Discovery of HSD-621 as a Potential Agent for the Treatment of Type 2 Diabetes

相似文献   

Neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole augment the effects of antidepressants acting via serotonergic system in the forced swimming test in rats

Treatment-resistant depression has necessitated new therapeutic strategies in augmenting the therapeutic actions of currently existing antidepressant drugs. The aim of this study was to investigate the possibility of synergistic interaction between 1-(2-trifluoromethylphenyl)-imidazole (TRIM), a novel neuronal nitric oxide synthase (nNOS) inhibitor and conventional antidepressants of different classes in the forced swimming test (FST) in rats. TRIM decreased the immobility time at 50 mg/kg doses in the FST in rats. Treatment with a behaviourally subeffective dose of TRIM (20 mg/kg) augmented the behavioural effect of tricyclic antidepressant imipramine, selective serotonin re-uptake inhibitor (SSRI) citalopram and fluoxetine or selective serotonin reuptake enhancer tianeptine but failed to augment the antidepressant effect of reboxetine, a noradrenaline re-uptake inhibitor, in this test. Therefore inhibition of NOS augments the effects of antidepressants acting on serotonergic system in the FST. Neither TRIM (10–50 mg/kg) nor other drug treatments affected the locomotor activity of animals. These findings are in agreement with the view that antidepressant effects or augmentation of these effects in the FST may be explained with inhibition of NOS activity and this may be a new approach in offering greater therapeutic efficacy of antidepressants acting via serotonergic system.     

Wound repair potential of Olea europaea L. leaf extracts revealed by in vivo experimental models and comparative evaluation of the extracts' antioxidant activity

Leaves and fruits of Olea europaea L. (olive) have been used externally as an emollient for skin ulcers and for healing of inflammatory wounds. n-Hexane and aqueous extracts, prepared from the dried leaves of olive, were evaluated for their wound healing activity by using in vivo wound models of linear incision and circular excision in comparison with the reference ointment Madecassol? (Bayer, Istanbul, Turkey). The group of animals treated with the aqueous extract demonstrated increased contraction (87.1%) on excision and a significant increase in wound tensile strength (34.8%) on incision models compared to the other groups. Moreover, the antioxidant activity assay showed that aqueous extract has higher scavenging ability than the n-hexane extract. According to the experimental data, the aqueous extract of O. europaea leaves displayed wound healing activity. Secoiridoid oleuropein (4.6059%) was identified as the major active compound according to high-performance liquid chromatography analysis of the aqueous extract.     

Bioassay-guided isolation of anti-inflammatory, antinociceptive and wound healer glycosides from the flowers of Verbascum mucronatum Lam.

Ethnopharmacological relevance

The leaves, flowers and whole aerial parts of Verbascum L. species have been used to treat respiratory problems, haemorrhoids and other types of inflammatory conditions in traditional Turkish medicine.

Aim of the study

In order to evaluate this traditional information, the anti-inflammatory, antinociceptive and wound healing activities of Verbascum mucronatum Lam. which is used as haemostatic in Turkish folk medicine were investigated.

Materials and methods

In vivo inhibitory effect of the extracts on the carrageenan-induced hind paw edema model in mice was studied for the assessment of anti-inflammatory activity. Moreover, the wound healing potential of the plant were evaluated by using in vivo wound healing experimental models, i.e. incision and excision models on mice and rats, were comparatively assessed with a reference ointment Madecassol^®. Skin samples were also evaluated histopathologically.

Results

The results of these experimental studies exhibited that Verbascum mucronatum displays anti-inflammatory, antinociceptive and wound healing activities. Through bioassay-guided fractionation and isolation procedures four iridoid glucosides, ajugol (1), aucubin (2), lasianthoside I (3), catalpol (4), two saponins, ilwensisaponin A (5) and C (6) and a phenylethanoid glycoside, verbascoside (7) were isolated and their structures were elucidated by spectral techniques. Verbascoside (7) was found to possess significant wound healing activity as well as antinociceptive and anti-inflammatory potentials, per os without inducing any apparent acute toxicity or gastric damage.

Conclusion

The experimental study revealed that Verbascum mucronatum displays remarkable antinociceptive, anti-inflammatory and wound healing activities.     

Malignant pleural mesothelioma with scalp, cerebellar, and finger metastases: a rare case

Malignant pleural mesothelioma (MPM) is a rare and asbestosis-associated tumor. MPM commonly invades locally, mostly in the lung, heart, pericardium, chest wall, and vertebrae. Distant metastasis of MPM is very rare. Here we report a patient with MPM who presented with multiple unusual distant metastases. The patient's thorax tomography demonstrated right-sided, irregularly-thickened pleura with nodular masses and invasion of the chest wall into the subcutaneous area. The patient underwent biopsy for a subcutaneous mass in the right anterior chest wall. Pathologic examination revealed a malignant mesenchymal tumor. During follow-up, he suffered from a painful nodule on the scalp and nodules on the fingers, as well as weakness in his right arm. Cranial magnetic resonance imaging illustrated a 1 cm nodule in the left cerebellar hemisphere. Histopathologic examination of the biopsy from the nodule on the scalp revealed a typical mixed type of MPM, with calretinin, vimentin and creatine 5/6 positivity. Distant metastases can be seen in MPM and a biopsy of metastatic regions can yield the diagnosis.     

Gabapentin, A GABA analogue, enhances cognitive performance in mice

Gabapentin is one of the new antiepileptic drugs (AEDs) launched recently. The advantage of new AEDs includes newer mechanism of action, broad spectrum of antiseizure effects, lesser drug interactions and fewer side effects. Gabapentin (GBP) a GABA analogue, is efficacious in several neurological and psychiatric conditions and it is conventionally used in the treatment of partial epilepsies. In this study, we aimed to evaluate the effects of GBP on learning and memory processes of naive mice in Morris water maze (MWM), passive avoidance (PA) and modified elevated plus maze (mEPM) tests. GBP (5 and 10mg/kg, i.p.) was administered on the probe trial of MWM and on the acquisation session of PA and mEPM tests. In the MWM test, GBP (10mg/kg) significantly increased the time spent in target quadrant and GBP (5 and 10mg/kg) significantly decreased the distance to platform compared to control group. In the mEPM test, GBP (5 and 10mg/kg) significantly decreased the transfer latency compared to control group on the second day and in the PA test, GBP (5 and 10mg/kg) significantly prolonged retention latency compared to control group. Our results indicate that GBP has improving effects on spatial and emotional cognitive performance of naive mice in MWM, PA and mEPM tasks.     

Comparision of the effects of subtenon’s and subconjunctival anesthesia on retroorbital hemodynamics

The aim of the study was to compare retroorbital blood flow hemodynamics between subconjunctival and sub-Tenon’s anesthesia. This was a prospective, blinded study and included 80 cases. Patients were monitored and treated in the First Ophthalmology Clinic, Ataturk Training and Research Hospital, Turkey. Sub-Tenon’s anesthesia was performed in 42 cases, and subconjunctival anesthesia was performed in 38 cases. Color Doppler imaging to measure ocular blood flow parameters was performed preoperatively and 21 days after cataract operation in each case. Preoperative and postoperative values of resistivity and pulsatility indices in the ophthalmic, central retinal, and short posterior ciliary arteries were compared. Postoperative mean blood flow velocity measurements of ophthalmic artery were not statistically different between the subconjunctival anesthesia group and the sub-Tenon’s anesthesia group (49.63 ± 14.00 vs. 45.85 ± 13.41; P=0.389). Postoperative RI values were higher in the Subtenon’s anesthesia group than in the subconjunctival anesthesia group, but the difference between two groups was not statistically significant (0.81 ± 0.14 vs. 0.74 ± 0.08; P=0.079). The postoperative pulsatility index of the ophthalmic artery, RI of ophthalmic artery, pulsatility index of the central retinal artery, RI of the central retinal artery, and pulsatility index of the posterior ciliary arteries were not significantly different between the subconjunctival and sub-Tenon’s anesthesia groups. In conclusion, the study suggests that postoperative retroorbital blood flow hemodynamics are the same following sub-Tenon’s and subconjunctival anesthesia.