Recent outbreaks of yellow fever virus (YFV) in West Africa and Brazil resulted in rapid depletio... more Recent outbreaks of yellow fever virus (YFV) in West Africa and Brazil resulted in rapid depletion of global vaccine emergency stockpiles and raised concerns about being unprepared against future YFV epidemics. Here we report that a live attenuated virus similar to the Japanese encephalitis virus (JEV) vaccine JE-CVax/Imojev that consists of YFV-17D vaccine from which the structural (prM/E) genes have been replaced with those of the JEV SA14-14-2 vaccine strain confers full protection in mice against lethal YFV challenge. In contrast to the YFV-17D-mediated protection against YFV, this protection is not mediated by neutralizing antibodies but correlates with YFV-specific nonneutralizing antibodies and T cell responses against cell-associated YFV NS1 and other YFV nonstructural (NS) proteins. Our findings reveal the potential of YFV NS proteins to mediate protection and demonstrate that chimeric flavivirus vaccines, such as Imojev, could confer protection against two flaviviruses. Th...
By infecting mice with the yellow fever virus vaccine strain 17D (YFV-17D; Stamaril®), the dose d... more By infecting mice with the yellow fever virus vaccine strain 17D (YFV-17D; Stamaril®), the dose dependence and evolutionary consequences of neurotropic yellow fever infection was assessed. Highly susceptible AG129 mice were used to allow for a maximal/unlimited expansion of the viral populations. Infected mice uniformly developed neurotropic disease; the virus was isolated from their brains, plaque purified and sequenced. Viral RNA populations were overall rather homogenous [Shannon entropies 0−0.15]. The remaining, yet limited intra-host population diversity (0−11 nucleotide exchanges per genome) appeared to be a consequence of pre-existing clonal heterogeneities (quasispecies) of Stamaril®. In parallel, mice were infected with a molecular clone of YFV-17D which was in vivo launched from a plasmid. Such plasmid-launched YFV-17D had a further reduced and almost clonal evolution. The limited intra-host evolution during unrestricted expansion in a highly susceptible host is relevant for vaccine and drug development against flaviviruses in general. Firstly, a propensity for limited evolution even upon infection with a (very) low inoculum suggests that fractional dosing as implemented in current YF-outbreak control may pose only a limited risk of reversion to pathogenic vaccine-derived virus variants. Secondly, it also largely lowers the chance of antigenic drift and development of resistance to antivirals.
Objective: Rheumatoid arthritis is a dreaded disease, characterized by pain, inflammation and sti... more Objective: Rheumatoid arthritis is a dreaded disease, characterized by pain, inflammation and stiffness of joints, leading to severe immobility problems. The disease shows circadian variation and usually gets aggravated in early morning hours. Aceclofenac, a BCS Class II compound is routinely used in the treatment of pain and inflammation associated with rheumatoid arthritis. The objective of this study was to develop an osmotic delivery system of Aceclofenac that after administration at bedtime would deliver the drug in the morning hours. Methods: A series of osmotically controlled systems of aceclofenac was developed by using lactose, sodium chloride and hydroxypropyl methylcellulose K100M as osmogens. Cellulose acetate (2% w/v in acetone) with varying concentrations of polyethylene glycol-400 was used as the coating polymer to create semi permeable membrane and dissolution was carried out in 290 mOsm phosphate buffer. Formulation optimization was done from four considerations: cu...
Because of the toxicity of vanadium in Ti-6Al-4V alloy, next generation of titanium alloys is pro... more Because of the toxicity of vanadium in Ti-6Al-4V alloy, next generation of titanium alloys is proposed to focus on niobium-containing alloy, but for clinical applications, it is crucial for this alloy to bond with acrylic resins with or without the use of primers. However, literature was lacking about the effect of primers on bonding of autopolymerizing resins to Ti-6Al-7Nb. To evaluate the effect of different metal primers on the shear bond strength of acrylic resin to Ti-6Al-7Nb. A total of 30 dis-shaped wax patterns (10 mm in diameter and 2 mm thickness) were prepared and casted using Ti-6Al-7Nb. After casting, the disk surfaces were finished with abrasive paper under water. Specimens were equally divided into three groups on the basis of the use of primer: metal primer (GC II metal primer) (Group 1), Universal Tokuyama primer (Group 2), no primer (Group 3). Tape of 50 μm thickness was applied on each of the specimens. Then, self-cure acrylic resin was mixed and applied on the ce...
Hepatitis E virus (HEV) is one of the prime causes of acute viral hepatitis, and chronic hepatiti... more Hepatitis E virus (HEV) is one of the prime causes of acute viral hepatitis, and chronic hepatitis E is increasingly recognized as an important problem in the transplant setting. Nevertheless, the fundamental understanding of the biology of HEV replication is limited and there are few therapeutic options. The development of such therapies is partially hindered by the lack of a robust and convenient animal model. We propose the infection of athymic nude rats with the rat HEV strain LA-B350 as such a model. A cDNA clone, pLA-B350, was constructed and the infectivity of its capped RNA transcripts was confirmed in vitro and in vivo Furthermore, a subgenomic replicon, pLA-B350/luc, was constructed and validated for in vitro antiviral studies. Interestingly, rat HEV proved to be less sensitive to the antiviral activity of α-interferon, ribavirin and mycophenolic acid than genotype 3 HEV (a strain that infects humans). As a proof-of-concept, part of the C-terminal polymerase sequence of pL...
Purpose: To describe a protocol for the immediate placement of implant into infected alveolar soc... more Purpose: To describe a protocol for the immediate placement of implant into infected alveolar socket. Materials & Method: A total number of 40 implants were placed immediately into extraction socket. The periapical conditions were different in all the cases (acute, endodontic and periodontal infection). Great care has been taken in debridement of the socket and extraction of tooth /teeth, guided bone regeneration along with the use of preoperative & postoperative anti-microbial agent. Results: All implants but three were osteo-integrated in six months to one year. Complications were related to the extraction process and bone regeneration process. Conclusion: Predisposing factors for failures are incomplete debridement of the socket, poor oral hygiene, incomplete closure of the wound, systemic factors like hormones. With this study we may conclude that an experienced maxillofacial surgeon may consider immediate implants as a viable treatment option for the patient having periapical infections.
Buccal carcinoma is one of the most common oral malignant neoplasms, especially in the South Asia... more Buccal carcinoma is one of the most common oral malignant neoplasms, especially in the South Asian region. Radiotherapy, which plays a significant role in the treatment of this carcinoma, has severe adverse effects. Different types of prosthesis may be constructed to protect healthy tissues from the adverse effects of treatment and concentrate radiation in the region of the tumor mass. However, the technique for fabrication of shielding stent with Lipowitz's alloy (cerrobend/Wood's alloy) has not been well documented. This article describes detailed technique for fabrication of such a stent for unilateral buccal carcinoma patients to spare the unaffected oral cavity from potential harmful effects associated with radiotherapy.
Radiation stents made of Lipowitz metal or cerrobend alloy are commonly used to shield uninvolved... more Radiation stents made of Lipowitz metal or cerrobend alloy are commonly used to shield uninvolved tissues from electron beams used in therapeutic radiation treatment of head and neck cancers. However, studies investigating the efficacy of cerrobend shielding stent in patients with unilateral buccal carcinoma remain rare. To evaluate the efficacy of cerrobend shielding stents in minimizing the potential adverse effects of radiation on oral tissues in buccal carcinoma patients. Twenty.eight participants were selected for the study based on predetermined inclusion criteria, out of which four participants were lost to follow-.up. Half of the remaining participants. (N = 12) were randomly given cerrobend shielding stent and the remaining 12 formed the control group. The effects of radiotherapy were evaluated by using Radiation Therapy Oncology Group. (RTOG) 0435 Head and Neck adverse effects grading tool. All participants were evaluated for xerostomia, mucositis, dysphagia, salivary chan...
Few studies compare the radiographic changes in bone density associated with immediate implant lo... more Few studies compare the radiographic changes in bone density associated with immediate implant loading protocols. The purpose of this longitudinal study was to quantitatively assess radiographic changes in alveolar bone density around immediate functionally and nonfunctionally loaded implants. A prospective longitudinal study was conducted in which 20 participants with partially edentulous mandibles received implants that were immediately loaded either functionally (IFL) or nonfunctionally (INFL). Standardized intraoral periapical radiographs were made at baseline, 3, and 6 months. These were digitized and analyzed using the histogram tool of the GNU Image Modulation Program for changes in alveolar bone density at crestal and lateral apical levels around the implant. An increase in the mean lateral apical pixel grayscale values of 4.68 ±0.80 at 3 months and 4.15 ±0.29 at 6 months was observed with IFL, while INFL demonstrated an increase of 5.66 ±0.53 at 3 months and 6.07 ±0.59 at 6 months. A decrease in the mean crestal pixel grayscale values of -24.40 ±7.41 with IFL and -16.86 ±5.14 with INFL was found from baseline to 3 months. On the basis of this longitudinal study, it was concluded that immediate loading stimulated alveolar bone formation at 6 months after implant placement. The immediate functional loading of implants resulted in a significantly greater degree of bone demineralization at the alveolar crest from implant placement up to 3 months compared with immediate nonfunctional loading.
Recent outbreaks of yellow fever virus (YFV) in West Africa and Brazil resulted in rapid depletio... more Recent outbreaks of yellow fever virus (YFV) in West Africa and Brazil resulted in rapid depletion of global vaccine emergency stockpiles and raised concerns about being unprepared against future YFV epidemics. Here we report that a live attenuated virus similar to the Japanese encephalitis virus (JEV) vaccine JE-CVax/Imojev that consists of YFV-17D vaccine from which the structural (prM/E) genes have been replaced with those of the JEV SA14-14-2 vaccine strain confers full protection in mice against lethal YFV challenge. In contrast to the YFV-17D-mediated protection against YFV, this protection is not mediated by neutralizing antibodies but correlates with YFV-specific nonneutralizing antibodies and T cell responses against cell-associated YFV NS1 and other YFV nonstructural (NS) proteins. Our findings reveal the potential of YFV NS proteins to mediate protection and demonstrate that chimeric flavivirus vaccines, such as Imojev, could confer protection against two flaviviruses. Th...
By infecting mice with the yellow fever virus vaccine strain 17D (YFV-17D; Stamaril®), the dose d... more By infecting mice with the yellow fever virus vaccine strain 17D (YFV-17D; Stamaril®), the dose dependence and evolutionary consequences of neurotropic yellow fever infection was assessed. Highly susceptible AG129 mice were used to allow for a maximal/unlimited expansion of the viral populations. Infected mice uniformly developed neurotropic disease; the virus was isolated from their brains, plaque purified and sequenced. Viral RNA populations were overall rather homogenous [Shannon entropies 0−0.15]. The remaining, yet limited intra-host population diversity (0−11 nucleotide exchanges per genome) appeared to be a consequence of pre-existing clonal heterogeneities (quasispecies) of Stamaril®. In parallel, mice were infected with a molecular clone of YFV-17D which was in vivo launched from a plasmid. Such plasmid-launched YFV-17D had a further reduced and almost clonal evolution. The limited intra-host evolution during unrestricted expansion in a highly susceptible host is relevant for vaccine and drug development against flaviviruses in general. Firstly, a propensity for limited evolution even upon infection with a (very) low inoculum suggests that fractional dosing as implemented in current YF-outbreak control may pose only a limited risk of reversion to pathogenic vaccine-derived virus variants. Secondly, it also largely lowers the chance of antigenic drift and development of resistance to antivirals.
Objective: Rheumatoid arthritis is a dreaded disease, characterized by pain, inflammation and sti... more Objective: Rheumatoid arthritis is a dreaded disease, characterized by pain, inflammation and stiffness of joints, leading to severe immobility problems. The disease shows circadian variation and usually gets aggravated in early morning hours. Aceclofenac, a BCS Class II compound is routinely used in the treatment of pain and inflammation associated with rheumatoid arthritis. The objective of this study was to develop an osmotic delivery system of Aceclofenac that after administration at bedtime would deliver the drug in the morning hours. Methods: A series of osmotically controlled systems of aceclofenac was developed by using lactose, sodium chloride and hydroxypropyl methylcellulose K100M as osmogens. Cellulose acetate (2% w/v in acetone) with varying concentrations of polyethylene glycol-400 was used as the coating polymer to create semi permeable membrane and dissolution was carried out in 290 mOsm phosphate buffer. Formulation optimization was done from four considerations: cu...
Because of the toxicity of vanadium in Ti-6Al-4V alloy, next generation of titanium alloys is pro... more Because of the toxicity of vanadium in Ti-6Al-4V alloy, next generation of titanium alloys is proposed to focus on niobium-containing alloy, but for clinical applications, it is crucial for this alloy to bond with acrylic resins with or without the use of primers. However, literature was lacking about the effect of primers on bonding of autopolymerizing resins to Ti-6Al-7Nb. To evaluate the effect of different metal primers on the shear bond strength of acrylic resin to Ti-6Al-7Nb. A total of 30 dis-shaped wax patterns (10 mm in diameter and 2 mm thickness) were prepared and casted using Ti-6Al-7Nb. After casting, the disk surfaces were finished with abrasive paper under water. Specimens were equally divided into three groups on the basis of the use of primer: metal primer (GC II metal primer) (Group 1), Universal Tokuyama primer (Group 2), no primer (Group 3). Tape of 50 μm thickness was applied on each of the specimens. Then, self-cure acrylic resin was mixed and applied on the ce...
Hepatitis E virus (HEV) is one of the prime causes of acute viral hepatitis, and chronic hepatiti... more Hepatitis E virus (HEV) is one of the prime causes of acute viral hepatitis, and chronic hepatitis E is increasingly recognized as an important problem in the transplant setting. Nevertheless, the fundamental understanding of the biology of HEV replication is limited and there are few therapeutic options. The development of such therapies is partially hindered by the lack of a robust and convenient animal model. We propose the infection of athymic nude rats with the rat HEV strain LA-B350 as such a model. A cDNA clone, pLA-B350, was constructed and the infectivity of its capped RNA transcripts was confirmed in vitro and in vivo Furthermore, a subgenomic replicon, pLA-B350/luc, was constructed and validated for in vitro antiviral studies. Interestingly, rat HEV proved to be less sensitive to the antiviral activity of α-interferon, ribavirin and mycophenolic acid than genotype 3 HEV (a strain that infects humans). As a proof-of-concept, part of the C-terminal polymerase sequence of pL...
Purpose: To describe a protocol for the immediate placement of implant into infected alveolar soc... more Purpose: To describe a protocol for the immediate placement of implant into infected alveolar socket. Materials & Method: A total number of 40 implants were placed immediately into extraction socket. The periapical conditions were different in all the cases (acute, endodontic and periodontal infection). Great care has been taken in debridement of the socket and extraction of tooth /teeth, guided bone regeneration along with the use of preoperative & postoperative anti-microbial agent. Results: All implants but three were osteo-integrated in six months to one year. Complications were related to the extraction process and bone regeneration process. Conclusion: Predisposing factors for failures are incomplete debridement of the socket, poor oral hygiene, incomplete closure of the wound, systemic factors like hormones. With this study we may conclude that an experienced maxillofacial surgeon may consider immediate implants as a viable treatment option for the patient having periapical infections.
Buccal carcinoma is one of the most common oral malignant neoplasms, especially in the South Asia... more Buccal carcinoma is one of the most common oral malignant neoplasms, especially in the South Asian region. Radiotherapy, which plays a significant role in the treatment of this carcinoma, has severe adverse effects. Different types of prosthesis may be constructed to protect healthy tissues from the adverse effects of treatment and concentrate radiation in the region of the tumor mass. However, the technique for fabrication of shielding stent with Lipowitz's alloy (cerrobend/Wood's alloy) has not been well documented. This article describes detailed technique for fabrication of such a stent for unilateral buccal carcinoma patients to spare the unaffected oral cavity from potential harmful effects associated with radiotherapy.
Radiation stents made of Lipowitz metal or cerrobend alloy are commonly used to shield uninvolved... more Radiation stents made of Lipowitz metal or cerrobend alloy are commonly used to shield uninvolved tissues from electron beams used in therapeutic radiation treatment of head and neck cancers. However, studies investigating the efficacy of cerrobend shielding stent in patients with unilateral buccal carcinoma remain rare. To evaluate the efficacy of cerrobend shielding stents in minimizing the potential adverse effects of radiation on oral tissues in buccal carcinoma patients. Twenty.eight participants were selected for the study based on predetermined inclusion criteria, out of which four participants were lost to follow-.up. Half of the remaining participants. (N = 12) were randomly given cerrobend shielding stent and the remaining 12 formed the control group. The effects of radiotherapy were evaluated by using Radiation Therapy Oncology Group. (RTOG) 0435 Head and Neck adverse effects grading tool. All participants were evaluated for xerostomia, mucositis, dysphagia, salivary chan...
Few studies compare the radiographic changes in bone density associated with immediate implant lo... more Few studies compare the radiographic changes in bone density associated with immediate implant loading protocols. The purpose of this longitudinal study was to quantitatively assess radiographic changes in alveolar bone density around immediate functionally and nonfunctionally loaded implants. A prospective longitudinal study was conducted in which 20 participants with partially edentulous mandibles received implants that were immediately loaded either functionally (IFL) or nonfunctionally (INFL). Standardized intraoral periapical radiographs were made at baseline, 3, and 6 months. These were digitized and analyzed using the histogram tool of the GNU Image Modulation Program for changes in alveolar bone density at crestal and lateral apical levels around the implant. An increase in the mean lateral apical pixel grayscale values of 4.68 ±0.80 at 3 months and 4.15 ±0.29 at 6 months was observed with IFL, while INFL demonstrated an increase of 5.66 ±0.53 at 3 months and 6.07 ±0.59 at 6 months. A decrease in the mean crestal pixel grayscale values of -24.40 ±7.41 with IFL and -16.86 ±5.14 with INFL was found from baseline to 3 months. On the basis of this longitudinal study, it was concluded that immediate loading stimulated alveolar bone formation at 6 months after implant placement. The immediate functional loading of implants resulted in a significantly greater degree of bone demineralization at the alveolar crest from implant placement up to 3 months compared with immediate nonfunctional loading.
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Papers by Niraj Mishra