and thiobarbituric acid (TBA) methods. Results: The D. esculentum extract inhibited acetylcholinesterase and NADH oxidase in a dose-dependent manner, with IC 50 values of 272.97±19.38 and 265.81±21.20 μg/mL, respectively. The extract also showed a potent DPPH radical scavenging activity with an IC 50 value of 402.88±12.70 μg/mL. Moreover, the extract showed 27.41% and 33.22% of total antioxidant activities determined by FTC and TBA methods, respectively. Conclusions: Results indicated that 70% methanolic extract of D. esculentum effectively inhibited the enzymes acetylcholinesterase and NADH oxidase and acted as a potent antioxidant and free radical scavenger. These in vitro assays indicate that this plant extract is a significant source of natural antioxidants, which may be helpful in preventing the progression of various neurodegenerative disorders associated with oxidative stress.

Background: The aim of the study was to identify and evaluate potentially inappropriate medication (PIM) in geriatric patients using Beers criteria and also to identify adverse drug events (ADEs) due to PIMs and various drug-drug interactions. Methods: The medications in the prescriptions of patients above 60 years of age, their dosage regimen respective of their diagnosis were analyzed. Each medication was then checked with Beers list tables, and any medication if mentioned in the Beers list, was noted along with its strength of recommendation and quality of evidence. Any adverse drug event (ADE) due to PIM was identified. Causality of the events was assessed by Naranjo’s Scale. The number of drug-drug interactions per prescription and the severity of each interaction were also analyzed. The collected data from 200 subjects were subjected to statistical treatments using Statistical Package for Social Sciences (SPSS) software version 16.0 for WINDOWS. Results: Based on the Beers criteria 2012, 106 out of 200 (53%) prescriptions had at least one PIM prescribed. A sum of 1690 medications was prescribed as a whole for the entire study subjects. Among which, 134 PIMs were identified. Most commonly prescribed PIMs were benzodiazepines (39, 19.5%), followed by sliding scale use of insulin (31, 15.5%), and prazosin at a rate of 11.5% (23). A total of 10 ADEs were identified during the study. The average number of drug interactions observed among total samples was found to be 3.0±6.0 with 0±5.0 serious interactions, 2±4.0 significant interactions requiring close monitoring, and 0±6.0 minor interactions. Conclusions: The study shows high prevalence of prescribing PIMs in hospitalized elderly patients; PIM also caused incidence of ADEs; and serious drug-drug interactions were scarce among the patients.

Background: Nerve growth factor (NGF) mediates a wide range of activities in the central nervous system including neuronal differentiation, synaptic plasticity, and neuroprotection. In addition, NGF places an important role in skeletal muscle physiology by some unknown mechanisms. We recently demonstrated that NGF conferred myoprotection toward ischemia in C2C12 skeletal muscle cell model, establishing an important trophic role for NGF in skeletal muscle. Methods: In this report, using ELISA and oxygen-glucose deprivation (OGD) assays, we investigated the potential contribution of prostaglandin E 2 (PGE 2 ) to NGF myoprotective effects toward C2C12 cultures exposed to OGD insults. Vipera lebetina obtusa disintegrin 5 (VLO5), a selective antagonist of α9β1 integrin, was used as an experimental tool to clarify α9β1 integrin role in NGF action. Results: NGF-induced mitogen-activated protein kinase type 1 or 2 (ERK1/2) phosphorylation in C2C12 cells and in a dose-response fashion stimulated PGE 2 release, both effects antagonized by VLO5 and PD98059. NGF-induced myoprotection of the cells exposed for 7 h to OGD, followed by 18 h of reoxygenation, was reversed by VLO5 treatment. Conclusions: These results suggest that NGF activation of α9β1 integrin induced myoprotection by stimulation of ERK phosphorylation and release of cytoprotective PGE 2 mediator. This effect may be also relevant for NGF-induced pain and hyperalgesia in the skeletal muscle.