Imidazoline Receptor Agonists for Managing Hypertension May Hold Promise for Treatment of Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH), which accounts for 10% of all strokes, leads to higher morbidity and mortality compared with other stroke subtypes. Hypertension has been recognized as a major risk factor for ICH. Current antihypertensive options have not been fully effective for either prevention of ICH or ameliorating its complications. Therefore, attempts should be made to use novel antihypertensive medications for more effective management of blood pressure (BP) in the acute phase of ICH. Imidazoline receptor (IR) agonists can potentially be effective agents for BP control with the adjunctive ability to attenuate post-ICH brain injury. IR agonists render neuroprotective effects including inhibition of inflammatory reactions, apoptotic cell death, excitotoxicity, and brain edema. Given these properties, the present review aims to focus on the application of IR agonists for managing BP in ICH patients.

Selective activation of α7 nicotinic acetylcholine receptor by PHA-543613 improves Aß25-35-mediated cognitive deficits in mice.

Agonists of α7 nicotinic acetylcholine receptors (nAChRs) are currently being considered as therapeutic approaches for managing cognitive deficits in Alzheimer's disease (AD). Present study was designed to evaluate the effect of α7 nAChR selective activation by PHA-543613 (PHA) on beta-amyloid (Aß)25-35-mediated cognitive deficits in mice. For this purpose, PHA (1mg/kg, i.p.), a selective α7 nAChR agonist, and galantamine (Gal) (3mg/kg, s.c.), an acetylcholine-esterase inhibitor (AChEI) effects on α7 nAChR were tested in Aß25-35-received (intracerebroventricular, 10 nmol) mice model of AD. Methyllycaconitine (MLA) (1mg/kg, i.p.), a α7 nAChR antagonist, was used for receptor blockage effects evaluation. Working and reference memory in animals was assessed by the Morris water maze (MWM) task. The mRNA and protein levels of α7 subunit were analyzed by real-time PCR and Western blotting, respectively. PHA and Gal, ameliorate Aß-impaired working and reference memory. However, Gal had less effect than PHA in this regard. Pretreatment with MLA reverses both Gal and PHA effects in MWM. PHA and Gal treatment prevent Aß-induced α7 subunit protein reduction, but Gal has lesser effect than PHA. This effect blocked by pretreatment with MLA. In neither the pretreatment nor treatment group, the mRNA levels of nAChR α7 subunit were significantly changed. Therefore, α7 nAChR activation, reduces Aß-induced cognitive deficits and increases the α7 protein level and subsequent neuron survival. However, blockage of receptor, increases Aß toxicity and cognitive impairment and reduces the α7 nAChR protein level and flowing neuroprotection.

Investigation of the memory impairment in rats fed with oxidized-cholesterol-rich diet employing passive avoidance test.

BACKGROUND: Recent studies have shown that hypercholesterolemia, besides being a risk factor for cardiovascular diseases, has also toxic effects on central nervous system. The design of the present study was to investigate the effects of dietary cholesterol and oxidized cholesterol on cognitive function. METHODS: Male Wistar rats were randomly divided into 3 groups. The animals were fed with three normal, 2% cholesterol-rich, and 2% oxidized cholesterol-rich diets for 14 weeks. Memory impairment was analyzed by passive avoidance test. Coenzyme Q10 content was also measured by a validate RP-HPLC method. Besides, lipid peroxidation in serum and brain tissue was determined by malondialdehyde concentration measurement. RESULTS: The results showed that feeding rats with high oxidized cholesterol diet for 14 weeks significantly impaired the cognitive function compared to the normal (P<0.001) and high cholesterol-fed groups (P<0.01). The memory impairment was positively correlated to the serum level of the oxidized LDL; it was significantly associated with the increased malondialdehyde concentration on the brain tissue of both groups (P<0.05 and P<0.001, respectively). The total antioxidant level in the serum was also decreased in rats fed with the oxidized cholesterol (P<0.05). Moreover, the brain coenzyme Q10 content was significantly declined in the animals fed with the oxidized cholesterol-rich diet compared to the animals fed with the normal (P<0.01) and cholesterol-rich diets (P<0.05). CONCLUSION: The results suggested that the high dietary intake of the oxidized-cholesterol might impair the memory that could be correlated to the oxidative stress and declined the coenzyme Q10 content of the brain tissue.

Polypharmacy-induced drug-drug interactions; threats to patient safety.

Patient safety is an increasingly recognized challenge and opportunity for stakeholders in improving health care delivery. Because of extensive use of medicines, life expectancy is increasing and elderly as well as comorbidities need polypharmacy, and therefore the risk of drug-drug interactions (DDIs) increases.We searched PubMed and ScienseDirect for epidemiology of articles describing the frequency of potential DDIs published up to 2011 in title, abstract, keywords and text.Studies show that the rate of DDIs both in outpatients and hospitalized patients is high. The elderly, <5 year-old children and women are at higher risks for it. Also, the rate of DDIs in patients who suffer from chronic kidney disease (CKD), cardiovascular disease (CVD) such as heart failure (HF) and hypertension (HTN) and cancers is significant.Physicians, for lowering the risk of DDIs, should take precise drug history, prescribe appropriate and lowest drugs and ultimately counsel with clinical pharmacologist as a key strategy in order to insure the patient safety. This article reviews the existing data concerning this problem to provide an aid for choosing the appropriate drugs and prescribe the most effective with the lowest DDIs for providing patient safety.

The effect of altitude on breaking seed dormancy and stimulation of seed germination of Persian hogweed (Heracleum persicum).

Persian hogweed is a perennial herb and aromatic plant which has pharmaceutical and fodder values, and the main propagation method of this species is seed. The goal of this study was to investigate the effect of altitude on breaking dormancy and stimulate seed germination of this species. The study was designed and carried out using the test of seed analysis. For our purpose, seeds were collected from three different altitudes (1700, 2200, 2700 masl) in Kojoor area. After initial purification, germination percent (GP) and speed (GS) of each elevation were determined by cold stratification compared to control. According to results, control seeds did not germinate, showing that the seeds of this species need to be treated. Statistical analysis of results showed that there are significant differences between GP and GS of each elevation, as seeds of higher elevation had slower and less germination in longer periods. So, changes in elevation are an effective factor on seed germination characteristics of this species and this factor has to be considered in seed preparation and restoration with this species.

Investigating the altitude effect on the quantity and quality of the essential oil in Tanacetum polycephalum Sch.-Bip. polycephalum in the Baladeh region of Nour, Iran.

Medicinal plant are grown and produced in different ecosystems and sites under the influence of different potential factors, including the altitude as one of the vital determinants in the quantity and quality of the plants. One of the species that grows in the highlands is Tanacetum polycephalum, an aromatic perennial of the Asteraceae. This species is characterized to be antiseptic, analgesic, anesthetic, disinfective, expectorant, anti-cancer, anti-allergic, and conducive to low blood pressure. The purpose of this study is to investigate the essential compositions in the aerial parts of T. polycephalum at the time of flowering, and in three different altitudes of the Baladeh region of Nour. Thus, the essential oil was extracted from the aerial parts in the flowering stage of the plant at three altitudes of 1 600, 2 400 and 3 200 m using a water distillation method, and the essential oil compositions were identified using GC and GC/MS instruments. One-way ANOVA method was conducted to analyze the obtained data using SPSS, and a Duncan test was administered to compare the means. The results indicated that the essential output obtained from the altitudes of 1 600, 2 400 and 3 200 m was (0.74 ± 0.01)%, (1.09 ± 0.02)%, and (1.32 ± 1.2)%, respectively, so that the altitude of 3 200 m revealed the greatest quantity, and the altitude of 1 600 m represented the smallest quantity. Moreover, the essential oil compositions showed the highest percentage in the altitude of 3 200 m and the lowest percentage at the altitude of 1 600 m. The results showed that as the altitude increases, the essential oil compositions revealed the greater quantity and percentage in the aerial parts of T. polycephalum.

5-HT(1A) receptor activation improves anti-cataleptic effects of levodopa in 6-hydroxydopamine-lesioned rats.

BACKGROUND AND THE PURPOSE OF THE STUDY: In Parkinson>s disease (PD) prolong use of L-DOPA causes some motor disorders such as wearing-off and L-DOPA induced dyskinesia (LID). In this investigation the effect of 8-OHDAPT, as a 5-HT(1A) agonist on anti-cataleptic effect of L-DOPA in 6-hydroxydopamine (6-OHDA) lesioned male Wistar rats was investigated. METHODS: Catalepsy was induced by unilateral injection of 6-OHDA (8 µg/2µl/rat) into the central region of the SNc. After 3 weeks as a recovery period, animals received intraperitoneally (i.p.) L-DOPA (15 mg/kg) twice daily for 20 days, and anti-cataleptic effect of L-DOPA was assessed by bar-test at days of 5, 10, 15 and 20. RESULTS AND MAJOR CONCLUSION: The results showed that L-DOPA had anti-cataleptic effect only until the day of 15, and its effect was decreased on the day of 20. On the day of 21, rats were co-injected with three different doses of 8-OHDAPT (0.1, 0.5 and 2.5 mg/kg, i.p.) and L-DOPA (15 mg/kg, ip). 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OHDAPT) improved anti-cataleptic effect of L-DOPA at the dose of 0.5 mg/kg. Moreover the effect of 8-OHDAPT on anti-cataleptic effect of L-DOPA (15 mg/kg, ip) was abolished by 1-(2-methyoxyphenyl)-4-[4-(2-phthalamido) butyl] piperazine hydrobromide (NAN-190; 0.5 mg/kg, i.p.) as a 5-HT(1A) receptor antagonist. According to the obtained results, it may be concluded that activation of 5-HT(1A) receptors by 8-OHDAPT may improve anti-cataleptic effect of L-DOPA in a 6-OHDA- induced rat model of PD. Further studies are required to clarify the exact mechanism of interaction between 5-HT(1A) and dopaminergic neurons.