Cholecystokinin Receptor Mechanism(s) and Morphine Tolerance in Mice

Abstract: In a previous work, the effects of cholecystokinin receptor agonists on tolerance to morphine antinociception were evaluated. In the present study, the influence of cholecystokinin antagonists on the inhibition of tolerance to morphine antinociception by cholecystokinin agonists has been investigated. Maximum tolerance to morphine antinociception was obtained by morphine administration (50 mg/kg) to mice once daily for 4 days. The cholecystokinin receptor agonists caerulein (0.005 mg/kg) or cholecystokinin-8 (0.01 mg/kg) but not unsulfated cholecystokinin-8 (0.01 mg/kg) decreased the development of tolerance to morphine (9 mg/kg). The cholecystokinin_A receptor antagonist MK-329 (1 mg/kg) or the cholecystokinin_B receptor antagonist L-365,260 (0.25, 0.5 and 1 mg/kg) also diminished the tolerance to morphine antinociception. When animals were challenged with different doses of MK-329 (0.25, 0.5 and 1 mg/kg) against cholecystokinin-8 (0.01 mg/kg), caerulein (0.005 mg/kg) or unsulfated cholecystokinin-8 (0.01 mg/kg) on day 4 in tolerant mice, different response were obtained. Higher doses of MK-329 (1 mg/kg) caused a small decrease in attenuation of the morphine tolerance induced by cholecystokinin-8 and caerulein. Low doses of L-365, 260 diminished the effect of cholecystokinin-8 on morphine tolerance. Conversely high doses of the drug potentiated the response of caerulein (0.005 mg/kg). When animals were treated with MK-329 or L-365,260 before unsulfated cholecystokinin-8, reduction of the tolerance to morphine antinociception was obtained. These data indicate that both cholecystokinin receptors may modulate morphine tolerance.     

A review on the role of antioxidants in the management of diabetes and its complications.

Diabetes is a prevalent systemic disease affecting a significant proportion of the population worldwide. The effects of diabetes are devastating and well documented. There is increasing evidence that in certain pathologic states, especially chronic diseases, the increased production and/or ineffective scavenging of reactive oxygen species (ROS) may play a critical role. High reactivity of ROS determines chemical changes in virtually all cellular components, leading to lipid peroxidation. Production of ROS and disturbed capacity of antioxidant defense in diabetic subjects have been reported. It has been suggested that enhanced production of free radicals and oxidative stress is central event to the development of diabetic complications. This suggestion has been supported by demonstration of increased levels of indicators of oxidative stress in diabetic individuals suffering from complications. Therefore, it seems reasonable that antioxidants can play an important role in the improvement of diabetes. There are many reports on effects of antioxidants in the management of diabetes. In this paper, after complete bibliography and criticizing all relevant articles, the relationships between diabetes and oxidative stress and use of antioxidants in the management of diabetes and its complications have been well reviewed. This review well indicates that oxidative stress is involved in the pathogenesis of diabetes and its complications. Use of antioxidants reduces oxidative stress and alleviates diabetic complications.     

Estimating the Cost of Illness of Prostate Cancer in Iran

Purpose

Prostate cancer is the second most common cancer among men worldwide. In the past 10 years in Iran, prostate cancer has increased and become more common among hormone-related cancers. As the percentage of seniors in the population increases, the economic burden of this cancer will likely increase significantly. This study aims to estimate direct and indirect costs of treatment at different stages of prostate cancer in Iran.

Induction of clinical response and remission of inflammatory bowel disease by use of herbal medicines: A meta-analysis

AIM:To evaluate the efficacy and tolerability of herbal medicines in inflammatory bowel disease(IBD)by conducting a meta-analysis.METHODS:Electronic databases were searched for studies investigating efficacy and/or tolerability of herbal medicines in the management of different types of IBD.The search terms were:"herb"or"plant"or"herbal"and"inflammatory bowel disease".Data were collected from 1966 to 2013(up to Feb).The"clinical response","clinical remission","endoscopic response","endoscopic remission","histological response","histological remission","relapse","any adverse events",and"seriousadverse events"were the key outcomes of interest.We used the Mantel-Haenszel,Rothman-Boice method for fixed effects and DerSimonian-Laird method for random-effects.For subgroup analyses,we separated the studies by type of IBD and type of herbal medicine to determine confounding factors and reliability.RESULTS:Seven placebo controlled clinical trials met our criteria and were included(474 patients).Comparison of herbal medicine with placebo yielded a significant RR of 2.07(95%CI:1.41-3.03,P=0.0002)for clinical remission;a significant RR of 2.59(95%CI:1.24-5.42,P=0.01)for clinical response;a non-significant RR of 1.33(95%CI:0.93-1.9,P=0.12)for endoscopic remission;a non-significant RR of 1.69(95%CI:0.69-5.04)for endoscopic response;a non-significant RR of 0.64(95%CI:0.25-1.81)for histological remission;a non-significant RR of 0.86(95%CI:0.55-1.55)for histological response;a non-significant RR of 0.95(95%CI:0.52-1.73)for relapse;a non-significant RR of 0.89(95%CI:0.75-1.06,P=0.2)for any adverse events;and a non-significant RR of 0.97(95%CI:0.37-2.56,P=0.96)for serious adverse events.CONCLUSION:The results showed that herbal medicines may safely induce clinical response and remission in patients with IBD without significant effects on endoscopic and histological outcomes,but the number of studies is limited to make a strong conclusion.     

Antioxidant therapy in the management of acute, chronic and post-ERCP pancreatitis： A systematic review

We systematically reviewed the clinical trials which recruited antioxidants in the therapy of pancreatitis and evaluated whether antioxidants improve the outcome of patients with pancreatitis. Electronic bibliographic databases were searched for any studies which investigated the use of antioxidants in the management of acute pancreatitis （AP） or chronic pancreatitis （CP） and in the prevention of post-endoscopic retrograde cholangio-pancreatography （post-ERCP） pancreatitis （PEP） up to February 2009. Twenty-two randomized, placebo-controlled, clinical trials met our criteria and were included in the review. Except for a cocktail of antioxidants which showed improvement in outcomes in three different clinical trials, the results of the administration of other antioxidants in both AP and CP clinical trials were incongruent and heterogeneous.Furthermore, antioxidant therapy including allopurinol and N-acetylcysteine failed to prevent the onset of PEP in almost all trials. In conclusion, the present data do not support a benefit of antioxidant therapy alone or in combination with conventional therapy in the management of AP, CP or PER Further double blind, randomized, placebo-controlled clinical trials with large sample size need to be conducted.     

Comparison of the Cost-utility Analysis of Electroacupuncture and Nonsteroidal Antiinflammatory Drugs in the Treatment of Chronic Low Back Pain

Introduction and objective

Chronic low back pain (CLBP) is among the most common and important reasons for visiting a spine surgeon by patients; it is the second cause of visiting a doctor. Low back pain can cause considerable suffering and is a major financial burden in the society. There are many different methods available for the treatment of CLBP. This study aimed to compare the cost-utility of electroacupuncture (EA) and nonsteroidal antiinflammatory drugs (NSAIDs), as two common treatment methods for patients with CLBP.

Increased morbidity and mortality in acute human organophosphate-poisoned patients treated by oximes: a meta-analysis of clinical trials

Organophosphates are one of the most common causes of poisoning, especially in the Third world, with high morbidity and mortality. The treatment of this type of poisoning involves the use of atropine and oximes. Atropine has been used successfully in large doses to counteract the muscarinic effects of organophosphate poisoning, but the efficacy of oximes in the management of this poisoning remains under question. In this study, we undertook a meta-analysis by reviewing all clinical trials to evaluate the efficacy of oximes in the management of organophosphate poisoning. The databases of PUBMED, EMBASE, Cochrane, SCOPUS, and the search engine of Google were searched for all clinical trials on the use of oximes in organophosphate poisoning. The inclusion criteria were death, development of intermediate syndrome, and need for ventilation. Six clinical trials met the inclusion criteria and were included in the metaanalysis. The chi2 tests for heterogeneity (P = 0.25, 0.16, and 0.33, respectively) indicated that the included studies were not significantly heterogeneous and could be combined. A significant relative risk (P = 0.0017) for death among oxime-exposed was 2.17 (95% CI of 1.34-3.51). The 'need for ventilation' in patients who received oxime was higher (P = 0.03) than those who did not receive oxime with a relative risk of 1.53 (1.16-2.02). The incidence of 'intermediate syndrome' for oxime-exposed patients was significantly higher (P = 0.01) than oxime non-exposed patients with a relative risk of 1.57 (95% CI 1.11-2.11). It can be concluded that oximes are not effective in the management of organophosphate-poisoned patients and, surprisingly, they can be dangerous and worsen the patient's clinical situation.