METHODS: The title amides (4a-j) were obtained by simple nucleophilic substitution reaction of dexibuprofen acid chloride with substituted amines in good yield and chemical structures were confirmed by FTIR, 1H NMR, 13C NMR and mass spectral data.
RESULTS: The brine shrimp lethality assay results showed that all of the synthesized compounds are non-toxic to shrimp larvae. The inhibitory effects on tumor growth were evaluated and it was observed that N-(2,5-dichlorophenyl)-2-(4-isobutylphenyl) propionamide (4e) and N-(2-chlorophenyl)-2-(4-isobutylphenyl) propionamide (4g) exhibited excellent antitumor activity compared to all other derivatives. The compound 4e bearing 2,5-dichloro substituted phenyl ring and 4g possesses 2-chloro substituted phenyl ring exhibited 100% inhibition of the tumor growth. The anticancer activity was evaluated against breast carcinoma cell line (MCF-7) and it was observed that derivative 4e exhibited excellent growth inhibition of cancer cells with IC50 value of 0.01±0.002 µm, which is better than the standard drugs. The docking studies against breast cancer type 1 susceptibility protein BRCA1 (PDBID 3K0H) exhibited good binding affinities, which are in good agreement with the wet lab results. The compounds 4e and 4g showed the binding energy values of -6.39 and -6.34 Kcal/mol, respectively. The molecular dynamic (MD) simulation was also carried out to evaluate the residual flexibility of the best docking complexes of compounds 4e and 4g. The MD simulation analysis assured that the 4e formed a more stable complex with the target protein than the 4g. The synthesized amide derivatives exhibited were devoid of gastrointestinal side effects and no cytotoxic effects against human normal epithelial breast cell line (MCF-12A) were found.
CONCLUSION: Based upon our wet lab and dry lab findings we propose that dexibuprofen analogue 4e may serve as a lead structure for the design of more potent anticancer drugs.
OBJECTIVE: This study aimed to evaluate the treatment paradigm of a single dose of GSK-3 inhibitor administration at various time courses for the protection of the CNS from EAE.
MATERIALS AND METHODS: Effects of GSK-3 inhibition on intracellular cytokine levels were evaluated from in vitro naïve CD4+ T cell cultures. Immunized C57BL/6 female mice with MOG35-55 in conjunction with CFA and Ptx were used as a chronic inflammatory EAE disease model. Tideglusib (NP12), a Thiadiazolidinone class, selective, and non-ATP competitive GSK-3 inhibitor, was injected intraperitoneally at pre-EAE, same-day of immunization or disease onset. After 30 days post-immunization, brain, and spinal cord tissues were collected for inflammation and demyelination analysis by H&E and luxol fast blue staining, respectively, whereas cytokine profiles of the serum were assessed by cytokine beads array.
RESULTS: The inhibition of GSK-3 in CD4+ T cells increased IL-10 production. The administration of Tideglusib during pre-EAE and same-day, but not during disease onset, significantly reduced clinical symptoms and delayed disease onset. Histopathological analysis of spinal cord tissues showed a significant decline in the number of inflammatory cell infiltration with a concomitant reduction in demyelination through the blocking of GSK-3, especially during pre-EAE and sameday. Upregulation of IL-10 via GSK-3 inhibition coincided with the downregulation of cytokineassociated effector T cells, including IFN-γ, IL-9, IL-17A, IL-17F, IL-21, and IL-23. Increased IL-4 production, however, was only significant in the pre-EAE group.
CONCLUSION: The neuroprotective effects of Tideglusib against EAE are time-dependent. Downregulation of Th1 and Th17 hallmark cytokines by Tideglusib in EAE may be associated with IL-10 production.
METHODS: In this study, we extracted retrospective data from Malaysian surveillance database. Analysis was carried out using WHONET software focusing noncholera Vibrio spp. including Vibrio parahaemolyticus, Vibrio vulnificus, Vibrio fluvialis, Vibrio alginolyticus, Vibrio hollisae (Grimontia hollisae), Vibrio mimicus, Vibrio metschnikovii, and Vibrio furnissii.
RESULTS: Here, we report the first distribution and prevalence of these species isolated in Malaysia together with the antibiotic sensitivity profile based on the species. We found that V. parahaemolyticus is the predominant species isolated in Malaysia. Noticeably, across the study period, V. fluvialis is becoming more prevalent, as compared to V. parahaemolyticus. In addition, this study also reports the first isolation of pathogenic V. furnissii from stool in Malaysia.
CONCLUSION: These data represent an important step toward understanding the potential emergence of noncholera Vibrio spp. outbreaks.
OBJECTIVE: This study explored, assessed and compared the current status of medicines labeling, patient's counseling, and symptomatic diagnosis by general practitioners and community pharmacists.
MATERIAL AND METHODS: This study used trained Simulated Patients (SP), who participated in a scenario of common cold symptoms at private clinics and community pharmacies. SPs explored medication labeling, patients counseling and symptomatic diagnosis undertaken by general practitioners and community pharmacists. Later, study authors assessed and compared these practices. The study was conducted during June 2011 in Penang, Malaysia.
RESULTS: The study used descriptive statistics and Fisher-exact test to analyze data. Regarding patients counseling standard, among 100 visits by simulated patients, 64 (64%) from community pharmacists provided information about the medicine name, its indication, dosage and route of administration versus 17 (42.5%) general practitioners during 40 visits (p=0.024). Concerning adherence to labeling standard, for instance, only in one pharmacy visit, (1%) the pharmacist wrote the name of the patient on the medication label versus in 32 (80%) of doctors' visits, the doctors adhered to this labeling standard (p<0.001). In all doctors' visits (n=40, 100%), SPs were asked about symptoms, whereas in 87 (87%) CPs' visits, pharmacists fulfilled this counseling standard (p=0.02).
CONCLUSION: Although pharmacists showed less compliance to medicine labeling and symptomatic diagnosis compared to doctors, their counseling of patients was better. Separation will definitely contribute to more concentration of each provider on his/her roles and improve and direct the experiences and skills towards being more patient oriented.
METHODS: A randomized controlled trial was conducted among 226 midwives from 10 health care facilities. The intervention group received an educational program on home birth. A validated questionnaire that evaluated knowledge, attitudes, norms, perceived control, and intention to provide planned home birth care was given at baseline, immediately after the intervention, and at three-months follow-up. Data were analyzed using linear mixed-effect model statistics.
RESULTS: Following the intervention, the intervention group demonstrated higher knowledge and more positive attitudes, norms, perceived control, and intention to provide planned home birth care compared with the control group (P 0.05).
DISCUSSION: Educating midwives on planned home birth increases their willingness to provide planned home birth care. Health system administrators, policymakers, and researchers may use similar interventions to promote skilled home birth attendance by midwives. Increasing the number of midwives who are willing to attend planned home births provides women at low risk for medical complications with safer options for labor, delivery, and postpartum care.
CASE SERIES: Here, we reported five cases of this disorder with different clinical presentations from two tertiary hospitals in Kelantan state, Malaysia within a two year-period. Most of them were elderly, except for one who presented at the age of 36 years old. No direct or secondary cause was identified except for one patient who had developed from pregnancy-related at 3 weeks postpartum. These patients presented with spontaneous bleeding typically into skin, muscles, and mucous membranes but also at rare site in the epidural space. All patients denied previous history of bleeding or family history of bleeding disorder. FVIII activities were recorded between <1% to 19%, while the inhibitor titre levels were between 3.9 BU to 340 BU. The treatment approaches especially at presentation were complicated by unfamiliarity of managing this rare condition but all these patients received appropriate medical attention.
DISCUSSION: Prompt diagnosis and management in the right hand are critical. Awareness of this disorder by medical personnel at all levels in the community and in various specialties is important.
METHODS: Six master dies were duplicated from the prepared maxillary first premolar tooth using nonprecious metal alloy (Wiron 99). Thirty copings (Procera AllCeram) of 0.6-mm thickness were manufactured. Three types of luting media were used: zinc phosphate cement (Elite), glass ionomer cement (Fuji I), and dual-cured composite resin cement (Panavia F). Ten copings were cemented with each type. Two master dies were used for each group, and each of them was used to lute five copings. All groups were cemented according to manufacturer's instructions and received a static load of 5 kg during cementation. After 24 hours of distilled water storage at 37 degrees C, the copings were vertically compressed using a universal testing machine at a crosshead speed of 1 mm/min.
RESULTS: ANOVA revealed significant differences in the load at fracture among the three groups (p < 0.001). The fracture strength results showed that the mean fracture strength of zinc phosphate cement (Elite), glass ionomer cement (Fuji I), and resin luting cement (Panavia F) were 1091.9 N, 784.8 N, and 1953.5 N, respectively.
CONCLUSION: Different luting agents have an influence on the fracture resistance of Procera AllCeram copings.