Synthesis and Biological Activities of Quercetin Amide Derivatives / 中国药学杂志

OBJECTIVE: To synthesize the quercetin amide derivatives and determine their biological activities. METHODS: Quercetin was used as a precursor whose hydroxyl group on 3-C of C ring was modified selectively. Using rutin as raw material, 13 quercetin amide derivatives were obtained by selective protection of benzyl group, Williamson ether reaction, amidation reaction and Pd/C catalytic hydrodebenzylation. The antioxidant activity of 13 target compounds was investigated by DPPH method. In addation, MTT assay was performed to investigate the proliferation-inhibition effects of these quercetin derivatives on the proliferation of human esophageal carcinoma cell line EC109, human esophageal carcinoma cell line EC9706, human gastric cancer cell line SGC7901 and mouse melanoma cell line B16-F10. RESULTS: The chemical structures of the target compounds were confirmed by IR, 1H-NMR, 13C-NMR and ESI-MS. Antioxidant experiments showed that the values of SC50 of most target compounds were less than or comparable to quercetin, indicating that 3-OH is not an essential group to maintain the antioxidant property of quercetin. Moreover, antitumor activity experiments showed that the anti-tumor activity of quercetin amide derivatives was enhanced. Among them, the inhibition effect of compound 7-13 on EC109 (IC50=10.25 μmol•L-1) was significantly outperformed the parent drug quercetin (IC50=31.884 μmol•L-1) and 5-FU (IC50=41.738 μmol•L-1), which is a very promising novel anti-tumor candidate compound. CONCLUSION: After structural modification of quercetin by chemical methods, the antioxidant activity is comparable to that of quercetin, and the antitumor activity in vitro is significantly enhanced.

Can a Novel Surgical Approach to the Temporomandibular Joint Improve Access and Reduce Complications?

PURPOSE: This clinical study investigated whether the vascular-guided multilayer preauricular approach (VMPA) to the temporomandibular joint (TMJ) could improve access and decrease complications. PATIENTS AND METHODS: This retrospective evaluation consisted of a consecutive series of patients who underwent TMJ surgeries through the VMPA from January through December 2013. Patients with a history of TMJ surgery were excluded. Clinical data, including operating times, subjective complaints of incision scars, functional conditions of the auriculotemporal nerve and facial nerve, and other complications, were recorded and analyzed. All patients in this study were followed for at least 6 months. RESULTS: All patients (606 joints) had successful TMJ surgeries through the VMPA. All incisions healed favorably with an uneventful recovery. No patient developed permanent weakness of the facial nerve or other severe complications. CONCLUSION: The VMPA can provide direct access and favorable visibility to the TMJ region and yield good esthetic and functional results. The VMPA can be considered the approach of choice for common TMJ surgeries.

Primary intra- and juxta-articular vascular malformations of the temporomandibular joint: a clinical analysis of 8 consecutive patients.

OBJECTIVE: To analyze primary intra- and juxta-articular vascular malformations of the temporomandibular joint. PATIENTS AND METHODS: This study retrospectively reviewed eight patients (seven venous malformations and one lymphatico-venous malformation) who were treated for intra- or juxta-articular vascular malformations of the temporomandibular joint from November 2005 to January 2011. All patients underwent magnetic resonance imaging (MRI) preoperatively. RESULTS: According to MRI findings, vascular malformations involving TMJ could be divided into 3 types; homogenous, lacunar and mixed types. All patients underwent surgical resection, and the final clinical diagnoses were confirmed by postoperative histopathology and immunohistochemical examinations. All treated patients had no clinical or radiographic signs of recurrence. CONCLUSION: Owing to the lower incidence and nonspecific clinical presentations, preoperative diagnosis of vascular malformations involving the TMJ region is very difficult. The classification based on MRI manifestations is proposed first, then it may greatly help in the initial diagnosis. Surgical resection is considered the first option for these TMJ lesions with excellent results.

Post-infectious myositis ossificans in medial, lateral pterygoid muscles: A case report and review of the literature.

Myositis ossificans (MO) is a disease where heterotropic bone forms within a muscle or other type of soft tissue. MO is classified into two groups, MO progressiva and post-traumatic MO. It rarely occurs in the masticatory muscles and thus, only 20 cases involving the masticatory muscles have been reported since 2001. The majority of the reported cases occurred due to trauma, repeated injury or surgical manipulation. However, in a small number of cases, no specific traumatic event was identified as the cause of MO. To the best of our knowledge, this is the first case of post-infectious MO to be reported in the medial and lateral pterygoid muscles.

Metastatic spread to the mandibular condyle as initial clinical presentation: radiographic diagnosis and surgical experience.

PURPOSE: Metastatic spread to the mandibular condyle is uncommon. The authors retrospectively evaluated a series of consecutive cases of condylar metastases presenting as the initial clinical event to increase awareness and provide a better understanding of this occurrence. PATIENTS AND METHODS: This study consisted of 6 cases of metastatic tumor of the mandibular condyle presenting as the initial clinical event from July 2004 to May 2011. Primary sites included the bladder, prostate, lung, penis, colon, and breast. In 3 cases, positron emission tomographic/computed tomographic scans were performed to detect the primary lesions, which stayed occult at presentation. Surgical removal of the metastatic condylar lesions was performed in 3 patients, and palliative therapy was provided to all patients except a patient with a solitary metastasis. RESULTS: Five patients developed disseminated systemic metastases and died within 12 months. Only the patient with a solitary metastasis stayed alive, without any sign or symptom of tumor recurrence or metastasis at the most recent follow-up visit. CONCLUSIONS: For adult patients without a history of cancer, metastasis should be taken into consideration when the mandibular condyle is irregularly disrupted. Positron emission tomography/computed tomography is effective for detecting occult malignant lesions, whereas surgery might be indicated only for a solitary condylar metastasis.

Septic arthritis of the temporomandibular joint: a retrospective review of 40 cases.

PURPOSE: Septic arthritis of the temporomandibular joint is an uncommonly reported entity. The aim of the present study was to review the cases treated at our clinic, analyze the characteristics of this disease and the responses to management, and recommend a protocol for managing suspected cases. PATIENTS AND METHODS: A total of 40 consecutive patients were included from 1995 to 2007. Their demographics, predisposing factors, clinical manifestations, radiologic findings, joint fluid analysis results, treatment, and outcomes were reviewed. RESULTS: The 40 patients included 26 men and 14 women, with an average age of 36 years. Original infections were found in 15 patients (local spread in 4 and hematogenous dissemination from a distant site in 11). All patients complained of trismus and tenderness in the temporomandibular joint. Sudden malocclusion was found in 33 patients. Joint space widening and limitation of condyle movement were demonstrated by plain film in 33 patients. Increased joint effusion was confirmed by magnetic resonance imaging in 7 patients. Joint fluid was obtained from 35 patients. A high level of neutrophils and fibrin were found under microscopy with hematoxylin-eosin staining. Staphylococcus saprophyticus and S. aureus were cultured from 5 patients. Arthrocentesis under low pressure was applied to 35 patients, and arthroscopy was used in 9 patients. Major sequelae occurred in 11 patients, including fibrosis in 2 and postinfectious osteoarthritis in 9. CONCLUSIONS: Septic arthritis of the temporomandibular joint mainly arises from hematogenous spread, but the original infection is often occult. Antibiotic therapy, arthrocentesis under low pressure, and joint immobilization are recommended for patients in the acute stage. The common sequela is osteoarthritis.

[Development of Chinese oral and maxillofacial surgery reflects the great achievements of China's reform and opening to the world for 30 years].

China's policy of reform and opening to the world provides unlimited vitality for Chinese oral and maxillofacial surgery. The academic organization is increasingly perfecting, the professional team is expanding, and international exchanges are increasingly active. However, new challenges are emerging accordingly. To overcome the current problems and difficulties, some constructive beneficial recommendations were proposed and discussed in this paper.

Combined and sequential treatment of oral and maxillofacial malignancies: an evolving concept and clinical protocol.

OBJECTIVE: To introduce the concept and rational regimens and present the latest development of combined treatment of oral and maxillofacial malignancies. Data sources The related published literature was searched through the CNKI database and MEDLINE using the terms of oral cancer, oral and maxillofacial malignancies, combined and sequential therapy, multidisciplinary approach. Study selection The available related literature was read and evaluated. Studies that met the inclusion criteria were selected. RESULTS: The results show that oral and maxillofacial malignancies diagnosed at an early stages (stages I and II) can be well treated with surgery alone and/or radiotherapy with optimal outcome, but advanced or recurrent diseases should be treated with rational combined and sequential treatment modalities. The use of concomitant chemoradiotherapy, taxane-containing, three-drug induction regimens and Cetuximab in combination with chemotherapy or radiotherapy demonstrated favorable results in previously untreated patients with head and neck squamous cell carcinoma. CONCLUSIONS: The concept of combined and sequential treatment of advanced oral and maxillofacial malignancies should be widely accepted, and the rational regimen for individual and each type of entity should be determined based on the anatomical site and the patient's performance status.

A murine model for septic arthritis of the temporomandibular joint.

PURPOSE: This study was designed to establish a murine model of hematogenously acquired bacterial arthritis of the temporomandibular joint (TMJ) to investigate the pathogenesis of this rare TMJ infection. MATERIALS AND METHODS: One hundred forty mice were inoculated intravenously with 3 different staphylococcal suspensions. They were sacrificed at intervals between 1 day and 2 months. Bacterial cultures were obtained from peripheral blood, liver, kidney, TMJs, knees, and interphalangeal joints. The TMJs were collected for histopathological examination. RESULTS: Staphylococcus aureus, isolated from the joint fluid of a patient with septic arthritis of the TMJ, was recovered from the liver, kidneys, knees, interphalangeal joints, and TMJs of several animals. Blood cultures were negative. Acute septic arthritis of the TMJs was confirmed in several animals as soon as 4 days after inoculation. Histopathology showed severe damage to chondrocytes and collagen fibers in the condyles and discs, leading to extensive degenerative changes. All cultures were negative, and there were no histopathologic changes in animals inoculated with bacteria from the other sources. CONCLUSIONS: A murine model for hematogenous septic arthritis of the TMJ was successfully developed with S. aureus isolated from a patient with a TMJ infection. The bacteria induced multiple organ and joint infections. Septic arthritis of the TMJ occurred in 21% of the animals inoculated. Onset was rapid. It produced extensive degenerative changes. The study confirms the need for prompt diagnosis and treatment of patients with septic arthritis. The model may prove to be very useful in the study of this rare infection.

[A retrospective study of 1420 oral and maxillofacial traumatic cases].

PURPOSE: This clinical retrospective study is aimed to offer the clinical epidemiologic information about oral and maxillofacial trauma based on 1420 cases. METHODS: From 2005-2006, 1420 oral and maxillofacial traumatic cases were treated in Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine. Data regarding age, gender, cause of injury, pattern of fracture and associated systemic injuries were reviewed. RESULTS: The male to female ratio of 1420 cases was 3.24:1;and 36.22% of patients were aged between 20 and 30 years.The most common cause of injury was road traffic accident (42.07%); the zygoma (41.83%) and mandible (29.50%) were the most frequent fracture sites; 43.6% of the cases were not treated or not treated properly in 3 weeks after trauma. CONCLUSIONS: Road traffic accident is the most common cause of hospitalized traumatic cases, and the zygoma and mandible was the susceptible sites to be fractured.Because of the high proportion of inappropriately treated cases,we should take much attention to dentofacial deformities resulting from delayed or inappropriate treatment of oral and maxillofacial trauma cases.

[Experimental study of hydroxycamptothecine and theprubicine in the treatment of adenoid cystic carcinoma lung metastases].

OBJECTIVE: To investigate anticancer effect of hydroxycamptothecine and theprubicine in the treatment of established human adenoid cystic carcinoma (ACC) lung metastasis of nude mice and to determine the best therapy sequence of the two drugs. METHODS: The model of ACC lung metastasis (60 animals) was established by injecting the ACC-M cells into the nude mice from their tail veins. Animals were divided into six groups: v acuity control group, HCPT group, THP group, HCPT and THP group 1, HCPT and THP group 2, HCPT and THP group 3 (No.1 - No.6). Different treatment sequence was performed on these groups. The lung samples were collected and observed after HE staining. The area of metastases and lung tissue were analyzed by the images analysis system. RESULTS: The size of the metastatic lesion in the treatment groups were smaller than that in the control group (P < 0.01). The treatment effects between the group with simultaneous administration of HCPT and THP and the group with single drug administration were not different (P > 0.05). No.5 and No.6 groups showed better effect of treatment than the other treatment groups (P < 0.05). CONCLUSIONS: There are two recommended sequences: (1) HCPT should be used after THP; (2) THP is used 48 hours, After HCPT is administered. Because using two drugs together will decrease the anticancer effect, HCPT and THP should not be used simultaneously.

[Strengthen the scientific research on oral hereditary diseases].

There are many kinds of oral hereditary diseases. Although some attempts have been tried to find the genetics of those diseases, still fewer information are available than the other hereditary diseases at present. Much is needed to do in the future. This article reviewed some cutting-edge findings on the genetics of several oral hereditary diseases including hereditary diseases involving the teeth, periodontal tissues, soft and hard tissues of the oral and maxillofacial region, as well as cleft lip and palate.

[Modulation of Chinese prescription Shenyang on Th1/Th2 cytokines in serum of SD rats with squamous cell carcinoma of the tongue].

PURPOSE: Prospective research demonstrated that Chinese prescription Shenyang could prolong the survival time and improve the survival rate of patients with oral squamous cell carcinoma (SCC). But the mechanism was not clear. The purpose of this study was to investigate effect of Shenyang on the level of Th1/Th2 cytokines in serum of SD rats with SCC of tongue and clarify its mechanism. METHODS: Among 80 SD rats fed by 0.002% 4-nitroquinoline-1-oxide (4NQO) drinking water for 36 weeks, 61 with SCC of tongue had been found and randomly divided into 4 groups, namely Shenyang A, Shenyang B, positive and negative control group. Before and after high and low dosage of Shenyang, acanthopanax senticoside and water had been given for 15 days respectively, peripheral blood serum was collected. Secretion of Th1-type cytokines, such as IFN-gamma, IL-2, TNF-alpha and Th2-type cytokines, such as IL-4, IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was made with paired t test. RESULTS: Shenyang significantly enhanced ,the serum levels of Th1-type cytokine, TNF-alpha and IL-2 (P<0.05), and decreased the expression of Th2-type cytokine, IL-4 and IL-10(P<0.05). Serum IFN-gamma had been increased to some extent. CONCLUSION: Reversing Th2 to Th1 cytokines and then enhancing the immunity may be one of the mechanisms in anti-tumor effect of Shenyang. Supported by Science and Technology Development Fund (No.014319359) of Shanghai Municipality.