http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2013 , Hindawi Publishing Corporation . All rights reserved. Tue, 18 Jun 2013 16:39:21 +0000 http://www.hindawi.com/journals/aps/2013/718313/ Background and Aim. Calcineurin inhibitors (CNIs) have shown to develop hypertension in transplant patients. The in vitro incubation effects of cyclosporine (CsA) and tacrolimus (Tac) on vascular relaxations of rat thoracic aorta (TA) and abdominal aorta (AA) need to be investigated. Methods. The optimal concentrations of CsA (1.0 mg/mL) and Tac (0.1 mg/mL) used to compare endothelium-dependent (acetylcholine (ACh)) and endothelium-independent (sodium nitroprusside (SNP)) vascular relaxation against the agonists in phenylephrine (PE-) constricted TA and AA of 13-week-old male Sprague Dawley rats (). Results. In TA, the maximal vasodilator response elicited by ACh (control: 98%) was significantly () inhibited by CsA ( 10%) but not by Tac ( 97%). In AA, (control: IC50 50 nM; 100%) CsA (IC50 7 μM; () showed strong sensitivity to inhibit ACh-dependent vascular relaxation than Tac (IC50 215 nM (); 98%). CsA and Tac failed to affect the inhibitory responses to SNP in both TA and AA. Conclusion. CsA exerts profound inhibitory effect on endothelium-dependent vasodilatation as compared to Tac in both TA and AA. Aortic rings from the thoracic region are more sensitive to CNIs, since the vasodilator response to ACh is solely mediated by NO while in the AA, ACh likely recruits other endothelial mediators besides NO to maintain vasodilatation. Ashok Jadhav, Venkat Gopalakrishnan, and Ahmed Shoker Copyright © 2013 Ashok Jadhav et al. All rights reserved. Sun, 12 May 2013 14:14:05 +0000 http://www.hindawi.com/journals/aps/2013/313858/ Methotrexate (MTX) is a nonbiological disease-modifying antirheumatic drug that has shown both a good control of clinical disease and a good safety. Usually drug-drug interactions (DDIs) represent the most limiting factor during the clinical management of any disease, in particular when several drugs are coadministered to treat the same disease. In this paper, we report the interactions among MTX and the other drugs commonly used in the management of rheumatoid arthritis. Using Medline, PubMed, Embase, Cochrane libraries, and Reference lists, we searched for the articles published until June 30, 2012, and we reported the most common DDIs between MTX and antirheumatic drugs. In particular, clinically relevant DDIs have been described during the treatment with MTX and NSAIDs, for example, diclofenac, indomethacin, or COX-2 inhibitors, and between MTX and prednisone or immunosuppressant drugs (e.g., leflunomide and cyclosporine). Finally, an increase in the risk of infections has been recorded during the combination treatment with MTX plus antitumor necrosis factor-α agents. In conclusion, during the treatment with MTX, DDIs play an important role in both the development of ADRs and therapeutic failure. Marinella Patanè, Miriam Ciriaco, Serafina Chimirri, Francesco Ursini, Saverio Naty, Rosa Daniela Grembiale, Luca Gallelli, Giovambattista De Sarro, and Emilio Russo Copyright © 2013 Marinella Patanè et al. All rights reserved. Thu, 11 Apr 2013 10:30:34 +0000 http://www.hindawi.com/journals/aps/2013/692613/ Microbial infections of various types of wounds are a challenge to the treatment of wounds and wound healing. The study was to investigate antimicrobial and antioxidant properties of methanol leaf and stem bark extracts of Kigelia africana and methanol leaf and root extracts of Strophanthus hispidus and also to determine wound healing properties of the extracts. The antimicrobial activities of the methanol extracts were determined against two Gram-positive and two Gram-negative bacteria and a fungus using agar diffusion and micro-dilution methods. The antioxidant activity was determined using 1,1-diphenyl-2-picryl–hydrazyl (DPPH) method. The influence of the extracts on rate of wound closure was investigated using the excision wound model and histopathological investigation of treated and untreated wound tissues performed. The MICs of leaf extract of K. africana against test organisms were 2.5–7.5 mg/mL and stem bark extract were 2.25–7.5 mg/mL. The leaf extract of S. hispidus had MIC range of 2.5–7.5 mg/mL and 2.5–10 mg/mL for root extract. The IC50 of leaf and stem bark extracts of K. africana were 56.9 and 13.7 μg/mL, respectively and leaf and root of S. hispidus were 49.8 and 45.1 μg/mL, respectively. K. africana extracts (7.5% w/w) showed significant () wound contraction at day 7 with 72% of wound closure whiles significant () wound contractions were observed on day 11 for stem bark of K. africana, leaf and root extracts of S. hispidus. Wound tissues treated with the extracts showed improved collagenation, re-epitheliazition and rapid granulation formation compared with untreated wound tissues. The extracts were found to contain alkaloids, saponins, tannins, flavonoids, carbohydrates, and sapogenetic glycosides. The HPLC finger-printing of the extracts were developed. The leaf, stem bark and root extracts of K. africana and S. hispidus exhibited antimicrobial, antioxidant, and enhanced wound healing properties and these may justify the medicinal uses of the plants for treatment of microbial infections and wounds. Christian Agyare, Anita Serwaa Dwobeng, Nicholas Agyepong, Yaw Duah Boakye, Kwesi Boadu Mensah, Patrick George Ayande, and Martin Adarkwa-Yiadom Copyright © 2013 Christian Agyare et al. All rights reserved. Thu, 17 Jan 2013 13:58:56 +0000 http://www.hindawi.com/journals/aps/2013/192408/ In the present study, we investigated the feasibility of the vaginal administration of drospirenone silicone IVR. The in vitro release characteristics of matrix-type and reservoir-type IVR were compared under sink conditions in 21 days. At the same time, API excipients compatibility and preformulation study was performed by HPLC, IR, and DSC methods. Biocompatibility of reservoir system was evaluated by tolerability on tissue level in rats. It was found that, under strong light exposure, high temperature, and high humidity conditions, drospirenone and excipients had no significant interactions. The daily release of reservoir-type IVR was about 0.5 mg/d sustaining 21 days, which significantly decreased the burst effect compared with the matrix system. When drospirenone was modified by the PVPk30 in the reservoir system formulation, the daily release rate increased to 1.0 mg/d sustaining 21 days. The cumulative release of reservoir-type IVR was fitted to zero release equation. In addition, biocompatibility of drospirenone IVR system in this dosage is safe. It is feasibility feasibile to further developed for safe, convenient, and effective contraceptive drug delivery with reduced dosing interval. Ying Zhang, Chun-Xiao Li, Mei-Ying Ning, Xue-Yan Duan, and Ying Liu Copyright © 2013 Ying Zhang et al. All rights reserved. Mon, 14 Jan 2013 08:00:52 +0000 http://www.hindawi.com/journals/aps/2013/512931/ Echinophora platyloba DC plant (Khousharizeh) is one of the indigenous medicinal plants which is used as a food seasoning and medicine in Iran. The objective of this study was to examine the in vitro cytotoxic activity and the mechanism of cell death of crude methanolic extracts prepared from Echinophora platyloba DC, on mouse fibrosarcoma cell line (WEHI-164). Cytotoxicity and viability of methanolic extract was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and dye exclusion assay. Cell death ELISA was employed to quantify the nucleosome production result from nuclear DNA fragmentation during apoptosis and determine whether the mechanism involves induction of apoptosis or necrosis. The cell death was identified as apoptosis using terminal deoxynucleotidyl transferase- (TdT-) mediated dUTP nick end labeling (TUNEL) assay. Our results demonstrated that the extract decreased cell viability, suppressed cell proliferation, and induced cell death in a time- and dose-dependent manner in WEHI-164 cells (IC50 = 196.673 ± 12.4 μg/mL) when compared with a chemotherapeutic anticancer drug, Toxol. Observation proved that apoptosis was the major mechanism of cell death. So the Echinophora platyloba DC extract was found to time- and dose-dependently inhibit the proliferation of fibrosarcoma cell possibly via an apoptosis-dependent pathway. Fatemeh Zare Shahneh, Samira Valiyari, Abbas Azadmehr, Reza Hajiaghaee, Saeid Yaripour, Ali Bandehagh, and Behzad Baradaran Copyright © 2013 Fatemeh Zare Shahneh et al. All rights reserved. Tue, 18 Dec 2012 07:48:49 +0000 http://www.hindawi.com/journals/aps/2012/376429/ The aim of the study was to evaluate the phytochemistry and the effect of methanolic root extract (MREt) of Rauwolfia serpentina on alloxan-induced diabetic Wister male mice. Mice were divided in control (distilled water at 1 mL/kg) and alloxan-induced diabetic mice which subdivided into diabetic (distilled water at 1 mL/kg), negative (0.05% dimethyl sulfoxide at 1 mL/kg), positive (glibenclamide at 5 mg/kg) controls, and three test groups (MREt at 10, 30, and 60 mg/kg). All treatments were given orally for 14 days. Qualitatively MREt showed the presence of alkaloids, carbohydrates, flavonoids, glycosides, cardiac glycosides, phlobatannins, resins, saponins, steroids, tannins, and triterpenoids, while quantitatively extract was rich in total phenols. The flavonoids, saponins and alkaloids were also determined in root powder. MREt found effective in improving the body weights, glucose and insulin levels, insulin/glucose ratio, glycosylated and total hemoglobin in test groups as compared to diabetic control. Similarly, significantly decreased levels of total cholesterol, triglycerides, low-density lipoprotein (LDL-c), and very low-density lipoprotein (VLDL-c) cholesterols were found in test groups. Significant lipolysis with improved glycogenesis was also found in liver tissues of all test groups. ALT levels were found normal in all groups. Thus, MREt improves the glycemic, antiatherogenic, coronary risk, and cardioprotective indices in alloxan-induced diabetic mice. Muhammad Bilal Azmi and Shamim A. Qureshi Copyright © 2012 Muhammad Bilal Azmi and Shamim A. Qureshi. All rights reserved. Mon, 17 Dec 2012 14:27:33 +0000 http://www.hindawi.com/journals/aps/2012/981461/ Nephrotoxicity is one of the limiting factors for using doxorubicin (Dox) as an anticancer chemotherapeutic. Here, we investigated possible protective effect of coenzyme-Q10 (CoQ10) on Dox-induced nephrotoxicity and the mechanisms involved. Two doses (10 and 100 mg/kg) of CoQ10 were administered orally to rats for 8 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of Dox (15 mg/kg) at day 4 of the experiment. Our results showed that the low dose of CoQ10 succeeded in reversing Dox-induced nephrotoxicity to control levels (e.g., levels of blood urea nitrogen and serum creatinine, concentrations of renal reduced glutathione (GSH) and malondialdehyde, catalase activity and caspase 3 expression, and renal histopathology). Alternatively, the high dose of CoQ10 showed no superior nephroprotection over the low dose, as there were no significant improvements in renal histopathology, catalase activity, or caspase 3 expression compared to the Dox-treated group. Interestingly, the high dose of CoQ10 alone significantly decreased renal GSH level as well as catalase activity and caused a mild induction of caspase 3 expression compared to control, probably due to a prooxidant effect at this dose of CoQ10. We conclude that CoQ10 protects from Dox-induced nephrotoxicity with a precaution to dosage adjustment. Azza A. K. El-Sheikh, Mohamed A. Morsy, Marwa M. Mahmoud, Rehab A. Rifaai, and Aly M. Abdelrahman Copyright © 2012 Azza A. K. El-Sheikh et al. All rights reserved. Mon, 17 Dec 2012 13:14:10 +0000 http://www.hindawi.com/journals/aps/2012/679013/ Multivessel coronary artery disease is more often treated either with coronary artery bypass surgery (CABG) or percutaneous coronary intervention (PCI) with stenting. The advent of drug-eluting stent (DES) has changed the revascularization strategy, and caused an increase in the use of DES in multivessel disease (MVD), with reduced rate of repeat revascularization compared to conventional bare metal stent. The comparative studies of DES-PCI over CABG have shown comparable safety; however, the rate of major adverse cerebrovascular and cardiac events and repeat revascularization was significantly higher with DES-PCI at long term. In diabetic patients with MVD, concern of repeat revascularization with DES-PCI is persistent. More recent, one-year economic outcomes have reported that the CABG is favored among patients with high angiographic complexity. The higher rate of repeat revascularization with DES-PCI in MVD would lead to increased economic burden on patient at long term besides bearing high cost of DES. In diabetic MVD patients, CABG is associated with having better clinical outcomes and being more cost-effective approach when compared to DES-PCI at long term. Kanaiya Panchal, Snehal Patel, and Parloop Bhatt Copyright © 2012 Kanaiya Panchal et al. All rights reserved. Sun, 09 Dec 2012 17:01:32 +0000 http://www.hindawi.com/journals/aps/2012/789796/ The effects of a polyherbal compound, containing six plants (Allium sativum, Cinnamomum zeylanicum, Nigella sativa, Punica granatum, Salvia officinalis and Teucrium polium) were tested on biochemical parameters in streptozotocin-induced diabetic rats. Streptozotocin caused an approximately 3-fold increase in fasting blood sugar level after 2 days. The diabetic control rats showed further increase in blood glucose after 30 days (384 ± 25 mg/dl in day 30 versus 280 ± 12 mg/dl in day 2, ). Administration of the compound blocked the increase of blood glucose (272 ± 7 and 269 ± 48 mg/dl at day 2 and day 30, respectively). Also, there was significant difference in the level of triglyceride (60 ± 9 versus 158 ± 37 mg/dl, ), total cholesterol (55 ± 2 versus 97 ± 11 mg/dl, P < 0.01) and aspartate amino transferase activity (75 ± 12 versus 129 ± 18 U/L, ) between treated rats and diabetic control group. In conclusion, the MSEC inhibited the progression of hyperglycemia and decreased serum lipids and hepatic enzyme activity in diabetic rats. Therefore, it has the potential to be used as a natural product for the management of diabetes. Reza Shafiee-Nick, Ahmad Ghorbani, Farzaneh Vafaee Bagheri, and Hassan Rakhshandeh Copyright © 2012 Reza Shafiee-Nick et al. All rights reserved. Wed, 05 Dec 2012 08:16:51 +0000 http://www.hindawi.com/journals/aps/2012/846163/ Objective. Study objectives were to assess temporal trends and identify patient- and practice-level predictors of the prescription of antiplatelet medications in a national sample of ischemic stroke (IS) patients seeking ambulatory care. Methods. IS-related outpatient visits by adults were identified using the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey for the years 2000–2007. We assessed prescribing of antiplatelet medications using the generic drug code and drug entry codes in these data. Temporal trends in antiplatelet prescribing were assessed using the Cochran-Mantel-Haenszel test for trend. Results. We identified 9.5 million IS-related ambulatory visits. Antiplatelet medications were prescribed at 35.5% of visits. Physician office prescribing of the clopidogrel-aspirin combination increased significantly from 0.5% in 2000 to 22.0% in 2007 (), whereas prescribing of aspirin decreased from 17.9% to 7.0% () during the same period. Conclusion. We observed a continued increase in prescription of the aspirin-clopidogrel combination from 2000 to 2007. Clinical trial evidence suggests that the aspirin-clopidogrel combination does not provide any additional benefit compared with clopidogrel alone; however, our study findings indicate that even with lack of adequate clinical evidence physician prescribing of this combination has increased in real-world community settings. Sudeep Karve, Deborah Levine, Eric Seiber, Milap Nahata, and Rajesh Balkrishnan Copyright © 2012 Sudeep Karve et al. All rights reserved. Wed, 28 Nov 2012 16:16:50 +0000 http://www.hindawi.com/journals/aps/2012/281768/ Drug self-administration procedures have played a critical role in the experimental analysis of psychoactive compounds, such as cocaine, for over 50 years. While there are numerous permutations of this procedure, this paper will specifically focus on choice procedures using concurrent schedules of intravenous drug self-administration. The aims of this paper are to first highlight the evolution of drug choice procedures and then review the subsequent preclinical body of literature utilizing these choice procedures to understand the environmental, pharmacological, and biological determinants of the reinforcing stimulus effects of drugs. A main rationale for this paper is our proposition that choice schedules are underutilized in investigating the reinforcing effects of drugs in assays of drug self-administration. Moreover, we will conclude with potential future directions and unexplored scientific space for the use of drug choice procedures. Matthew L. Banks and S. Stevens Negus Copyright © 2012 Matthew L. Banks and S. Stevens Negus. All rights reserved. Thu, 01 Nov 2012 14:26:06 +0000 http://www.hindawi.com/journals/aps/2012/357368/ The present study was designed to evaluate the effect of palmatine on memory of Swiss young male albino mice. Palmatine (0.1, 0.5, 1 mg/kg, i.p.) and physostigmine (0.1 mg/kg, i.p.) per se were administered for 10 successive days to separate groups of mice. Effect of drugs on learning and memory of mice was evaluated using elevated plus maze and Morris water maze. Brain acetylcholinesterase activity was also estimated. Effect of palmatine on scopolamine- and diazepam-induced amnesia was also investigated. Palmatine (0.5 and 1 mg/kg) and physostigmine significantly improved learning and memory of mice, as indicated by decrease in transfer latency using elevated plus maze, and decrease in escape latency during training and increase in time spent in target quadrant during retrieval using Morris water maze. The drugs did not show any significant effect on locomotor activity of the mice. Memory-enhancing activity of palmatine (1 mg/kg) was comparable to physostigmine. Palmatine (1 mg/kg) significantly reversed scopolamine- and diazepam-induced amnesia in mice. Palmatine and physostigmine also significantly reduced brain acetylcholinesterase activity of mice. Thus, palmatine showed memory-enhancing activity in mice probably by inhibiting brain acetylcholinesterase activity, through involvement of GABA-benzodiazepine pathway, and due to its antioxidant activity. Dinesh Dhingra and Varun Kumar Copyright © 2012 Dinesh Dhingra and Varun Kumar. All rights reserved. Mon, 22 Oct 2012 08:46:45 +0000 http://www.hindawi.com/journals/aps/2012/912041/ The present study examined the anxiolytic and antidepressant effects of the aqueous extract of Alafia multiflora Stapf (AM) stem barks (150 and 300 mg/kg, 7 days administration) on rats and mice, using experimental paradigms of anxiety and depression. In the open field, the aqueous extract increased significantly the number of center square crossed and the time spent at the center of the field as well as the rearing time, while the grooming time was reduced significantly. In the elevated plus maze, the aqueous extract increased the time spent and the number of entries in the open arms. All these effects were also completely reversed by flumazenil, an antagonist of benzodiazepine receptors and pindolol a β-adrenoceptors blocker/5-HT 1A/1B receptor antagonist. The time spent in the light compartment, the latency time, and the number of the light-dark transitions increased significantly in the light/dark exploration test after the treatment with AM. The extract was able to reduce significantly the immobility time and increase swimming as well as climbing duration. Taken together, the present work evidenced anxiolytic effects of the aqueous extract of AM that might involve an action on benzodiazepine-type receptors and an antidepressant effect where noradrenergic mechanisms will probably play a role. Harquin Simplice Foyet, David Emery Tsala, Armand Abdou Bouba, and Lucian Hritcu Copyright © 2012 Harquin Simplice Foyet et al. All rights reserved. Mon, 15 Oct 2012 15:19:20 +0000 http://www.hindawi.com/journals/aps/2012/507278/ Methylsulfonylmethane (MSM) is naturally occurring organic sulfur that is known as a potent antioxidant/anti-inflammatory compound. The aim of this study was to investigate the effect of MSM on hemodynamics functions and oxidative stress in rats with monocrotaline- (MCT-) induced pulmonary arterial hypertension (PAH). Wistar rats were randomly assigned to 38-days treatment. MSM was administered to rats at 100, 200, and 400 mg/kg/day doses 10 days before a single dose of 60 mg/kg, IP, MCT. Hemodynamics of ventricles were determined by Powerlab AD instrument. Blood samples were obtained to evaluate changes in the antioxidative system including activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and the level of reduced glutathione (GSH) and malondialdehyde (MDA). Improvements in cardiopulmonary hemodynamics were observed in the MSM-treated pulmonary arterial hypertensive rats, with a significant reduction in right ventricular systolic pressure (RSVP) and an increase in the mean arterial pressure (MAP). The values of CAT, SOD, GSH-px activities, and GSH were significantly lower in MCT-induced PAH (), but they were recovered to control levels of MSM-treated groups. Our present results suggest that long-term administration of the MSM attenuates MCT-induced PAH in rats through modulation of oxidative stress and antioxidant defense. Sadollah Mohammadi, Moslem Najafi, Hossein Hamzeiy, Nasrin Maleki-Dizaji, Masoud Pezeshkian, Homayon Sadeghi-Bazargani, Masoud Darabi, Sara Mostafalou, Shahab Bohlooli, and Alireza Garjani Copyright © 2012 Sadollah Mohammadi et al. All rights reserved. Wed, 10 Oct 2012 11:54:39 +0000 http://www.hindawi.com/journals/aps/2012/494367/ In the present study, the effect of aqueous extracts of saffron on morphine-induced memory impairment was investigated. On the training trial, the mice received an electric shock when the animals were entered into the dark compartment. Twenty-four and forty-eight hours later, the time latency for entering the dark compartment was recorded and defined as the retention trial. The mice were divided into (1) control, (2) morphine which received morphine before the training in the passive avoidance test, (3–5) three groups treated by 50, 150 and 450 mg/kg of saffron extract before the training trial, and (6 and 7) the two other groups received 150 and 450 mg/kg of saffron extract before the retention trial. The time latency in morphine-treated group was lower than control (P < 0.01). Treatment of the animals by 150 and 450 mg/kg of saffron extract before the training trial increased the time latency at 24 and 48 hours after the training trial (P < 0.05 and P < 0.01). Administration of both 150 and 450 mg/kg doses of the extract before retention trials also increased the time latency (P < 0.01). The results revealed that the saffron extract attenuated morphine-induced memory impairment. Sayede Maryam Naghibi, Mahmoud Hosseini, Fatemeh Khani, Motahare Rahimi, Farzaneh Vafaee, Hassan Rakhshandeh, and Azita Aghaie Copyright © 2012 Sayede Maryam Naghibi et al. All rights reserved. Thu, 13 Sep 2012 10:30:46 +0000 http://www.hindawi.com/journals/aps/2012/182671/ For decades, it has been suggested that dysfunction of dopaminergic pathways and their associated modulations in dopamine levels play a major role in the pathogenesis of neurological disorders. Dopaminergic system is involved in the stress response, and the neural mechanisms involved in stress are important for current research, but the recent and past data on the stress response by dopaminergic system have received little attention. Therefore, we have discussed these data on the stress response and propose a role for dopamine in coping with stress. In addition, we have also discussed gastric stress ulcers and their correlation with dopaminergic system. Furthermore, we have also highlighted some of the glucocorticoids and dopamine-mediated neurological disorders. Our literature survey suggests that dopaminergic system has received little attention in both clinical and preclinical research on stress, but the current research on this issue will surely identify a better understanding of stressful events and will give better ideas for further efficient antistress treatments. Naila Rasheed and Abdullah Alghasham Copyright © 2012 Naila Rasheed and Abdullah Alghasham. All rights reserved. Wed, 15 Aug 2012 16:21:25 +0000 http://www.hindawi.com/journals/aps/2012/614046/ 6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major bioactive compound in wasabi (Wasabia japonica), which is a typical Japanese pungent spice. Recently, in vivo and in vitro studies demonstrated that 6-MSITC has several biological properties, including anti-inflammatory, antimicrobial, antiplatelet, and anticancer effects. We previously reported that 6-MSITC strongly suppresses cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and cytokines, which are important factors that mediate inflammatory processes. Moreover, molecular analysis demonstrated that 6-MSITC blocks the expressions of these factors by suppressing multiple signal transduction pathways to attenuate the activation of transcriptional factors. Structure-activity relationships of 6-MSITC and its analogues containing an isothiocyanate group revealed that methylsulfinyl group and the length of alkyl chain of 6-MSITC might be related to high inhibitory potency. In this paper, we review the anti-inflammatory properties of 6-MSITC and discuss potential molecular mechanisms focusing on inflammatory responses by macrophages. Takuhiro Uto, De-Xing Hou, Osamu Morinaga, and Yukihiro Shoyama Copyright © 2012 Takuhiro Uto et al. All rights reserved. Tue, 17 Jul 2012 09:30:48 +0000 http://www.hindawi.com/journals/aps/2012/304317/ St. John's Wort herb extracts often contain undesirable or volitional polysaccharides. As polysaccharides exhibit structure-dependent biological functions in the present study water-soluble polysaccharides were extracted from herb material, fractionated by anion exchange chromatography into four main polysaccharide fractions (denominated as Hp1, Hp2, Hp3 and Hp4) and characterized by HPAEC-PAD, CE, IR and GC-MS. Biological activity on human skin keratinocytes and fibroblasts was assessed by investigation of their effect on proliferation, metabolism, cytotoxicity, apoptosis and differentiation. The underlying mechanisms were investigated in gene expression studies. Polysaccharide fraction Hp1 was mainly composed of β-D-glucose. Hp2, Hp3 and Hp4 contained pectic structures and arabinogalactan proteins varying in composition and quantity. Polysaccharides of Hp1 induced the keratinocyte differentiation by inhibiting the gene expression of the epidermal growth factor and insulin receptor. While the collagen secretion of fibroblasts was stimulated by each polysaccharide fraction only Hp1 stimulated the synthesis. The fibroblast proliferation was reduced by Hp1 and increased by Hp4. This effect was related to the influence on genes that referred to oxidative stress, metabolism, transcription processes and extracellular proteins. In conclusion polysaccharides have been shown as biologically active ingredients of aqueous St. John's Wort extracts with a relation between their structural characteristics and function. S. Abakuks and A. M. Deters Copyright © 2012 S. Abakuks and A. M. Deters. All rights reserved. Tue, 19 Jun 2012 13:12:13 +0000 http://www.hindawi.com/journals/aps/2012/312041/ No study has ever examined the effect of 5-HT7 receptor agonists on nociception by using 5-HT7 receptor knockout mice. Basal sensitivity to noxious heat stimuli and formalin-induced nociception in both phase I and II of the formalin test did not differ in 5-HT7 receptor knockout mice and paired wild-type controls. Similarly, there was no significant difference in basal body temperature between both genotypes. Subcutaneous administration of 5-HT7 receptor agonists AS-19 (10 mg/kg), E-57431 (10 mg/kg), and E-55888 (20 mg/kg) significantly reduced formalin-induced licking/biting behavior during the phase II of the test in wild-type but not in 5-HT7 receptor knockout mice. At these active analgesic doses, none of the three 5-HT7 receptor agonists modified the basal body temperature neither in wild-type nor in 5-HT7 receptor knockout mice. However, a significant decrease in body temperature was observed at a higher dose (20 mg/kg) of AS-19 and E-57431 in both genotypes. Our data strongly suggest that the 5-HT7 receptor agonists AS-19, E-57431, and E-55888 produce antinociception in the formalin test by activating 5-HT7 receptors. These results also strengthen the idea that the 5-HT7 receptor plays a role in thermoregulation, but by acting in concert with other receptors. Alex Brenchat, Maria Rocasalbas, Daniel Zamanillo, Michel Hamon, José Miguel Vela, and Luz Romero Copyright © 2012 Alex Brenchat et al. All rights reserved. Thu, 14 Jun 2012 10:52:15 +0000 http://www.hindawi.com/journals/aps/2012/245431/ The Chir Pine, Pinus roxburghii, named after William Roxburgh, is a pine native to the Himalaya. Pinus roxburghii Sarg. (Pinaceae) is traditionally used for several medicinal purposes in India. As the oil of the plant is extensively used in number of herbal preparation for curing inflammatory disorders, the present study was undertaken to assess analgesic and anti-inflammatory activities of its bark extract. Dried and crushed leaves of Pinus roxburghii Sarg. were defatted with petroleum ether and then extracted with alcohol. The alcoholic extract at the doses of 100 mg/kg, 300 mg/kg, and 500 mg/kg body weight was subjected to evaluation of analgesic and anti-inflammatory activities in experimental animal models. Analgesic activity was evaluated by acetic acid-induced writhing and tail immersion tests in Swiss albino mice; acute and chronic anti-inflammatory activity was evaluated by carrageenan-induced paw oedema and cotton pellet granuloma in Wistar albino rats. Diclofenac sodium and indomethacin were employed as reference drugs for analgesic and anti-inflammatory studies, respectively. In the present study, the alcoholic bark extract of Pinus roxburghii Sarg. demonstrated significant analgesic and anti-inflammatory activities in the tested models. Dhirender Kaushik, Ajay Kumar, Pawan Kaushik, and A. C. Rana Copyright © 2012 Dhirender Kaushik et al. All rights reserved. Sun, 03 Jun 2012 14:19:44 +0000 http://www.hindawi.com/journals/aps/2012/265724/ There is evidence that individuals with posttraumatic stress disorder (PTSD) may smoke in part to regulate negative affect. This pilot fMRI study examined the effects of nicotine on emotional information processing in smokers with and without PTSD. Across groups, nicotine increased brain activation in response to fearful/angry faces (compared to neutral faces) in ventral caudate. Patch x Group interactions were observed in brain regions involved in emotional and facial feature processing. These preliminary findings suggest that nicotine differentially modulates negative information processing in PTSD and non-PTSD smokers. Brett Froeliger, Jean Crowell Beckham, Michelle Feldman Dennis, Rachel Victoria Kozink, and Francis Joseph McClernon Copyright © 2012 Brett Froeliger et al. All rights reserved. Sun, 27 May 2012 08:46:58 +0000 http://www.hindawi.com/journals/aps/2012/476985/ Esra Küpeli Akkol, Srijit Das, Satyajit D. Sarker, and Lutfun Nahar Copyright © 2012 Esra Küpeli Akkol et al. All rights reserved. Thu, 17 May 2012 15:41:12 +0000 http://www.hindawi.com/journals/aps/2012/576086/ Mangrove plants are specialised plants that grow in the tidal coasts of tropic and subtropic regions of the world. Their unique ecology and traditional medicinal uses of mangrove plants have attracted the attention of researchers over the years, and as a result, reports on biological activity of mangrove plants have increased significantly in recent years. This review has been set out to compile and appraise the results on antinociceptive, anti-inflammatory, and antipyretic activity of mangrove plants. While the Web of Knowledge, Google Scholar, and PubMed were the starting points to gather information, other pieces of relevant published literature were also adequately explored for this purpose. A total of 29 reports on 17 plant species have been found to report such activities. While 19 reports were on the biological activity of the crude extracts, 10 reports identified the active compound(s) of various chemical classes of natural products including terpenes, steroids, and flavonoids. This review finds that antinociceptive, anti-inflammatory, and antipyretic activity appears to be widespread in mangrove plants. J. A. Shilpi, M. E. Islam, M. Billah, K. M. D. Islam, F. Sabrin, S. J. Uddin, L. Nahar, and S. D. Sarker Copyright © 2012 J. A. Shilpi et al. All rights reserved. Mon, 07 May 2012 14:36:04 +0000 http://www.hindawi.com/journals/aps/2012/465634/ Background. The objectives were (i) to evaluate the impact of acute pulmonary tuberculosis (PTB) and anti-TB therapy on the relationship between AST, ALT, and GGT levels in absence of conditions related to hepatotoxicity; (ii) to evaluate the rate and the time of alterations of AST, ALT, and GGT. Design and Methods. A prospective followup of 40 adults (21 males; mean age of 34.7±5.8 years) with active PTB on initial phase and continuation phase anti-TB. Results. Only 3% (𝑛=1) developed a transient and benign ADR at day 30 without interruption of anti-TB treatment. Within normal ranges, GGT decreased significantly from day 0 to day 60, while AST and ALT increased significantly and respectively. During day 0–day 60, there was a significant, negative, and independent association between GGT and AST. Conclusion. The initial two months led to significant improvement of oxidative stress. Values of oxidative markers in normal ranges might predict low rate of ADR. Etienne Mokondjimobe, Benjamin Longo-Mbenza, Jean Akiana, Ulrich Oswald Ndalla, Regis Dossou-Yovo, Joseph Mboussa, and Henri-Joseph Parra Copyright © 2012 Etienne Mokondjimobe et al. All rights reserved. Wed, 18 Apr 2012 09:03:44 +0000 http://www.hindawi.com/journals/aps/2012/529861/ Naheed R. Mirza, John Atack, and Keith Wafford Copyright © 2012 Naheed R. Mirza et al. All rights reserved. Thu, 29 Mar 2012 11:48:51 +0000 http://www.hindawi.com/journals/aps/2012/416864/ Despite decades of basic and clinical research, our understanding of how benzodiazepines tend to lose their efficacy over time (tolerance) is at least incomplete. In appears that tolerance develops relatively quickly for the sedative and anticonvulsant actions of benzodiazepines, whereas tolerance to anxiolytic and amnesic effects probably does not develop at all. In light of this evidence, we review the current evidence for the neuroadaptive mechanisms underlying benzodiazepine tolerance, including changes of (i) the GABAA receptor (subunit expression and receptor coupling), (ii) intracellular changes stemming from transcriptional and neurotrophic factors, (iii) ionotropic glutamate receptors, (iv) other neurotransmitters (serotonin, dopamine, and acetylcholine systems), and (v) the neurosteroid system. From the large variance in the studies, it appears that either different (simultaneous) tolerance mechanisms occur depending on the benzodiazepine effect, or that the tolerance-inducing mechanism depends on the activated GABAA receptor subtypes. Importantly, there is no convincing evidence that tolerance occurs with α subunit subtype-selective compounds acting at the benzodiazepine site. Christiaan H. Vinkers and Berend Olivier Copyright © 2012 Christiaan H. Vinkers and Berend Olivier. All rights reserved. Thu, 15 Mar 2012 11:17:56 +0000 http://www.hindawi.com/journals/aps/2012/706905/ Osteoporosis is characterized by skeletal degeneration with low bone mass and destruction of microarchitecture of bone tissue which is attributed to various factors including inflammation. Women are more likely to develop osteoporosis than men due to reduction in estrogen during menopause which leads to decline in bone-formation and increase in bone-resorption activity. Estrogen is able to suppress production of proinflammatory cytokines such as IL-1, IL-6, IL-7, and TNF-𝛼. This is why these cytokines are elevated in postmenopausal women. Studies have shown that estrogen reduction is able to stimulate focal inflammation in bone. Labisia pumila (LP) which is known to exert phytoestrogenic effect can be used as an alternative to ERT which can produce positive effects on bone without causing side effects. LP contains antioxidant as well as exerting anti-inflammatory effect which can act as free radical scavenger, thus inhibiting TNF-α production and COX-2 expression which leads to decline in RANKL expression, resulting in reduction in osteoclast activity which consequently reduces bone loss. Hence, it is the phytoestrogenic, anti-inflammatory, and antioxidative properties that make LP an effective agent against osteoporosis. M. E. Nadia, A. S. Nazrun, M. Norazlina, N. M. Isa, M. Norliza, and S. Ima Nirwana Copyright © 2012 M. E. Nadia et al. All rights reserved. Sun, 26 Feb 2012 11:30:05 +0000 http://www.hindawi.com/journals/aps/2012/768720/ The cellular cytoskeleton, adhesion receptors, extracellular matrix composition, and their spatial distribution are together fundamental in a cell's balanced mechanical sensing of its environment. We show that, in lung injury, extracellular matrix-integrin interactions are altered and this leads to signalling alteration and mechanical missensing. The missensing, secondary to matrix alteration and cell surface receptor alterations, leads to increased cellular stiffness, injury, and death. We have identified a monoclonal antibody against β1 integrin which caused matrix remodelling and enhancement of cell survival. The antibody acts as an allosteric dual agonist/antagonist modulator of β1 integrin. Intriguingly, this antibody reversed both functional and structural tissue injury in an animal model of degenerative disease in lung. Rehab AlJamal-Naylor, Linda Wilson, Susan McIntyre, Fiona Rossi, Beth Harrison, Mark Marsden, and David J. Harrison Copyright © 2012 Rehab AlJamal-Naylor et al. All rights reserved. Wed, 22 Feb 2012 11:47:53 +0000 http://www.hindawi.com/journals/aps/2012/708428/ An attempt to find pharmacological therapies to treat stroke patients and minimize the extent of cell death has seen the failure of dozens of clinical trials. As a result, stroke/cerebral ischemia is the leading cause of lasting adult disability. Stroke-induced cell death occurs due to an excess release of glutamate. As a consequence to this, a compensatory increased release of GABA occurs that results in the subsequent internalization of synaptic GABAA receptors and spillover onto perisynaptic GABAA receptors, resulting in increased tonic inhibition. Recent studies show that the brain can engage in a limited process of neural repair after stroke. Changes in cortical sensory and motor maps and alterations in axonal structure are dependent on patterned neuronal activity. It has been assumed that changes in neuronal excitability underlie processes of neural repair and remapping of cortical sensory and motor representations. Indeed, recent evidence suggests that local inhibitory and excitatory currents are altered after stroke and modulation of these networks to enhance excitability during the repair phase can facilitate functional recovery after stroke. More specifically, dampening tonic GABA inhibition can afford an early and robust improvement in functional recovery after stroke. Andrew N. Clarkson Copyright © 2012 Andrew N. Clarkson. All rights reserved. Sun, 29 Jan 2012 15:33:58 +0000 http://www.hindawi.com/journals/aps/2012/134523/ Various 𝛼2,3 subtype selective partial GABA-A agonists are in development to treat anxiety disorders. These compounds are expected to be anxiolytic with fewer undesirable side effects, compared to nonselective GABA-A agonists like benzodiazepines. Several 𝛼2,3 subtype selective and nonselective GABA-A agonists have been examined in healthy volunteers, using a battery addressing different brain domains. Data from five placebo-controlled double-blind studies were pooled. Lorazepam 2 mg was the comparator in three studies. Three 𝛼2,3-selective GABAA agonists (i.e., TPA023, TPACMP2, SL65.1498), one 𝛼1-selective GABAA agonists (zolpidem), and another full agonist (alprazolam) were examined. Pharmacological selectivity was assessed by determination of regression lines for the change from baseline of saccadic-peak-velocity- (ΔSPV-) relative effect, relative to changes in different pharmacodynamic endpoints (ΔPD). SPV was chosen for its sensitivity to the anxiolysis of benzodiazepines. Slopes of the ΔSPV-ΔPD relations were consistently lower with the 𝛼2,3 selective GABA-A agonists than with lorazepam, indicating that their PD effects are less than their SPV-effects. The ΔSPV-ΔPD relations of lorazepam were comparable to alprazolam. Zolpidem showed relatively higher impairments in ΔPD relative to ΔSPV, but did not significantly differ from lorazepam. These PD results support the pharmacological selectivity of the 𝛼2,3-selective GABA-A agonists, implying an improved therapeutic window. Xia Chen, Sanne de Haas, Marieke de Kam, and Joop van Gerven Copyright © 2012 Xia Chen et al. All rights reserved.