Agomelatine: An Astounding Sui-generis Antidepressant?

Major depressive disorder (MDD) is one of the foremost causes of disability and premature death worldwide. Although the available antidepressants are effective and well tolerated, they also have many limitations. Therapeutic advances in developing a new drug's ultimate relation between MDD and chronobiology, which targets the circadian rhythm, led to a renewed focus on psychiatric disorders. In order to provide a critical analysis about antidepressant properties of agomelatine, a detailed PubMed (Medline), Scopus (Embase), Web of Science (Web of Knowledge), Cochrane Library, Google Scholar, and PsycInfo search was performed using the following keywords: melatonin analog, agomelatine, safety, efficacy, adverse effects, pharmacokinetics, pharmacodynamics, circadian rhythm, sleep disorders, neuroplasticity, MDD, bipolar disorder, anhedonia, anxiety, generalized anxiety disorder (GAD), and mood disorders. Agomelatine is a unique melatonin analog with antidepressant properties and a large therapeutic index that improves clinical safety. Published articles revealed that agomelatine is a melatonin receptors (MT1 and MT2) agonist and 5HT2C receptor antagonist. The effects receptors' on melatonin receptors enable the resynchronization of irregular circadian rhythms with beneficial effects on sleep architectures. In this way, agomelatine is accredited for its unique mode of action, which helps to exert antidepressant effects and resynchronize the sleep-wake cycle. To sum up, an agomelatine has not only antidepressant properties but also has anxiolytic effects.

New application of an old drug proparacaine in treating epilepsy via liposomal hydrogel formulation.

Proparacaine (PPC) is a previously discovered topical anesthetic for ophthalmic optometry and surgery by blocking the central Nav1.3. In this study, we found that proparacaine hydrochloride (PPC-HCl) exerted an acute robust antiepileptic effect in pilocarpine-induced epilepsy mice. More importantly, chronic treatment with PPC-HCl totally terminated spontaneous recurrent seizure occurrence without significant toxicity. Chronic treatment with PPC-HCl did not cause obvious cytotoxicity, neuropsychiatric adverse effects, hepatotoxicity, cardiotoxicity, and even genotoxicity that evaluated by whole genome-scale transcriptomic analyses. Only when in a high dose (50 mg/kg), the QRS interval measured by electrocardiography was slightly prolonged, which was similar to the impact of levetiracetam. Nevertheless, to overcome this potential issue, we adopt a liposome encapsulation strategy that could alleviate cardiotoxicity and prepared a type of hydrogel containing PPC-HCl for sustained release. Implantation of thermosensitive chitosan-based hydrogel containing liposomal PPC-HCl into the subcutaneous tissue exerted immediate and long-lasting remission from spontaneous recurrent seizure in epileptic mice without affecting QRS interval. Therefore, this new liposomal hydrogel formulation of proparacaine could be developed as a transdermal patch for treating epilepsy, avoiding the severe toxicity after chronic treatment with current antiepileptic drugs in clinic.

[Performance and Microbial Characteristics of Ammonium-limited and Nitrite-limited ANAMMOX Systems].

The performance and microbial characteristics of ammonium-limited and nitrite-limited ANAMMOX reactors were studied in two continuously stirred tank reactors. The influent TN concentrations were controlled below 50 mg·L-1. The hydraulic retention time and water temperature were maintained at 2.0 h and 20℃, respectively. Results showed that though both ANAMMOX reactors demonstrated similar TN removal loading rates[0.45-0.5 kg·(m3·d)-1] and TN removal efficiencies (around 70%), the ΔNO3-/ΔNH4+ ratio of the ammonium-limited ANAMMOX reactor showed a faster upward trend. Batch tests and high-throughput sequencing results indicated that the ammonium-limited ANAMMOX reactor had more significant functional and population heterogeneity than the nitrite-limited ANAMMOX reactor. Candidatus_Brocadia was the predominant ANAMMOX bacteria in both reactors. The relative abundance of Candidatus_Brocadia in large granules (53.9%) was significantly higher than that in flocs (19.1%) under the ammonium-limited conditions, whereas only a small difference in relative abundance of Candidatus_Brocadia was observed between the granules (28.1%) and flocs (21.3%) in the nitrite-limited ANAMMOX reactor. Nitrospira-like NOB were detected in both ANAMMOX reactors, which primarily inhabited flocs, seemingly driven by the availability of oxygen. Moreover, the ammonium-limited (i.e., excess nitrite) conditions seemingly favored the growth of Nitrospira. Building upon these results, a control strategy for optimal operation of the ammonium-limited ANAMMOX reactor was proposed based on selective floc discharge.

Astaxanthin Combine with Human Serum Albumin to Abrogate Cell Proliferation, Migration, and Drug-resistant in Human Ovarian Carcinoma SKOV3 Cells.

BACKGROUND: Astaxanthin (AST) shows a large range of beneficial effects together with anti-cancer and antioxidation properties. Human Serum Albumin (HSA) is the most abundant protein in blood plasma which plays the role of a depot and transport protein for many exogenous compounds. However, whether HSA could enhance AST-induced cytotoxic effects in human ovarian cancer cells has not been examined to date. OBJECTIVE: This study aims to explore the anticancer effect and the molecular mechanism of AST combine with HSA induced cytotoxicity in ovarian cancer SKOV3 cells. METHODS: The ovarian cancer SKOV3 cells were treated by AST combined with HSA to study the effects of cell proliferation, cell morphology, cell cycle arrest, related protein expression, nuclear transfer, cell migration, and drug-resistant. RESULTS: Our data confirmed that AST+HSA treatment enhanced the anticancer effects of AST, arrested G1 phase cell cycle and induced apoptosis in SKOV3 cells. AST+HSA induced apoptosis via mitochondrial apoptotic pathways was related to the increased ratio of Bcl-2/Bax and activation of caspase-3. Besides, exposure of cells to AST+HSA triggered the inactivation of NF-κB and activation p53 and MAPKs signaling pathways. Furthermore, AST+HSA significantly overcome the drug-resistant and inhibited the migration of SKOV3 cells. CONCLUSION: AST combined treatment with HSA considerably inhibited NF-κB expression and translocation to nucleus, thereby improving the AST-induced cytotoxic effect on SKOV3 cells. These findings may provide rationale to combine AST with HSA for the treatment of ovarian cancer.

[Effects of topical application of doxycycline on avulsed permanent teeth].

PURPOSE: To evaluate the treatment effect of topical doxycycline on avulsed permanent teeth compared with normal saline. METHODS: A total of 44 avulsed teeth from 38 patients (22 boys and 16 girls, aged 7-14 years) were recruited. Twenty-one teeth in group A were treated with doxycycline for 5 min before replantation while 23 teeth in group B were treated with saline solution. All participants were followed up for at least 12 months. The clinical outcome differences between 2 groups was evaluated by Mann-Whitney U test. RESULTS: In group A, 18 teeth were found pulp necrosis, 3 with infection-related resorption, 13 with ankylosis-related resorption and 6 were extracted. In group B, 16 were diagnosed with pulp necrosis, 4 with infection-related resorption, 12 with ankylosis-related resorption and 7 were extracted. No significant differences were found between the two groups on pulp survival and periodontal healing. CONCLUSIONS: Compared with treatment with normal saline, avulsed permanent teeth treated with doxycycline did not show a better clinical outcome.

Chemoreversal Metabolites from the Endophytic Fungus Penicillium citrinum Isolated from a Mangrove Avicennia marina.

Two new compounds, named (Z)-7,4'-dimethoxy-6-hydroxyaurone-4-O-ß-glucopyranoside (1) and (-)-4-O-(4-O-ß-D-glucopyranosylcaffeoyl)quinic acid (2), were isolated from the endophytic fungus Penicillium citrinum of Avicennia marina. Their structures were elucidated on the basis of spectroscopic analysis. Additionally, compound 2 exhibited potent chemoreversal activity, mainly by inhibiting P-glycoprotein efflux pump function.

[Effect of amount of silane coupling agent on flexural strength of dental composite resins reinforced with aluminium borate whisker].

PURPOSE: To evaluate the effect of amount of silane coupling agent on flexural strength of dental composite resins reinforced with aluminium borate whisker (ABW). METHODS: ABW was surface-treated with 0%, 1%, 2%, 3% and 4% silan coupling agent (γ-MPS), and mixed with resin matrix to synthesize 5 groups of composite resins. After heat-cured at 120 degrees centigrade for 1 h, specimens were tested in three-point flexure to measure strength according to ISO-4049. One specimen was selected randomly from each group and observed under scanning electron microscope (SEM). The data was analyzed with SAS 9.2 software package. RESULTS: The flexural strength (117.93±11.9 Mpa) of the group treated with 2% silane coupling agent was the highest, and significantly different from that of the other 4 groups (α=0.01). CONCLUSIONS: The amount of silane coupling agent has impact on the flexural strength of dental composite resins reinforced with whiskers; The flexual strength will be reduced whenever the amount is higher or lower than the threshold. Supported by Research Fund of Science and Technology Committee of Shanghai Municipality (08DZ2271100).

[Analysis of Shanghai residents' cognition and approbation to dental practical clinic].

PURPOSE: To know about Shanghai residents' cognition and approbation to dental practical clinic and discuss the appropriate mode of clinical teaching. METHODS: 100 residents were chosen in five super-markets in five different districts randomly to fill in a questionnaire. RESULTS: 475 questionnaires were effective among 502 questionnaires and the efficiency was 94.62%; 10.32% informants knew the practical clinic, 56.84% informants would like to know it; 40.21% informants would like to choose the specialists, meanwhile 37.68% informants would choose the interns; 65.43% informants were satisfied with the dental interns. CONCLUSIONS: The cognition and approbation of residents to dental practical clinic should be enhanced, hospitals and schools should strengthen propaganda and improve teaching, in order to advancing the approbation based on upgrading the cognition.

[Effect of different polishing time on microleakage of resin composite restorations].

PURPOSE: To evaluate the effect of different polishing time on microleakage of different resin composite restorations (Filtek Z350 and Filtek Z250). METHODS: Standardized preparation (the box-type cavities, 3 mm in length and width,2 mm in depth) was performed at the cemento-enamel junction on buccal surface of 80 premolars.They were randomly divided into two groups,and restored with composite resin(Filtek Z350 or Filtek Z250). According to polishing time, the specimens of each group were randomly classified into four subgroups. They were the subgroups of no polishing, polishing immediately after restoring, polishing after 10 minutes and polishing after 24 hours. All of the restorations were polished with Sof-lex discs. After thermal circulation and soaked for 24 hours in 2% methyl blue solution, the specimens were cut through the midline of the restoration, the microleakage at the occlusal margin and the gingival margin were observed under a stereomicroscope and the leakage depth was measured with Spot version 4.6 software package. The microleakage degree and microleakage depth of different groups were analyzed with SPSS 17.0 software package for Mann -Whitney U test and Kruskal -Wallis test. RESULTS: The microleakage depth of Filtek Z350 groups were(0.655±0.486)mm,(0.626±0.497)mm,(0.648±0.370)mm and (0.639±0.453)mm,respectively. The microleakage depths of Filtek Z250 groups were (0.785±0.553)mm,(0.763±0.491)mm,±0.749±0.608)mm and (0.715±0.588)mm,respectively. No significant differences (P>0.05) of microleakage was found among the different groups and subgroups. CONCLUSION: The polishing system of Sof-lex discs have no significant influence on microleakage of resin composite restorations at different polishing time.

[Analysis of patients' trust and satisfaction with dental interns].

PURPOSE: To analyze the patients' trust and satisfaction with dental interns and discuss the countermeasure to improve the trust of patients. METHODS: One hundred and eighteen patients who came to our clinic were asked to fill in a questionnaire, including the content and trust of patients to dental interns. RESULTS: 95.24% of the patients were satisfied with dental interns and 84.13% of them considered that interns were better than they had expected; 51.09% of the patients would like to accept dental interns' diagnose and therapy; 47.83% of the patients were worry about interns medical activities while 28.26% of them did not. CONCLUSIONS: Because of various reasons, patients have some inimical emotion to dental interns and unwilling to cooperate with their performance. Interns, clinicians, hospitals and schools should enhance patients' content and trust to upgrade the quality and efficiency of clinical training and practice.

[Application of case-based learning in clinical practice of dental students].

PURPOSE: To evaluate the result that students accommodate themselves to the case-based learning(CBL) in the practice of dental trauma. METHODS: A total of 60 students were randomly assigned to two groups: CBL group and traditional group. Before and after the learning completed, an exam was fulfilled by each student. A questionnaire was fulfilled by CBL group. The questionnaire included the participants' attitudes toward the challenges through CBL and the suggestions for education reform from traditional to CBL method. All statistical analysis was performed using SAS9.0 software package. RESULTS: There was significant difference (P<0.01) in score improvement between experimental group and control group of students. Questionnaires survey showed that students generally liked the CBL teaching methods. CONCLUSIONS: CBL model can improve not only scores but also the capability of self-study of students. It can also culture the students' good thinking habit in clinic.

[Clinical effect of three kinds of rotary nickel-titanium instruments on root canal preparation of molars].

PURPOSE: To evaluate three kinds of nickel-titanium instruments applied to molar root canal preparation. METHODS: A total of 90 molars treated by root canal therapy were randomly assigned to three groups: ProTaper group. K3 group and Mtwo group. Crown-down technique was used in ProTaper and K3 group, while Mtwo group was treated with routine preparation technique. All teeth in 3 groups were filled by lateral condensation technique. Treatment effect of 3 groups was evaluated according to pre- and post-operative X-ray films. Wearing and tearing degree of equipment, preparation time and postoperative complications incidence of 3 groups were also compared. All statistical analysis was performed using SAS9.0 software package. Data of root canal curvatures and preparation time was compared using t test; the incidence of complications of root canal treatment and postoperative pain was analyzed using Chi-square test. RESULTS: In three groups, root canals had no deviation or no ledge, could maintain the root canal anatomy in early form, and achieved good preparation results. In this study, four ProTapers, three K3s and one Mtwo instrument were fractured. The average root canal preparation time of the Mtwo group was 3.94 min, significantly less than the ProTaper (4.71 min) group and the K3(4.58 min) group. CONCLUSIONS: Three rotary nickel-titanium systems tested in this study are effective in the molar root canal preparation. The Mtwo instrument is much easier and faster during preparation with routine preparation technique.Supported by Research Fund of Science and Technology Commission of Shanghai Municipality(Grant No.08DZ2271100).