Effective Pharmaceutical Products Research Articles

Assessing the utility of in silico tools in early drug development: The case of a pharmaceutically relevant formulation of the prodrug psilocybin

(1) Background: Depressive disorders contribute to an excruciating global mental health burden. Recently, there has been a great shift in interest towards substances with psychedelic potential as treatment for patients with resistant forms of depression, one of these substances being psilocybin. The need to expedite processes within the drug development pipeline and make potential therapy available for patients with treatment-resistant forms of depression is great. Approaches to combine computational and traditional experimental drug development are more consequential due to their potential to shorten development times and aid in setting product specifications. To date, the full extent to which in silico methods for early drug development yield valid and robust data which can be directly used for translation into safe and effective pharmaceutical products, remains unknown, especially for prodrug containing formulations. (2) Methods: Herein we explore the robustness and applicability of in silico generated data for the aid of experimental drug development by directly comparing computationally generated data to experimentally and literature derived data. Furthermore, by utilizing different computational approaches, we investigate to which extent these computational models can by utilized to create a novel capsule containing psilocybin, having in mind that psilocybin is a prodrug and psilocin is the active. (3) Results: In silico models provided valid data including intrinsic dissolution and capsule dissolution behavior, but were not able to predict stability issues. Simulations of the expected in vivo performance showed deviations from previously published clinical studies. Significant improvements in predictive accuracy were made by implementing physicochemical surface pH models and entering in vitro and in vivo data. (4) Conclusions: Computational models provide a valuable resource to aid in the planning and implementation of experimental drug product development. Prodrug and active were simulated for their in vitro and in vivo behavior. Even though the results appear to be robust, these models exhibit potential for improvement in predictive accuracy, and thus, applicability of computationally generated data for drug development. Moreover, the models are yet unable to perform a completely accurate drug development process solely supported by in silico data. Lastly, we were able to report psilocybin as a BCS class III drug and psilocin as a BCS class I drug in terms of a provisional classification supported by our data.

Determination of Antimicrobial Activity of Cream Formulation Developed with Hibiscus rosa-sinensis Extract and Probiotic

Medicinal plants are an indispensable source of new and effective pharmaceutical products. In the study, the biological activities of water extract obtained from the H. rosa-sinensis leaf was determined and its potential for use in the pharmaceutical and cosmetic industries was investigated. Disc diffusion assay and micro-dilution method against clinical origin test microorganisms were used to assess biological activity. The Extract showed a zone of inhibition on the tested bacteria and yeasts in the 6.85 mm to 10.74 mm range. MIC and MBC or MFC values of the Extract was determined as 6.25-12.50 µg/µL and 12.50-50 µg/µL. Then, the cream formulation containing H. rosa-sinensis leaf water extract and/or human milk originated probiotic candidate Limosilactobacillus fermentum MA-7 strain have been developed. The Extract and probiotic containing cream formulations showed variable antibacterial and antifungal effects on the tested clinical originated microorganisms. The highest inhibition zone diameters of Cream + Extract + Probiotic formulation group was obtained against Candida glabrata RSKK 04019 (9.09 mm) and Escherichia coli O157:H7 (9.04 mm). The results indicate that L. fermentum MA-7 and H. rosa-sinensis water extract, alternative to synthetic antimicrobials, may be used as a natural bioactive ingredient in daily personal care and clinical applications in the near future.

Novel acyclovir-loaded film-forming gel with enhanced mechanical properties and skin permeability

To develop a novel acyclovir (ACV)-loaded film-forming gel (FFG) with the advantage of providing skin protection and continuous drug release upon application, various FFGs and FFG-films were prepared using drug, chitosan, hydrophilic polymer, plasticizer, lactic acid, water, and ethanol. The mechanical and physiochemical properties were evaluated by film formation time, tensile strength, break elongation, Young's modulus, SEM, FTIR, DSC, and XRD. To identify skin permeation of drug, in vitro skin permeation study was conducted with a Franz diffusion cell using dorsal skin of SD-rat. The ACV-loaded FFG consist of ACV/chitosan/PVP/PEG600/lactic acid/water/ethanol at the weight ratio of 1/1.5/0.5/3/2/40/60 exhibited rapid film formation within about 5 min, resulting in rapid film formation. Furthermore, this ACV-loaded FFG film provided excellent flexibility and showed a low degree of drug crystallization as a result of physicochemical properties evaluation. The ACV-loaded FFG with a high ratio of PEG600 showed a high skin permeability compared to other formulations and significantly improved skin permeability compared to commercial products. Consequently, this novel ACV-loaded FFG would be an effective pharmaceutical product with excellent mechanical properties and skin permeability for herpes labialis.

Recruiting for Resilience

Bringing a safe and effective pharmaceutical product or medical device to market requires an astonishing amount of time and money. This research features interviews with the Chief Executive Officers (CEOs), Chief Scientific Officers (CSOs) and Chief Medical Officers (CMOs) of many of the most successful life science firms in the USA with the goal of to capturing their thoughts on the recruitment of new hires. The executives screened candidates for emotional commitment as an essential quality to complete the long process of bench science, regulatory clearance and product positioning in the market. They sought to hire experienced team members who thought of set-backs as problems to be solved on the way to providing life-altering options for patients. These C-suite leaders needed to create a productive workplace culture, enhanced by a diverse group of professionals with a variety of experiences and temperaments. Participants noted that shared vision and resilience played a greater role in predicting performance than any particular skill-set discernible from a resume.

Unravelling the bioprospects of mycoendophytes residing in Withania somnifera for productive pharmaceutical applications

Microorganisms are narrowly exploited, inspite of their limitless potential in synthesizing bioactive compounds having therapeutic applications. In our continuous search for novel, effective and safe therapeutics, endophytic fungi have proved their role as an alternative and reliable source of medically important bioactive compounds which have diverse medicinal applications. Medicinal herbs are generally considered as a storehouse of endophytes. Mycoendophytes residing in medicinal plants are renowned for their potentiality to synthesize active secondary metabolites such as alkaloids, aliphatic compounds, phenylpropanoids, polyketides, peptides, terpenoids etc. having medicinal value. They are also credited for their diverse biological activities including antibacterial, cytotoxic and antioxidant properties. They can be applied successfully in treating diseases like cancer, cardiovascular diseases and many other deadly ailments. With the emergence of various life threatening diseases, an imperative exploration of novel bioactive natural products produced by mycoendophytes residing in medicinal plants for developing potent drugs seems to appear as a promising approach. This review article aims to provide a detailed account on mycoendophytes residing in Withania somnifera , a medicinal herb renowned for its high pharmacological action. Various bioactive secondary metabolites produced by these mycoendophytes having therapeutic applications in various diseases with reference to their structure-activity studies are being discussed in this article. • Mycoendophytes are considered as an elective source for novel compounds with therapeutic applications. • Withania somnifera , an esteemed medicinal plant in Ayurveda, embraces a plethora of mycoendophytes. • Mycoendophytes associated with Withania somnifera produces various bioactive compounds with biopharmaceutical effects. • Hence, these bioactive compounds may be exploited for the development of effective pharmaceutical products.

Oxytetracycline and Florfenicol Concentrations in Food-Additive Premixes Authorised for Broiler Chickens: Assessing Degree of Agreement with Manufacturers Labelling.

Simple SummaryIn this study, two analytical methodologies were developed for the analysis of florfenicol and oxytetracycline premixes, which were applied in the analysis of pharmaceutical formulations manufactured at the national level. These premixes were assessed, since florfenicol and oxytetracycline are widely used in poultry farming, as they are active against several types of bacteria and their cost/effectiveness ratio is quite attractive and are administered for the therapeutic treatment of bacterial infections. However, these premixes must actually contain the active ingredients at a concentration that matches what the manufacturer states on their labels. Otherwise, they will not reach plasma concentrations that are therapeutically effective. In this work we set forth to verify via LC-MS/MS whether three commercial formulations of oxytetracycline premixes, and two of florfenicol, effectively matched their labels or not. Interestingly, this methodology detected oxytetracycline at a higher concentration than expected for those formulations, whereas the concentrations of florfenicol were lower than the on-label statement for both formulations.Antimicrobials premixes are the presentation of choice to administer drugs simultaneously to groups of animals in intensive husbandry systems that require treatment for pathologies of bacterial origin. Among the premixes available for use in poultry, florfenicol and oxytetracycline are commonly administered via food or water. However, their actual concentration in premixes must meet on-label statements to ensure plasma concentrations reach effective therapeutic levels. Hence, this work was designed for the purpose of verifying whether the concentration of antimicrobial present in five premixes matched their on-label statement. Three oxytetracycline premixes, and two of florfenicol, were analysed using a Xevo TQ-S micro UPLC-MS/MS, and an ABSciex API4000 HPLC-MS/MS, respectively. Analytical methodologies were implemented and validated, showing an R2 ≥ 0.99 for the calibration curves. Oxytetracycline was detected in these premixes at concentrations exceeding on-label statements by 13.28%, 21.54%, and 29.68%, whereas florfenicol concentrations detected in premixes were 13.06% and 14.75% lower than expected. Consequently, this work shows that the concentration of active ingredients that are present in commercial formulations effectively differ from those stated on premix labels, and it also highlights how unpredictable their range of variability might be. This must be addressed through solid and updated laws that guarantee an effective pharmaceutical product.

Inhibition of extracellular vesicle pathway using neutral sphingomyelinase inhibitors as a neuroprotective treatment for brain injury.

Traumatic brain injury is a sudden trauma or blow on the head, and severe traumatic brain injury is a major cause of death and disability worldwide. The acute and chronic consequences following traumatic brain injury can lead to progressive secondary neurodegenerative changes and cognitive dysfunction. To date, there is no effective pharmaceutical products for the treatment to reduce secondary damage after brain injury. The discovery of extracellular vesicles has attracted considerable scientific attention due to their role in cell-to-cell communication. Extracellular vesicles have shown their potential to carry not only biological molecules but also as a drug delivery vehicle. As a carrier of molecular information, extracellular vesicles have been involved in physiological functions as well as in the modulation of immune responses. Here, we aim to provide new insights into the contrasting role of extracellular vesicles in the propagation of inflammatory responses after brain injury. As a carrier of pro-inflammatory molecules, their role as functional mediators in the pathophysiology of brain injury is discussed, addressing the inhibition of the extracellular vesicle pathway as an anti-inflammatory or neuroprotective approach to improve the outcome of both acute and chronic inflammation following brain injury. Here, we summarize therapeutic strategies to diminish the risk the neurodegeneration post brain injury and propose that neutral sphingomyelinase inhibitors could be used as potentially useful therapeutic agents for the treatment of brain injury associated neuroinflammation.

Simultaneous Determination of Medicinal Drugs with Overlapping Profiles Contained in Low Chromatographic Resolution Data using HPLC-DAD and Multivariate Curve Resolution

Background: The increasing demand of effective pharmaceutical products directed to fight against malaria lead to the combination of at least two antimalarial drugs. This combination aims to minimize the Plasmodium falciparum resistance which is found when the most frequently used drugs are taken individually. Within this context, proguanil hydrochloride and chloroquine phosphate which have independent modes of action are taken together to prevent malaria. This paper aims to develop a fast and powerful analytical method for the simultaneous determination of proguanil hydrochloride and chloroquine phosphate in the commercial Paludrine/Avloclor dosage forms using a multi-way chromatographic calibration based on high-performance liquid chromatography with diode array detection (HPLC-DAD) and multivariate curve resolution – alternating leastsquares (MCR-ALS). Methods: A rapid and powerful analytical method based on HPLC-DAD and MCR-ALS was developed for the simultaneous quantification of proguanil hydrochloride and chloroquine phosphate in the commercial Paludrine/Avloclor antimalarial drugs. An isocratic mobile phase composed by 0.2 M ammonium acetate, acetonitrile, and methanol (40:25:35) and a flow rate of 1.2 mL min-1 were employed in the chromatographic runs with an elution time about 5 min. Results: This approach demonstrates that chromatographic analysis may become considerably simpler and economical in terms of time, cost, and organic solvent consumption when coupled to multiway calibration models such as MCR-ALS. In fact, this multi-way chromatographic calibration based on second-order HPLC-DAD data matrices (with extremely low chromatographic resolution) and MCR-ALS allows the development of greener analytical methods for complex samples. The proposed analytical method allowed the simultaneous quantification of two antimalarial APIs present in the commercial Paludrine/Avloclor drugs with low REP values below 8% for the simultaneous determination of proguanil hydrochloride and chloroquine phosphate. Conclusion: The proposed multi-way chromatographic strategy can be used for routine control of pharmaceutical dosage forms. It should be highlighted that MCR-ALS allowed to: (a) achieve the second- order advantage and the quantification of analytes in the presence of uncalibrated compounds such as coeluted profile measured in different magnitude of the signal in each successive chromatographic run and significant overlapping profiles and (b) separate the contribution of several components from chromatographic runs with extremely low separation of peaks through the deconvolution of the signal obtained, performing the so-called mathematical chromatography.

Impact of pharmaceutical companies upon the economy and public finance in Poland: The Sanofi case study

The paper discusses a two-channel impact of pharmaceutical companies upon the economy and public finance. Firstly, pharmaceutical companies predominantly impact the net value added, employment, income of people employed by their suppliers and customers as well as public finance revenue in the countries where they are based. The mechanisms of such an influence are presented in the input-output matrix (input-output analysis) that shows how output from one industrial sector in the economy may become an input to another industrial sector. The input-output model was developed by Leontief and earned him the Nobel Prize. This kind of influence upon the Polish economy has been illustrated with the case study of the Sanofi company. Secondly, pharmaceutical products improve the effectiveness of medical treatment, by which they contribute to the higher standard of living and economic growth.In this part of investigation into the impact of pharmaceutical companies upon the economy the key method consists in calculating indirect costs, that is, the lost productivity (lost GDP). Non-generated GDP as well as the negative impact of diseases and the treatment thereof on public finance can be significantly reduced by using more effective pharmaceutical products. This second channel through which pharmaceutical companies exert influence on the economy has been illustrated with an example of economic consequences calculated from the social viewpoint for three gynaecological–oncology diseases. Our calculations for both channels in this exercise have led us to conclude that a pharmaceutical company positively influences its business partners and the economy while by improving the health of the population it exerts a positive impact upon the economy and public finance.

The Unregistered Drugs Coverage in the Media in Malaysia: Content Analysis of the Public Newspapers

Newspaper is the most common media that can be used as a reference to know the current issues that happened in the countries. Also, there are a lot of articles about unregistered drugs published in newspapers in Malaysia. The purpose of this research to explore the content of the unregistered drugs in Malaysia based on the interviewee statements in the articles or news in the selected newspapers. The two most popular newspapers online available chosen (Kosmo and Utusan Malaysia newspaper online). About 56 articles identified for the year 2000 until 2014. The selected data was analysed using content analysis method. The production of unregistered drugs articles are increasing trend since 2000 until 2014. The findings from the content analysis indicate that majority of the articles are finally sub-categorized to certain themes which are, contributing factors, the impact of unregistered drugs and management of the unregistered drugs. The limited of references in this scope made these findings as benchmark findings. This findings used as the problem statement in designing research for the future to combat unregistered drugs in order to achieve authorities’ aims which are to provide the quality, safety and effective pharmaceutical products to the public.

Taurochenodeoxycholic acid induces NR8383 cells apoptosis via PKC/JNK-dependent pathway

Our former studies have suggested that taurochenodeoxycholic acid (TCDCA) as a signaling molecule shows obvious anti-inflammatory and immune regulation properties. In this research, we tentatively explored the potential effects and the possible mechanism that involve in the apoptotic process in NR8383 cells induced by TCDCA. Using flow cytometry analysis, we evaluated the apoptosis rate. Gene expression levels were determined by qPCR. The expressions of protein kinase C (PKC), Jun N-terminal kinase (JNK) and their phosphorylation were measured by Western Blot. We observed the activities of caspase-3 and caspase-8 with Caspase-Glo® regent. The results demonstrated that TCDCA dramatically improved the apoptosis rate of NR8383 cells in a concentration-dependent manner. In the meantime, PKC mRNA levels and activities were significantly augmented by TCDCA treatments. In addition, JNK, caspase-3 and caspase-8 mRNA expression levels and activities were increased by TCDCA, while they were markedly decreased by specific inhibitors. We conclude that TCDCA contributes to the apoptosis through the activation of the caspase cascade in NR8383 cells, and the PKC/JNK signaling pathway may be involved in this process. These results indicate that TCDCA may be a latent effective pharmaceutical product for apoptosis-related diseases.

Novel neomycin sulfate-loaded hydrogel dressing with enhanced physical dressing properties and wound-curing effect

To develop a novel neomycin sulfate-loaded hydrogel dressing (HD), numerous neomycin sulfate-loaded HDs were prepared with various amounts of polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP) and sodium alginate (SA) using freeze-thawing technique, and their physical dressing properties, drug release, in vivo wound curing and histopathology in diabetic-induced rats were assessed. SA had a positive effect on a swelling capacity, but a negative effect on the physical dressing properties and drug release of HD. However, PVP did the opposite. In particular, the neomycin sulfate-loaded HD composed of drug, PVA, PVP and SA at the weight ratio of 1/10/0.8/0.8 had excellent swelling and bioadhesive capacity, good elasticity and fast drug release. Moreover, this HD gave more improved wound curing effect compared to the commercial product, ensured the disappearance of granulation tissue and recovered the wound tissue to normal. Therefore, this novel neomycin sulfate-loaded HD could be an effective pharmaceutical product for the treatment of wounds.

Novel sodium fusidate-loaded film-forming hydrogel with easy application and excellent wound healing

To develop a novel sodium fusidate-loaded film-forming hydrogel (FFH) for easy application and excellent wound healing, various FFH formulations and corresponding FFH dried films were prepared with drug, polyvinylalcohol (PVA), polyvinylpyrrolidone (PVP), propylene glycol, ethanol and water, and their film forming times, mechanical properties, drug release, in vivo wound healing in rat and histopathology were assessed. The sodium fusidate-loaded FFH composed of sodium fusidate/PVP/PVA/propylene glycol/ethanol/water at the weight ratio of 1/2/12/3/8/74 could form a corresponding dried film in the wound sites promptly due to fast film-forming time of about 4min. This FFH showed an appropriate hardness and adhesiveness. Furthermore, this corresponding dried film provided an excellent flexibility and elasticity, and gave relatively high drug release. As compared with the sodium fusidate-loaded commercial product, it significantly improved excision and infection wound healing in rats. This FFH was stable at 45°C for at least 6 months. Therefore, this novel sodium fusidate-loaded FFH would be an effective pharmaceutical product with easy application for the treatment of wounds.

Development of a novel therapeutic approach using a retinoic acid-loaded microneedle patch for seborrheic keratosis treatment and safety study in humans

Seborrheic keratosis is one of the most common skin benign tumors in humans with a high occurrence rate of 80%–100% in people >50years of age; however, its pathogenesis is still unclear. The standard treatment includes cryotherapy and laser surgery for physically removing lesions. Drug therapy for this condition has not been well established. We aimed to evaluate the use of all-trans retinoic acid (ATRA)-loaded microneedle (MN) patches as a simple, alternative therapeutic option to traditional surgical treatments. This therapeutic strategy was designed to induce the proliferation of basal keratinocytes and accelerate stratum corneum turnover, leading to the lesion falling off the surface of the skin. The MN patch induced epidermal hyperplasia and marked expression of heparin-binding epidermal growth factor-like growth factor mRNA and protein corresponding to ATRA activity in the skin of HR-1 hairless mice. The acceleration of stratum corneum turnover was also observed by the dansyl chloride method. The skin irritation study in mice and safety study in humans support the safety findings of our study. Overall, MN patches can offer an effective and safe means of ATRA delivery into the skin, and the ATRA-loaded MN patch appears to be an effective pharmaceutical product providing a novel therapeutic option for seborrheic keratosis.

Performance and characteristics evaluation of a sodium hyaluronate-based microneedle patch for a transcutaneous drug delivery system

The MicroHyala(®) microneedle (MN) patch was developed to provide a simple, safe, and effective drug delivery system. In this study, we examined the performance and characteristics of our fabricated MN patch to identify potential quality issues with future commercial application. Mechanical failure force analysis identified that the strength of the MN patch was affected by environmental humidity, because higher moisture levels weakened the strength of the MN. Incorporation of all-trans retinoic acid (ATRA) or ovalbumin (OVA) into the MN patch decreased the mechanical failure force by almost 50% of the strength of placebo (without drug) patches. ATRA-loaded MN patches displayed good stability after storage at 4 °C, with more than 90% and 85% of the drug remaining in the patch after 8 and 24 weeks of storage, respectively. Tetanus toxoid- and diphtheria toxoid-loaded MN patches stored for 12 months induced robust antigen-specific immune responses similar to the responses by freshly prepared MN patches. Fluorescence imaging findings suggested that prolonged antigen deposition was induced by MN-mediated fluorescein isothiocyanate-labeled (FITC)-OVA vaccination. Overall, although the strength of MN requires improvement, our developed MN patch appears to be an effective pharmaceutical product providing a simple, safe, and relatively painless approach.

Antileishmanial Effect of Echinacea purpurea Root Extract Cultivated in Iran

Due to the limited availability of effective pharmaceutical products and serious side effects of the available therapy for leishmaniasis, search for useful medicinal plants is necessary. Previous studies reported preventative effect of Echinacea against Leishmania infections through immunologic stimulation. Here we tested concentrated ethanolic extract of the root of Echinacea purpurea prepared from Zardband Pharmaceutical Co. for its direct leishmanicidal activity in Leishmania culture. Leishmania major promastigotes (stationary phase) were cultured in different concentrations of the extract (0.5–125 mg/ml) for 30 min. Then the extract was removed and cell viability was determined during 120 h. LD 50 for the promastigotes were determined as 22.3, 16.7, 3.66, 1.98 and 1.23 mg at 8, 16, 24, 48 and 72 h respectively. The results showed the irreversible leishmanicidal activity of the E. purpurea. Although all concentrations of the extract had antileishmanial effect, we suggest using this crude extract in concentrations of 50 mg/ml and more for application in related medicinal targets.

Gene delivery using cationic liposomes

The development of cationic liposomes for gene delivery has been ongoing for almost 20 years; however, despite extensive efforts to develop a successful therapeutic agent, there has been limited progress towards generating an effective pharmaceutical product. Since the introduction of N-(1-[2,3-dioleyloxy]propyl)-N,N,N-trimethylammonium chloride, an immense number of different cationic lipids have been synthesised and used to formulate cationic liposome–DNA complexes. Structural modification of the cationic lipids and the addition of components within the delivery system that can facilitate the fusion, cellular uptake and targeting of liposome–DNA complexes have all been used in a bid to enhance their transfection efficiency. Unfortunately, the overall impact of these improvements is still nominal, with the vast majority of clinical trials (∼ 85%) continuing to rely on more potent viral delivery of DNA despite their associated toxicity issues. Key characteristics of the most effective cationic liposomes for the delivery of plasmid DNA (from a consensus of the literature) is identified here and the problems of converting these attributes into an effective pharmaceutical product are outlined.

Measurement and modeling of CO 2 absorption in poly(lactic-co-glycolic acid)

High-pressure CO 2 absorption into polymers was measured by a gravimetric method. The amount of CO 2 absorbed in the polymer was extrapolated using the CO 2 release profile from polymeric samples measured at standard conditions by an external balance. The polymers studied were poly-(methyl methacrylate) (PMMA) and poly(lactic-co-glycolic acid) (PLGA) with different molecular weights (MW) and lactide–glycolide copolymer ratios. Experimental results for PMMA well agree with literature data of Wissinger and Paulaitis [J. Polym. Sci.: Part B: Polym. Phys. 25 (1987) 2497] and Chang et al. [J. Supercrit. Fluids 13 (1998) 113]. For PLGA, CO 2 absorption measurements were performed at 313 K and in the pressure range 0.6–4.0 MPa. The method gave reproducible results within the accuracy of ±0.002 for mass fraction, ±0.1 MPa for pressure and ±0.15 K for temperature. A perturbed-hard-sphere-chain equation of state (PHSC EOS) was used to correlate CO 2–PLGA absorption isotherms. Pure EOS parameters were estimated by a group contribution method, whereas only one interaction parameter was necessary to fit the measured data. The model fairly describes the experimental data points for all PLGAs considered in this work. These results may be very useful to examine the possibility of successfully using a biodegradable amorphous PLGA polymer for developing effective pharmaceutical products by high-pressure CO 2 techniques.

Genetically modified viruses: vaccines by design.

Vaccination has been one of the most successful and cost-effective health interventions ever employed. One disease (smallpox) has been eradicated, another (poliomyelitis) should disappear early in the new millennium and a third (measles) should follow shortly after. Conventional vaccines usually depend on one of three development processes, attenuation of virulent organisms (by passage in cell culture and/or experimental animals), killing of virulent organisms (by chemical inactivation) or the purification of immunogenic molecules (either proteins or carbohydrates) from whole organisms. These traditional processes, although serendipitous and poorly understood, have produced effective pharmaceutical products which give excellent protection against diseases such as smallpox, rabies, measles, yellow fever, tetanus and diphtheria. In spite of these successes however, the application of these protocols have failed to produce safe and efficacious vaccines against other infectious diseases which kill or maim tens of millions of people every year. The most important of these are malaria, AIDS, herpes, dengue fever and some forms of viral hepatitis. Consequently, fundamentally new technologies are required to tackle these important infections. One of the most promising has been the development of genetically modified viruses. This process normally involves taking a proven safe and efficacious vaccine virus, such as vaccinia or adenovirus, and modifying its genome to include genes coding for immunogenic proteins from other viruses such as HIV or measles. This review will describe the generation of such novel vaccine vectors and compare their advantages and shortcomings. In addition the literature describing their use as experimental vaccines will also be reviewed.

Pharmacogenomics: Genetic Polymorphism of Receptors and Variation in Drug Response.

Human Genome Project (information and technology) provides insights so profound that it has the ability to change everything we know about medicine and how medicines are developed. Genetic factors contribute substantially to variable drug effects and constitute a critical element of a product's profile that must be considered in clinical use. Pharmacogenomics is a rapidly emerging field focused on understanding the genetic factors underlying drug action and applying this information to improve the clinical use and development of pharmaceutical products. In clinical practice, the understanding of how genetic variation leads to variable drug effects can be used to prescribe drugs selectively to individuals in regimens and doses that are most likely to be safe and effective (Personalized Medicine or “Tailor-made Medicine”). Also, pharmacogenomics will promote to develop novel pharmaceutical products targeted to the normal genetic variance of human populations. In drug development, knowledge of genetic variation that may affect drug action can be used to reduce the cost and complexity of clinical trials, increase the success rate of achieving regulatory approval, and achieve approvals for new classes of diagnostic and therapeutic products. Pharmacogenomics programs, thus, enhances the development, commercialization, and clinical use of conventional pharmaceutical products for common diseases, and eventually a powerful tool for Evidence-Based Medicine. Advanced genetic variance discovery technologies to optimize drug treatments and to develop safer and more effective pharmaceutical products, and clinical trial system to test for these variances are clearly required even in Japan, who unfortunately is still far behind in establishing this important discipline.