In silico identification and characterization of common epitope-based peptide vaccine for Nipah and Hendra viruses

Objective To explore a common B- and T-cell epitope-based vaccine that can elicit an immune response against encephalitis causing genus Henipaviruses, Hendra virus (HeV) and Nipah virus (NiV). Methods Membrane proteins F, G and M of HeV and NiV were retrieved from the protein database and subjected to different bioinformatics tools to predict antigenic B-cell epitopes. Best B-cell epitopes were then analyzed to predict their T-cell antigenic potentiality. Antigenic B- and T-cell epitopes that shared maximum identity with HeV and NiV were selected. Stability of the selected epitopes was predicted. Finally, the selected epitopes were subjected to molecular docking simulation with HLA-DR to confirm their antigenic potentiality in silico. Results One epitope from G proteins, one from M proteins and none from F proteins were selected based on their antigenic potentiality. The epitope from the G proteins was stable whereas that from M was unstable. The M-epitope was made stable by adding flanking dipeptides. The 15-mer G-epitope (VDPLRVQWRNNSVIS) showed at least 66% identity with all NiV and HeV G protein sequences, while the 15-mer M-epitope (GKLEFRRNNAIAFKG) with the dipeptide flanking residues showed 73% identity with all NiV and HeV M protein sequences available in the database. Molecular docking simulation with most frequent MHC class-II (MHC II) and class-I (MHC I) molecules showed that these epitopes could bind within HLA binding grooves to elicit an immune response. Conclusions Data in our present study revealed the notion that the epitopes from G and M proteins might be the target for peptide-based subunit vaccine design against HeV and NiV. However, the biochemical analysis is necessary to experimentally validate the interaction of epitopes individually with the MHC molecules through elucidation of immunity induction.

In silico identification and characterization of common epitope-based peptide vaccine for Nipah and Hendra viruses

OBJECTIVE@#To explore a common B- and T-cell epitope-based vaccine that can elicit an immune response against encephalitis causing genus Henipaviruses, Hendra virus (HeV) and Nipah virus (NiV).@*METHODS@#Membrane proteins F, G and M of HeV and NiV were retrieved from the protein database and subjected to different bioinformatics tools to predict antigenic B-cell epitopes. Best B-cell epitopes were then analyzed to predict their T-cell antigenic potentiality. Antigenic B- and T-cell epitopes that shared maximum identity with HeV and NiV were selected. Stability of the selected epitopes was predicted. Finally, the selected epitopes were subjected to molecular docking simulation with HLA-DR to confirm their antigenic potentiality in silico.@*RESULTS@#One epitope from G proteins, one from M proteins and none from F proteins were selected based on their antigenic potentiality. The epitope from the G proteins was stable whereas that from M was unstable. The M-epitope was made stable by adding flanking dipeptides. The 15-mer G-epitope (VDPLRVQWRNNSVIS) showed at least 66% identity with all NiV and HeV G protein sequences, while the 15-mer M-epitope (GKLEFRRNNAIAFKG) with the dipeptide flanking residues showed 73% identity with all NiV and HeV M protein sequences available in the database. Molecular docking simulation with most frequent MHC class-II (MHC II) and class-I (MHC I) molecules showed that these epitopes could bind within HLA binding grooves to elicit an immune response.@*CONCLUSIONS@#Data in our present study revealed the notion that the epitopes from G and M proteins might be the target for peptide-based subunit vaccine design against HeV and NiV. However, the biochemical analysis is necessary to experimentally validate the interaction of epitopes individually with the MHC molecules through elucidation of immunity induction.

Immunoglobulin levels of vitiligo patients

In the present study, the serum immunoglobulin profiles of vitiligo patients were compared with that of cohort control and evaluated the correlation between immunoglobulin level with their socioeconomic factors and nutritional status. Thirty vitiligo patients were recruited randomly from the Department of Dermatology and Venereology, Bangabandhu Sheikh Mujib Medical University Hospital, Dhaka, Bangladesh for this study. Thirty healthy individuals as control group matched by age, sex, education and socioeconomic factors to the patient group were selected. Serum immunoglobulin concentrations were determined by turbidimetry method using immunoglobulin kit. The concentration of IgG and IgA decreased significantly [P<0.05], but the change of IgM was not significant. Socioeconomic data revealed that most of the patients were young and female. Moreover statistical analysis revealed that there was significant correlation between immunoglobulin [IgG and IgA only] concentrations and BMI and number of depigmented patches with IgG concentrations. Finally it can be concluded that the change of serum immunoglobulin concentration in vitiligo patients could be due to the disease condition as pathomechanism suggested the aberrations in cellular immunity. But study with larger number of population is required for further evaluation of the relationship between the immune response and disease state to confirm these findings

Interaction study between levofloxacin and omeprazole using urinary pharmacokinetic data

The objective of this study was to observe the drug interaction between levofloxacin and omeprazole using urinary excretion data. Levofloxacin tablet and omeprazole capsule were administered separately as well as in combination in fasting condition with a wash out period of two weeks after each administration. Urine was collected at different time intervals of 0, 0-2, 2-4, 4-8, 8-12, 12-24, 24-36 and 36-48 hr post-dose and analyzed using a validated HPLC with UV detection. Different pharmacokinetic parameters for both drugs were determined using non-compartmental method. The maximum rate of excretion [R[max]] of levofloxacin was not decreased significantly when co-administered with omeprazole [p>0.05]. Similarly no significant difference [p = 0.350] was observed for R[max] of omeprazole when co-administered with levofloxacin. Again the fraction of levofloxacin excreted [f[e]/f] was not changed significantly [p = 0.953] due to the co-administration of omeprazole. Similarly fraction of omeprazole excreted [f[e] /f] also remained unaffected [p = 0.672] when co-administered with levofloxacin. No significant change was observed for the area under the rate of excretion versus midpoint of time interval curve from zero to 48 hours [AURC[0-48] for levofloxacin and omeprazole [p = 0.816 and 0.792 respectively] when administered separately and co-administered with each other. The study clearly revealed that levofloxacin and omeprazole do not undergo any kind of interactions when administered together. So it can be concluded that these two drugs can be prescribed together to achieve optimum therapeutic activity

Theophylline loaded gastroretentive floating tablets based on hydrophilic polymers: preparation and in vitro evaluation

This investigation describes the preparation and in vitro evaluation of gastroretentive floating tablet of theophylline. Two hydrophilic cellulose derivatives, Methocel K100M and Methocel K15MCR were evaluated for their gel forming and release controlling properties. Sodium bicarbonate and citric acid were incorporated as gas generating agents. The effects of soluble components [sodium bicarbonate and citric acid], gel forming agents and amount variation of theophylline on drug release profile and floating properties were investigated. Tablets were prepared by direct compression technique. Formulations were evaluated for in vitro buoyancy and drug release study was evaluated for eight hours using USP XXII paddle-type dissolution apparatus using 0.1N HCl as dissolution medium. The release mechanisms were explored and explained with zero order, first order, Higuchi and Korsmeyer equations. The release rate, extent and mechanisms were found to be governed by polymer and floating agent content. The content of active ingredient was also a vital factor in controlling drug release pattern. It was found that polymer content and amount of floating agent significantly affected the mean dissolution time, percentage drug release after 8 hours, release rate constant and diffusion exponent

Natural course of fulminant hepatic failure: the scenario in Bangladesh and the differences from the west

Fulminant hepatic failure [FHF] is a devastating complication of acute viral hepatitis, leading to death in most cases. The etiology and predictors of outcome differ according to the geographical region. This study was conducted with the aim of evaluating the etiology, complications, and outcome of FHF in Bangladesh. In this prospective study, we included 67 consecutive cases of FHF presenting to the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, between November 2003 and May 2008. Thirty-nine of the patients were male and 28 were female. Data was analyzed using SPSS, version 13.0. The mean age of the subjects was 31.9 +/- 11 .7 years. Hepatitis E virus [HEV] was the commonest etiological factor for FHF [50 cases, 74.6%]; of the 50 cases with HEV infection, 43 [64.2%] were not coinfected with any other virus, four cases were Hepatitis B virus [HBV] carriers, and three had coinfection with hepatitis A virus [HAV]. HBV was the cause of FHF in nine [13.4%] patients. HCV, paracetamol, and alcohol were not responsible for any of the cases. Most of the patients [57 patients, 85%] developed FHF within 2 weeks of the onset of jaundice. Of the 67 patients, 49 [73.1%] died. Cerebral edema was the single most common cause of death [48 patients, 71.6%]. Other complications were renal failure [23 patients, 34.3%], sepsis [15 patients, 22.4%], electrolyte imbalance [12 patients 17.9%], and bleeding tendency [7 patients, 10.4%]. Occurrence of cerebral edema, longer prothrombin time, higher grade of encephalopathy, and longer jaundice-to-encephalopathy interval had significant negative influence on outcome. The etiology of FHF in Bangladesh is different from that in the West. Prolongation of prothrombin time and occurrence of cerebral edema are predictors of the worst prognosis