In vitro antioxidant and antihyperlipidemic activities of Bauhinia variegata Linn

Objectives:

To evaluate the ethanolic and aqueous extracts of Bauhinia variegata Linn. for in vitro antioxidant and antihyperlipidemic activity.

Materials and Methods:

Ethanolic and aqueous extracts of the stem bark and root of B. variegata Linn. were prepared and assessed for in vitro antioxidant activity by various methods namely total reducing power, scavenging of various free radicals such as 1,2-diphenyl-2-picrylhydrazyl (DPPH), super oxide, nitric oxide, and hydrogen peroxide. The percentage scavenging of various free radicals were compared with standard antioxidants such as ascorbic acid and butylated hydroxyl anisole (BHA). The extracts were also evaluated for antihyperlipidemic activity in Triton WR-1339 (iso-octyl polyoxyethylene phenol)-induced hyperlipidemic albino rats by estimating serum triglyceride, very low density lipids (VLDL), cholesterol, low-density lipids (LDL), and high-density lipid (HDL) levels.

Result:

Significant antioxidant activity was observed in all the methods, (P < 0.01) for reducing power and (P < 0.001) for scavenging DPPH, super oxide, nitric oxide, and hydrogen peroxide radicals. The extracts showed significant reduction (P < 0.01) in cholesterol at 6 and 24 h and (P < 0.05) at 48 h. There was significant reduction (P < 0.01) in triglyceride level at 6, 24, and 48 h. The VLDL level was also significantly (P < 0.05) reduced from 24 h and maximum reduction (P < 0.01) was seen at 48 h. There was significant increase (P < 0.01) in HDL at 6, 24, and 48 h.

Conclusion:

From the results, it is evident that alcoholic and aqueous extracts of B. variegata Linn. can effectively decrease plasma cholesterol, triglyceride, LDL, and VLDL and increase plasma HDL levels. In addition, the alcoholic and aqueous extracts have shown significant antioxidant activity. By the virtue of its antioxidant activity, B. variegata Linn. may show antihyperlipidemic activity.     

In-house preparation of iodine -131 metaiodo benzyl guanidine for scintigraphy of neuroendocrine tumors. Fourteen years experience in South India

Iodine-131 metaiodobenzyl guanidine ((131)I-MIBG) is routinely used for imaging and treatment of neuroendocrine tumors (NET). As the commercially available radiopharmaceutical was very expensive, we developed an in-house method of labeling MIBG with (131)I in 1993. A total of 247 batches of (131)I-MIBG were prepared and used in our hospital between April 1993 and September 2006. We report our experience over these 14 years of preparation of this tracer in our hospital radiopharmacy, for the scintigraphy of NET. The technique of preparation is simple and the labeled product was found to be of acceptable quality. With the routine availability and cost effectiveness, the utilization of this radiopharmaceutical for scintigraphy increased remarkably in our institution.     

Active and Passive Immunizations with Bordetella Colonization Factor A Protect Mice against Respiratory Challenge with Bordetella bronchiseptica

Bordetella colonization factor A (BcfA) is an outer membrane immunogenic protein, which is critical for efficient colonization of the murine respiratory tract. These properties of BcfA prompted us to examine its utility in inducing a protective immune response against Bordetella bronchiseptica in a mouse model of intranasal infection. Mice vaccinated with BcfA demonstrated reduced pathology in the lungs and harbored lower bacterial burdens in the respiratory tract. Immunization with BcfA led to the generation of BcfA-specific antibodies in both the sera and lungs, and passive immunization led to the reduction of B. bronchiseptica in the tracheas and lungs. These results suggest that protection after immunization with BcfA is mediated in part by antibodies against BcfA. To further investigate the mechanism of BcfA-induced immune clearance, we examined the role of neutrophils and macrophages. Our results demonstrate that neutrophils are critical for anti-BcfA antibody-mediated clearance and that opsonization with anti-BcfA serum enhances phagocytosis of B. bronchiseptica by murine macrophages. We show that immunization with BcfA results in the production of gamma interferon and subclasses of immunoglobulin G antibodies that are consistent with the induction of a Th1-type immune response. In combination, our findings suggest that the mechanism of BcfA-mediated immunity involves humoral and cellular responses. Expression of BcfA is conserved among multiple clinical isolates of B. bronchiseptica. Our results demonstrate the striking protective efficacy of BcfA-mediated immunization, thereby highlighting its utility as a potential vaccine candidate. These results also provide a model for the development of cell-free vaccines against B. bronchiseptica.Respiratory pathogens are a major cause of morbidity and mortality in humans and animals, making the development of efficacious vaccines that protect against these infections a top priority. Bordetellae are small, aerobic, gram-negative coccobacilli that colonize the respiratory tracts of humans and animals (31). Bordetella pertussis infects only humans and causes the acute respiratory disease whooping cough (6). Bordetella parapertussis strains can be divided into two genetically distinct types: those which infect humans, causing a pertussis-like illness, and those which cause respiratory infections in sheep (22, 38). Bordetella avium infects mainly commercially grown turkeys and wild and domesticated birds (43, 45). In contrast, Bordetella bronchiseptica has a broader host range and is considered a cocontributor to a number of respiratory syndromes in agriculturally important and food-producing animals, pets, and nonhuman primates (17). B. bronchiseptica is also a primary etiological agent and/or a predisposing factor that results in porcine reproductive and respiratory disease complex, pneumonia and atrophic rhinitis in swine, infectious tracheobronchitis (i.e., kennel cough) in dogs, and bronchopneumonia in sheep, guinea pigs, rats, mice, rabbits, cats, and nonhuman primates (5, 31). According to the 2000 National Animal Health Monitoring System (NAHMS) survey, respiratory disease was the greatest cause of mortality in swine, accounting for 28.9% of nursery deaths and 39.1% of deaths in grower/finisher pigs. The annual economic impact of atrophic rhinitis and porcine reproductive and respiratory disease complex in the United States alone is estimated to be about $17 million and $40 million, respectively. B. bronchiseptica is also capable of infecting humans, mostly immunocompromised individuals with AIDS or cystic fibrosis (14, 26, 46, 52), although it was recently isolated from an immunocompetent individual (39).Currently available and proposed vaccines against this pathogen include live, attenuated, heat-killed, or genetically modified bacteria (2, 30, 32, 48, 49). Problems associated with these various whole-cell vaccination approaches include the following: persistence of the vaccine strain in animals, poor induction of an antibody response and/or protective immunity, and retention of some of the virulence characteristics by the vaccine strains (2, 30, 32, 48, 49). The genetic mutations that result in the attenuation of many of the commercially available live, attenuated vaccines are unknown, making it likely that these strains may revert to virulent forms because of survival pressures in the host, such as coinfections with other pathogenic organisms. B. bronchiseptica can predispose animals to other infectious agents or exacerbate disease symptoms. For example, B. bronchiseptica colonization leads to increased severity of canine parainfluenza virus 2 infections and predisposition of pigs and rabbits to subsequent Pasteurella multocida colonization (8, 12, 15). Infection of porcine tracheal rings with B. bronchiseptica has also been shown to enhance the adherence of P. multocida bacteria (13).Despite vaccination, animals continue to be carriers, resulting in outbreaks among herds. For laboratory animals like rats, mice, and rabbits, experimental infection with B. bronchiseptica results in a chronic and asymptomatic colonization of the upper respiratory tract. We have been able to isolate B. bronchiseptica from the rat nasopharynx even 85 days after inoculation (our unpublished results), and this bacterium has previously been reported to exist in this site for the life of the infected animals (30). Theoretically, persistent colonization of the upper respiratory tract of the animals vaccinated with live or attenuated strains can create a reservoir of infectious bacteria from which animal-animal and zoonotic transmission can occur. Although transmission of a vaccine strain to humans has not been experimentally proven, a number of such human cases have occurred in individuals exposed to infected, sick, or recently immunized farm and companion animals (20).We propose that an effective acellular vaccination regimen capable of providing long-lasting protective immunity will limit the spread of B. bronchiseptica not only among animals in a herd but also from animals to humans. For B. pertussis, there has been a shift to acellular vaccines because of the high frequency of side effects and multiple adverse reactions associated with the whole-cell vaccines (34). Similarly, development of acellular vaccines capable of protecting against B. bronchiseptica should be given a priority.BcfA (Bordetella colonization factor A) is an outer membrane protein which is positively regulated by the BvgAS signal transduction system (50). We were encouraged to examine the role of BcfA in protective immunity because our previously published research revealed its role in the colonization of the rat trachea. In addition, sera from rats infected with B. bronchiseptica specifically recognized BcfA (50). In the current report, we have evaluated the immunogenicity and protective efficacy of BcfA in an intranasal mouse model of respiratory infection. Both active and passive immunization with BcfA provided protection against subsequent intranasal challenge with B. bronchiseptica, which significantly correlated with the production of subclasses of immunoglobulin G (IgG) antibodies with high opsonic activity. Our results also suggested a role for a Th1-type cellular response in BcfA-mediated protection. Finally, we demonstrated that BcfA is expressed by multiple clinical isolates of B. bronchiseptica. Data presented in the current study underscore the potential utility of an acellular vaccine approach for B. bronchiseptica and highlight the importance of BcfA as a critical protective antigen against B. bronchiseptica infections.     

Hansch analysis for the prediction of antimycobacterial activity of ofloxacin derivatives

The present study was attempted to predict the antimycobacterial activity of ofloxacin derivatives. The QSAR results indicated the importance of electronic properties of molecules viz. energy of the lowest unoccupied molecular orbital (LUMO), total energy (T _e), dipole moment (μ) and the topological parameter, third order shape index Kappa (κ₃) in describing the antimycobacterial activity of ofloxacin derivatives. The validity of developed models has been supported by significant statistical parameters.     

Liquid antisolvent precipitation process for solubility modulation of bicalutamide

Liquid antisolvent process was explored as a solubility modulating tool. Bicalutamide, a poorly water soluble drug, was used as a candidate. Low aqueous solubility and poor dissolution of bicalutamide results into poor and variable bioavailability. Therefore, the objective of the present work was to modify the solubility of bicalutamide using the liquid antisolvent precipitation process. HPMC E5 and Poloxamer 407 were shortlisted as a hydrophilic polymer and surfactant, respectively, for the process. Process optimization was done with respect to the hydrophilic polymer, surfactant and drug loading concentration. The resultant microcrystals were characterized with various instrumental techniques for material characterization such as IR, DSC, SEM, XRD, particle size, specific surface area and dissolution kinetics.     

Polymer Chemistry Influences Monocytic Uptake of Polyanhydride Nanospheres

Purpose  To demonstrate that polyanhydride copolymer chemistry affects the uptake and intracellular compartmentalization of nanospheres by THP-1 human monocytic cells. Methods  Polyanhydride nanospheres were prepared by an anti-solvent nanoprecipitation technique. Morphology and particle diameter were confirmed via scanning election microscopy and quasi-elastic light scattering, respectively. The effects of varying polymer chemistry on nanosphere and fluorescently labeled protein uptake by THP-1 cells were monitored by laser scanning confocal microscopy. Results  Polyanhydride nanoparticles composed of poly(sebacic anhydride) (SA), and 20:80 and 50:50 copolymers of 1,6-bis-(p-carboxyphenoxy)hexane (CPH) anhydride and SA were fabricated with similar spherical morphology and particle diameter (200 to 800 nm). Exposure of the nanospheres to THP-1 monocytes showed that poly(SA) and 20:80 CPH:SA nanospheres were readily internalized whereas 50:50 CPH:SA nanospheres had limited uptake. The chemistries also differentially enhanced the uptake of a red fluorescent protein-labeled antigen. Conclusions  Nanosphere and antigen uptake by monocytes can be directly correlated to the chemistry of the nanosphere. These results demonstrate the importance of choosing polyanhydride chemistries that facilitate enhanced interactions with antigen presenting cells that are necessary in the initiation of efficacious immune responses.     

The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice

Autophagy is the principal cellular pathway for degradation of long-lived proteins and organelles and regulates cell fate in response to stress. Recently, autophagy has been implicated in neurodegeneration, but whether it is detrimental or protective remains unclear. Here we report that beclin 1, a protein with a key role in autophagy, was decreased in affected brain regions of patients with Alzheimer disease (AD) early in the disease process. Heterozygous deletion of beclin 1 (Becn1) in mice decreased neuronal autophagy and resulted in neurodegeneration and disruption of lysosomes. In transgenic mice that express human amyloid precursor protein (APP), a model for AD, genetic reduction of Becn1 expression increased intraneuronal amyloid beta (Abeta) accumulation, extracellular Abeta deposition, and neurodegeneration and caused microglial changes and profound neuronal ultrastructural abnormalities. Administration of a lentiviral vector expressing beclin 1 reduced both intracellular and extracellular amyloid pathology in APP transgenic mice. We conclude that beclin 1 deficiency disrupts neuronal autophagy, modulates APP metabolism, and promotes neurodegeneration in mice and that increasing beclin 1 levels may have therapeutic potential in AD.     

Synthesis, antimicrobial and antiviral evaluation of substituted imidazole derivatives

In the present study, we have synthesized 2-(substituted phenyl)-1H-imidazole (1-12) and (substituted phenyl)-[2-(substituted phenyl)-imidazol-1-yl]-methanone (13-26) analogues and screened them for their antimicrobial activity against gram positive, gram negative and fungal species. The results of antibacterial study indicated that compounds 15, 17 and 24 showed appreciable antibacterial activity and compound 26 emerged as the most potential antifungal agent. The results of SAR studies indicated that the presence of electron withdrawing groups is necessary for the antimicrobial activity of the synthesized compounds. The results of the present study indicated that compounds 15, 17 and 24 might be of interest for the identification of new antimicrobial molecules as their antibacterial activity is equivalent to the standard drug norfloxacin. Further, the antiviral screening of (substituted phenyl)-[2-(substituted phenyl)-imidazol-1-yl]-methanones (13-26) against a panel of viral strains indicated that compounds 16 and 19 can be selected as lead compounds for the development of novel antiviral agents.