Synthesis and free radical scavenging activity of coumarin derivatives containing a 2-methylbenzothiazoline motif

Coumarin and benzothiazole scaffolds can be found in a number of natural or synthetic antioxidants. In an effort to develop a novel radical scavenger and potential antioxidant, a series of coumarin derivatives containing 2‐methylbenzothiazoline motif and related compounds was synthesized and evaluated for their DPPH (1,1‐diphenyl‐2‐picrylhydrazyl) and ABTS^?+ (2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) radicals scavenging activities. Among them, 7‐hydroxy‐3‐(2‐methyl‐2,3‐dihydrobenzo[d]thiazol‐2‐yl)‐2H‐chromen‐2‐one ( 3e ) has shown a significant free radical scavenging activity. From the structure–activity point of view, it was found that phenolic coumarin ring and benzothiazoline moiety in target compounds may contribute to the scavenging activity against free radicals.     

Non-medical factors affecting antenatal preferences for delivery route and actual delivery mode of women in southwestern Iran

Objective: Assessment of the contribution of non-medical factors to mode of delivery and birth preference in Iranian pregnant women in southwestern Iran.

Study design: This cohort study used data from a structured questionnaire completed in early pregnancy and information about the subsequent delivery obtained through personal contact. Women were recruited by random sampling from antenatal clinics when scheduling visits over the course of 5 weeks from December 2012 to February 2013 and were followed-up 1 month after birth. Of the 2199 women recruited, 99.63% were eligible for the study.

Results: Of the 748 women who expressed a desire to deliver their babies by cesarean section (CS) in early pregnancy, 87% had an elective cesarean section. The logistic regression analyses showed that normative beliefs (odds ratio [OR] 1.792, 95% confidence interval (1) 1.073–2.993), control beliefs (OR: 0.272, 95% CI: 0.162–0.459), and evaluation of outcomes (OR: 0.431, 95% CI: 0.268–0.692) favored the preference for cesarean section. The desire for delivery by elective cesarean section was associated with normative beliefs (OR: 1.138; 95% CI: 1.001–1.294), control beliefs (OR: 0.804; 95% CI: 0.698–0.927), and expectations about maternity care (OR: 0.772; 95% CI: 0.683–0.873), medical influences (OR: 1.150; 95% CI: 1.023–1.291), evaluation of outcome (OR: 0.789; 95% CI: 0.696–0.894), age, preference for cesarean section (OR: 5.445; 95% CI: 3.928–7.546), spouse educational level, and number of live births.

Conclusions: A woman’s preference for delivery by cesarean section influenced their subsequent mode of delivery. Asking women in early pregnancy about their preferred mode of delivery provides the opportunity to extend their supports which might reduce the rate of elective cesarean section. This decision is affected by age, spouse educational level, number of live births, and preconceived maternal attitudes about delivery.     

Anti-inflammatory and analgesic properties of Heracleum persicum essential oil and hydroalcoholic extract in animal models

Ethnopharmacological relevance

Fruits of Heracleum persicum (Apiaceae) are used as pain killer in Iranian folkloric medicine.

Aims of study

To evaluate the anti-inflammatory and analgesic effects of the hydroalcoholic extract and essential oil of the plant fruits and analyzing the essential oil.

Materials and methods

Essential oil and hydroalcoholic extracts of the fruits were prepared according to standard methods and the components of essential oil were identified using GC–MS method. The acetic acid-induced writhing response and formalin test were used in male mice to assess analgesic activity. For evaluation of anti-inflammatory effect, carrageenan-induced rat paw edema was used.

Results

Hexyl butyrate (56.5%), octyl acetate (16.5%), hexyl 2-methylbutanoate (5.2%) and hexyl isobutyrate (3.4%) were identified as the major constituents of the oil. Oral or intraperitoneal administration of Heracleum persicum essential oil (HPEO) at doses of 50–200 mg/kg and Heracleum persicum hydroalcoholic extract (HPHE) at doses of 250 and 500 mg/kg significantly reduced acetic acid-induced abdominal constrictions. HPEO and HPHE also significantly attenuated the pain response of the second phase of formalin test.In carrageenan test HPEO at doses of 100 and 200 mg/kg and HPHE at a dose of 400 mg/kg induced a significant reduction of paw edema.

Conclusions

These results clearly show the analgesic and anti-inflammatory effects of the plant essential oil and hydroalcoholic extract. Further studies are needed to clarify the mechanism of action and the components responsible for these pharmacological effects.     

A placebo-controlled study of tropisetron added to risperidone for the treatment of negative symptoms in chronic and stable schizophrenia

Rational

A growing body of evidence illustrates that 5-HT3 receptor antagonist drugs may be of benefit in the treatment of negative symptoms in schizophrenia.

Objective

The objective of this study was to assess the efficacy and tolerability of tropisetron add-on to risperidone on negative symptoms in patients with chronic stable schizophrenia.

Methods

In a double-blind, placebo-controlled 8-week trial, 40 patients with chronic schizophrenia who were stabilized on risperidone were randomized into tropisetron or placebo add-on groups. Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) every 2 weeks. Furthermore, extrapyramidal and depressive symptoms as well as side effects were assessed. The primary outcome measure was the difference in change from baseline of negative subscale scores between the two groups at week 8.

Results

Tropisetron resulted in greater improvement of the total PANSS scores [F(1.860,70.699)?=?37.366, p?<?0.001] as well as negative scores [F(2.439,92.675)?=?16.623, p?<?0.001] and general psychopathology [F(1.767,67.158)?=?4.602, p?=?0.017], but not positive subscale scores [F(1.348, 51.218)?=?0.048, p?=?0.893] compared to placebo. In a multiple regression analysis controlling for positive, extrapyramidal, and depressive symptoms, treatment group (standardized β?=??0.640) significantly predicted changes in primary negative symptoms. The side effect profile did not differ significantly between the two groups.

Conclusion

Tropisetron add-on to risperidone improves the primary negative symptoms of patients with chronic stable schizophrenia.     

The effect of sodium valproate on acetic acid-induced colitis in rats

Ulcerative colitis is a chronic recurrent disease with incomplete treatment options. The current article evaluated the effect of sodium valproate on acetic acid-induced ulcerative colitis in rats. Rats were randomly distributed into six groups including Sham group, colitis control group, sodium valproate treatment groups (50, 100 and 300 mg/kg, i.p.) and dexamethasone-treatment group. Dexamethasone was used as a reference drug. Colitis was induced by intracolonic instillation of 2 mL of 3% acetic acid solution. The efficacy of sodium valproate was evaluated by macroscopical and histopathological scoring systems, hematocrit measurement as well as biochemical analysis including myeloperoxidase (MPO) and pro-inflammatory cytokines assessment. Sodium valproate, particularly with doses of 100 and 300 mg/kg significantly improved weight loss, and macroscopic damage, reduced ulcer area, colon weight, microscopic colitis index and elevated hematocrit level. Biochemical experiments showed elevated levels of colonic MPO activity, interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in colitis control group. Treatment with sodium valproate at the doses of 100 and 300 mg/Kg) decreased the MPO activity and colonic concentrations of IL-1β, IL-6 and TNF-α. The results provide evidence that sodium valproate has a protective effect in acetic acid-induced ulcerative colitis which might be due to its anti-inflammatory activities, and it may be useful in patients with ulcerative colitis.     

Periorbital ecchymosis as a sign of perforating injury of the globe

The distinction between penetrating eye injury with retained intraocular foreign body and perforating globe injuries is not always easy clinically. The case is presented of a 25-year-old man who sustained a perforating eye injury that was through a clear self-sealing corneal entry site and had no conjunctival or periorbital injury. He had periorbital ecchymosis on presentation suggesting that the globe had been perforated with resulting retro-orbital blood tracking to the periorbital region. This sign would not be expected had the foreign body remained intraocular. The management options of these cases are discussed.     

Effects of UV Absorber on Zirconia Fabricated with Digital Light Processing Additive Manufacturing

This study evaluated the effect of UV absorbers on the dimensional accuracy of zirconia specimens fabricated by additive manufacturing using a digital light process. Zirconia suspension for additive manufacturing was prepared by setting the volume fractions (0, 0.005, 0.05, and 0.1%) of various UV absorbers. The effect of UV absorber content was evaluated through curing thickness, geometric overgrowth model design, linear deviation, and microstructure evaluation before and after sintering. Statistical analysis was performed by Kruskal–Wallis H and post-tested by the Bonferroni correction method. There was no significant difference in the cure depth according to the presence or absence of the UV absorber, the difference in geometric overgrowth was from 2.1 to 12.5%, and the overgrowth significantly decreased as the amount of added UV absorber increased. This result may contribute to improved precision of 3D multilayer ceramic products.     

Novel Derivatives of Tetrahydrobenzo (g) Imidazo[α-1,2] Quinoline Induce Apoptosis Via ROS Production in the Glioblastoma Multiforme Cells,U-87MG

Background:Despite newer therapeutic approaches against glioblastoma multiforme (GBM), the severely poor prognosis and treatment resistance are still disadvantages that slow down the patient’s recovery process. Consistent with the need to develop more effective and optimized therapies to control GBM cell growth, the effects of a new series of tetrahydrobenzo(g)imidazo[α-1,2]quinolone derivatives on GBM cell growth and the underlying mechanism is investigated in the current study. Methods:U-87MG cell line, glioblastoma multiforme and normal skin fibroblast cell line, AGO1522 were used to study the anticancer effects of 5 derivatives of tetrahydrobenzo(g)imidazo[α-1,2]quinolone and paclitaxel as a standard drug. The cytotoxic effect on cell growth was assessed using the MTT assay. Annexin V FITC staining and PI staining were applied to detect apoptosis and cell cycle distribution using flow cytometry. The extent of reactive oxygen species (ROS) formation was assessed using the fluorescent probe 7-dichlorofluorescin diacetate and caspase-3 activity using the colorimetric assay kit. Results:Among the 5 derivatives of tetrahydrobenzo(g)imidazo[α-1,2]quinolone, the 5c derivative (5-(6-bromo-2-chloroquinolin-3-yl)-9a-hydroxy-8,8-dimethyl-4-Nitro-2,3,5,5a,7,8,9,9a-octahydroimidazo[α-1,2]quinoline-6(1H)) showed the strongest cytotoxic effect on U-87MG cells in a time and Dose-dependent manner compared to the other derivatives and paclitaxel. The IC₅₀ (11.91 M) of the 5c derivative induced apoptosis accompanied by a significant increase in sub-G1 and super-G2 phases of U-87MG cells. The increased level of cellular ROS and caspase 3 activity after treatment of U-87MG cells with 5c derivative was significant compared to untreated cells. Conclusion:Our data provide insights into the potent anticancer effects of the 5c-derivative of tetrahydrobenzo(g)imidazo[α-1,2]quinolone on GBM cells via the caspase-dependent apoptotic pathway, which may merit further attention.Key Words: Glioblastoma multiforme, imidazoquinoline, apoptosis, ROS, reactive oxygen species