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Showing 14 results for Ahmadiani

Abolhassan Ahmadiani, Saeed Semnanian, Masoud Fereydouni,
Volume 1, Issue 2 (Fall and Winter 1997)

  Pharmacologists believe analgesic and anti-inflammatory drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) and opioid compounds, due to their side-effects and, in some cases, inadequacy, are not always useful. Therefore it seems necessary to search for newer analgesic compounds. In traditional Iranian Medicine, the leaf and rhizome of Sambucus ebulus is used as a topical medication in the treatment of pain caused by bee stings, nettle stings and joint inflammation. We therefore decided to study the analgesic effects of this plant. Two methods, the tail flick test for acute pain and the formalin test for chronic pain were employed to measure pain. Analgesic effects of 50, 100 and 200 mg/kg doses of S. ebulus rhizome extract were compared with 300 mg/kg sodium salicylate as a positive control. The plant extract relieved pain in the tail flick test and in both phases of the formalin test, while sodium salicylate only treated pain in the formalin test. In none of the two tests was naloxone effective in inhibiting the analgesic effect of S. ebulus extract. Phytochemical investigations and previous reports suggest flavinoids to be the probable analgesic compounds.

Mohammad Hossein Pourgholami, Habibollah Saadat, Abolhassan Ahmadiani, Majid Golkar, Hossein Amini, Maryam Goudarzvand,
Volume 2, Issue 1 (Spring and Summer 1998)


  In this double blind crossover study we assessed the bioequivalence of 200 mg enteric coated sodium valproate tablets manufactured by Roozdarou with 200 mg enteric coated sodium valproate (Orlept) manufactured by Desitin, Germany. Twelve healthy male volunteers were administered a single dose of 600 mg sodium valproate manufactured by Roozdarou, followed by a similar dose of Orlept, 2 weeks later. During the first 48 hours following each administration, 11 blood samples were obtained from each volunteer. Plasma levels of valproate were measured with a sensitive and selective HPLC method. Pharmacokinetic parameters were calculated for each administration to determine the bioequivalence of the two products, including maximum plasma concentration (Cmax), time to attain maximum plasma concentration (Tmax), and area under the plasma concentration-time curve (AUC). Comparison of these figures demonstrated no significant difference therefore 200 mg enteric coated sodium valproate tablets manufactured by Roozdarou are bioequivalent to 200 mg enteric coated Orlept tablets.

Abolhassan Ahmadiani, Tahereh Jesmani, Mohammad Javan,
Volume 3, Issue 2 (Fall and Winter 1999)

  Tolerance and dependence are two main problems that have limited morphine administration as an analgesic drug and they might be as a result of changes in the number and affinity of receptors, dysfunction of adenylate cyclase, impaired coupling between activated µ receptor and K+ channels, and changes in the K+ and Ca2+ channels. There are several reports concerning the role of some of these factors in the occurrence of tolerance and dependence. It has been suggested that KATP channels are involved in morphine-induced analgesia. In this study the effect of a constitutive KATP opening state by chronic administration of minoxidil (a KATP opener) on morphine tolerance and dependence was studied using tail-flick test. A single dose (5 mg/kg) of morphine, but not its chronic administration produced analgesia (p<0.001). In addition single and chronic (2 mg/kg) administration of minoxidil produced analgesia (p<0.0001 vs ethanol) and chronic co-administration of morphine and minoxidil did not reduce morphine tolerance, while It reduced jumping (p<0.01) and weight loss (p<0.05) as signs of dependence. Naloxone did not antagonize minoxidil analgesia. Morphine analgesia was reduced by glibenclamide 2 mg/kg (p<0.001). These results may suggest that co-administration of morphine and minoxidil is able to reduce some dependence signs of morphine. Since this treatment reduced the jumping and weight loss, but not the writhing sign, it is concluded that different mechanisms and sites of action are involved in the development of each of the dependence signs.

Alireza Parvizpour, Abolhassan Ahmadiani, Mohammad Javan, Mohammad Kamalinejad,
Volume 3, Issue 2 (Fall and Winter 1999)

  There are several reports on the therapeutic effects of TFG in Iranian traditional medical literature such as antinociceptive, antipyretic, and anti-inflammatory, antidiabetic and antidiuretic effects. The anti-inflammatory and anti-pyretic effects of TFG have been confirmed in experimental models. In the present study, the antinociceptive effect of TFG extract in formalin and tail flick tests and its site of action were investigated on NMRI rats (220 ± 20 g). The TFG extract was administered by three routes, i.e. i.c.v., i.t. and i.p. at different doses. The effect of i.p. administration was also examined in tail flick test. The results showed that i.p. administration of aqueous extract of TFG leaves induced analgesia in tail flick and both phases of formalin test. The i.t. administration at doses of 0.5, 1, 2 and 3 mg/rat showed significant antinociceptive effect in formalin test, however i.c.v. administration of extract had no antinociceptive effect. The results of the present study supported the facts that: 1) TFG extract has antinociceptive effect in first and second phases of formalin and tail flick tests and 2) the site of its action in the first and second phase of formalin test might be at spinal cord and with regard to its anti-inflammatory effect, peripheral mechanisms may be involved in its analgesic effect in the second phase of formalin test.

Mohammad Javan, Fereshteh Motamedi, Abolhasan Ahmadiani, Fatemeh Masoudnia,
Volume 7, Issue 1 (Spring and Summer 2003)

It has been reported that morphine tolerance does not develop in the presence of chronic pain. Therefore, this study was conducted to find out whether chronic inflammatory pain is able to eliminate or attenuate the developed tolerance to analgesic effect of morphine and also to investigate the role of lumbar spinal cord as a candidate site for this interaction. Tolerance was induced in adult male NMRI rats using daily injection of morphine at a dose of 20 mg/kg (i.p.) for 4 days, or using daily injection of morphine at a dose of 15 pg/rat (i.t.) for 7 days. Chronic inflammatory pain was induced using 50 µl of 5% formalin, injected into the hind paws. The antinociceptive effect of morphine at a dose of 10 mg/kg on day 5 (for i.p. treated rats) or morphine at a dose of 15 pg/rat on day 8 (for i.t. treared rats) were assessed using tail flick test. The results showed that those animals receiving saline (i.t. or i.p.) have potent analgesia (p<0.001), while animals treated with chronic morphine have only a weak analgesia for i.p. treatment (p<0.05). In addition, animals treated with both repeated morphine and 5% formalin (s.c.) into the hind paw showed potent analgesia (p<0.01). Meanwhile, the developed tolerance was reversed by chronic pain induction in the following days (p<0.01). It is concluded that chronic formalin-induced inflammatory pain, not only could prevent tolerance development, but also is able to reverse the developed tolerance to antinociceptive effect of morphine. Since in i.t.-treated animals, tolerance was induced in lumbar spinal cord level, it can be concluded that chronic formalin-induced inflammatory pain, as a stress (through HPA axis) or as a factor which directly exerts some modulations on pain transmission system, is able to prevent tolerance to analgesic effect of morphine through lumbar spinal cord.
Shohreh Movahedi, Mohammad Javan, Abolhassan Ahmadiani,
Volume 10, Issue 2 (Summer 2006)

Introduction: Ultra low dose (ULD) morphine induces hyperalgesia which is mediated by excitatory Gscoupled opioid receptors. This study was designed to investigate the development of tolerance to hyperalgesic effect of morphine. Also we attempt to seek possible similarity, in view of Gs proteins, between hyperalgesic effect of ULD and hyperalgesic effect after tolerance to HD. Method: Male Wistar rats weighing 180-220 g were used. All injections were given intra peritoneally. For tolerance induction animals received ULD or HD for 5 days and at the 6th day tail flick test was performed before and 30 min after morphine administration. Effect of pretreatment with ULD on analgesic tolerance was assessed by injection of ULD before HD in 5 consecutive days then TF record was done after HD injection on 6th day. Time interval between injections was 15 minutes. Cross tolerance assay was measured by recording the response to a specified dose in 6th day after 5 days treatment with another dose. Oseltamivir, as a GM1 ganglioside inhibitor, was used for inhibition of Gs signaling. . Results: Our results showed that: 1) tolerance was established after chronic injection of ultra low dose (ULD) of morphine. 2) Pre-treatment by ULD reduced tolerance to therapeutic dose of morphine. 3) Cross tolerance to analgesia was observed after chronic administration of ULD. 4) Combination therapy with oseltamivir blocked hyperalgesia reduced analgesic tolerance and attenuated the development of tolerance to hyperalgesic effect of morphine. Conclusion: The results showed the partially common mechanism for development of tolerance to hyperalgesic and analgesic effect of morphine. Signaling through Gs proteins seems to be a common pathway.
Masoud Fereidoni, Mohammad Javan, Saeed Semnanian, Abolhasan Ahmadiani,
Volume 10, Issue 4 (Winter 2007)

Introduction: Different mechanisms are involved in stress induced analgesia (SIA) and hyperalgesia (SIH). Repeated stress induces development of tolerance to SIA. The role of HPA axis and Gs signaling pathway in these effects are investigated in the current study. Methods: Forced swim stress (5 min/day) in water (20±1 ºC) was employed to adult male Wistar rats (200-250 g). The nociceptive threshold was assessed using tail flick test. Adrenalectomized (ADX) rats were also subjected to stress tests. Oseltamivir was used to block Gs signaling pathway. Results: Stress produced analgesia for 1 h (p<0.001) and hyperalgesia during 3-24 h after its induction (p<0.05). Repeated administration of the stress caused tolerance development to SIA and increased SIH recorded at 24 h after each session (p<0.001). Oseltamivir couldn’t reverse the SIH. Dexamethasone produced hyperalgesia from 30 min (p<0.001) to 24 h after its administration (p<0.01). Repeated injection of dexamethasone increased the hyperalgesia recorded at 24 h after treatment (p<0.001). In ADX animals SIA continued for 24 h (p<0.01). Adrenalectomy attenuated the chronic stress-induced SIA tolerance and eliminated SIH. Conclusion: SIH is suggested to be related to adrenal activity which also has a role in SIA tolerance. Upper parts of HPA axis seems to be responsible for SIA. Oseltamivir could not reverse the SIH. Therefore, the Gs signaling pathway activation by opioid system may not be responsible for SIH.
Parichehr Hassanzadeh, Abolhassan Ahmadiani,
Volume 11, Issue 1 (Spring 2007)

Introduction: Dark neurons which their morphological characteristics are consistent with those of cells undergoing apoptosis, are generated as an acute or delayed consequence of several pathological situations. The present study was designed to evaluate whether inflammatory pain regarding the role of NO and JNK lead to the formation of dark neurons in the dorsal horn of the lumbar spinal cord in rats. Methods: Acute or chronic inflammatory pain was induced by intraplantar injection of 1%, 2.5% or 5% formalin in male Wistar rats weighing 250-300 g (n=7). Spectrophotometrical analysis of the serum nitrite (metabolite of NO) and histological procedures for detection of dark neurons were performed at definite time intervals. Pretreatment with celecoxib 10, 20 or 40 mg/kg/i.p. quercetin 40 or 100 μg/rat/i.t. as an inhibitor of JNK pathway, and PTIO 20 or 30 μg/rat/i.t, as NO scavenger, were performed to investigate the role of NO and JNK. Results: Injection of formalin led to the increase of the serum nitrite in the concentration and time-dependent manners. The effect of 5% formalin was significantly eminent which was blocked by celecoxib 40 mg/kg. Visual inspections of the spinal cord sections showed that on day 5, following chronic injections of 5% formalin, numbers of dark neurons were significantly increased in the lumbar dorsal horn. Acute and chronic administration of other concentrations of formalin did not induce any remarkable dark phenotype. Injections of celecoxib 40 mg/kg, quercetin 100 μg/rat/i.t. or PTIO 30 μg/rat/i.t. before each injection of 5% formalin, led to a reliable reduction of dark neurons. Conclusion: The results showed that the intensity and duration of the inflammatory pain play a major role in its peripheral and central developed disorders. According to the role of NO and JNK it seems that administration of their inhibitors, or an appropriate dose of celecoxib may exert a protective effect against the aforementioned consequences.
Mojtaba Dolatshahi-Somesofla, Fereshteh Motamedi, Abolhasan Ahmadiani, Saeed Esmaili-Mahani,
Volume 11, Issue 3 (Fall 2007)

Nimodipine, an L-type calcium channel blocker, can induce analgesia. However, it is not clear that this analgesic effect is at the level of spinal or supraspinal pain pathway. In addition, it has been reported that the analgesic effect of nifedipine, another L-type calcium channel blocker is related to the HPA axis, but there is no report indicating the role of this axis in the analgesic effect of nimodipine. Methods: Analgesia was measured by tail-flick (TF) test involving spinal reflexes and by hot-plate (HP) requiring an intact central nervous system. Assays were done before and 15, 30, 60 and 120 min after drug administration in the intact, sham operated and adrenalectomized rats. To identify the interaction between nimodipine and HPA axis, plasma corticosterone level was measured using the radioimmunoassay. Results: Nimodipine significantly decreased the plasma corticosterone level, and showed significant antinociception in both tests. Adrenalectomy potentiated the analgesic effect of nimodipine which was reversed by corticosterone replacement. Furthermore, nimodipine analgesic effect in ADX rats was more potent in HP test (compared to TF test). Nimodipine, at mentioned doses, did not alter animal’s movement indices in activity monitoring test. Conclusion: Nimodipine involves both spinal and supraspinal sites to control thermal pain transmission in presence of adrenal gland. It seems that there is a mutual interaction between nimodipine and HPA axis, especially at supraspinal levels.
Leila Khalaj, Habibollah Peirovi, Fariba Khaodagholi, Azadeh Abdi, Leila Dargahi, Fatemeh Mohagheghi, Abolhassan Ahmadiani,
Volume 14, Issue 1 (Spring 2010)

Introduction: Postoperative neurological deficit is the most devastating complication after thoracoabdominal aortic aneurysm repair. Despite demonstrated neuroprotective effects of estradiol, its protective efficacy against spinal cord ischemia-reperfusion and underlying mechanisms are not yet elucidated. Methods: Two groups, each of 10 New Zealand white male rabbits, were studied. Control group received sesame oil (vehicle) while the treatment group received 17-β-Estradiol Cypionate (1 mg/kg) dissolved in sesame oil, 30 minutes before abdominal aortic clamping for 18 minutes. A group of sham operated animals was also included, which consisted of 5 rabbits subjected to operative dissections without aortic occlusion. After 48 h reperfusion we investigated the efficacy of estradiol in attenuating the spinal cord ischemia-induced pathology through neurological, histopathological, and western blot assessments. Results: The results showed that administration of estradiol 30 minutes before induction of spinal cord ischemia in rabbits improved functional outcome and prevented the worsening pattern of neurological function over 48 hours. Near to normal histopathological outcome of lumbar part of spinal cords in these animals confirmed neuroprotective effects of estradiol. Estradiol also reduced spinal cord Heat shock protein 70 and cleaved caspase-3 in this ischemic context. Conclusion: Estradiol can be considered as a potential candidate to protect against spinal cord ischemiareperfusion- induced paraplegia resulting from thoracoabdominal aortic aneurysm repairs.
Azadeh Abdi, Fatemeh Mohagheghi, Homayoon Sadraei, Leila Dargahi, Leila Khalaj, Abolhassan Ahmadiani,
Volume 14, Issue 3 (Fall 2010)

Introduction: Evidence suggests that neuronal apoptosis in neurodegenerative diseases is correlated with inflammatory reactions. The beneficial or detrimental role of apoptosis in neuroinflammation is unclear. Elucidating this question may be helpful in management of neurodegenerative diseases. Since TNF-α is able to induce apoptosis as well as increased viability of the cells by activation of caspases or NF-kB, respectively, the question is what will happen if the balance between the two pathways is disturbed by inhibition of apoptosis. Methods: In this study, we used β–amyloid peptide (soluble Aβ monomer) injection into the Wistar male rat prefrontal cortex for induction of neuroinflammation in the hippocampus. Levels of TNF-α and caspase-3 were determined via western blot analysis. Using chronic intracerebroventricular administration of caspase inhibitors, z-VAD –fmk and z-DEVD-fmk, we inhibited apoptosis. Exploring consequences of apoptosis inhibition, activity of NF-kB was evaluated via western blotting. Results: After β–amyloid peptide injection we observed an increase in TNF-α and caspase3 as an inflammatory cytokine and apoptotic marker, respectively (P<0.001 and P<0.0001, respectively). As a consequences of apoptosis inhibition, nuclear NF-κB was decreased and cytosolic NF-κB was increased and these changes were significant compared to Aβ-injected group (P<0.001 and P<0.05, respectively). Conclusion: Caspase inhibition as an initiator of apoptosis, probably by attenuation of NF-kB activity, protect cells from abnormal survival and proliferation.
Fereshteh Pourabdolhossein, Sabah Mozafari, Mohammad Javan, Sied Javad Mirnajafizadeh, Abolhassan Ahmadiani,
Volume 14, Issue 4 (Winter 2011)

Introduction: Demyelination is one of the main causes of neurological disability. It is the end product of numerous pathological processes, multiple sclerosis (MS) being the most common cause. More than 70% of the MS patients suffer from optic disturbances. This disease commonly affects the optic pathway, particularly the optic nerves and chiasm. Several attempts have been made to produce a suitable model of demyelination in optic apparatus up to now. Methods: Local demyelination model was generated using direct injection of lysolecithin (LPC) into the optic chiasm of C57/BLJ6 mice without any undesirable distributions of gliotoxin into other brain structures. Histological and electrophysiological assessments of the processes of demyelination and remyelination in the animal model were done with specific myelin staining and visual evoked potential (VEP) recordings. Results: In this study, both electrophysiological and histological results demonstrated that maximum level of demyelination was observed on day 7 post lesion and an incomplete yet significant remyelination took place on day 14 post lesion. Conclusion: Results showed a relatively rapid endogenous myelin repair in mice optic chiasm. Furthermore, this report might offer a new tool to address possible involvement of new origins of myelin-forming cells and subsequently their manipulation to promote myelin repair in the adult central nervous system.
Mir-Shahram Safari, Abbas Haghparast, Saeed Semnanian, Abolhassan Ahmadiani,
Volume 15, Issue 1 (Spring 2011)

Introduction: Previous studies have shown that stimulation of lateral hypothalamus (LH) produces antinociception. Orexin-A (OXA) receptor is strongly expressed in the nucleus locus coeruleus (LC) and orexinergic fibers densely project from LH to LC. In this study, we assessed the role of LC and its OXA receptors in antinociceptive response induced by LH chemical stimulation in the rat. Methods: The cholinergic agonist carbachol (125nmol/0.5μl saline) and lidocaine (2% 0.5μl) were unilaterally microinjected into the LH with the concurrent LC inactivation. In another set of experiments, SB-334867 an OXA selective antagonist or its vehicle were unilaterally infused in LC to study its effect on LH stimulation-induced antinociception. Antinociceptive responses were obtained by the tail flick test and were presented as maximal possible effect (MPE) at 5, 10, 15, 20, 30 and 60 min after drug administrations. Results: The results showed that microinjection of carbachol into the LH significantly induced antinociception at 5 and 10 min (p<0.001). This effect was significantly blocked by microinjection of lidocaine into the LC. Additionally, intra-LC administration of SB-334867 (4.5 μg) could suppress the LH stimulation-induced antinociception by carbachol at 5 and 10 min post-injection times (p<0.001). Conclusion: Our findings showed that analgesic response induced by LH stimulation is mediated in part by the subsequent activation of LC neurons and results from the activation of orexinergic inputs into the LC that can modulate the pain processing.
Sara Nikseresht, Fariba Khodagholi, Abolhassan Ahmadiani,
Volume 21, Issue 2 (June 2017)

Necroptosis, as a novel concept, has been recently introduced in scientific literature. Much of our knowledge about necroptosis comes from ligation of tumor necrosis factor-α to its receptor, TNF receptor 1. Receptor-interacting protein kinase 1, receptor-interacting protein kinase 3 and its substrate, the pseudokinase mixed lineage kinase domain-like protein, have been comprehensively studied as influential components of this process. Emerging pioneering evidence suggests that many molecules, organelles and mechanisms are involved in necroptosis pathway. The aim of this review is presentation of molecular mechanisms of necroptosis in three phases including initiation, regulation and execution of necroptosis. Moreover, this review will summarize unprecedented insights into the contribution of various organelles and cell compartments such as mitochondria, endoplasmic reticulum, nucleus, lysosomes and Golgi apparatus in necroptosis pathway.

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