37 research outputs found

    Alternative whooping cough vaccines: A minireview

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    Bordetella pertussis, the aetiological agent of an acute upper respiratory tract disease of humans, “whooping cough”, can infect all age groups with adolescents and adults acting as major source of transmission of this pathogen to infants. This transmission is promoted by the fact that adolescents and adults do not exhibit the characteristic cough, the infection being either asymptomatic or manifested as a mild but persistent upper respiratory tract infection. It is established now that both antibodies and cell-mediated immune [CMI] responses are crucial for protection against whooping cough, the former being important in the early phase of the disease, with the latter being important forlong-term protection. The protection offered by vaccination with the currently-marketed acellular pertussis vaccines is predominantly due to antibodies against vaccine antigens associated with a Th2-polarised immune response and has been found to be relatively short-term protection. There is an urgent need to develop alternative vaccines capable of inducing both protective antibody and CMI responses particularly given the resurgence of this vaccinepreventable disease in infants and children worldwide. While current strategies are aimed at the development of recombinant vaccines using an adjuvant that may stimulate both arms of the immune response, no discovery of a cost-effective and non-toxic adjuvant to improve protection against pertussis has been reported thus far. This reviewdetails the oral presentation on alternative whooping cough vaccines and their future potential delivered at the 2nd World Conference on Vaccines and Vaccination organised by the OMICS Publishing Group

    Novel artificial cell microencapsulation of a complex gliclazide-deoxycholic bile acid formulation: A Characterization Study

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    Gliclazide (G) is an antidiabetic drug commonly used in type 2 diabetes. It has extrapancreatic hypoglycemic effects, which makes it a good candidate in type 1 diabetes (T1D). In previous studies, we have shown that a gliclazide-bile acid mixture exerted a hypoglycemic effect in a rat model of T1D. We have also shown that a gliclazide-deoxycholic acid (G-DCA) mixture resulted in better G permeation in vivo, but did not produce a hypoglycemic effect. In this study, we aimed to develop a novel microencapsulated formulation of G-DCA with uniform structure, which has the potential to enhance G pharmacokinetic and pharmacodynamic effects in our rat model of T1D. We also aimed to examine the effect that DCA will have when formulated with our new G microcapsules, in terms of morphology, structure, and excipients’ compatibility. Microencapsulation was carried out using the Büchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared: G-SA (control) at a ratio of 1:30, and G-DCA-SA (test) at a ratio of 1:3:30. Complete characterization of microcapsules was carried out. The new G-DCA-SA formulation was further optimized by the addition of DCA, exhibiting pseudoplastic-thixotropic rheological characteristics. The size of microcapsules remained similar after DCA addition, and these microcapsules showed no chemical interactions between the excipients. This was supported further by the spectral and microscopy studies, suggesting microcapsule stability. The new microencapsulated formulation has good structural properties and may be useful for the oral delivery of G in T1D

    Microencapsulation as a novel delivery method for the potential antidiabetic drug, Probucol

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    Introduction: In previous studies, we successfully designed complex multicompartmental microcapsules as a platform for the oral targeted delivery of lipophilic drugs in type 2 diabetes (T2D). Probucol (PB) is an antihyperlipidemic and antioxidant drug with the potential to show benefits in T2D. We aimed to create a novel microencapsulated formulation of PB and to examine the shape, size, and chemical, thermal, and rheological properties of these microcapsules in vitro. Method: Microencapsulation was carried out using the BĂĽchi-based microencapsulating system developed in our laboratory. Using the polymer, sodium alginate (SA), empty (control, SA) and loaded (test, PB-SA) microcapsules were prepared at a constant ratio (1:30). Complete characterizations of microcapsules, in terms of morphology, thermal profiles, dispersity, and spectral studies, were carried out in triplicate. Results: PB-SA microcapsules displayed uniform and homogeneous characteristics with an average diameter of 1 mm. The microcapsules exhibited pseudoplastic-thixotropic characteristics and showed no chemical interactions between the ingredients. These data were further supported by differential scanning calorimetric analysis and Fourier transform infrared spectral studies, suggesting microcapsule stability. Conclusion: The new PB-SA microcapsules have good structural properties and may be suitable for the oral delivery of PB in T2D. Further studies are required to examine the clinical efficacy and safety of PB in T2D

    Development of Affordable Effective Vaccines against Whooping Cough for the Developing World

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    The rate of mortality in children associated with serious infectious diseases is significantly higher in the developing world and in socioeconomically disadvantaged populations in developed industrialized countries. The reasons underpinning the higher incidence of whooping cough (pertussis) in these populations include overcrowding and poor hygiene, poor coverage with available pertussis containing vaccines and waning immunity following immunisation and infection. Two types of vaccines are currently used for vaccinating infants and children. The whole cell pertussis vaccine, the most used vaccine worldwide, consisting of a killed B pertussis strain, origin of which may differ in different countries, is generally given in combination with chemically or genetically inactivated diphtheria and tetanus toxoids [DTwP or DTPw], with or without combination with Haemophilus influenzae type b [Hib], hepatitis B or inactivated polio virus vaccine [IPV], depending upon the vaccine manufacturer

    Shared primer PCR combined with hybridisation for the detection of Bordetella Pertussis and B. Parapertussis

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    A method of detecting Bordetella pertussis and Bordetella parapertussis infection is provided. The method includes amplification of a Bordetella porin gene fragment from a sample such as a human nasopharyngeal aspirate using a Bordetella-specific primer, a Bordetella pertussis-specific primer and a Bordetella parapertussis-specific primer. The presence of the Bordetella gene fragment is then detected by hybridization to a Bordetella-specific probe. If positive, hybridization to a Bordetella pertussis-specific probe and/or a Bordetella parapertussis-specific probe is used to determine whether the porin gene fragment is indicative of Bordetella pertussis and/or Bordetella parapertussis infection. The method of the invention is designed so that errors introduced by amplification are minimized by generating amplification products of similar size and by incorporating amplification of a reference nucleic acid as an internal control

    RNA interference therapeutics for cancer: challenges and opportunities

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    Abstract. RNA interference (RNAi) is a sequence-specific, post-transcriptional gene silencing mechanism in animals and plants, which is mediated by double-stranded RNA (dsRNA). There has recently been an increasing interest in harnessing the gene silencing activity of dsRNA to develop novel drugs for the treatment of various diseases, such as cancer, neurological disorders, age-related macular degeneration and viral infections. Small interfering RNA (siRNA)-based drugs have distinct advantages over conventional small molecule or protein-based drugs, including high specificity, higher potency and reduced toxicity. However, there are several technical obstacles to overcome before siRNA-based drugs reach the clinic. Delivery of siRNA to the target tissues and stability in the serum remain a major challenge and are the main focus of current research and development efforts. This review focused primarily on the progress made in developing RNAi as therapeutics for cancer and the challenges associated with its clinical development. Use of ligands recognizing cell-specific receptors to achieve tumor-specific delivery of siRNA, methods for enhanced siRNA delivery, improving the bioavailability and pharmacokinetic properties of siRNA and reducing the off-target effects and non-specific gene silencing are discussed in the light of current evidence

    Defective entities and uses therefor

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    The present invention discloses the structure and sequence of aroQ from Bordetella pertussis, which are useful inter alia for the production of the genetically modified attenuated Bordetella strains of the present invention and for detecting and isolating variant aroQ genes and expression products. The present invention also discloses attenuated Bordetella strains of pathogenic origin, and more particularly genetically modified Bordetella strains, which have been attenuated by disruption or inactivation of the aroQ gene. The genetically modified Bordetella strain of the present invention has a reduced capacity to propagate in a mammalian host, but remains viable in the host for a period of time sufficient to induce a protective immune response against the natural pathogenic Bordetella counterpart. The present invention is also directed to the use of such genetically modified Bordetella strains in immunopotentiating compositions for treating and/or preventing inter alia Bordetella infections, and particularly pathogenic infections, caused by Bordetella
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