Comparison between proactive and retroactive models of medication reconciliation in patients hospitalized for acute decompensated heart failure.

BACKGROUND: Most research on the impact of medication reconciliation on patient safety focused on the retroactive model, with limited attention given to the proactive model. OBJECTIVE: This study was conducted to compare the proactive and retroactive models in patients hospitalized for acute decompensated heart failure. METHODS: This prospective, quasi-experimental study was conducted over six months, from June to November 2022, at the cardiology unit of an academic hospital in Iran. Eligible patients were those hospitalized for acute decompensated heart failure using a minimum of five regular medications before admission. Medication reconciliation was performed in 81 cases using the proactive model and in 81 using the retroactive model. RESULTS: 556 medications were reconciled using the retroactive model, and 581 were reconciled using the proactive model. In the retroactive cases, 341 discrepancies (both intentional and unintentional) were identified, compared to 231 in the proactive cases. The proportion of patients with at least one unintentional discrepancy was significantly lower in the proactive cases than in the retroactive cases (23.80% versus 74.03%). Moreover, the number of unintentional discrepancies was significantly lower in the proactive cases compared to the retroactive cases (22 out of 231 discrepancies versus 150 out of 341 discrepancies). In the retroactive cases, medication omission was the most frequent type of unintentional discrepancy (44.00). About, 42.70% of reconciliation errors detected in the retroactive cases were judged to have the potential to cause moderate to severe harm. While the average time spent obtaining medication history was similar in both models (00:27 [h: min] versus 00:30), the average time needed to complete the entire process was significantly shorter in the proactive model compared to the retroactive model (00:41 min versus 00:51). CONCLUSION: This study highlighted that the proactive model is a timely and effective method of medication reconciliation, particularly in improving medication safety for high-risk patients.

N-Acetyl Cysteine as an Add-on Therapy is Useful in Treating Acute Lumbar Radiculopathy Caused by Disc Herniation: Results of a Randomized, Controlled Clinical Trial.

BACKGROUND: Available experimental and clinical evidence indicates that N-Acetyl cysteine (NAC) may have an analgesic role in specific pain conditions, particularly neuropathic pain. Thus, we hypothesized that NAC supplementation might be also helpful in decreasing pain and improving pain-related disability in patients with acute radiculopathy. We designed this study to investigate the potential use of NAC-adjunctive treatment to Nonsteroidal Anti- Inflammatory Drugs (NSAIDs) in patients with acute radiculopathy secondary to lumbar intervertebral disc herniation. METHODS: Sixty-two patients diagnosed with acute lumbar radiculopathy associated with disc herniation were randomly allocated to the NAC or the placebo groups. Besides naproxen at a dose of 500 mg twice a day, participants based on their allocation group started with NAC or matched placebo at a dose of 600 mg twice a day for eight weeks. The pain severity, measured by the Visual Analog Scale (VAS), and pain-related disability measured by the Oswestry Disability Index (ODI) were measured at baseline and weeks 2, 4, and 8 of treatment. Global improvement of symptoms rated by Patient and Clinical Global Impressions of Change (PGIC and CGIC) was also recorded at the end of week 8. All analyses were conducted on an Intentionto- Treat (ITT) analysis data set. RESULTS: A comparison of the VAS and ODI scores at weeks 2 and 4 of the treatment between the two groups did not show a significant difference. In contrast, from week 4 to week 8, we noticed a significantly greater reduction in the mean VAS and ODI scores in the NAC group compared to the placebo group (p-value <0.001 for both variables). In parallel with these results, also, more NAC-treated than placebo-treated patients achieved treatment success defined as ''very much'' or ''much improved'' on CGIC and PGIC scales, and these differences reached a significant level (p-value = .011 and p-value = .043). CONCLUSIONS: This study suggested that NAC might be a relevant candidate for adjunct therapy in managing acute lumbar radiculopathy. Additional clinical trials are needed to validate these findings.

The effects of AdipoRon on cytochrome P450-related gene expression, acute steroidogenic regulatory protein, and structure of ovary in polycystic ovary syndrome model.

PURPOSE: One of the most common causes of infertility in adult women is polycystic ovary syndrome (PCOS) which has been identified with symptoms such as chronic hyperandrogenism, anovulation, and polycystic ovaries. Adiponectin modulates steroidogenesis and the expression of ovulation-related genes. Herein, we assessed the effect of AdipoRon (adiponectin agonist) in the PCOS model mice. METHODS: The PCOS model was induced with letrozole in the adult female mice and the animals received intraperitoneal injection of AdipoRon (5 mg/kg) for 10 days. Expression of CYP11A, CYP17A, and CYP19A genes, StAR protein, and histomorphology of the ovary were evaluated using real-time RT-PCR, western blotting, and histochemistry methods, respectively. RESULTS: Although administration of letrozole caused an increase in the expression of CYP11A, CYP17A, and StAR and a decrease in the CYP19A1 expression, injection of AdipoRon reversed these changes. Moreover, AdipoRon treatment resulted in an improvement of folliculogenesis and a reduction of cysts compared to the letrozole-treated mice. CONCLUSION: It is likely that AdipoRon has protective effects on the PCOS through modulation of cytochrome P450-related genes and steroidogenesis but needs further study to be sure.

Prevention of contrast induced-acute kidney injury using coenzyme Q10 in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

PURPOSE: We assessed the potential effect of CoQ10 administration for the prevention of contrast induced-acute kidney injury (CI-AKI) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS: One hundred fifty STEMI patients who were candidates for primary PCI, along with intravenous saline hydration, randomly received a placebo or CoQ10. CoQ10 was administrated orally, 400 mg before the procedure and 200 mg twice daily after the procedure for three consecutive days. Serum creatinine concentration and corresponding creatinine clearance (estimated by the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation) were measured at baseline and 24, 48, and 72 h after primary PCI. Furthermore, the serum level of superoxide dismutase (SOD), total antioxidant capacity (TAC), and malondialdehyde (MDA) was measured before and 72 h after primary PCI. RESULTS: The mean serum creatinine concentration before contrast administration was similar in the two groups (0.98 ± 0.08 versus 0.99 ± 0.09 mg/dL). While in both study groups, compared to baseline, the mean serum creatinine concentration increased at 48 and 72 h after contrast exposure, the CoQ10 group showed a lower serum creatinine concentration than the placebo group (P-value = 0.017 and 0.004, respectively). However, comparing the mean values of creatinine clearance between the groups at the study time points did not demonstrate a statistically significant difference. CI-AKI, defined as a > 25% or 0.5 mg/dL increase in baseline serum creatinine concentration, occurred in 8.00% of the cases in the CoQ10 group versus 20.00% in the placebo group (P-value = 0.034). Furthermore, at 72 h, the CoQ10-treated group exhibited higher serum levels of SOD and TAC and a lower MDA level than the placebo-treated group. CONCLUSIONS: Our research's findings proposed CoQ10 supplementation as an adjuvant to saline hydration as a preventive approach against CI-AKI. TRIAL REGISTRATION: The trial was registered at Iranian Registry of Clinical Trials ( https://www.irct.ir/trial/60435 , identifier code: IRCT20120215009014N414). Registration date: 2021-12-29.

Melatonin supplementation may benefit patients with acute ischemic stroke not eligible for reperfusion therapies: Results of a pilot study.

BACKGROUND: We explored the potential efficacy of melatonin in the treatment of patients with acute ischemic stroke. METHODS: This double-blind, placebo-controlled single-center clinical trial was conducted on 65 patients with acute ischemic stroke not eligible for reperfusion therapy. All patients received routine acute stroke management. Melatonin and placebo were administrated orally at a dose of 20 mg once daily for five days. The severity of neurological deficit and stroke-related functional disability was assessed on the National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale score (mRS), respectively, on days 5, 30, and 90 after treatment. RESULTS: All patients completed the 5-day treatment period, and no serious adverse event was observed. While on day 5, the neurological status and stroke-related functional disability were comparable in both groups, on days 30 and 90, melatonin treatment resulted in a higher reduction in the median NIHSS and mRS score than placebo. Moreover, the overall changes in the NIHSS and mRS scores through a three-month follow-up assessment were significantly greater in the melatonin group than in the placebo group. The analysis of NIHSS scores distribution on day 90 showed a significant difference between the study groups in favor of the melatonin treatment. However, in relation to the functional independence criteria, defined as an mRS < 3, there were no significant differences between the groups at different study time points. CONCLUSIONS: Although preliminary, our findings support the hypothesis that early treatment with melatonin may be helpful in improving functional and neurological recovery following stroke. TRIAL REGISTRATION: The trial was registered at Clinicaltrials.gov (identifier code: IRCT20120215009014N378). Registration date: 2021-01-28.

Clinical Pharmacists' Contribution to Medication Reconciliation in Outpatient Specialty Clinics in Iran.

BACKGROUND: The majority of research in medication reconciliation has focused on the inpatient settings, and little is known about the outpatient settings, particularly in developing countries. As such, we conducted this study to evaluate direct clinical pharmacist involvement in medication reconciliation in outpatient specialty clinics in Iran. METHODS: This prospective interventional study was conducted from September 2019 to February 2020 in a University-affiliated clinic in Iran. For 196 patients over 18 years of age who were scheduled for an appointment with a physician, medication reconciliation intervention was carried out by a clinical pharmacist. The number and type of unintentional discrepancies, their potential harm to the patients, their correlation with the patients' demographic and clinical characteristics, and the number of accepted recommendations upon the unintentional discrepancies by the clinicians were assessed and recorded. Additionally, patients' understanding of any change made to their current medication regimen was also assessed. RESULTS: In total, 57.14% of patients had at least one or more unintentional medication discrepancies, with an overall rate of 1.51 (±0.62) per patient. This is while the patient understanding of their medication changes was inadequate in a significant proportion of the study patients (62.2%). Patients with older ages, lower educational levels, and a higher number of medications and comorbidities were at a higher risk of having unintentional discrepancies. The most common type of unintentional discrepancy was the omission of a drug, and almost half of the reconciliation errors might have had the potential to cause moderate or severe harm to the patient. From 145 recommendations suggested by the clinical pharmacist upon unintentional discrepancies, 131 cases (90.34%) were accepted and implemented by the clinicians. CONCLUSION: These findings further support the need for conducting medication reconciliation in outpatient settings to identify discrepancies and enhance the safety of patient medication use.

Adulteration of the Herbal Weight Loss Products by the Illegal Addition of Synthetic Antiobesity Medications: A Pilot Study.

BACKGROUND: Some anorexic agents are used to fraudulent augmentation herbal weight loss formulations. This study was designed to evaluate the potential existence of illicit substances in 63 herbal weight loss formulations collected from local apothecaries in Hamadan, Iran. METHODS: The thin-layer chromatography method was applied for the primary screening of potential illicit substances in the samples. The positive samples were analyzed using an isocratic high-performance liquid chromatography method. RESULTS: The results showed that 26.98% of the samples contained 17.76 ± 6.02 mg/cap of sibutramine. Daily therapeutic dose intake of sibutramine is in the range of 5 to 15 mg daily. CONCLUSION: Since apothecaries have advised consumers to take at least two capsules a day, it seems that the blood concentration of sibutramine will likely rise beyond the therapeutic concentration and become toxic. Therefore, the usage of such products could pose serious risks to consumers' health.

Bupleurum falcatum L. alleviates nociceptive and neuropathic pain: Potential mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: In Iranian folkloric medicine, Bupleurum falcatum L. (Chinese Thoroughwax) has been used as a selective analgesic remedy for several centuries. OBJECTIVE: The current research was conducted to explore the anti-nociceptive and anti-allodynic action of Bupleurum falcatum L. roots essential oil (BFEO) in Swiss mice. MATERIALS AND METHODS: Formalin-induced paw licking (FIPL) model was applied for exploring of BFEO antinociceptive effects (neurogenic or inflammatory pain). The involvements of L-arginine-NO-cGMP-KATP channel pathway and several receptors such as opioid, peroxisome proliferator-activated (PPA), cannabinoid, transient receptor potential vanilloid, and adrenergic receptors were assesses to detect the anti-nociceptive activity of BFEO. Cervical spinal cord contusion (CSC) paradigm was employed for induction of neuropathic pain. RESULTS: BFEO (100 mg/kg), in the FIPL model, produced significant antinociception compared to the control mice (p < 0.01). Furthermore, L-arginine, methylene blue, glibenclamide, naloxonazine, GW9662, and SR141716A pre-treatments restored the BFEO anti-nociceptive effects (p < 0.05) in the FIPL (second phase) test (p < 0.05). Intraperitoneal administration of saikosaponin A (one of the main constituents of BFEO) partially alleviated (p < 0.05) pain in FIPL test. Likewise, in CSC mice, the von Frey assay exhibited that BFEO could alter mechanical allodynia. CONCLUSION: Finally, it seems that, in male mice, BFEO has both anti-allodynic and anti-nociceptive effects. The present data also suggest activating the L-arginine-NO-cGMP-KATP channel pathway as well as interaction of opioid, PPA, and cannabinoid receptors in the BFEO anti-nociceptive activities. These results also propose that BFEO could effectively attenuate allodynia in CSC mice.

A randomized, double-blind, placebo-controlled study to assess efficacy of mirtazapine for the treatment of diarrhea predominant irritable bowel syndrome.

BACKGROUND: Ample evidence indicates the efficacy of serotonin type 3 (5-HT3) receptor antagonists in the treatment of patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Mirtazapine is an atypical antidepressant with a well-known 5-HT3 receptor antagonist property. This study, therefore, was undertaken to investigate whether compared to placebo, mirtazapine would be efficacious and safe in the treatment of patients with IBS-D. METHODS: From November 2019 until July 2020, 67 patients meeting Rome IV criteria for IBS-D were randomized in a double-blind fashion into either the mirtazapine treatment group (n = 34) or the placebo treatment group (n = 33). Patients started with mirtazapine 15 mg/day at bedtime for one-week; after which the dose was increased to 30 mg/day for an additional 7-week. Outcomes included changes in the total IBS symptom severity score (IBS-SSS), Hospital anxiety and depression scale score (HADS), and IBS Quality of Life. Additionally, changes in the diary-based symptoms scores including pain, urgency of defecation, bloating, stool frequency, and stool consistency based on the 7-point Bristol Stool Form Scale (BSFS), and a number of days per week with pain, urgency, diarrhea, or bloating, once during the 1-week run-in period, and once during the last week of treatment were recorded. RESULTS: All analyses were performed on an Intention-to-Treat (ITT) analysis data set. The results showed compared to placebo, mirtazapine is more efficacious in decreasing the severity of IBS symptoms (P-value = 0.002). Further, at the end of the treatment period, all diary-derived symptoms except bloating showed significantly more improvement in the mirtazapine-treated subjects compared to the placebo-treated subjects. While was well-tolerated, mirtazapine also significantly improved the patients' quality of life (P-value = 0.04) and anxiety symptoms (P-value = 0.005). CONCLUSIONS: Overall, mirtazapine seems to have a potential benefit in the treatment of patients with IBS-D, particularly those with concomitant psychological symptoms. However, further studies are warranted to determine whether these findings are replicated. TRIAL REGISTRATION: Trial registration: Registration number at Iranian Registry of Clinical Trials: IRCT20120215009014N311 . Registration date: 2019-10-21.

Pentoxifylline Attenuates Arsenic Trioxide-Induced Cardiac Oxidative Damage in Mice.

This study was undertaken to evaluate the therapeutic potential effect of pentoxifylline (PTX) against arsenic trioxide (ATO)-induced cardiac oxidative damage in mice. Thirty-six male albino mice were divided into six groups and treated intraperitoneally with normal saline (group 1), ATO (5 mg/kg; group 2), PTX (100 mg/kg; group 3), and different doses of PTX (25, 50, and 100 mg/kg; groups 4, 5, and 6, respectively) with ATO. After four weeks, the blood sample was collected for biochemical experiments. In addition, cardiac tissue was removed for assessment of oxidative stress markers and histopathological changes (such as hemorrhage, necrosis, infiltration of inflammatory cells, and myocardial degeneration). The findings showed that ATO caused a significant raise in serum biochemical markers such as lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and troponin-I (cTnI), glucose, total cholesterol (TC), and triglyceride (TG) levels. In addition to histopathological changes in cardiac tissue, ATO led to the significant increase in cardiac lipid peroxidation (LPO) and nitric oxide (NO); remarkable decrease in the activity of cardiac antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx); and the depletion of the total antioxidant capacity (TAC) and total thiol groups (TTGs). PTX was able to reduce the increased levels of serum cardiac markers (LDH, CPK, cTnI, TC, and TG), cardiac LPO, and improve antioxidant markers (TAC, TTGs, CAT, SOD, and GPx) alongside histopathologic changes. However, no significant changes were observed in elevated serum glucose and cardiac NO levels. In conclusion, the current study showed the potential therapeutic effect of PTX in the prevention of ATO-induced cardiotoxicity via reversing the oxidative stress.

Erratum: A Behavioral Study of Promethazine Interaction with Analgesic Effect of Diclofenac: Pain Combination Therapy.

[This corrects the article on p. 18 in vol. 23, PMID: 32322431.].

Artemisia biennis Willd.: Anti-Nociceptive effects and possible mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia biennis Willd. (Dermane in Persian) has been used as an antinociceptive remedy in Iranian folkloric medicine. OBJECTIVE: The aim of the present study was to evaluate the anti-nociceptive effects of Artemisia biennis Willd. aerial part essential oil (ABAEO) on male Swiss mice. MATERIALS AND METHODS: Nociceptive pain techniques including acetic acid-induced writhing (AAIW), formalin-induced paw licking (FPL), glutamate-induced paw licking (GPL), and tail-flick (TF) models were applied. We assessed opioid and L-arginine-NO-cGMP-KATP pathways to detect the possible anti-nociceptive properties of ABAEO. In addition, neuropathic pain was induced by the cervical spinal cord contusion model. RESULTS: ABAEO (120 mg/kg) had a significant anti-nociceptive activities in comparison to the control animals (p < 0.05) in the AAIW, TF, GPL, and FPL assays. The selective opioid antagonist (naloxonazine) administration in the AAIW test alleviated the anti-nociceptive effect of ABAEO (p < 0.05). L-arginine, methylene blue, and glibenclamide treatment prevented the ABAEO anti-nociceptive effects (p < 0.05); however, sodium nitroprusside could profoundly potentiate the ABAEO-associated antinociception in the FPL (phase II) test (p < 0.05). In nociceptive pain models, Cr (one of the main constituents of ABAEO) showed significant anti-nociceptive effects (p < 0.05). Moreover, the von Frey results indicated that ABAEO could attenuate mechanical allodynia in mice. CONCLUSION: Our observation revealed the anti-nociceptive effects of ABAEO in male mice. These effects could include, at least in part, modulating glutamatergic mechanisms via opioid systems. Our data output also indicates activating the L-arginine-NO-cGMP-KATP system in ABAEO anti-nociceptive activities.

Biochemical and Histological Evidence on the Protective Effects of Allium hirtifolium Boiss (Persian Shallot) as an Herbal Supplement in Cadmium-Induced Hepatotoxicity.

MATERIALS AND METHODS: Thirty-six male Wistar rats were divided into six groups: groups 1, 2, and 3 received vehicle, Cd (100 mg/L/day by drinking water), and A. hirtifolium extract (200 mg/kg/day; orally), respectively. Groups 4, 5, and 6 were Cd groups which were treated with A. hirtifolium extract (50, 100, and 200 mg/kg/day, respectively). After 2 weeks, liver enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) and also oxidative stress biomarkers including lipid peroxidation (LPO), total antioxidant capacity (TAC), total thiol molecule (TTM), and the histopathological changes were determined using standard procedure. RESULTS: The findings showed that Cd caused a remarkable rise in levels of serum hepatic enzymes such as ALT (P < 0.001), AST (P < 0.01) and ALP (P < 0.001) compared with the control group. In addition, Cd led to the decreasing of the levels of TTM (P < 0.001) and TAC (P < 0.001) and increasing of LPO (P < 0.001) in liver tissue in comparison with the control group. In this regard, remarkable vascular congestion, hepatocellular degeneration, and vacuolization were observed in hepatic tissue of Cd-treated rats. Following the administration of A. hirtifolium extract, a significant improvement was observed in the functional and oxidative stress indices of hepatic tissue alongside histopathologic changes. CONCLUSION: The current study indicated that the A. hirtifolium extract might prevent hepatic oxidative injury by improving oxidant/antioxidant balance in rats exposed to Cd.

A Behavioral Study of Promethazine Interaction with Analgesic Effect of Diclofenac: Pain Combination Therapy.

OBJECTIVES: Pain is considered as a cause of sickness and the most prevalent symptom which makes people visit a physician. Nowadays, combination therapy is becoming useful to relieve chronic and postsurgical pain. The aim of this study was to study the promethazine (as an antihistamine) interactions with antinociceptive effect of diclofenac (as a non-steroidal anti-inflammatory drugs). METHODS: In initial part of the study, we investigate the analgesic effect of diclofenac. Using writhing test, we demonstrate that diclofenac significantly reduces writhe response induced by acetic acid in a dose-dependent manner. In this study, we evaluate the combination effect of promethazine on diclofenac analgesic effect. RESULTS: We observed that diclofenac inhibited pain in the dose dependent manner which means that by increasing dose of diclofenac a significant decrease in pain was observed. This experimental setup allowed calculation of the dose that caused 50% antinociception (ED50) for diclofenac. The ED50 for diclofenac in this study was determined to be 9.1 mg/kg according our previous study. Additionally, promethazine was showed a dose-dependent inhibition of writhes. The combination of different doses of promethazine (2, 4, 6 mg / kg) with diclofenac ED50 (9.1 mg / kg) was injected to mice. Promethazine 4 and 6 mg / kg in combination with diclofenac had significantly led to increase analgesic effect of diclofenac. CONCLUSION: In conclusion, these results add important information to the existing knowledge on combination of diclofenac and antihistamine in pain therapies to be used in clinical practice and maybe helpful in designing the future guidelines.

The Efficacy of Colloidal Oatmeal Cream 1% as Add-on Therapy in the Management of Chronic Irritant Hand Eczema: A Double-Blind Study.

BACKGROUND: Irritant contact dermatitis (ICD) is the most frequent cause of hand eczema (HE). There is promising evidence with the use of topical oatmeal compounds in the management of inflammation- and itch-responses associated with diverse dermatologic conditions. This study aimed to evaluate the clinical benefit of colloidal oatmeal cream in the management of chronic irritant HE. METHODS: From October 2018 to November 2019, 79 patients with diagnosis of chronic irritant HE were allocated into either intervention or control groups by block randomization method. Besides fluocinolone 0.025% ointment for the first 2 weeks of treatment period, patients in the intervention and control groups were asked to use colloidal oatmeal 1% cream or base cream for additional 4 weeks as monotherapy. Changes in the HE severity based on the hand eczema severity index (HESCI) score, pruritus severity based on the visual analogue scale (VAS), and impact of skin disorder on patients quality of life based on the Dermatology Life Quality Index (DLQI) from baseline to weeks 2, 4, and 6 were assessed in the study groups. RESULTS: Fifty subjects, 26 in intervention and 24 in control, completed the course of the study. The results indicated, though relatively comparable decrease in mean HESI and VAS scores was observed in both groups by the end of week 2, thereafter until end of the study a non-return of symptoms to baseline conditions was observed in the intervention group, while there was a significant return of symptoms to baseline conditions in the control group (p value<0.001 in both conditions). Further, a noticeable improvement in the DLQI score was seen in the intervention group compared with the control group (p value<0.001). CONCLUSION: Findings demonstrate that colloidal oatmeal, a natural product with proven barrier protection, moisturization, anti-inflammatory, and soothing properties, can have ameliorative effects on eczema severity symptoms in patients with chronic irritant HE.

Antinociceptive activity of Cnicus benedictus L. leaf extract: a mechanistic evaluation.

BACKGROUND AND PURPOSE: Cnicus benedictus, a medicinal herb, traditionally had been used for the treatment of stomachache pain. In this study, the possible efficacy of Cnicus benedictus leaf methanolic extract (CBHE) and also cnicin, one of its major constituents, was measured on pain. EXPERIMENTAL APPROACH: In this study, pain assessment tests include writhing, tail-flick (TF), and formalin- induced paw licking test (FIPLT) were used. To understand the possible mediated anti-nociceptive mechanism of CBHE, the opioid mechanism(s), and involvement of the L-arginine/ nitric oxide/cGMP/ATP-sensitive potassium channel pathway (LNCaP) were scrutinized. FINDINGS/RESULTS: In TF and writhing tests, CBHE (150 and 300 mg/kg, i.p) remarkably exhibited an anti-nociceptive effect compared to that of the control. Furthermore, CBHE (150 and 300 mg/kg, i.p) in comparison with the control showed a noteworthy anti-nociceptive effect (P < 0.01) in the tonic phase of FIPLT. In the writhing test, administration of selective opioid antagonist (naltrindole, nor-binaltorphimine, and naloxonazine) attenuated the anti-nociceptive effect of CBHE (300 mg/kg) in comparison with control. Moreover, pre-treatment with Nω-nitro-L-arginine methyl ester hydrochloride, L-arginine hydrochloride, and glibenclamide significantly blocked the CBHE (300 mg/kg) anti-nociception (P < 0.05) while administration of sodium nitroprusside remarkably potentiated (P < 0.05) the antinociception induced by CBHE in the tonic phase of the FIPLT. Besides, cnicin (30 mg/kg) showed noteworthy anti-nociceptive effects in writhing, TF, and FIPLT paradigms. CONCLUSION AND IMPLICATIONS: Taken together, we elucidate that both CBHE and cnicin demonstrated antinociceptive effects in behavioral tests. The possible mechanisms of CBHE antinociception may involve in various neural signaling and modulatory pathways including LNCaP and opioidergic mechanisms.

The role of ghrelin and tumor necrosis factor alpha in diazinon-induced dyslipidemia: insights into energy balance regulation.

The evidence shows that organophosphate compounds (OPCs), as toxic agents that stimulate the cholinergic system, can increase the incidence of metabolic disorders such as dyslipidemia. In the present study, we focused on the role of tumor necrosis factor alpha (TNF-α) and serum leptin and ghrelin in Diazinon (DZN)-induced dyslipidemia. The rats were randomly divided into five groups comprising eight animals, and all were treated via oral gavage for 28 consecutive days as follows: group one received only corn oil daily, while groups two through five received different doses of DZN dissolved in corn oil equal to 1/40, 1/20, 1/10 and 1/5 of the LD50 daily, respectively. The alteration of the serum lipid profile, such as triglycerides, high-density lipoprotein (HDL) and very-low-density lipoprotein (VLDL), was confirmed the occurrence of dyslipidemia in the range of doses 1/20-1/5 LD50 of DZN. Although no changes were found in the serum leptin levels, a significant increase was observed in the size of adipocytes, as well as in the TNF-α and ghrelin serum levels, and in the accumulation of epididymal fat, especially at a dose of 1/5 LD50 of DZN. It seems that interactions among the inflammatory reaction, cholinergic pathways and ghrelin secretion may be effective causes of DZN-induced dyslipidemia.

The occurrence of acetaminophen/codeine as an adulterant in herbal analgesic supplements in Hamadan, Iran: A pilot study.

Analgesics, such as acetaminophen (APAP) and codeine (COD), are used to adulterate medicinal herbs and/or herbal supplements. This study evaluated the APAP and COD levels in 60 herbal supplement and/or herb-based medicine samples collected from apothecaries in Hamadan, Iran. The samples were analysed using a high-performance liquid chromatography (HPLC) system. The results showed that 15% of the samples contained 38900-165200 ng/g and 31.1-603.3 ng/g of APAP and COD, respectively. Due to the side-effects of analgesic drugs in human, control of these drugs is recommended in herbal supplements.

Occurrence of bacterial and toxic metals contamination in illegal opioid-like drugs in Iran: a significant health challenge in drug abusers.

BACKGROUND: The toxic metals and/or bacterial contaminants in illicit drugs are the main health problems in drug users worldwide. Hence, the potential risks of these contaminants were evaluated in some of the illicit drugs during 2015 and 2016. METHODS: The metals analysis were performed using graphite furnace atomic absorption spectrophotometry. In addition, all microbiological analysis stages, including handling procedures, dilution, and culture media, were conducted in accordance with the US Pharmacopeia (USP) which are harmonized with the European Pharmacopoeia (EP). RESULTS: In the present study, the highest lead (Pb; 138.10 ± 75.01 µg/g) and chromium (Cr; 447.38 ± 20.27 µg/g) levels were detected in opium samples. In addition, the highest prevalence of microbial contamination was observed in opium samples, and the lowest was recorded in heroin samples. Clostridium tetani, with about 50% of contaminant, was the most common bacteria in the analyzed samples. CONCLUSIONS: Our results indicate that Pb exposure as well as bacterial contamination could be the major threats for drug users. Graphical Abstract ᅟ.

Protective effect of amlodipine on diazinon-induced changes on oxidative/antioxidant balance in rat hippocampus.

Oxidative stress (OS) is a main mechanism in organophosphorus poisoning. The effects of calcium channel blockers have been confirmed in decreasing of oxidative stress. In the current study, the effects of amlodipine (AM), as a calcium channel blocker, were evaluated on oxidative damages induced by diazinon (DZN) in hippocampus tissue of Wistar rats. Forty-two rats were divided into six groups and treated intraperitoneally for two weeks. Group 1 served as control received vehicle, group 2 was treated with 9 mg/kg of AM, group 3 (positive control) received DZN (32 mg/kg), Groups 4, 5, and 6 were treated with 3, 6, and 9 mg/kg of AM adjunct with DZN (32 mg/kg), respectively. After 14 days, all the animals were sacrificed under anesthesia and hippocampus tissue and blood samples were collected for biochemical analysis and histopathology experiments. The results showed that DZN caused significant increase in lipid peroxidation (P < 0.001), nitric oxide (P < 0.001) and lactate dehydrogenase (P < 0.001) levels, depletion of total antioxidant capacity (P < 0.01), and structural changes in hippocampus tissues. Following AM administration, a significant improvement was observed in oxidative biomarkers in hippocampus tissues. Additionally, our biochemical findings were related well with histopathological examinations. In conclusion, the data of this study indicated that AM administration may prevent oxidative damages via improving of energy production and preventing of free radical formation in DZN-exposed animals.