Difference of cardiac rehabilitation in the morning or evening on indexes of left ventricular and N-terminal pro-brain natriuretic peptide: a randomized controlled trial.

The present study aimed to evaluate the effects a cardiac rehabilitation program (CRP) performed in the morning or evening on left ventricular (LV) filling indices and the level of N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in patients undergoing percutaneous coronary angioplasty during the COVID-19 pandemic. Methods: This was a randomized controlled single-blinded clinical trial. Ninety-six patients (mean age: 50.2 ± 8.1 years, 36 women and 44 men) with percutaneous coronary angioplasty were divided into two groups of intervention and control. In each group, the CRP was performed in either morning or evening. The CRP included walking and performing push-ups and sit-ups for 8 weeks. The participants of the control groups received routine care. The functional indices of LV, including LV ejection fraction, systolic function, and diastolic function (i.e. the transmitral flow), the E/e' to left atrium peak strain ratio (as an estimation for LA stiffness), and NT-proBNP level were measured in all participants before starting and at the end of the CRP. Results: In the intervention group, the individuals performing the CRP in the evening had significantly higher E-wave (0.76±0.02 vs. 0.75±0.03; P=0.008), ejection fraction (52.5±5.64 vs. 55.5±3.59; P=0.011), and diastolic function velocity (E/A ratio, 1.03±0.06 vs. 1.05±0.03; P=0.014) and significantly lower A-wave (0.72±0.02 vs. 0.71±0.01; P=0.041), E/e' ratio (6.74±0.29 vs. 6.51±0.38; P=0.038), and NT-proBNP level (2007.9±214.24 vs. 1933.9±253.13; P=0.045) compared with those performing the program in the morning. Conclusions: A supervised CRP performed in the evening compared with morning was more effective in improving LV functional indices. Therefore, such home-based interventions are recommended to be performed in the evening during the COVID-19 pandemic.

Comparing the effect of body wash with marshmallow plant and lukewarm water on reducing the temperature of febrile children: a randomized clinical trial.

BACKGROUND: Fever is the most common reason for children's visits to medical centers. Its management is an essential duty of a pediatric nurse. The aim of this study was to determine the effect of body wash with Marshmallow plant on children's fever. METHODS: This parallel clinical trial was performed on 92 children aged 6 months to 10 years with a tympanic temperature above 38.3 °C. Participants were randomly assigned to groups. Simultaneously with receiving acetaminophen, body wash was performed in the control group with lukewarm water and in the intervention group with white Marshmallow extract. The children's temperature; from the beginning of the study was checked and recorded every 15 min in the first hour and in the 4th and 6th hours. The time duration to resolve fever, the frequency of afebrile children at different times of the study, and the value of temperature reduction were primary outcomes. Heart rate, the need to administer the next dose of acetaminophen, and the time of fever recurrence were recorded as secondary outcomes. RESULTS: The mean time duration to resolve fever in the intervention group was shorter than in the control group (B = 8.181, 95% CI 3.778-12.584, p < 0.001). The frequency of the children without fever was higher in the intervention group during different times of the study (p < 0.001). The mean value of temperature reduction in the intervention group was higher than the control group (B = -0.27 °C, 95% CI: -0.347 to -0.193, P < 0.001), although, after adjusting the effect of confounding variables it was not significant (P = 0.127). The mean of adjusted heart rate change (p = 0.771), the time of fever recurrence (P = 0.397), and the frequency of children requiring the next dose of acetaminophen (p = 0.397) did not show a significant difference between the groups. CONCLUSION: Body wash with Marshmallow extract reduced children's fever in a shorter period of time and to some extent a greater extent than the control group without side effects. Therefore, it can be used as an effective and safe complementary method to help reduce fever. However, more studies are necessary for this field. TRIAL REGISTRATION: Registration in Iranian Clinical Trials (RCTs) on 31.08.2020 with registration code: IRCT20200809048345N1.

The efficacy of olive leaf extract on healing herpes simplex virus labialis: A randomized double-blind study.

OBJECTIVE: Herpes simplex virus (HSV), as a common infection in healthy individuals, is treated symptomatically, but drug resistance and the side effects of drugs have drawn the attention of researchers to complementary medicine. Olive Leaf Extract (OLE) has antiviral effects that may treat HSV. The current study aimed to compare the clinical effects of OLE and Acyclovir on HSV-1. METHODS: This randomized double-blind clinical trial was conducted on 66 patients who had already been diagnosed with HSV-1. The participants were randomized into two groups, receiving 2% OLE cream or 5% acyclovir cream five times a day for six days. The symptoms were evaluated before, and three and six days after the interventions. Data were analyzed using the SPSS software through the Kolmogorov-Smirnov test, chi-squared, t-test, and repeated measures ANOVA. RESULTS: The results showed clinical symptoms decreased in both groups during the study and both medications were effective in the treatment of HSV-1. However, the OLE group experienced less bleeding (P = 0.038), itching (P = 0.002), and pain (P = 0.001) on the third day as well as less irritation (P = 0.012), itching (P = 0.003) and color change (P = 0.001) on the sixth day compared to the acyclovir group. The treatment course for participants in the OLE group was shorter than in the acyclovir group (P = 0.001). CONCLUSION: The evidence from these trials suggests the OLE cream is superior in the healing of episodes of HSV-1 over the acyclovir cream. Future studies are recommended to investigate if OLE could be an adjunct to acyclovir treatment.

Pixel Selection by Successive Projections Algorithm Method in Multivariate Image Analysis for a QSAR Study of Antimicrobial Activity for Cephalosporins and Design New Cephalosporins.

Thirty-one Cephalosporin compounds were modeled using the multivariate image analysis and applied to the quantitative structure activity relationship (MIA-QSAR) approach. The acid dissociation constants (pKa) of cephalosporins play a fundamental role in the mechanism of activity of cephalosporins. The antimicrobial activity of cephalosporins was related to their first pKa by different models. Bidimensional molecular structures (images) were used to calculate some pixel descriptors. The selection of pixels by successive projections algorithm (SPA) was done to achieve simple MIA-QSAR models; based on a small subset of pixels. In the present study, the performance of pixel selection technique using SPA for partial least squares (PLS) model was evaluated. The obtained model showed nice prediction ability with root mean square error of prediction (RMSEP) values of 0.402, 0.315, and 0.160 for principal component regression (PCR), PLS and SPA-PLS models respectively. Among the three methods, SPA-PLS was potentially useful in predicting the pKa of cephalosporins. The study showed the maximum structural efficacy is on pKa in a, b and c regions.

Effects of oleuropein on pentylenetetrazol-induced seizures in mice: involvement of opioidergic and nitrergic systems.

Oleuropein, a well-known olive polyphenol, has been shown to mediate neuroprotection in Alzheimer's disease and cerebral ischemia. We investigated the effects of oleuropein on pentylenetetrazole (PTZ)-induced seizures in male NMRI mice, with diazepam as the standard drug. We also examined the possible involvement of opioidergic/nitrergic pathways in the probable effects of oleuropein. Intraperitoneal (i.p.) administration of different doses of oleuropein (10, 20 and 30 mg/kg) significantly increased the seizure threshold 60 min prior to induction of seizure, in a dose-dependent manner. Administration of naltrexone (10 mg/kg, i.p.), an opioid receptor antagonist, completely reversed the anticonvulsant effects of oleuropein (10 mg/kg). On the other hand, the anticonvulsant effect of oleuropein (10 mg/kg) was blocked by a non-effective dose of nonspecific inhibitor of nitric oxide synthase (NOS), L-NAME (1 and 10 mg/kg, i.p) and a selective inhibitor of neuronal NOS, 7-nitroindazole (30 mg/kg, i.p.). However, the nitric oxide precursor, L-arginine (30 and 60 mg/kg, i.p.) potentiated the anticonvulsant activity of oleuropein (10 mg/kg). A selective inducible NOS inhibitor, aminoguanidine (100 mg/kg, i.p.) did not change the anticonvulsant activity of oleuropein. It seems that the opioidergic system and constitutive neuronal NOS may be involved in the anticonvulsant properties of oleuropein.

Antileishmanial, antioxidant, and cytotoxic activities of Quercus infectoria Olivier extract.

Currently, there is no effective vaccine available, and chemotherapy is the main approach for treatment of cutaneous leishmaniasis (CL). During recent decades, studies have demonstrated that a number of plant-derived compounds may act as new therapeutic tools against leishmaniasis. This study was evaluated the antileishmanial, antioxidant, and cytotoxic activities of Quercus infectoria Olivier (oak) extract. The total amount of phenolic and flavonoid compounds was measured in oak extract. High performance liquid chromatography (HPLC) analysis was also performed to determine the amount of quercetin and gallic acid in this plant. This extract (0-80g/mL) was evaluated in vitro against promastigote and intracellular amastigote forms of Leishmania major (MRHO/IR/75/ER) using MTT assay and in a macro-phage model, respectively. Then oak extract was tested on CL in infected male BALB/c mice with L. major in order to evaluate the antileishmanial activity topically. Moreover, cytotoxicity effects of oak in murine macrophage cells were tested by MTT assay. Antioxidative activity of oak was also determined by the 2,2-diphenyl-1,1-picrylhydrazyl (DPPH) scavenging test. The amount of phenolic and flavonoid compounds in the oak extract was 57.50 and 1.86%, respectively. The amount of quercetin and gallic acid in the oak extract was 0.0064 and 0.22%, respectively. The findings revealed that oak significantly (P<0.05) inhibited the growth rate of promastigote of (IC50 12.65µg/mL) and amastigotes (IC50 10.31µg/mL) as a dose-dependent response. In the in vivo assay, after 4 weeks of treatment, 91.6, 66.66, and 50% recovery was observed in the infected mice treated with 20, 10, and 5mg/kg of oak extract, respectively. After treatment of the infected mice with the concentration of 10 and 20mg/kg of oak, the mean diameter of lesions, parasite load and mean number of parasites was significantly (P<0.05) reduced. Selectivity index of greater than 10 for oak revealed that oak extract had no cytotoxic effects on macrophage cells. Moreover, DPPH test demonstrated that radical inhibition occurred at greater power with increasing the concentration of oak. To conclude, the present study showed potent antileishmanial and antioxidant activity of oak extract; whereas this plant had no toxic effect on mammalian cells.

Neuroprotective effects of oleuropein against cognitive dysfunction induced by colchicine in hippocampal CA1 area in rats.

Alzheimer's disease is a progressive neurodegenerative disorder with decline in memory. The role of oxidative stress is well known in the pathogenesis of the disease. The purpose of this study was to evaluate pretreatment effects of oleuropein on oxidative status and cognitive dysfunction induced by colchicine in the hippocampal CA1 area. Male Wistar rats were pretreated orally once daily for 10 days with oleuropein at doses of 10, 15 and 20 mg/kg. Thereafter, colchicine (15 µg/rat) was administered into the CA1 area of the hippocampus to induce cognitive dysfunction. The Morris water maze was used to assess learning and memory. Biochemical parameters such as glutathione peroxidase and catalase activities, nitric oxide and malondialdehyde concentrations were measured to evaluate the antioxidant status in the rat hippocampus. Our results indicated that colchicine significantly impaired spatial memory and induced oxidative stress; in contrast, oleuropein pretreatment significantly improved learning and memory retention, and attenuated the oxidative damage. The results clearly indicate that oleuropein has neuroprotective effects against colchicine-induced cognitive dysfunction and oxidative damage in rats.

Cirrhosis-induced morphological changes in the retina: possible role of endogenous opioid.

AIM: To investigate the impact of cirrhosis on retinal morphology and to evaluate the role of endogenous opioids as a mediator in cirrhosis induced retinal change. METHODS: Thirty-six male rats were divided into 3 main groups; the common bile duct ligated (BDL) group, the sham-operated (Sham) group and the unoperated (Unop) group. Then each of these three main groups was divided into two subgroups; the first subgroup received daily injection of naltrexone hydrochloride (NTX) and the second group was injected with normal saline (Saline) daily. After 28d, rats were anesthetized and their right eyes were enucleated and assessed for histological changes. The thickness of the rod and cons layer, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer and ganglion cell layer for each eye were measured in micrometers by light microscope. RESULTS: Ganglion cell layer showed significant increase in thickness in the BDL group (P<0.05). This increase was eliminated in the group where BDL rats received daily intraperitoneal injection of naltrexone hydrochloride (20 mg/kg). No other histological changes were detected in the other 5 layers we measured. CONCLUSION: The morphological change we detected in the retina of cirrhotic rats is probably due to opioids increased tone in cirrhosis since the increase in thickness in the ganglion cell layer was almost eliminated when naltrexone hydrochloride was injected. These results suggest a possible role for endogenous opioids in the morphological retinal changes detected in cirrhotic rats.

Identifying effective medicinal plants for cold in Lorestan province, West of Iran.

Cold is a kind of mild and self-limiting viral illness that is considered as a prevalent disease with global occurrence and is caused by more than 200 types of viruses. Ethnobotanical studies and the use traditional experiences have increased the probability of detecting effective medicinal substances for cold by 40%. This study aimed to identify effective medicinal plants for cold in Lorestan province. Traditional medical information of this work was obtained from information from indigenous people in 8 cities of Lorestan province. A previously prepared questionnaire was given to trained health liaisons to record the people's beliefs about the plants. The results showed that 23 medicinal plants were used in Lorestan province for treating cold and its symptoms (cough, sore throat, sneezing, runny nose, etc). Plants studied in this article contained bioactive substances that are recommended as the most popular traditional treatments. More research studies should be done on the efficacy and the potential harms of medicinal plants used by people, and in the case of their positive pharmacological impacts, they can be used to produce natural and effective drugs for cold.

A review on most important herbal and synthetic antihelmintic drugs.

Parasites and parasitic diseases are widely spread in the world. Their adverse effects on health and social-economic society cause tremendous public health problems. Parasitic infections in different ways (water, soil, food and vegetables) can affect humans and induce other complications such as gastrointestinal disorders, malnutrition, anemia and allergies and sometimes even life threatening. Medicinal plants are being widely used, either as a single drug or in combination with synthetic drugs. These medicinal plants are considered as a valuable source of unique natural products and drugs for development of medicines against various disorders and diseases. In this article the recently published papers about medicinal plants and parasites were reviewed, using scientific sites such as Medline, PubMed and Google Scholar. The used terms included: herbal medicine, medicinal plants, and antihelmintic drugs, antinematoda, anticestoda, antitrematoda. From the above collected literature it might be concluded that these plants are promising potential sources for preparation of new drugs or for pharmacological and therapeutic applications.

Identification of medicinal plants affecting on headaches and migraines in Lorestan Province, West of Iran.

OBJECTIVE: To identify medicinal plants witch are used for headaches and migraines treatment in Lorestan province of Iran. METHODS: Traditional medical herbs information was acquired from indigenous people with the cooperation of health centers of Doroud, Borujerd, Khorramabad, Aleshtar Poldokhtar, Aligoodarz, Nourabad and Kouhdasht cities. The prepared questionnaires were given to trained health volunteers. They attended in the villages and recorded people beliefs in herbal therapy by the questionnaires. RESULTS: The results of this study showed that people used 15 herbs traditionally to treat headaches. Because of the importance of the medicinal plants in the study area, it is neccessary to determine sociological studies the plenty of plant species. CONCLUSIONS: Because of the widespread use of traditional medicinal plants and high tendency to herbal medicine and traditional medicine, more extensive researches should be designed in several areas of pharmacy and pharmacology of medicinal plants to prepare proper information for pharmaceutical industries.

Chemical composition, antioxidant activity and antibacterial effect of essential oil of the aerial parts of Salvia sclareoides.

OBJECTIVE: To determine the chemical composition, antioxidant activity and antibacterial properties of essential oils of the aerial parts of Salvia sclareoides (S. sclareoides). METHODS: The essential oil of the areal parts of S. sclareoides was obtained by using hydrodistillation method and the composition of the volatile components analyzed by gas chromatography method coupled with mass spectrometry detector. The antimicrobial capacity of the essential oil of S. sclareoides was investigated by microdilution technique. The antioxidant activities were determined employing inhibition of 2,2-diphenyl-1-picrylhydrazyl hydrate radical method. RESULTS: Mass spectra were searched against mass spectrometry databases and sixty components were recognized. Non-terpenoids (41.6%) and sesquiterpenes (39.7%) were determined as the main components of the essential oil. The main identified components were, linalool (27.6%), trans-caryophyllene (16.6%), beta.-trans-ocimene (11.831%), germacrene-D (10%), bicyclogermacrene (3.3%) and caryophyllene oxide (2.8%). Two monoterpens (13.2%) and three oxygenated sesquiterpenes (5.5%) were also obtained from the essential oil of the S. sclareoides CONCLUSIONS: Results indicated that essential oil of S. sclareoides includes rather higher proportions of non-terpenoid and sesquiterpenes compounds with good antioxidant and antibacterial properties.

The plant histaminase: a promising enzyme with antioxidant properties versus histamine release in isoprenaline-induced myocardial infarction in rats.

The present study was designed to evaluate possible protective effects of purified histaminase from Lathyrus sativus L. seedling on the myocardial injuries upon isoprenaline-induced myocardial infarction in rats. In this regard, blood histamine concentration, creatine kinase-MB (CK-MB) activity, antioxidant status, and histopathological changes of the hearts were measured. A total of 40 adult male Sprague-Dawley rats were divided into five equal groups and treated in the following order: control (normal saline), isoprenaline (isoproterenol 110 mg/kg BW), Isopren.-H1 (isoprenaline plus histaminase 80 U/kg BW), Isopren.-H2 (isoprenaline plus histaminase 120 U/kg BW), and Isopren.-H3 (isoprenaline plus histaminase 160 U/kg BW). Myocardial infarction was manifested by a significant elevation in the level of CK-MB and histopathological findings in isoprenaline group when compared to controls. In contrast, histaminase pretreatment at dose of 160 U/kg prevented isoprenaline-induced histamine release and significantly decreased CK-MB activity as well as histopathological changes in Isopren.-H3 group. A significant increase in the catalase (CAT) and superoxide dismutase (SOD) activities was also observed by histaminase treatment in Isopren.-H2 and Isopren.-H3 groups. Although the activity of glutathione peroxidase (GPx) increased significantly to suppress oxidative stress in isoprenaline group, it was not able to prevent lipid peroxidation (as shown by TBARS concentration) in the heart of rats. In conclusion, the plant-originated histaminase presented as a promising enzyme with antioxidant properties against histamine release and myocardial infarction in rats, and it seems be a suitable therapeutic agent for future clinical trials in humans.

The plant histaminase: a promising enzyme with antioxidant properties versus histamine release in isoprenaline-induced myocardial infarction in rats

The present study was designed to evaluate possible protective effects of purified histaminase from Lathyrus sativus L. seedling on the myocardial injuries upon isoprenaline-induced myocardial infarction in rats. In this regard, blood histamine concentration, creatine kinase-MB (CK-MB) activity, antioxidant status, and histopathological changes of the hearts were measured. A total of 40 adult male Sprague-Dawley rats were divided into five equal groups and treated in the following order: control (normal saline), isoprenaline (isoproterenol 110 mg/kg BW), Isopren.-H1 (isoprenaline plus histaminase 80 U/kg BW), Isopren.-H2 (isoprenaline plus histaminase 120 U/kg BW), and Isopren.-H3 (isoprenaline plus histaminase 160 U/kg BW). Myocardial infarction was manifested by a significant elevation in the level of CK-MB and histopathological findings in isoprenaline group when compared to controls. In contrast, histaminase pretreatment at dose of 160 U/kg prevented isoprenaline-induced histamine release and significantly decreased CK-MB activity as well as histopathological changes in Isopren.-H3 group. A significant increase in the catalase (CAT) and superoxide dismutase (SOD) activities was also observed by histaminase treatment in Isopren.-H2 and Isopren.-H3 groups. Although the activity of glutathione peroxidase (GPx) increased significantly to suppress oxidative stress in isoprenaline group, it was not able to prevent lipid peroxidation (as shown by TBARS concentration) in the heart of rats. In conclusion, the plant-originated histaminase presented as a promising enzyme with antioxidant properties against histamine release and myocardial infarction in rats, and it seems be a suitable therapeutic agent for future clinical trials in humans

Protective effect of hydroalcoholic olive leaf extract on experimental model of colitis in rat: involvement of nitrergic and opioidergic systems.

The aim of the present study is to investigate the possible protective effect of dry olive leaf extract (OLE) against acetic acid-induced ulcerative colitis in rats, as well as the probable modulatory effect of nitrergic and opioidergic systems on this protective impact. Olive leaf extract was administered (250, 500 and 750 mg/kg) orally for two successive days, starting from the colitis induction. To assess the involvement of nitrergic and opioidergic systems in the possible protective effect of OLE, L-NG-Nitroarginine Methyl Ester (10 mg/kg) and naltrexone (5 mg/kg) intraperitoneal (i.p.) were applied 30 min before administration of the extract for two successive days, respectively. Colonic status was investigated 48 h following induction through macroscopic, histological and biochemical analyses. Olive leaf extract dose-dependently attenuated acetic acid-provoked chronic intestinal inflammation. The extract significantly reduces the severity of the ulcerative lesions and ameliorated macroscopic and microscopic scores. These observations were accompanied by a significant reduction in the elevated amounts of TNF-α and interlukin-2 markers. Moreover, both systems blockage reversed protective effects of OLE in the rat inflammatory bowel disease model. These finding demonstrated, for the first time, a possible role for nitrergic and opioidergic systems in the aforementioned protective effect, and the extract probably exerted its impact increasing nitric oxide and opioid tones.

Sucrose-induced analgesia in mice: role of nitric oxide and opioid receptor-mediated system.

BACKGROUND: The mechanism of action of sweet substance-induced analgesia is thought to involve activation of the endogenous opioid system. The nitric oxide (NO) pathway has a pivotal role in pain modulation of analgesic compounds such as opioids. OBJECTIVES: We investigated the role of NO and the opioid receptor-mediated system in the analgesic effect of sucrose ingestion in mice. MATERIALS AND METHODS: We evaluated the effect of intraperitoneal administration of 10 mg/kg of NO synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME) and 20 mg/kg of opioid receptor antagonist, naltrexone on the tail flick response in sucrose ingesting mice. RESULTS: Sucrose ingestion for 12 days induced a statistically significant increase in the latency of tail flick response which was unmodified by L-NAME, but partially inhibited by naltrexone administration. CONCLUSIONS: Sucrose-induced nociception may be explained by facilitating the release of endogenous opioid peptides. Contrary to some previously studied pain models, the NO/cyclic guanosine monophosphate (cGMP) pathway had no role in thermal hyperalgesia in our study. We recommend further studies on the involvement of NO in other animals and pain models.

Curcumin downregulates aquaporin-1 expression in cultured rat choroid plexus cells.

Aquaporin-1 (AQP1) is a water channel that is highly expressed on the apical side of the choroid plexus epithelium (CP) and thought to be one of the major pathways for the high water permeability of this structure. Blockade of AQP1 in the CP reduce the production of cerebrospinal fluid (CSF). Downregulation of AQP1 might be protective against some neurological disorders correlated with increased intracranial pressure and/or poor drainage of CSF. Curcumin, the major constituent of the rhizome of Curcuma longa, has been shown to inhibit potassium channels, Na⁺-K⁺ ATPase, as well as AQP3 in some cells. We therefore speculated that curcumin might be a useful tool to inhibit and/or decrease AQP1, and thus might be useful in the regulation of CSF production in pathophysiological conditions, including traumatic brain injury, hydrocephalus, stroke, systemic hyponatremia, acute cerebral edema, and hypertension. Choroidal epithelial cells of the lateral ventricle of Wistar rats were isolated and grown in in-vitro cultures for 24 h. Curcumin was then added to the medium at different concentrations, and the cell viability tested by the (3,4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay. Additional wells of cells were tested for AQP1 protein expression using immunocytochemistry, immunoblotting, and flow cytometry. Our results showed that curcumin treatment decreases AQP1 expression in rat choroid epithelium cells in a dose-dependent manner. We conclude that curcumin may be a useful tool to regulate CSF production in pathophysiological conditions such as hydrocephalus, systemic hyponatremia, hypertension, and other neurological conditions.

Microextraction in a packed syringe for the analysis of olive biophenols in rat plasma using CMK-3 nanoporous sorbent.

A carbon-based nanoporous sorbent was first used for microextraction in a packed syringe (MEPS) before HPLC/UV analysis of some biophenols in rat plasma. A laboratory-made programmable apparatus was designed and used for automation of the extraction procedure. The MEPS syringe was packed with 2 mg of CMK-3 sorbent, between the barrel and the injection needle, and mounted on an apparatus for programming of the conditioning, sampling, washing, elution and cleaning steps. All steps of the microextraction procedure were carefully optimized on the system. For optimization of important factors, such as the number of adsorption and elution cycles, elution volume and pH, a multivariate central composite design method was used. The highest recoveries were obtained for 24 and 10 times of adsorption and elution cycles, respectively, using 100 µL of acetonitrile as the eluent and a sample pH of 2. Good results were obtained in terms of the precision (RSD 1.6, 2.5 and 2.3%) and detection limit (0.7, 4.7 and 0.25 µM) for caffeic acid, tyrsol and oleuropein, respectively. The method was simple, efficient and appropriate for sample clean up before analysis by HPLC, and was successfully applied to the determination of biophenols in the plasma of several rats that received an olive leaves extract either by a gavage or an intraperitoneal injection method. A positive correlation was found between the amount of olive extract's feeding of the rats and the level of their plasma biophenols.

The cardioprotective effects of an antiemetic drug, tropisetron, on cardiomyopathy related to doxorubicin.

Cardiotoxicity is a life-threatening side effect of doxorubicin (DOX). Although the responsible mechanisms are largely unknown, it is demonstrated that DOX induces an elevation in the level of creatine kinase isoenzyme, lactic dehydrogenase, creatine phosphokinase, and troponin T in serum and reduces body/heart weight. In addition, cardiotoxicity is further confirmed by changes in ECG parameters and papillary muscle contractile force. Tropisetron is an effective antiemetic drug for chemotherapy-induced emesis. There is ample evidence that tropisetron exerts immune modulatory and anti-inflammatory properties. The present study was designed to investigate the protective effects of tropisetron pretreatment against DOX-induced cardiotoxicity in rats. In this study, DOX toxicity was induced by a single intraperitoneal injection (15 mg/kg), and in treated group, tropisetron (3 mg/kg; i.p) was administered 1 h prior to DOX injection. Our results indicated that tropisetron potently decreased body/heart weight loss and mortality rate and also improved ECG changes as well as heart contractility. In addition, tropisetron robustly counteracted the increase in the levels of serum biomarkers and alleviated the histopathological changes in rats' hearts as compared with the DOX group. Taken together, these results demonstrate that tropisetron has potent cardioprotective effects against DOX-induced cardiotoxicity.

Possible involvement of PPAR-gamma receptor and nitric oxide pathway in the anticonvulsant effect of acute pioglitazone on pentylenetetrazole-induced seizures in mice.

UNLABELLED: Besides the receptor-mediated effects of pioglitazone, the involvement of nitric oxide (NO) has been previously demonstrated in some pioglitazone-induced central and peripheral effects. In the present study, the effects of acutely administered pioglitazone on pentylenetetrazole (PTZ)-induced seizures and involvement of NO were evaluated in mice. To determine the threshold for clonic seizures, PTZ was administered intravenously. A single dose of pioglitazone (10, 20, 40 and 80 mg/kg, p.o.) was administered either 2 or 4h prior to induction of seizures. For determination of possible role of peroxisome proliferator activated receptor gamma (PPAR-γ) and nitric oxide pathway in this effect, the effects of a PPAR-γ antagonist, GW9662 (2 mg/kg); a non-specific nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 0.3, 1, 3, and 10 mg/kg); a specific iNOS inhibitor, aminoguanidine (100mg/kg, i.p.) or a nitric oxide precursor, L-arginine (30, 60, 100 and 200mg/kg, i.p.); each administered 15 min prior to pioglitazone, were investigated on the anticonvulsant effect of this drug. Administration of pioglitazone (40 and 80 mg/kg) increased the threshold of PTZ-induced seizure in a dose-dependent, and time-dependent manner. GW9662 reversed the anticonvulsant effect of pioglitazone (40 mg/kg). Acute administration of L-NAME (1, 3 and 10mg/kg) inhibited the anticonvulsant effect of pioglitazone (40 mg/kg), the same result was detected with aminoguanidine (100mg/kg); whereas L-arginine, in the noneffective dose (100mg/kg), potentiated the seizure threshold when co-administered with a subeffective dose of pioglitazone (20mg/kg). CONCLUSION: The present study demonstrates the anticonvulsant effect of acute pioglitazone on PTZ-induced seizures in mice. This effect was reversed by PPAR-γ antagonist, and both a specific- and a non-specific nitric oxide synthase inhibitors, and augmented by nitric oxide precursor, L-arginine. These results support that the anticonvulsant effect of pioglitazone is mediated through PPAR-γ receptor-mediated pathway and also, at least partly, through the nitric oxide pathway.