Wheat grass is used as a general health tonic and is reported to be effective against several medical disorders, although detailed literature is not available. Besides drug therapy, a number of medicinal plants are effective in treating hyperlipidemia. This study examined the effects of wheat grass on high-fat diet-induced hyperlipidemia in rabbits. Thirty rabbits were divided into 3 groups of 10 rabbits each, group I receiving a control diet, group II a high-fat diet and group III a high-fat diet together with wheat grass over a period of 10 weeks. Fasting serum samples from the animals were analyzed for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), reduced glutathione (GSH) and vitamin C, and the results were compared. The high-fat diet resulted in hyperlipidemia and an increase in oxidative stress, indicated by a significant rise in MDA levels, whereas antioxidant levels of GSH and vitamin C were significantly reduced. Wheat grass supplementation with a high-fat diet resulted in improved lipid levels (decreased total cholesterol and increased HDL-C) together with significantly reduced MDA levels and increased GSH and vitamin C levels. These results indicate the beneficial role of wheat grass in ameliorating hyperlipidemia and the associated oxidative stress.
In this study, we investigated the therapeutic potential of diphenhydramine (DPH), a H(1) receptor antagonist, on taurocholate-induced acute pancreatitis and the underlying mechanisms involved. Rats were randomly divided into sham-operated, model, DPH-treated, octreotide-treated and the DPH plus octreotide combination therapy groups (n = 30 per group). Animals were sacrificed 3, 6 and 24 h after modeling and drug administration (n = 10 per time point) and sera, pancreas and lungs were harvested for further studies. DPH and octreotide monotherapy relieved histopathological injuries in multiple organs when compared to the model group. Combination therapy (DPH + octreotide) demonstrated better therapeutic potential than monotherapy. Data indicated that combination therapy had a better ability to reduce average mortality rates in rats, decrease the number of inflammatory cells, attenuate necrosis, upregulate the levels of amylase, TNF-alpha and IL-8 and downregulate the levels of IL-10 in the serum. Moreover, enhanced expression of Bax in the pancreas and lung were recorded suggesting a pro-apoptotic mechanism involved in the therapeutic potential of DPH. Our study demonstrated the therapeutic potential of DPH in acute pancreatitis and suggested a novel strategy for clinical management of this disease.
The purpose of this study was to investigate the effects of capsaicin (CAP) and resiniferatoxin (RTX) on substance P (SP) release and transient receptor potential vanilloid type 1 (TRPV1) expression of cultured rat dorsal root ganglion (DRG) neurons. Dissociated DRG cells of embryonic 15-day-old Wistar rat were cultured for 3 days and then exposed to CAP (1 micromol/L, 10 micromol/L) or RTX (10 nmol/L, 100 nmol/L) for 10 min. At 3 days of culture growth, SP release increased significantly after 10 min of stimulation with CAP or RTX as compared with controls. Six days after acute exposure to CAP or RTX, SP release and SP expression of cultured rat DRG neurons decreased significantly in both CAP- and RTX-treated cultures as compared with controls. Preprotachykinin (PPT) mRNA, TRPV1 mRNA and TRPV1 protein expression decreased in CAP-treated cultures and RTX cultures treated with the higher concentration, whereas RTX cultures treated with the lower concentration were not affected. The results indicate that CAP and high concentrations of RTX are more neurotoxic to cultured rat DRG neurons while the inability of the neurons to express SP or TRPV1 after acute exposure to the lower concentration of RTX could be partially reversed after a period of incubation. The efficacy and therapeutic potential of the reversible action of RTX are more applicable as strategies for pain or neurogenic inflammation therapy.
The purpose of this study was to compare the efficacy of a 14-day course of prulifloxacin 600 mg with standard antibiotic therapy for the treatment of chronic prostatitis due to Chlamydia trachomatis (Ct) infection. All patients with clinical and instrumental diagnosis of bacterial chronic prostatitis (CP) due to Ct infection were enrolled. After randomization, all patients were administered oral prulifloxacin 600 mg once daily for 14 days or doxycycline 100 mg orally twice daily for 21 days. At enrollment and 30 days after beginning treatment, all patients underwent microbiological cultures for uropathogens bacteria and yeasts, DNA extraction and mucosal IgA evaluation for Ct diagnosis, seminal plasma IL-8 evaluation and serum IgA and IgG anti-Ct analysis. The National Institutes of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) was given to each patient. A total of 109 patients received prulifloxacin and 102 received standard therapy. Prulifloxacin had clinical efficacy rates equivalent to standard therapy (82.5% vs. 79.9%) (P = 0.08) and showed superior microbiological efficacy rates compared to standard therapy, in terms of decreasing mucosal IgA (P < 0.001) and IL-8 levels (P < 0.001). Prulifloxacin was also equivalent to standard therapy for clinical success, as demonstrated by a decrease in the number of patients affected by CP due to Ct infection.
[¹¹C]RAC; (18)F-Fluoromisonidazole; 89-12; 9-[¹⁸F]Fluoropropyl-(+)-dihydrotetrabenazine; Adalimumab, Adecatumumab, ADMVA, ADXS-11-001, Aflibercept, Agatolimod sodium, AGS-004, Alglucosidase alfa, Aliskiren fumarate, Alvocidib hydrochloride, AMG-108, AMG-853, Apixaban, Aripiprazole, Armodafinil, Atazanavir sulfate, Atomoxetine hydrochloride; Bevacizumab, BioMatrix Flex drug eluting stent, Biphasic insulin aspart, Bortezomib, Bosentan; Caspofungin acetate, Cediranib, Cetuximab, ChimeriVax-Dengue, Choriogonadotropin alfa, Cinacalcet hydrochloride, Cizolirtine citrate, Clofarabine, Cocaine conjugate vaccine, CX-717; Darbepoetin alfa, Dasatinib, Decitabine, Denosumab, Desvenlafaxine succinate, Dexamethasone sodium phosphate, Dienogest, Diphencyprone, Doripenem, DTaP-HepB-IPV, Dutasteride; E-7010, Ecallantide, Ecstasy, Eicosapentaenoic acid/docosahexaenoic acid, Emtricitabine, Enfuvirtide, Erlotinib hydrochloride, Eszopiclone, Etonogestrel/ethinyl estradiol, Etoricoxib, Everolimus, Everolimus-eluting coronary stent EVT-201, Ezetimibe, Ezetimibe/simvastatin; Ferumoxytol, Fesoterodine fumavate, Figitumumab, Filgrastim, Fingolimod hydrochloride, Fluticasone furoate, Fluval P, Fluzone, Fondaparinux sodium, Fulvestrant, Fungichromin; Gamma-hydroxybutyrate sodium, Gefitinib, GHB-01L1, GLY-230, GSK-1349572; Hib-MenCY-TT, Hib-TT, HPV-6/11/16/18, Hydrocodone bitartrate; IC-51, Icatibant acetate, Imatinib mesylate, Immunoglobulin intravenous (human), Indetanib, Influenza A (H1N1) 2009 Monovalent Vaccine, Inhalable human insulin, Insulin glargine, Insulin glulisine, Interferon-beta, Ispinesib mesylate, Ixabepilone; Laromustine, Latanoprost/timolol maleate, L-Citrulline, Lenalidomide, Lexatumumab, Linezolid, Lopinavir/ritonavir, Lutropin alfa; Mapatumumab, MDX-066, MDX-1388, Mepolizumab, Methoxy polyethylene glycol-epoetin-beta, Metreleptin, Micafungin sodium, Mometasone furoate/oxymetazoline hydrochloride, Mx-dnG1, Mycophenolic acid sodium salt; Nabiximols, Natalizumab, Nemonoxacin, Norelgestromin/ethinyl estradiol; Oblimersen sodium, Ocriplasmin, Olmesartan medoxomil, Omacetaxine mepesuccinate; Paclitaxel-eluting stent, Pagoclone, Paliperidone, Panitumumab, Pazopanib hydrochloride, PCV7, Pegaptanib octasodium, Peginterferon alfa-2a, Peginterferon alfa-2b/ ribavirin, Pegvisomant, Pemetrexed disodium, Perifosine, Pimecrolimus, Pitavastatin calcium, Plerixafor hydrochloride, Plitidepsin, Posaconazole, Pregabalin, Progesterone capriate; Raltegravir potassium, Ramucirumab, Ranelic acid distrontium salt, Rasburicase, Recombinant Bet V1, Recombinant human insulin, rhFSH, Rolofylline, Romidepsin, Romiplostim, Rosuvastatin calcium; Sapacitabine, Sevelamer carbonate, Sinecatechins, Sirolimus-eluting stent, Sitagliptin phosphate monohydrate, SN-29244, Sorafenib, Sugammadex sodium, Sunitinib malate; Tadalafil, Tafenoquine, Talnetant, Tanezumab, Tapentadol hydrochloride, Tasocitinib citrate, Technosphere/Insulin, Telcagepant, Tenofovir disoproxil fumarate, Teriparatide, Ticagrelor, Tigecycline, Tiotropium bromide, Tipifarnib, Tocilizumab, TS-041; Ulipristal acetate, Urtoxazumab, Ustekinumab; Vandetanib, Varenicline tartrate, Vicriviroc, Voriconazole, Vorinostat, VRC-HIVADV014-00-VP, VRC-HIVDNA016-00-VP; Zoledronic acid monohydrate.
Tapentadol is a novel, centrally acting analgesic combining micro-opioid receptor (MOR) agonism and noradrenaline (NA) reuptake inhibition in a single molecule. Many classic opioids form active metabolites that contribute to analgesia and/or side effects, and the involved cytochrome P450 enzyme complex can give rise to pharmacokinetic drug-drug interactions and variability in drug efficacy due to enzyme polymorphisms. Here we report on the relevance of tapentadol metabolites. Nine metabolites, including the major metabolite tapentadol-O-glucuronide, had no analgesic effects in the tail-flick test in mice. In the phenylquinone writhing test in mice, only 5 of these metabolites showed analgesic effects. The absence or presence of analgesia correlated with moderate activity (0.5 microM < K(i) < 1.1 microM) at the NA transporter or MOR. However, the systemic exposure for these metabolites found in humans after therapeutic oral doses of tapentadol was far below their respective K(i) values at these binding sites (by a factor of > 45). Thus, it is highly unlikely that tapentadol forms metabolites that contribute in any relevant degree to its analgesic activity.
Pentylenetetrazol (PTZ)-induced oxidative stress results in disturbance of the antioxidant enzyme status accompanied by neuronal injury and the development of epilepsy in rats. The present study evaluated the antioxidant effects of curcumin against PTZ-induced convulsions. Over a period of 30 days, i.p. injections of subconvulsive doses of PTZ on alternate days resulted in the development of a well-known kindling model of epilepsy. Spectrophotometric analysis revealed a markedly elevated activity of the antioxidant enzymes malondialdehyde (MDA), catalase and glutathione S-transferase (GST) in the cerebrum and cerebellum of epileptic rats due to PTZ-induced oxidative stress. Oral supplementation of curcumin at a dose of 2 g/kg for 30 days resulted in a transient decrease in MDA, catalase and GST levels in the rat cerebrum and cerebellum. Piperine (20 mg/kg orally) was administered along with curcumin to enhance the bioavailability of the latter up to 20-fold more. Combined treatment with curcumin and carbamazepine (3.6 mg/kg orally) also gave similar results, indicating that the potent antioxidant curcumin can be used as an adjuvant in antiepileptic therapy.
The present study was conducted to investigate the reactivity of the corpus cavernosum smooth muscle after unilateral cavernous nerve neurotomy in rabbits. Rabbits (18) were randomly divided into two groups: sham-operated (n = 9) and those subjected to unilateral neurotomy of a 5-mm segment of the cavernous nerve (n = 9). The reactivity of the corpus cavernosum tissue from the neurotomized and sham groups was studied in organ chambers at 4 weeks postoperation. In the neurotomized group, endothelium-dependent relaxation of the corpus cavernosum smooth muscle to carbachol was significantly increased when compared to the sham group. In addition, the sensitivity (i.e., pD(2)) of neurotomized strips to carbachol was also increased when compared to controls. Electrical field stimulation-induced neurogenic relaxation was significantly reduced in the neurotomized group. Relaxation to the nitric oxide (NO) donor sodium nitroprusside and to papaverine was similar in the cavernosal tissue of both groups. There was no change in agonist potency. Furthermore, neurotomy had no effect on KCl-induced contractile responses. When tissue contraction was induced with phenylephrine to study relaxation to various stimuli, the tension induced was similar in the neurotomized and the sham control groups. We conclude that unilateral, chronic cavernous nerve neurotomy causes significant functional changes to the penile erectile tissue of rabbits, which may contribute to the development of impotence.
Cantharidin (CA) is partially water-soluble. Solid dispersion of CA (CA-SD) in polyethylene glycol 4000 (PEG 4000) was carried out by a solvent-fusion method to increase its dissolution rate and oral bioavailability. The physicochemical properties of this solid dispersion (SD) were evaluated immediately after preparation by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM), and the oral in vivo bioavailability was studied. In in vitro experiments CA was analyzed by high-pressure liquid chromatography (HPLC) and by gas chromatography-mass spectrometry (GC-MS) in in vivo experiments. The solubility and dissolution rate of CA were improved by the SD technique. A comparison of the pharmacokinetics between CA-SD and free CA was performed in rats. The results showed that CA-SD had a higher bioavailability than free CA after oral dosing. By comparing the AUC(0-t) of CA and CA-SD, the relative bioavailability of CA-SD to free CA was 295.4%. From these observations it could be concluded that the CA-SD has a higher absorption than pure CA and this corresponds with the dissolution result in vitro.
Squamous cell carcinoma of the head and neck (SCCHN) have been reported to be related to both genetic and environmental factors, including alcohol consumption and alcohol-metabolizing enzymes such as alcohol dehydrogenase (ADH). We conducted a hospital-based, case-control study including 50 cases with diagnosed SCCHN and 100 controls with non-neoplastic conditions such as upper respiratory tract infection. The genomic DNA was isolated from peripheral blood leukocytes. The ADH1C*1 wild-type and ADH1C*2 variant alleles were analyzed with an RFLP method by using SspI as restriction enzyme. The ADH1C*1 allele frequencies were 0.89 (CI95% = 0.84-0.91) in controls and 0.77 (CI95% = 0.71-0.83) in cases, and respective frequencies of the ADH1C*2 allele were 0.11 (CI95% = 0.07-0.14) and 0.23 (CI95% = 0.17-0.29) among controls and cases (P = 0.01). The ADH1C*1/*1 genotype frequency was significantly higher in the control group (77%) compared to that of the cases (58%) (P = 0.02).These findings suggest that a lower presence of ADH1C*1 allele is associated with SCCHN, but larger numbers are needed to more precisely estimate the interaction, if any, with ADH1C. Interestingly, the ADH1C allele and genotype frequencies in our control group living in Denizli were significantly different compared to a previously published report from healthy volunteers living in Ankara (P < 0.0001).
The present study evaluated the protective action of calcium dobesilate (CDO) in various experimental models of cataract. CDO was studied in hydrocortisone-induced cataract in developing chick embryos and selenite-induced cataract in pups. CDO anti-cataract activity was also evaluated after oral and topical application as eye drops in galactose (30%) fed rats. This study was further extended to evaluate the intraocular penetration of a single dose of 1% CDO (50 microL) in rabbits. CDO exhibited significant protection against cataract in experimental models and considerable penetration after single topical application. Anti-cataract activity may be due to its antioxidant as well as aldose reductase inhibitor properties. Further studies are in progress to evaluate its clinical efficacy in diabetic cataract.
Iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) combined with laser Doppler fluximetry (LDF) is a tool used to determine microvascular endothelial function. Our aim was to study the reproducibility of different parameters of this technique using iontophoresis with low current strength on the forearm skin of healthy subjects. Baseline skin perfusion was done before application of five current pulses with 1 min of current-free interval. Current strength of 0.007 mA, current density of 0.01 mA/cm(2) and charge density of 6 mC/cm(2) were used, along with 1% ACh and 1% SNP. The absolute maximum change in perfusion (max), percent change in perfusion (% change), peak change in perfusion (peak) and area under the curve during iontophoresis (AUC) at the anodal and cathodal leads were recorded. Measurements were performed in three sessions for 2 days. The coefficient of variation (CV) was calculated for each parameter. Among the parameters studied, maximum change in perfusion and peak flux were the most reproducible parameters.
The present study was designed to investigate the effects of angiotensin(1-7) (Ang(1-7)) a Mas receptor agonist, and A-779, a Mas receptor antagonist, in streptozotocin-induced diabetic nephropathy (DN). A single administration of streptozotocin (STZ) (50 mg/kg i.p.) to rats produced diabetes, and diabetic nephropathy developed after 8 weeks of STZ administration. The extent of DN was assessed biochemically and morphologically by measuring serum creatinine, creatinine clearance, blood urea nitrogen (BUN), proteinuria, urinary N-acetyl-beta-D glucosaminadase activity, renal collagen contents, lipid profile, serum nitrite/nitrate concentration and kidney weight/body weight (%). Treatments with Ang(1-7) (576 microg/kg/day i.p. for 4 weeks) and Ang(1-7) plus A-779 (744 microg/kg/day i.p. for 4 weeks) were started after 4 weeks of STZ administration. The treatment with Ang(1-7) attenuated STZ-induced nephropathy in rats by decreasing proteinuria, renal collagen content and by improving endothelial functions without preventing tubular damage. It has been shown for the first time that treatment with Ang(1-7) decreases dyslipidemia and BUN in diabetic rats, implying a renoprotective effect of the peptide. However, serum creatinine, creatinine clearance and kidney weight/body weight (%) remained unaffected with Ang(1-7) treatment. It may be concluded that activation by specific agonists of the Mas receptor may be useful in combating glomerular damage in DN.
Several gene delivery reagents were analyzed for their transfection efficiency. Genes studied belonged to the class of mammalian proteins termed regulators of G-protein signaling (RGS), ranged in size up to 2.2 Kb long and were transfected into the NG108-15, SH-SY5Y and CHO-K1 cell lines. Prior to transfection, genes were cloned into a nonviral vector pcDNA 6.2/EmGFP, so as to express a green fluorescent protein tag at the 3' end. Flow cytometry was used to analyze cell fluorescent activity and thereby transfection efficiency. Gene delivery reagents Lipofectamine 2000 and ExGen 500 produced more effective transfection in NG108-15 cells whereas Lipofectamine 2000, ExGen 500 and TurboFectin 8.0 were more effective in CHO-K1 cells. In both these cell lines, transfection efficiency reached 60-80%. In SH-SY5Y cells, TurboFectin 8.0 produced the best transfection result; however efficiency level was only 5%. Gene size had no effect on transfection efficiency. Unlike Lipofectamine 2000, cells transfected using ExGen 500 showed morphological deformation. Our results suggest that Lipofectamine 2000 is the most suitable transfection medium for gene delivery to NG108-15 and CHO-K1 cells.
Primary Helicobacter pylori eradication rate using triple therapy (a proton pump inhibitor [PPI] + amoxicillin [AMPC] + clarithromycin [CAM], over 7 days) is showing a declining trend. In this study we report recent eradication rates and have evaluated the usefulness of a pack preparation of three drugs. H. pylori eradication rate was 85.1% (57/67) in 2004 but then fell to 75.2% (79/105) in 2005, 70.1% (68/97) in 2006 and 69.9% (58/83) in 2007. With the introduction of packs (lansoprazole [LPZ] 60 mg, AMPC 1500 mg, CAM 400 mg) the eradication rate recovered to 78.0% (110/141) in 2008. A comparative study in 2008 delineated that the eradication rate in the pack group (88.4%, 38/43) was significantly higher than that of the conventional group (73.5%, 72/98). These results suggest that packs of eradication medicine are useful in increasing eradication success.
Inappropriate drug combinations occur frequently and may lead to serious adverse events. In Iran, drug overdose and interactions are relatively common but rarely reported and are mainly derived from admitted subjects. The aim of this study was to determine the prevalence of possible drug-drug interactions via a population database survey in Mashhad, Iran. In this survey all prescriptions paid by insurance companies in the period 21rst March 2006 to 20th March 2008 were studied retrospectively. Data were gathered from the Division of Rational Use Drug, Food and Drug Vice Chancellor of Mashhad University of Medical Sciences, Iran. Drug interactions were categorized based on severity, onset and dynamic/kinetic nature. Incidence was calculated based on the number of interactions/1000 prescriptions. In total 11,562,808 prescriptions were studied, among which 5% showed interactions. Two hundred and four types of potential interactions were detected. Belladonna, phenytoin sodium, cimetidine, propranolol hydrochloride, gentamicin, acetylsalicylic acid (ASA), Antacid, theophylline and carbamazepine were the most common medications. Among them, 54% showed dynamic and 34% kinetic interactions, 11% were categorized to be both and 76% displayed rapid-onset interactions. Moderate interactions were the most dominant (70%) phenomenon. Dynamic and kinetic interactions significantly differed with respect to the onset of interactions (P < 0.001). A rather different pattern of drug-drug interaction exists in Iran, highlighting the need for a nationwide program on related education and a stronger focus on severe and rapid-onset interactions. Further studies warrant the need to explore high-risk patients.
The effects of fluoxetine, a serotonin reuptake inhibitor, were studied in the isolated rat small intestine. Electrical field stimulation (EFS) triggered relaxant and/or contractile responses that were sensitive to tetrodotoxin and fluoxetine at 1.0-10.0 μM. In 0.1 mM hexamethonium-treated tissues, fluoxetine (1.0 μM) induced a relaxant response at 10.0 Hz, while it decreased the attenuation of the contractile responses to EFS. In PCPA pretreated rat jejunum and ileum, 1.0 μM of fluoxetine induced a greater relaxation response to EFS and significantly attenuated the contractile responses to EFS (10.0 Hz) in the duodenum. In a separate experiment, the application of reboxetine (1.0-10.0 μM), a noradrenergic reuptake inhibitor, reduced the contraction and increased the relaxation responses to EFS at 10.0 Hz in most regions. In the presence of hexamethonium (0.1 mM) the application of 10.0 μM reboxetine reduced contractile responses to ESF while enhancing the relaxant responses to EFS at 10.0 Hz. The data suggest that the effects of fluoxetine appear to be related to the selected region of the intestine and may contribute to a better understanding of the serotonergic and cholinergic transmitter mechanisms involved in ileal activity and the gastrointestinal discomfort associated with the clinical use of fluoxetine.
The effects of melatonin and quercetin on the contractile responses of cisplatin-treated rat detrusor smooth muscle were tested. Detrusor strips obtained from four separate rat groups (control, cisplatin, melatonin+cisplatin and quercetin+cisplatin) were mounted in 25 mL organ baths containing Krebs-Henseleit solution (KHS) at 37°C, continuously gassed with 95% O₂ and 5% CO₂. The vasoconstriction induced by acetylcholine (ACh) and potassium chloride (KCl) were compared within the groups. Furthermore, histopathological parameters such as edema, congestion, inflammatory cells, microvascular proliferation, fibrosis, eosinophil, mast cells and epithelial damage were noted. In routine experiments ACh and KCl triggered concentration-dependent contractions. Pretreatment with cisplatin increased the sensitivity but not the maximal response to ACh and KCl. In rats treated with melatonin or quercetin before cisplatin, the EC₅₀ values, but not the maximal response, to both agents were significantly higher than in the cisplatin-treated (CII) group. Histopathological parameters such as edema, congestion, inflammatory cells, microvascular proliferation, fibrosis, eosinophil, mast cells and epithelial damage were all higher in the cisplatin-treated group than in the controls. Melatonin pretreatment significantly decreased mast cell numbers and epithelial damage when compared to cisplatin treatment alone but these effects were not recorded with quercetin pretreatment. These results demonstrate for the first time that melatonin can attenuate urinary bladder injury produced by cisplatin treatment.
Cannabis sativa L. has been used for the treatment of various gynecological diseases in traditional medicine. The potential of this plant to protect against complications of menopause has been raised but rarely studied. Twenty female rats were divided into five groups: sham-operated (sham), ovariectomized (OVX) and three other ovariectomized groups: HST1%, HST2% and HST10% which received 1%, 2% and 10% hempseed, respectively, in their diet for 3 weeks. The effects of hempseed on plasma lipid and lipoprotein profiles, estradiol and calcium levels were evaluated. Rats were tested for behavioral changes using the forced swimming test. The results showed that ovariectomy, independent of the type of diet, caused elevation of plasma calcium, total cholesterol and HDL-cholesterol levels, while hempseed modified this effect. Plasma estradiol levels were significantly lower in the OVX group compared to other groups. The swimming times for the OVX and sham groups were significantly shorter than that of the HSD10% group. All hempseed-treated groups were less anxious and showed significant declines in fecal boli compared to the sham group. The exploratory diving percent decreased in the HST10% group compared with other groups. These results suggest that hempseed may improve post-ovariectomy complications in rats.
Angiotensin (AT) II plays a key role in the regulation of blood pressure and water-salt balance and modulates nociception. Peptides based on AT influence central functions through the activation of AT₁, AT₂ or AT₄ receptors. The aim of this study was to elucidate the role of AT₁ receptors in diurnal variation in nociception in spontaneously hypertensive rats (SHR). Male Wistar rats (16 weeks old) and SHR were caged individually and exposed to light from 08:00 to 20:00 h. The tail cuff method for noninvasive measurement of arterial blood pressure (ABP), paw pressure test for the determination of pain threshold and rotarod test to study motor coordination were used. Chronic treatment was administered to the SHR with the AT₁ receptor antagonist losartan (10 mg/kg/day, s.c.) for 14 days. Spontaneously hypertensive rats showed lower pain threshold and smaller day-night variations of nociception as compared to Wistar rats. Chronic losartan decreased the ABP and produced an inverted diurnal pattern of nociception in SHR, increasing the pain threshold at 03:00 h. Neither strain differences nor changes in motor coordination after losartan treatment were observed in SHR. Our results suggest that SHR have disturbances in diurnal variation in nociception and that the AT₁ receptor plays a role in the regulation of the circadian rhythm of mechanical pain threshold in SHR.
