Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Concurrent Use of Crocin During Chemoradiation for Esophageal Squamous Cell Carcinoma.

Crocin is the major active carotenoid of saffron (Crocus sativus L.). Its pluripotent effects have led to a growing body of literature investigating its antitumor properties as well as its diverse potentials for mood stabilization, normal tissue protection, and inflammation reduction; However, there is a gap in clinical trials testing this substance in cancer patients. In this randomized, double-blind, placebo-controlled clinical trial, patients with newly diagnosed esophageal squamous cell carcinoma were randomly assigned to either 30 mg/day of crocin or placebo, prescribed during the neoadjuvant chemo-radiotherapy. The primary endpoints were pathological response and toxicity, and secondary endpoints were depression and anxiety levels and survival analysis.

Beneficial effects of celery seed extract (Apium graveolens), as a supplement, on anxiety and depression in hypertensive patients: a randomized clinical trial.

BACKGROUND: Anxiety and depression are crucial public health issues, affecting the rising in hospitalizations and death. Anxiety and depression can worsen hypertension and vice versa. OBJECTIVE: The current study has investigated the effects of celery seed extract, as a drug supplement, with the active ingredient of 3-n-butylphthalide, on mental problems primarily anxiety and secondary depression in hypertensive patients. DESIGN: The current study was a randomized, triple-blind, placebo-controlled, cross-over, 4-week clinical trial with a 4-week washout period. Fifty hypertensive patients received 4 placebo or celery seed extract capsules (1.34 g per day) for 4 weeks as a supplement to their usual medication regimen. The blood pressure parameters were assessed using 24-h ambulatory blood pressure monitoring device. Anxiety and depression and their wide range of symptoms were evaluated using Beck anxiety and depression inventories (BAI and BDI). RESULTS: In the celery treatment step, the mean reduction in BAI and BDI scores were 6.78 (P < 0.001) and 3.63 (P < 0.01), respectively. Some symptoms of anxiety including unable to relax, nervousness, numbness, dizziness, flushed face, sweating, and breathing difficulty were significantly improved by celery consumption (P < 0.001). Celery could decrease symptoms of depression such as sadness, crying, loss of energy, insomnia, irritability, fatigue, loss of interest in sex, and punishment feeling (P < 0.01). The mean reduction in blood pressure parameters was also significant during celery therapy (P < 0.001). CONCLUSIONS: The psychometric properties of anxiety and depression were investigated and the results were promising. The results indicated the anti-anxiety and anti-depressive properties of celery seed extract as a supplement in hypertensive patients. CLINICAL TRIAL REGISTRATION: Registry name: Iranian Registry of Clinical Trials (IRCT), Registration number: IRCT20130418013058N8, Registration link: https://www.irct.ir/trial/30021 . The study was carried out between 2018-09-21 and 2020-07-20.

Effect of celery (Apium graveolens) seed extract on hypertension: A randomized, triple-blind, placebo-controlled, cross-over, clinical trial.

In the present work, the antihypertensive effects of celery seed extract (Apium graveolens) with active ingredients, such as 3-n-butylphthalide, were studied as a drug supplement in the treatment of hypertension. This study was a randomized, triple-blind, placebo-controlled, cross-over clinical trial. Fifty-two patients were divided into two groups (celery and placebo) and completed the two-step clinical trial. Four celery seed extract capsules (totally 1.34 g per day) or 4 placebo capsules per day were administered to the patients during a 4-week clinical trial. The blood pressure was assessed using a 24-hr ambulatory blood pressure monitoring method. In celery group, systolic blood pressure changed from 141.2 ± 5.91 to 130.0 ± 4.38 mmHg (p < .001) while diastolic blood pressure changed from 92.2 ± 5.74 to 84.2 ± 4.87 mmHg (p < .001). Moreover, the mean arterial blood pressure changed from 108.5 ± 5.76 to 99.5 ± 4.66 mmHg (p < .001), and pulse pressure decreased from 49.0 ± 6.21 to 45.8 ± 6.01 mmHg (p < .01). However, no significant changes were observed in placebo group in terms of the above-mentioned parameters (p > .05). Furthermore, no significant side effect was reported in the celery group, compared to the placebo group (p > .05). The results were promising and indicated the therapeutic effects of celery seed extract as a supplement in the management of hypertension.

Safety evaluation and biochemical efficacy of celery seed extract (Apium Graveolens) capsules in hypertensive patients: a randomized, triple-blind, placebo-controlled, cross-over, clinical trial.

The present study was conducted to evaluate the safety of celery seed extract (Apium graveolens), as a medicinal herb with active ingredients such as 3-n-butylphthalide (NBP), in hypertensive patients. This study was a randomized, triple-blind, placebo-controlled, cross-over clinical trial. Hypertensive patients (51 participants) received 4 celery seed capsules (a total of 1.34 g extract per day) or 4 placebo capsules per day for 4 weeks as a supplement to their usual medication regimen. The results indicated that the celery seed capsule not only was safe for hypertensive patients but also caused a reduction in BP, FBS, and lipid profile values. Also, it had beneficial effects on kidney and liver functions. No significant change was observed in blood cells and serum electrolytes (p > 0.05). The mean reduction in BUN and SCr were 3.43 and 0.075 mg/dL, and in SGPT and SGOT were 4.08 and 3.03 U/L, respectively (p < 0.05). FBS reduced from 108.53 to 97.96 mg/dL after 4 weeks of celery administration (p < 0.01). The decrease in TC, TG, LDL, and increase in HDL were 16.37, 16.22, 11.84, and 2.52 mg/dL, respectively (p < 0.001). According to the promising results of this clinical trial, celery seed extract can be considered a safe supplement for hypertensive patients. The study is limited by the small sample size; therefore, larger randomized trials are required.

Design and synthesis of new carbamates as inhibitors for fatty acid amide hydrolase and cholinesterases: Molecular dynamic, in vitro and in vivo studies.

As anandamide (N-arachidonoylethanolamine, AEA) shows neuroprotective effects, the inhibition of its degradative enzyme, fatty acid amide hydrolase (FAAH) has been considered as a hopeful avenue for the treatment of neurodegenerative diseases, like Alzheimer's disease (AD). Memory loss, cognitive impairment and diminution of the cholinergic tone, due to the dying cholinergic neurons in the basal forebrain, are common hallmarks in patients with AD. By taking advantage of cholinesterase inhibitors (ChEIs), the degradation of acetylcholine (ACh) is decreased leading to enhanced cholinergic neurotransmission in the aforementioned region and ultimately improves the clinical condition of AD patients. In this work, new carbamates were designed as inhibitors of FAAH and cholinestrases (ChEs) (acetylcholinestrase (AChE), butyrylcholinestrase (BuChE)) inspired by the structure of the native substrates, structure of active sites and the SARs of the well-known inhibitors of these enzymes. All the designed compounds were synthesized using different reactions. All the target compounds were tested for their inhibitory activity against FAAH and ChEs by employing the Cayman assay kit and Elman method respectively. Generally, compounds possessing aminomethyl phenyl linker was more potent compared to their corresponding compounds possessing piperazinyl ethyl linker. The inhibitory potential of the compounds 3a-q extended from 0.83 ± 0.03 µM (3i) to ˃100 µM (3a) for FAAH, 0.39 ± 0.02 µM (3i) to 24% inhibition in 113 ± 4.8 µM (3b) for AChE, and 1.8 ± 3.2 µM (3i) to 23.2 ± 0.2 µM (3b) for BuChE. Compound 3i a heptyl carbamate analog possessing 2-oxo-1,2-dihydroquinolin ring and aminomethyl phenyl linker showed the most inhibitory activity against three enzymes. Also, compound 3i was investigated for memory improvement using the Morris water maze test in which the compound showed better memory improvement at 10 mg/kg compared to reference drug rivastigmine at 2.5 mg/kg. Molecular docking and molecular dynamic studies of compound 3i into the enzymes displayed the possible interactions of key residues of the active sites with compound 3i. Finally, kinetic study indicated that 3i inhibits AChE through the mixed- mode mechanism and non-competitive inhibition mechanism was revealed for BuChE.

Effect of crocin versus fluoxetine in treatment of mild to moderate obsessive-compulsive disorder: A double blind randomized clinical trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a common disabling disorder. Crocin, the active component of the saffron plant (Crocus Sativus L.) has various pharmacological activities. The present study compared the efficacy and safety of crocin and fluoxetine in treatment of mild to moderate OCD. METHODS & MATERIALS: Fifty patients with OCD, aged 18 to 60 years, were randomized to receive either crocin (15 mg) or fluoxetine (20 mg) capsules for 8 weeks. Eligible participants received one capsule/day in the first month, which followed by two capsules daily in the second month. The patients were evaluated using Yale-Brown Obsessive-compulsive scale (Y-BOCS) and Hamilton Anxiety Rating scale (HARS). RESULTS: The mean Y-BOCS score in both groups decreased significantly during 2 months (p-value = 0.0001). Also, HARS score in the crocin group was changed from 17.16 to 13.04 whereas, in the fluoxetine group was decreased from 18.28 to 12.34. The results indicated no difference between the two groups in Y-BOCS and HARS score changes after 2-month trial (p-value >0.5). Also, fewer adverse effects were reported in the crocin group compared to the fluoxetine group. CONCLUSION: According to our study, it seems that crocin is effective in treatment of patients with mild to moderate OCD with possibly fewer adverse effects compared to fluoxetine.

Preparation, evaluation, and application of dummy molecularly imprinted polymer for analysis of hesperidin in lime juice.

Lime juice as the most commonly used natural source production can be characterized using determination of flavonoids contents such as hesperidin. So, development of analyzing methods for checking the quality and healthiness of lime juices is necessary. In this study, we aimed to set up a selective solid phase extraction method using dummy molecularly imprinting approach for extraction and separation of hesperidin in lime juice to check the quality of commercial lime juice products of Mashhad city market. The imprinted polymers were synthesized by hesperitin as dummy template due to the hesperitin solubility in the wide range of porogenic solvents. The specificity extent of synthesized polymers toward hesperidin was tested and optimum one was used as adsorbent in solid-phase extraction cartridge. The dummy molecularly imprinted polymer with high adsorption capacity for hesperidin (dissociation constant 0.12 µM) was successfully used for extraction and clean-up of hesperidin in the lime juice matrix prior to analysis by high-performance liquid chromatography. The analysis of hesperidin was done in the range of 0.312-50 µg/mL with detection limit of 0.05 µg/mL. This technique was successfully set up to remove the interfering compounds for analysis of hesperidin in commercial lime juice products.

Evaluation of green tea extract and epigallocatechin gallate effects on bisphenol A-induced vascular toxicity in isolated rat aorta and cytotoxicity in human umbilical vein endothelial cells.

This study was designed to assess bisphenol A (BPA)-induced vascular toxicity, the effectiveness of green tea extract and epigallocatechin gallate (EGCG) against BPA toxicity, and possible underlying mechanisms. In isolated rat aorta, contractile and relaxant responses as well as malondialdehyde levels were evaluated. Cell viability and effects on the protein levels of apoptotic (bax, bcl2, and caspase-3), autophagic (LC3), and cell adhesion molecules were calculated using the MTT method and western blotting in human umbilical vein endothelial cells (HUVECs). BPA increased aorta MDA levels (p < .0001) and decreased vascular responses to KCl [20 and 40 mM (p < .0001), 80 mM (p < .001)], phenylephrine [10-8 , 10-6 , and 10-5 M (p < .001), 10-7 and 10-4 M (p < .0001)], and acetylcholine [10-6 M (p < .01), 10-5 and 10-4 M (p < .0001)]. In HUVECs, BPA enhanced the levels of LC3A/B, bax/bcl2 ratio, cleaved caspase-3, and vascular cell adhesion molecule-1. Green tea extract, EGCG, and vitamin E co-treatment with BPA diminished the toxic effects of BPA. These findings provide evidence that green tea extract and EGCG possess beneficial effects in preventing BPA-induced vascular toxicity through increasing the antioxidant activities and the regulation of signaling pathways.

Amelioration of anxiety, depression, and chemotherapy related toxicity after crocin administration during chemotherapy of breast cancer: A double blind, randomized clinical trial.

The effects of saffron (Crocus sativus L.) on mood disorders have already been established. More recently, its anti-neoplastic effects have provoked a great attention. This study aims to assess the effects of crocin administration during doxorubicin-based chemotherapy of breast cancer on anxiety, depression, and chemotherapy toxicity profile. Seventy-two patients with non-metastatic Her2/neu positive or triple negative breast cancer were enrolled and randomly assigned to receive either 30 mg/day of crocin or placebo during chemotherapy [2:2]. Beck's Depression and Anxiety Inventories were used at baseline and end of the trial. In addition, the ECOG Common Toxicity Criteria were applied to assess chemotherapy side-effects. After the intervention, the degree of anxiety and depression decreased significantly in the crocin group (p = .001 for both) and increased significantly in the placebo-group (p = .006 and p = .036, respectively). There were significantly higher grade II-IV leukopenia (47.2% vs. 19.4%, p = .012) in the crocin group, and grade II-IV hypersensitivity-reaction (30.6% vs. 5.6%, p = .006) in addition to neurological disorders (66.7% vs. 41.7%, p = .03) in the placebo-group. The results indicate that using crocin during chemotherapy in patients with breast cancer has ameliorated anxiety and depression. Moreover, leucopenia increased whereas hypersensitivity reaction and neurological disorders decreased in the crocin group. In addition, a trend toward survival improvement was observed, which is going to be investigated on longer follow up.

Beneficial effects of celery (Apium graveolens) on metabolic syndrome: A review of the existing evidences.

The metabolic syndrome (MetS) is a cluster of multiple conditions that includes hypertension, dyslipidemia, abdominal obesity, and hyperglycemia disorders. Most studies revealed that the MetS is accompanied with an increased risk for cardiovascular disease, Type 2 diabetes mellitus, and insulin resistance. It can be said that, in treating or preventing the MetS and its components, lifestyle adjustment and weight loss have a vital role. According to various studies, among natural compounds, celery (Apium graveolens) is one of the most important sources of phytochemicals such as phenolic acids, flavones, flavonols, and antioxidants such as vitamin C, beta-carotene (Provitamin A), and manganese. These antioxidants have a role in decreasing the oxidative damage. The phytochemicals in celery decrease the activity of proinflammatory cytokines and prevent inflammation. Also, flavonoids in celery suppress cardiovascular inflammation. Oxidative stress and inflammation in the blood stream are the main risk factors in increasing cardiovascular disease, especially atherosclerosis. Celery phthalides leads to expanding of smooth muscle in the blood vessels and lower blood pressure. As a result, the most active ingredients in celery (A. graveolens (have shown hypolipidemic, antidiabetic, and hypotensive properties. In this review, we summarized the mechanisms underlying the protective effects of celery components on insulin action, glucose, lipid metabolism, and blood pressure.

Herbal medicine as a promising therapeutic approach for the management of vascular dementia: A systematic literature review.

Vascular dementia (VaD) generally refers to memory deficits and cognitive abnormalities that are resulted from vascular disease. In this study, we aimed to systematically review the literature wherein therapeutic effects of medicinal plants have been studied on VaD. A systematic literature search was performed in the PubMed, Scopus, Web of Science, Google Scholar, and other databases using VaD, and medicinal plants as key terms. No strict inclusion criteria were defined, and almost all clinical studies were included. A total of 524 articles were found, of which only 28 relevant articles with 3461 studied patients were included to this systematic review. The results showed that medicinal plants, particularly Sancaijiangtang and Ginkgo biloba could improve behavioral and psychological symptoms, working memory, Mini-Mental State Examination, and activities of daily living as well as neuropsychiatric features. It was also shown that the age, average progression of the disease, and the type of folk medicines effective in treating the disease are important factors in the management of VaD. The results of this review indicated that herbal therapy can be a potential candidate in the treatment of VaD; however, further studies are needed to confirm such efficiency.

Preparation and Characterization of Herbicide Mecoprop Imprinted Polymer and Its Application as a Selective Sorbent in Water Sample.

Bulk polymerization method was used to prepare a homogeneous molecularly imprinted polymer (MIP) for the specific extraction of herbicide mecoprop (MCPP). Thereafter, the binding performance of this functional polymer was evaluated under optimal condition, compared to a non-imprinted polymer. From the Scatchard plot analysis, two types of binding sites were detected in the MIP, the high affinity binding sites with a KD (equilibrium dissociation constant) of 6.4 µM and the low affinity ones with a KD of 55.9 µM. In addition, the possibility of using synthesized MIP for MCPP extraction from environmental aqueous samples was explored. The adsorption capacity of MIP in spiked bottled water and groundwater samples showed that the polymer could effectively extract MCPP from bottled water and groundwater (p < 0.05) with the recovery of 70.5% and 65.1%, respectively, demonstrating the potential of imprinted polymers for cost-effective and effective water treatment.

Plant toxins and acute medicinal plant poisoning in children: A systematic literature review.

BACKGROUND: For many years, medicinal plants and herbal therapy have been widely used in different societies for the treatment of various diseases. Besides their therapeutic potency, some of the medicinal plants have strong toxicity in human, especially in children and elderly. Despite common beliefs that natural products are safe, there have been few reports on their toxicities. MATERIALS AND METHODS: In the present study, we aimed to systematically review the literature wherein acute plant poisoning and herbal intoxication have been reported in pediatric patients. After literature search and selection of the appropriate documents, the desired data were extracted and described qualitatively. RESULTS: A total of 127 articles with overall 1453 intoxicated cases were collected. The results of this study showed that some medicinal plants can cause acute poisoning and complications such as hepatic and renal failure in children. CONCLUSION: The findings of this survey showed that acute plant poisoning can be life?threatening in children, and since a single?ingested dose of toxic plants can cause acute poisoning, parents should be aware of these toxic effects and compare the side effects of self?medication with its potential benefits.

Development of solid-phase microextraction coupled with liquid chromatography for analysis of tramadol in brain tissue using its molecularly imprinted polymer.

In this work, performance of a molecularly imprinted polymer (MIP) as a selective solid-phase microextraction sorbent for the extraction and enrichment of tramadol in aqueous solution and rabbit brain tissue, is described. Binding properties of MIPs were studied in comparison with their nonimprinted polymer (NIP). Ten milligrams of the optimized MIP was then evaluated as a sorbent, for preconcentration, in molecularly imprinted solid-phase microextraction (MISPME) of tramadol from aqueous solution and rabbit brain tissue. The analytical method was calibrated in the range of 0.004 ppm (4 ng mL-1 ) and 10 ppm (10 µg mL-1 ) in aqueous media and in the ranges of 0.01 and 10 ppm in rabbit brain tissue, respectively. The results indicated significantly higher binding affinity of MIPs to tramadol, in comparison with NIP. The MISPME procedure was developed and optimized with a recovery of 81.12-107.54% in aqueous solution and 76.16-91.20% in rabbit brain tissue. The inter- and intra-day variation values were <8.24 and 5.06%, respectively. Finally the calibrated method was applied for determination of tramadol in real rabbit brain tissue samples after administration of a lethal dose. Our data demonstrated the potential of MISPME for rapid, sensitive and cost-effective sample analysis.

Extended Ciprofloxacin Release Using Vitamin E Diffusion Barrier From Commercial Silicone-Based Soft Contact Lenses.

OBJECTIVES: Ciprofloxacin (Cipro) is an antibiotic, widely used in form of ophthalmic drops (0.3%) for the treatment of eye infections. In this study, vitamin E was used as a hydrophobic barrier to improve and prolong the amount and time of Cipro release from silicone-based soft contact lenses. METHODS: Three different commercial contact lenses (Air Optix, Biofinity, and Acuvue Oasys) were soaked in vitamin E solutions (0.1 and 0.2 g/mL). The effect of vitamin E on Cipro loading amount and drug releasing profile was evaluated in artificial tear. Swelling properties and diameter changes of the lenses were also investigated in aqueous media in presence and absence of vitamin E. RESULTS: The data indicated that vitamin E, as a hydrophobic barrier, significantly decreased the water content of silicone-based soft contact lenses. After vitamin E loading, a 5% to 18% increase was observed in lens diameter in the hydrated state, whereas the lens diameter increased by 11% to 23% in the dry state. In all commercial lenses, vitamin E loading in a 0.2-g/mL solution caused a 27.94% to 37.08% increase in Cipro binding. The results indicated that applying vitamin E loading solutions, with 0.1 and 0.2 g/mL concentrations, could effectively enhance Cipro release time from 2 hr (in a pure non-vitamin E-loaded lens) to 14 to 17 and 30 to 33 days, respectively. These values showed an increase by a factor of 168 to 204 and 360 to 396 in Cipro release time after using vitamin E loading solutions with 0.1 and 0.2 g/mL concentrations, respectively, compared with pure non-vitamin E-loaded soft contact lenses. CONCLUSIONS: This study indicated that vitamin E acts as an effective hydrophobic barrier, in increasing the Cipro loading capacity of silicone-based contact lenses and prolonging the drug release into the artificial tear.

Ciprofloxacin-imprinted hydrogels for drug sustained release in aqueous media.

In this study several ciprofloxacin (CFX) imprinted and non-imprinted hydrogels were prepared and evaluated as ocular drug delivery systems in aqueous media. 2-Hydroxyethyl methacrylate (HEMA) was used as a solvent and backbone monomer, ethylene glycol dimethacrylate (EGDMA) as a cross-linker, methacrylic acid (MAA) as a functional monomer and CFX as the template molecule. CFX-imprinted hydrogels (MIPs) were prepared applying different CFX:MAA molar ratios (1:16, 1:20 and 1:32) in feed composition of monomer solutions. Thermal polymerization was applied and hydrogels were synthesized in a polypropylene mold (0.4 mm thickness). Swelling and binding properties of hydrogels were evaluated in water. Release profile of the MIPs was evaluated in NaCl (0.9%) and artificial tears. The data showed that enhancing the MAA concentration, as a co-monomer, and using molecular imprinting improved binding properties of the synthesized hydrogels. The optimized MIPs with 400 mM MAA and CFX: MAA molar ratio of 1:20 and 1:16 showed the greatest affinity for CFX and the highest ability to control drug release. In vitro antibacterial activity of hydrogels was studied and demonstrated the effect of CFX-loaded hydrogels against Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) isolated from patients' eyes. This study indicated antibacterial efficacy of CFX-loaded MIP hydrogels.

Controlled release of betamethasone from vitamin E-loaded silicone-based soft contact lenses.

CONTEXT: Betamethasone (BMZ) is an effective drug which is commonly used as an eye drop for the management of ophthalmic inflammations. Due to low ocular bioavailability, it is necessary to prepare and optimize an ocular drug delivery system for BMZ. OBJECTIVE: In this study we tried to use vitamin E diffusion barrier for sustaining BMZ release. MATERIALS AND METHODS: Three commercial contact lenses were soaked in vitamin E solutions and swelling percentage, diameter, transmittance, binding capacity and release amount and time were evaluated in comparison with non-vitamin E-loaded pure lenses. RESULTS: The results showed that vitamin E significantly decreased water content of contact lenses whereas, increased the lens diameter in both dry and wet states. It effectively blocked UV radiation which is harmful for the eye surface while had no significant effect on visible transmittance. BMZ loading capacity enhanced and release rate remarkably decreased after using vitamin E as a hydrophobic diffusion barrier. DISCUSSION AND CONCLUSIONS: This study revealed that vitamin E can be applied as a hydrophobic diffusion barrier for controlling and sustaining BMZ release from silicone-based soft contact lenses into the lachrymal fluid. It can also protect eye tissues as an antioxidant by blocking the UV radiation.

Development of ocular drug delivery systems using molecularly imprinted soft contact lenses.

Recently, significant advances have been made in order to optimize drug delivery to ocular tissues. The main problems in ocular drug delivery are poor bioavailability and uncontrollable drug delivery of conventional ophthalmic preparations (e.g. eye drops). Hydrogels have been investigated since 1965 as new ocular drug delivery systems. Increase of hydrogel loading capacity, optimization of drug residence time on the ocular surface and biocompatibility with the eye tissue has been the main focus of previous studies. Molecular imprinting technology provided the opportunity to fulfill the above-mentioned objectives. Molecularly imprinted soft contact lenses (SCLs) have high potentials as novel drug delivery systems for the treatment of eye disorders. This technique is used for the preparation of polymers with specific binding sites for a template molecule. Previous studies indicated that molecular imprinting technology could be successfully applied for the preparation of SCLs as ocular drug delivery systems. Previous research, particularly in vivo studies, demonstrated that molecular imprinting is a versatile and effective method in optimizing the drug release behavior and enhancing the loading capacity of SCLs as new ocular drug delivery systems. This review highlights various potentials of molecularly imprinted contact lenses in enhancing the drug-loading capacity and controlling the drug release, compared to other ocular drug delivery systems. We have also studied the effects of contributing factors such as the type of comonomer, template/functional monomer molar ratio, crosslinker concentration in drug-loading capacity, and the release properties of molecularly imprinted hydrogels.

Haloperidol imprinted polymer: preparation, evaluation, and application for drug assay in brain tissue.

Several molecularly imprinted polymers (MIPs) were prepared in the present work, and their binding properties were evaluated in comparison with a nonimprinted polymer (NIP). An optimized MIP was selected and applied for selective extraction and analysis of haloperidol in rabbit brain tissue. A molecularly imprinted solid-phase extraction (MISPE) method was developed for cleanup and preconcentration of haloperidol in brain samples before HPLC-UV analysis. Selectivity of the MISPE procedure was investigated using haloperidol and some structurally different drugs with similar polarity that could exist simultaneously in brain tissue. The extraction and analytical process was calibrated in the range of 0.05-10 ppm. The recovery of haloperidol in this MISPE process was calculated between 79.9 and 90.4%. The limit of detection (LOD) and the limit of quantification (LOQ) of the assay were 0.008 and 0.05 ppm, respectively. Intraday precision and interday precision values for haloperidol analysis were less than 5.86 and 7.63%, respectively. The MISPE method could effectively extract and concentrate haloperidol from brain tissue in the presence of clozapine and imipramine. Finally, the imprinted polymer was successfully applied for the determination of haloperidol in a real rabbit brain sample after administration of a toxic dose. Therefore, the proposed MISPE method could be applied in the extraction and preconcentration before HPLC-UV analysis of haloperidol in rabbit brain tissue.

Effect of split foliar fertilisation on the quality and quantity of active constituents in saffron (Crocus sativus L.).

BACKGROUND: Saffron (Crocus sativus L.) is one of the most expensive medicinal and aromatic plants in the world. Due to the excessive application of chemical fertilisers in saffron farms and alkalinity of most cultivated soils, split foliar fertilisation has been suggested. The primary goal of this study was to propose split foliar fertilisation as a technique in increasing the quality and quantity of active constituents in saffron. HPLC analysis was used to quantify the most important saffron components; crocins (colour), picrocrocin (taste), and safranal (odour). This study was carried out in Kashmar, Iran, to determine the effect of split foliar fertilisations on quality and quantity of saffron in 2011 and 2012. A split-plot design experiment based on randomised complete block with three replications was conducted to examine three fertiliser types in three regimes for split foliar fertilisation. RESULTS: Statistical analysis showed that split foliar fertilisation and the fertiliser type significantly increased saffron yield, number of flowers and crocin; whereas it decreased the picrocrocin and safranal content of the saffron stigmas (P < 0.05). CONCLUSION: Overall, split foliar fertilisation increased saffron yield and colour but decreased the taste and the odour of saffron.