Search results for: antibody drugs

Authors: Nabil Ahmed Kamal Badawy, Ali Falah Alhajraf, Mawaheb Falah Alsamdan

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Objectives: To estimate the prevalence of self-medication with over-the-counter pain relievers (acetaminophen, ibuprofen, and aspirin) among Kuwaiti citizens above the age of 16 years old and describe their patterns of use, perceived awareness of, and concerns about the drugs’ potential side effects. Design: A descriptive cross-sectional questionnaire-based survey. Setting: Samples were selected from the six Kuwaiti governorates. Subjects: The data were collected over a four-month period in 2012, from 850 subjects who identified as Kuwaiti citizens. These subjects were recruited using stratified random sampling. Results: Overall, a 67% response rate was obtained. In total, 68% (573) of the respondents reported the use of over-the-counter pain relievers. Women, middle-aged or single individuals, and those who had completed higher education used these drugs more than any other subgroup (p<0.05). We found evidence of inappropriate use of these drugs, with 15% (88) of the consumers using them almost daily. Further, 19% (111) of the consumers exceeded the recommended dosage at least once. Not only were 81% of the consumers unaware of the potential side effects, but also more than 61% were not concerned about them. Women were more knowledgeable than men regarding the maximum dose (p=0.036, OR 1.49, CI 1.03–2.17). Consumers with higher levels of education did not show distinct knowledge regarding the maximum allowed dose of the drugs (p=0.252, OR 1.71, CI 0.68-4.25). Conclusion: The results showed a high prevalence of self-medication with over-the-counter pain relievers among Kuwaiti citizens. The subjects showed marked unawareness and a lack of concern regarding the potential complications resulting from the inappropriate use of these analgesics. This demonstrates the need for educational interventions directed toward both patients and health care workers.

Keywords: awareness of side effects, concern, patterns of use, prevalence

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Authors: Ghebremedhin Tsegay, Weldu Tesfagaber, Yuanmao Zhu, Xijun He, Wan Wang, Zhenjiang Zhang, Encheng Sun, Jinya Zhang, Yuntao Guan, Fang Li, Renqiang Liu, Zhigao Bu, Dongming Zhao*

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African swine fever (ASF) is a highly infectious viral disease of pigs, resulting in significant economic loss worldwide. As there is no approved vaccines and treatments, the control of ASF entirely depends on early diagnosis and culling of infected pigs. Thus, highly specific and sensitive diagnostic assays are required for accurate and early diagnosis of ASF virus (ASFV). Currently, only a few recombinant proteins have been tested and validated for use as reagents in ASF diagnostic assays. The most promising ones for ASFV antibody detection were p72, p30, p54, and pp62. So far, three ELISA kits based on these recombinant proteins have been commercialized. Due to the complex nature of the virus and variety forms of the disease, robust serodiagnostic assays are still required. ASFV p22 protein, encoded by KP177R gene, is located in the inner membrane of viral particle and appeared transiently in the plasma membrane early after virus infection. The p22 protein interacts with numerous cellular proteins, involved in processes of phagocytosis and endocytosis through different cellular pathways. However, p22 does not seem to be involved in virus replication or swine pathogenicity. In this study, E.coli expressed recombinant p22 protein was used to generate a monoclonal antibody (mAb), and its potential use for the development of blocking ELISA (bELISA) was evaluated. A total of 806 pig serum samples were tested to evaluate the bELISA. Acording the ROC (Reciever operating chracteristic) analysis, 100% sensitivity and 98.10% of specificity was recorded when the PI cut-off value was set at 47%. The novel assay was able to detect the antibodies as early as 9 days post infection. Finaly, a highly sensitive, specific and rapid novel p22-mAb based bELISA assay was developed, and optimized for detection of antibodies against genotype I and II ASFVs. It is a promising candidate for an early and acurate detection of the antibodies and is highly expected to have a valuable role in the containment and prevention of ASF.

Keywords: ASFV, blocking ELISA, diagnosis, monoclonal antibodies, sensitivity, specificity

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Authors: P. O. Ughachukwu, P. O. Okonkwo, P. C. Unekwe, J. O. Ogamba

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Background: The prevalence of hepatitis B viral infection is high worldwide with liver cirrhosis and hepatocellular carcinoma as important complications. Cases of poor antibody response to hepatitis B vaccination abound. Immunosuppression, especially from glucocorticoids, is often cited as a cause of poor antibody response and there are documented evidences of irrational administration of glucocorticoids to children and adults. The study was, therefore, designed to find out if administration of glucocorticoids affects immune response to vaccination against hepatitis B in mice. Methods: Mice of both sexes were randomly divided into 2 groups. Daily intramuscular methylprednisolone injections, (15 mg kg-1), were given to the test group while sterile deionized water (0.1ml) was given to control mice for 30 days. On day 6 all mice were given 2 μg (0.1ml) hepatitis B vaccine and a booster dose on day 27. On day 34, blood samples were collected and analyzed for anti-HBs titres using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was done using Graph Pad Prism 5.0 and the results taken as statistically significant at p value < 0.05. Results: There were positive serum anti-HBs responses in all mice groups but the differences in titres were not statistically significant. Conclusions: At the dosages and length of exposure used in this study, methylprednisolone injection did not significantly inhibit anti-HBs response in mice following immunization against hepatitis B virus. By extrapolation, methylprednisolone, when used in the usual clinical doses and duration of therapy, is not likely to inhibit immune response to hepatitis B vaccinations in man.

Keywords: anti-HBs, hepatitis B vaccine, immune response, methylprednisolone, mice

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Authors: Lisdey Espinoza Pedraza

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Organised crime in Mexico evolves faster that our capacity to understand and explain it. Organised gangs have become successful entrepreneurs in many ways ad they have somehow mimicked the working ways of the authorities and in many cases, they have successfully infiltrated the governmental spheres. This business model is only possible under a clear scheme of rampant impunity. Impunity, however, is not exclusive to the PRI. Nor the PRI, PAN, or PRD can claim the monopoly of corruption, but what is worse is that none can claim full honesty in their acts either. The current security crisis in Mexico shows a crisis in the Mexican political party system. Corruption today is not only a problem of dishonesty and the correct use of public resources. It is the principal threat to Mexican democracy, governance, and national security.

Keywords: security, war on drugs, drug trafficking, Mexico, Latin America, United States

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Authors: Alieh Farshbaf

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Introduction: Current anti-retroviral drugs have some restrictions for treatment of HIV-1 infection. The efficacy of retroviral drugs is not same in different infected patients and the virus rebound from latent reservoirs after stopping them. Recently, the engineering of stem cells and gene therapy provide new approaches to eliminate some drug problems by induction of resistance to HIV-1. Literature review: Up to now, AIDS-restriction genes (ARGs) were suitable candidate for gene and cell therapies, such as cc-chemokine receptor-5 (CCR5). In this manner, CCR5 provide effective cure in Berlin and Boston patients by inducing of HIV-1 resistance with allogeneic stem cell transplantation. It is showed that Zinc Finger Nuclease (ZFN) could induce HIV-1 resistance in stem cells of infected patients by homologous recombination or non-end joining mechanism and eliminate virus loading after returning the modified cells. Then, gene modification by HIV restriction factors, as TRIM5, introduced another gene candidate for HIV by interfering in infection process. These gene modifications/editing provided by stem cell futures that improve treatment in refractory disease such as HIV-1. Conclusion: Although stem cell transplantation has some complications, but in compare to retro-viral drugs demonstrated effective cure by elimination of virus loading. On the other hand, gene therapy is cost-effective for an infected patient than retroviral drugs payment in a person life-long. The results of umbilical cord blood stem cell transplantation showed that gene and cell therapy will be applied easier than previous treatment of AIDS with high efficacy.

Keywords: stem cell, AIDS, gene modification, cell engineering

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Authors: M. Dahiru, O. I. Enabulele

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The research wish to investigate the occurrence of multidrug- resistant Acinetobacter, in carrot and estimate the role of carrot in its transmission, in a rapidly growing urban population. Thus, 50 carrot samples were collected from Jakara wastewater irrigation farms and analyzed on MacConkey agar and screened by Microbact 24E (Oxoid) and susceptibility of isolates tested against 10 commonly used antibiotics. Acinetobacter baumannii and A. lwoffii were isolated in 22.00% and 16% of samples respectively. Resistance to ceporex and penicillin of 36.36% and 27.27% in A. baumannii, and sensitivity to ofloxacin, pefloxacin, gentimycin and co-trimoxazole, were observed. However, for A. lwoffii apart from 37.50% resistance to ceporex, it was also resistant to all other drugs tested. There was a similarity in the resistant shown by A. baumannii and A. lwoffii to fluoroquinolones drugs and β- lactame drugs families in addition to between sulfonamide and animoglycoside demonstrated by A. lwoffii. Interestingly, when resistant similarities to different antibiotics were compared for A. baumannii and A. lwoffii as a whole, significant correlation was observed at P < 0.05 to CPX to NA (46.2%), and SXT to AU (52.6%) respectively, and high multi drug resistance (MDR) of 27.27% and 62.50% by A. baumannii and A. lwoffii respectively and overall MDR of 42.11% in all isolates. The occurrence of multidrug-resistance pathogen in carrot is a serious challenge to public health care, especially in a rapidly growing urban population where subsistence agriculture contributes greatly to urban livelihood and source of vegetables.

Keywords: urban agriculture, public health, fluoroquinolone, sulfonamide, multidrug-resistance

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Authors: T. Hojageldiyev, Y. Bolmammedov, S. Gurbanaliyev

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It is known that drugs used in the treatment of tuberculosis show toxic effect to organism especially to liver besides its therapeutic effect. Because of ineffectiveness of drugs used in the treatment regimen of tuberculosis against multidrug resistance (MDR) and extensively drug-resistance (XDR) tuberculosis requires the development of new treatment methods and new, novel drugs. Considering the usage of Artemisia absinthium in traditional medicine in treatment of wounds which suggests its antibacterial activity it seems that, also it may have significant antimycobacterial activity. The objective of present study was to evaluate antibacterial activity of ethanolic extract of A. absinthium against M. tuberculosis. In this study, the effect of ethanolic extract of A. absinthium was tested against tuberculosis and pharmaco-toxicological properties evaluated on laboratory animals. The 20%, 40%, 70% and 96% ethanolic extracts of A. absinthium prepared then its bacteriostatic and bactericidal activities were evaluated by validated methods. Data were analyzed by GraphPad Prism 7.0 at the level P < 0.05. Results showed that ethanolic extracts of A. absinthium show no toxicological properties with having high LD50. All concentrations of extract show high bacteriostatic activity on M. tuberculosis. 96% ethanolic extract has highest bactericidal effect among other concentrations. By conducting further studies, as a result of our study, antimycobacterial drug can be prepared from A. absinthium.

Keywords: Artemisia absinthium, antimycobacterial, ethanolic extract, Mycobacteria tuberculosis

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Authors: Ajit Kumar Sah, Rajesh Kumar Jha, Phoolgen Sah, Dev Kumar Shah

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Older individuals often suffer from multiple systemic diseases and are particularly more vulnerable to potentially inappropriate medicine prescribing. Inappropriate medication can cause serious medical problem for the elderly. The purpose of this study was to determine the prevalence of potentially inappropriate medicine (PIM) prescribing in older Nepalese patients in a medicine outpatient department. Beers’ criteria are the most widely used tools to assess PIM to elderly patients. Prospective observational analysis of drugs prescribed in medicine out-patient department (OPD) of a hospital of Bharatpur, Chitwan, Nepal during November 2011 to October 2012 to 869 older adults aged 65 years and above. The use of potentially inappropriate medications (PIM) in elderly patients was analyzed using Beers Criteria updated to 2013. In the 869 patients included the average number of drugs prescribed per prescription was 5.56. The most commonly used drugs were atenolol (24.3%), amlodipine (23.16%), paracetamol (17.6%), salbutamol (15.72%) and vitamin B complex (13.26%). The total number of medications prescribed was 4833. At least one instance of PIM was experienced by approximately 26.3% of patients when evaluated using the Beers criteria. Potentially inappropriate medications are highly prevalent among older patients attending medical OPD and are associated with a number of medications prescribed. Further research is warranted to study the impact of PIMs towards health-related outcomes in these elderly.

Keywords: Beers criteria, elderly, polypharmacy, potentially inappropriate medicines

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Authors: Asmaa Mandour, Ramzia El-Bagary, Asmaa El-Zaher, Ehab Elkady

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Background: An UHPLC (ultra high performance liquid chromatography) method for the simultaneous determination of norfloxacin (NOR), metronidazole (MET) and tinidazole (TNZ) using monolithic column is presented. Purpose: The method is considered an environmentally friendly method with relatively low organic composition of the mobile phase. Methods: The chromatographic separation was performed using Phenomenex® Onyex Monolithic C18 (50mmx 20mm) column. An elution program of mobile phase consisted of 0.5% aqueous phosphoric acid : methanol (85:15, v/v). Where elution of all drugs was completed within 3.5 min with 1µL injection volume. The UHPLC method was applied for the stability indication of NOR in the presence of its acid degradation product ND. Results: Retention times were 0.69, 1.19 and 3.23 min for MET, TNZ and NOR, respectively. While ND retention time was 1.06 min. Linearity, accuracy, and precision were acceptable over the concentration range of 5-50µg mL-1for all drugs. Conclusions: The method is simple, sensitive and suitable for the routine quality control and dosage form assay of the three drugs and can also be used for the stability indication of NOR in the presence of its acid degradation product.

Keywords: antibacterial, monolithic cilumn, simultaneous determination, UHPLC

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Authors: Luphumlo Ncanywa, Paul Watts

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Malaria is a disease that kills approximately one million people annually. Children and pregnant women in sub-Saharan Africa lost their lives due to malaria. Malaria continues to be one of the major causes of death, especially in poor countries in Africa. Decrease the burden of malaria and save lives is very essential. There is a major concern about malaria parasites being able to develop resistance towards antimalarial drugs. People are still dying due to lack of medicine affordability in less well-off countries in the world. If more people could receive treatment by reducing the cost of drugs, the number of deaths in Africa could be massively reduced. There is a shortage of pharmaceutical manufacturing capability within many of the countries in Africa. However one has to question how Africa would actually manufacture drugs, active pharmaceutical ingredients or medicines developed within these research programs. It is quite likely that such manufacturing would be outsourced overseas, hence increasing the cost of production and potentially limiting the full benefit of the original research. As a result the last few years has seen major interest in developing more effective and cheaper technology for manufacturing generic pharmaceutical products. Micro-reactor technology (MRT) is an emerging technique that enables those working in research and development to rapidly screen reactions utilizing continuous flow, leading to the identification of reaction conditions that are suitable for usage at a production level. This emerging technique will be used to develop antimalarial drugs. It is this system flexibility that has the potential to reduce both the time was taken and risk associated with transferring reaction methodology from research to production. Using an approach referred to as scale-out or numbering up, a reaction is first optimized within the laboratory using a single micro-reactor, and in order to increase production volume, the number of reactors employed is simply increased. The overall aim of this research project is to develop and optimize synthetic process of antimalarial drugs in the continuous processing. This will provide a step change in pharmaceutical manufacturing technology that will increase the availability and affordability of antimalarial drugs on a worldwide scale, with a particular emphasis on Africa in the first instance. The research will determine the best chemistry and technology to define the lowest cost manufacturing route to pharmaceutical products. We are currently developing a method to synthesize Lumefantrine in continuous flow using batch process as bench mark. Lumefantrine is a dichlorobenzylidine derivative effective for the treatment of various types of malaria. Lumefantrine is an antimalarial drug used with artemether for the treatment of uncomplicated malaria. The results obtained when synthesizing Lumefantrine in a batch process are transferred into a continuous flow process in order to develop an even better and reproducible process. Therefore, development of an appropriate synthetic route for Lumefantrine is significant in pharmaceutical industry. Consequently, if better (and cheaper) manufacturing routes to antimalarial drugs could be developed and implemented where needed, it is far more likely to enable antimalarial drugs to be available to those in need.

Keywords: antimalarial, flow, lumefantrine, synthesis

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Authors: Moetazza M. Al-Shafei, Hala Abdel Karim, Eitedal M. Daoud, Hassan Zaki Hassuna

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Epilepsy is a common neurological disorder affecting all age groups. It is one of the world's most prevalent non-communicable diseases. Increased evidence suggesting that long term usage of anti-epileptic drugs can have adverse effects on bone mineralization and bone molding .Aiming to study these effects and to give guide lines to support bone health through early intervention. From Neurology Out-Patient Clinic kaser Elaini University Hospital, 60 Patients were enrolled, 40 patients on antiepileptic drugs for at least two years and 20 controls matched with age and sex, epileptic but before starting treatment both chosen under specific criteria. Patients were divided into four groups, three groups with monotherapy treated with either Phynetoin, Valporic acid or Carbamazipine and fourth group treated with both Valporic acid and Carbamazipine. Estimation of serum Carboxy-Terminal Telopeptide of Type I- Collagen(ICTP) bone resorption marker, serum 25(OH )vit D3, calcium ,magnesium and phosphorus were done .Results showed that all patients on AED had significant low levels of 25(OH) vit D3 (p<0.001) ,with significant elevation of ICTP (P<0.05) versus controls. In group treated with Phynotoin highly significant elevation of (ICTP) marker and decrease of both serum 25(OH) vit D3 (P<0, 0001) and serum calcium(P<0.05)versus control. Double drug group showed significant decrease of serum 25(OH) vit D3 (P<0.0001) and decrease in Phosphorus (P<0.05) versus controls. Serum magnesium showed no significant differences between studied groups. We concluded that Anti- epileptic drugs appears to be an aggravating factor on bone mineralization ,so therapeutically it can be worth wile to supplement calcium and vitamin D even before initiation of antiepileptic therapy. ICTP marker can be used to evaluate change in bone resorption before and during AED therapy.

Keywords: antiepileptic drugs, bone minerals, carboxy teminal telopeptidetype-1-collagen bone resorption marker, vitamin D

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Authors: Salwa M. Almomen, Mona A. Almaghrabi, Saja M. Alhabardi, Adel A. Alrwisan

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Background: Hepatotoxicity is a major reason for medication withdrawal from the markets. Unfortunately, serious adverse hepatic effects can occur after marketing with limited indicators during clinical development. Therefore, finding possible predictors for hepatotoxicity might guide the monitoring program of various stakeholders. Methods: We examined the clinical review documents for drugs approved in the US from 2011 to 2016 to evaluate their hepatic safety profile. Predictors: we assessed whether these medications meet Hy’s Law with hepatotoxicity grade ≥ 3, labeled hepatic adverse effects at approval, or accelerated approval status. Outcome: post-marketing regulatory action related to hepatotoxicity, including product withdrawal or updates to warning, precaution, or adverse effects sections. Statistical analysis: drugs were included in the analysis from the time of approval until the end of 2019 or the first post-marketing regulatory action related to hepatotoxicity, whichever occurred first. The hazard ratio (HR) was estimated using Cox-regression analysis. Results: We included 192 medications in the study. We classified 48 drugs as having grade ≥ 3 hepatotoxicities, 43 had accelerated approval status, and 74 had labeled information about hepatotoxicity prior to marketing. The adjusted HRs for post-marketing regulatory action for products with grade ≥ 3 hepatotoxicity was 0.61 (95% confidence interval [CI], 0.17-2.23), 0.92 (95%CI, 0.29-2.93) for a drug approved via accelerated approval program, and was 0.91 (95%CI, 0.33-2.56) for drugs with labeled hepatotoxicity information at approval time. Conclusion: This study does not provide conclusive evidence on the association between post-marketing regulatory action and grade ≥ 3 hepatotoxicity, accelerated approval status, or availability of labeled information at approval due to sampling size and channeling bias.

Keywords: accelerated approvals, hepatic adverse effects, drug-induced liver injury, hepatotoxicity predictors, post-marketing withdrawal

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Authors: V. Surena, B. Nazemisalman, F. Noghrehkar

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Introduction: Gingival overgrowth (GO) is a common side effect involving users of antiepileptic, immunosuppressive and calcium channel blocker drugs. Cyclosporine and phenytoin are amongst the most widely used drugs associated with GO. Gingival fibroblasts seem to have a significant role in the production of certain enzymes after administration of the drugs contributing to GO. Previous studies have shown a higher prevalence of GO in children and adolescents. The aim of this study was to compare normal human gingival fibroblasts with those exposed to Cyclosporine or phenytoin in measuring the production levels of certain enzymes that could have a possible role in GO. Methods: samples were obtained from the gingival biopsies of seven adult and seven children and were cultured into plates. With the growth of fibroblast cells, they were treated with or without either Cyclosporine or phenytoin. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine the expressed levels of R-EGF, cathepsin B,L, Lysyl oxidase, COL1, TGF β1, MMP-1,2, and TIMP1. Results: according to RT-PCR analyses, the expressed levels of R-EGF, cathepsin B, L, Lysyl oxidase, COL1, TGF β1, MMP-1, 2 and TIMP1 were affected by Cyclosporine and phenytoin. TGF-β1, TIMP, Cathepsin B and EGF showed comparable values in the adult and pediatric groups. Conclusions: Different expressed levels of enzymes after treatment of the gingival fibroblasts of adults and pediatrics with phenytoin or Cyclosporine could be the reason for the higher severity of GO in children. More studies need to be performed on the pathogenesis of GO at different age groups.

Keywords: cyclosporine, fibroblasts, phenytoin, gingivae

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Authors: Shirin Jalili, Sadegh Hasannia, Hadi Shirzad, Afshin Khara

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Morphine is one of the most medicinally important analgesics and narcotics. Structurally, it is classified as an alkaloid because of the presence of nitrogen. Its structure is similar to that of codeine, thebaine, and heroin. An immunoassay to accurately discriminate between these analogous alkaloids would be highly beneficial. A key factor for such an assay is specificity with high sensitivity, which is totally dependent on the antibody employed. However, most antibodies against haptens are polyclonal serum antibodies that exhibit significant cross-reactivities with closely related compounds. The camel-derived single-chain antibody fragments (VHH) are the smallest molecules with antigen-binding capacity, possessing unique properties compared to other conventional antibodies. In this study, a library containing the VHH genes of a camel immunized with with morphine conjugated BSA following phage display technology was generated. By screening the camel-derived variable region of the heavy chain cDNA phage display library with the ability to bind the desired hapten, we obtained some nanobodies that recognize this hapten. Phage display expression of the Nbs from this library and pannings against this hapten resulted in a clear enrichment of four distinct Nb-displaying phages with specificity for morphine that could be a potential target site for the development of new strategies for the development of a biosensor for detecting illicit drug.

Keywords: phage display, nanobody, Morphine-3, glucuronide, ELISA, biosensor

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Authors: Jay Ananth

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The drug discovery process currently requires numerous years of clinical testing as well as money just for a single drug to earn FDA approval. For drugs that even make it this far in the process, there is a very slim chance of receiving FDA approval, resulting in detrimental hurdles to drug accessibility. To minimize these inefficiencies, numerous studies have implemented computational methods, although few computational investigations have focused on a crucial feature of drugs: lipophilicity. Lipophilicity is a physical attribute of a compound that measures its solubility in lipids and is a determinant of drug efficacy. This project leverages Artificial Intelligence to predict the impact of a drug’s lipophilicity on its performance by accounting for factors such as binding affinity and toxicity. The model predicted lipophilicity and binding affinity in the validation set with very high R² scores of 0.921 and 0.788, respectively, while also being applicable to a variety of target receptors. The results expressed a strong positive correlation between lipophilicity and both binding affinity and toxicity. The model helps in both drug development and discovery, providing every pharmaceutical company with recommended lipophilicity levels for drug candidates as well as a rapid assessment of early-stage drugs prior to any testing, eliminating significant amounts of time and resources currently restricting drug accessibility.

Keywords: drug discovery, lipophilicity, ligand-receptor interactions, machine learning, drug development

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Authors: Abhishek Pandey

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Capping and lamination are the most common tablet defects with poorly compressible drugs the common example of that Ibuprofen and Acetaminophen. Generally both these drugs are compressed by wet granulation method which is very time consuming process Ibuprofen and Acetaminophen is widely used as prescription & non-prescription medicine. Ibuprofen mainly used in the treatment of mild to moderate pain related to headache, migraine, postoperative condition and in the management of spondylitis, osteoarthritis Acetaminophen used as an analgesic and antipyretic drug. Ibuprofen having high tendency of sticking to punches of tablet punching machine while Acetaminophen is not ordinarily compressible to tablet formulation because Acetaminophen crystals are very hard and brittle in nature and fracture very easily when compressed producing capping and laminating tablet defects therefore wet granulation method is used to make them compressible. The aim of study was to prepare Ibuprofen and Acetaminophen tablets by direct compression technique and their evaluation. In this Investigation tablets were prepared by using directly compressible grade excipients. Dibasic calcium phosphate, lactose anhydrous (DCL21), microcrystalline cellulose (Avicel PH 101). In order to obtain best or optimize formulation nine different formulations were generated among them batch F5, F6, F7 shows good results and within the acceptable limit. Formulation (F7) selected as optimize product on the basis of evaluation parameters.

Keywords: capping, lamination, tablet defects, direct compression

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Authors: A. Julio, R. Caparica, S. Costa Lima, S. Reis, J. G. Costa, P. Fonte, T. Santos De Almeida

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The Mycobacterium leprae causes a chronic and infectious disease called leprosy, which the most common symptoms are peripheral neuropathy and deformation of several parts of the body. The pharmacological treatment of leprosy is a combined therapy with three different drugs, rifampicin, clofazimine, and dapsone. However, clofazimine and dapsone have poor solubility in water and also low bioavailability. Thus, it is crucial to develop strategies to overcome such drawbacks. The use of ionic liquids (ILs) may be a strategy to overcome the low solubility since they have been used as solubility promoters. ILs are salts, liquid below 100 ºC or even at room temperature, that may be placed in water, oils or hydroalcoholic solutions. Another approach may be the encapsulation of drugs into polymeric nanoparticles, which improves their bioavailability. In this study, two different classes of ILs were used, the imidazole- and the choline-based ionic liquids, as solubility enhancers of the poorly soluble antileprotic drugs. Thus, after the solubility studies, it was developed IL-PLGA nanoparticles hybrid systems to deliver such drugs. First of all, the solubility studies of clofazimine and dapsone were performed in water and in water: IL mixtures, at ILs concentrations where cell viability is maintained, at room temperature for 72 hours. For both drugs, it was observed an improvement on the drug solubility and [Cho][Phe] showed to be the best solubility enhancer, especially for clofazimine, where it was observed a 10-fold improvement. Later, it was produced nanoparticles, with a polymeric matrix of poly(lactic-co-glycolic acid) (PLGA) 75:25, by a modified solvent-evaporation W/O/W double emulsion technique in the presence of [Cho][Phe]. Thus, the inner phase was an aqueous solution of 0.2 % (v/v) of the above IL with each drug to its maximum solubility determined on the previous study. After the production, the nanosystem hybrid was physicochemically characterized. The produced nanoparticles had a diameter of around 580 nm and 640 nm, for clofazimine and dapsone, respectively. Regarding the polydispersity index, it was in agreement of the recommended value of this parameter for drug delivery systems (around 0.3). The association efficiency (AE) of the developed hybrid nanosystems demonstrated promising AE values for both drugs, given their low solubility (64.0 ± 4.0 % for clofazimine and 58.6 ± 10.0 % for dapsone), that prospects the capacity of these delivery systems to enhance the bioavailability and loading of clofazimine and dapsone. Overall, the study achievement may signify an upgrading of the patient’s quality of life, since it may mean a change in the therapeutic scheme, not requiring doses of drug so high to obtain a therapeutic effect. The authors would like to thank Fundação para a Ciência e a Tecnologia, Portugal (FCT/MCTES (PIDDAC), UID/DTP/04567/2016-CBIOS/PRUID/BI2/2018).

Keywords: ionic liquids, ionic liquids-PLGA nanoparticles hybrid systems, leprosy treatment, solubility

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Authors: M. A. Sohaly, M. A. Elfouly

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Parkinson's disease (PD) is a heterogeneous movement disorder that often appears in the elderly. PD is induced by a loss of dopamine secretion. Some drugs increase the secretion of dopamine. In this paper, we will simply study the stability of PD models as a nonlinear delay differential equation. After a period of taking drugs, these act as positive feedback and increase the tremors of patients, and then, the differential equation has positive coefficients and the system is unstable under these conditions. We will present a set of suggested modifications to make the system more compatible with the biodynamic system. When giving a set of numerical examples, this research paper is concerned with the mathematical analysis, and no clinical data have been used.

Keywords: Parkinson's disease, stability, simulation, two delay differential equation

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Authors: Majid Goudarzi

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This experiment was designed to study the effects of feeding different levels of Peganum harmala seeds (PHS) and antibiotic on serum biochemical parameters, immune response and intestinal microflora composition in Ross broiler chickens. A total of 240 one-d-old unsexed broiler chickens were randomly allocated to each of the four treatment groups, each with four replicate pens of 15 chicks. The dietary treatments included of control (C) - without PHS and antibiotic - the diet contains 300 mg/kg Lincomycin 0.88% (A) and the diets contain 2 g/kg (H1) and 4 g/kg (H2) PHS. The chicks were raised on floor pens and received diets and water ad libitum for six weeks. Blood samplings were performed for the determination of antibody titer against Newcastle disease on 14 and 21 days and for biochemical parameters on 42 days of age. The populations of Lactobacilli spp. and Escherichia coli were enumerated in ileum by conventional microbiological techniques using selective agar media. Inclusion of PHS in diet resulted in a significant decrease in total cholesterol and significant increase in HDL relative to the control and antibiotic groups. Antibody titer against NDV was not affected by experimental treatments. E. coli population in birds supplemented with antibiotic and PHS was significantly lower than control, but Lactobacilli spp. population increased only by antibiotic and not by PHS. In conclusion, the results of this study showed that addition of PHS powder seem to have a positive influence on some biochemical parameters and gastrointestinal microflora.

Keywords: antibiotic, biochemical parameters, immune system, Peganum harmala

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Authors: Tadesse Eguale, Ephrem Engdawork, Wondwossen Gebreyes, Dainel Asrat, Hile Alemayehu, John Gunn

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Salmonella is one of the major zoonotic pathogens affecting wide range of vertebrates and humans worldwide. Consumption of contaminated dairy products and contact with dairy cattle represent the common sources of non-typhoidal Salmonella infection in humans. Fecal samples were collected from 132 dairy herds in central Ethiopia and cultured for Salmonella to determine the prevalence, serotype distribution and antimicrobial susceptibility. Salmonella was recovered from the feces of at least one cattle in 10(7.6%) of the dairy farms. Out of 1193 fecal samples 30(2.5%) were positive for Salmonella. Large farm size, detection of diarrhea in one or more animals during sampling and keeping animals completely indoor compared to occasional grazing outside were associated with Salmonella positivity of the farms. Farm level prevalence of Salmonella was significantly higher in young animals below 6 months of age compared to other age groups(X2=10.24; p=0.04). Nine different serotypes were isolated. The four most frequently recovered serotypes were S. Typhimurium (23.3%),S. Saintpaul (20%) and S. Kentucky and S. Virchow (16.7%) each. All isolates were resistant or intermediately resistant to at least one of the 18 drugs tested. Twenty-six (86.7%), 20(66.7%), 18(60%), 16(53.3%) of the isolates were resistant to streptomycin, nitrofurantoin, sulfisoxazole and tetracycline respectively. Resistance to 2 drugs was detected in 93.3% of the isolates. Resistance to 3 or more drugs were detected in 21(70%) of the total isolates while multi-drug resistance (MDR) to 7 or more drugs were detected in 12 (40%) of the isolates. The rate of occurrence of MDR in Salmonella strains isolated from dairy farms in Addis Ababa was significantly higher than those isolated from farms outside of Addis Ababa((p= 0.009). The detection of high MDR in Salmonella isolates originating from dairy farms warrants the need for strict pathogen reduction strategy in dairy cattle and spread of these MDR strains to human population.

Keywords: salmonella, antimicrobial resistance, fecal prevalence

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Authors: Alaa A. Shamaun Al-Abboodi, Yunis A. A. Bapeer

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400 one-day-old male broiler chicks (Ross-308) randomly divided to 2 main groups, 1st main group (GA) was feeding basal diet with medium chain fatty acid (MCFA) at rate of 0.15% and divided to four subgroups, 3 subgroups vaccinated with different routes with Newcastle Disease Virus (NDV) and non-vaccinated group. The 2nd main group (GB) feeding basal diet without MCFA and divided the same as 1st main group. The parameters used in this study included: ND antibody titers at 1, 10, 21, 28, 35 and 42 days of age and values of CD4 and CD8 at 1, 20, 30 and 42 days of age. This experiment detected increase in ND antibodies titers in (G1, G2, G3) groups were fed on basal diet MCFA comparing to groups were fed without adding MCFA (G5, G6, G7) and control groups (G4, G8). The results of cellular immune response (CD4 and CD8) T-cells in broiler chicks indicated that there was obviously significant relationship between dietary Fatty Acid (FA) versus the diet without FA on the level of CD4 parameter, for the entire experimental period. The effect of different ages was statistically significant in creating different values of CD4 level, whereas the CD4 level decreases markedly with age. However, analyzing the data of different vaccination methods, oculonasal method of vaccination led to the highest value of CD4 compared with the oral, S/C and control groups. There were statistical differences in CD8 values due to supplementation of FA versus the basal diet and due to the effect of different age periods. As for the age effect, the CD8 value at 20 days of age was significantly higher than at 42 and 30 days.

Keywords: broiler, CD4 and CD8, fatty acids, Newcastle Disease

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Authors: Syeda Kiran Shahzadi, Nasir Mahmood, Muhammad Abdul Qadir

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In the current research, three recombinant human interferon alpha-2b proteins (two modified and one normal form) were produced and Pegylated with an aim to produce more effective drugs against viral infections and cancers. The modified recombinant human interferon alpha-2b proteins were produced by site-directed modifications of interferon alpha 2b gene, targeting the amino acids at positions ‘R23’ and ‘H34’. The resulting chemically modified and unmodified forms of human interferon alpha 2b were conjugated with methoxy-polyethylene glycol propanealdehyde (400 KDa) and methoxy-polyethylene glycol succinimidyl succinate (400 KDa). Pegylation of normal and modified forms of Interferon alpha-2b prolong their release time and enhance their efficacy. The conjugation of PEG with modified and unmodified human interferon alpha 2b protein drugs was also characterized with 1H-NMR, HPLC, and SDS-PAGE. Antiproliferative assays of modified and unmodified forms of drugs were performed in cell based bioassays using MDBK cell lines. The results indicated that experimentally produced recombinant human interferon alpha-2b proteins were biologically active and resulted in significant inhibition of cell growth.

Keywords: protein refolding, antiproliferative activities, biomedical applications, human interferon alpha-2b, pegylation, mPEG-propionaldehyde, site directed mutagenesis, E. coli expression

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Authors: Stanely Nsubuga

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Background In Uganda, injection drug use is a growing but less studied problem. Preventing the transition to injection drug use may help prevent blood-borne viral transmission, but little is known about when and how people transition to injection drug use. A greater understanding of this transition process may aid in the country’s efforts to prevent the continued growth of injection drug use, HIV, and hepatitis C Virus (HCV) infection among people who inject drugs (PWID). Methods Using a rapid situation assessment framework, we conducted semi-structured interviews among 125 PWID (102 males and 23 females)—recruited through outreach and snow-ball sampling. Participants were interviewed about their experiences on when and how they transitioned into injection drug use and these issues were also discussed in 12 focus groups held with the participants. Results All the study participants started their drug use career with non-injecting forms including chewing, smoking, and sniffing before transitioning to injecting. Transitioning was generally described as a peer-driven and socially learnt behavior. The participants’ social networks and accessibility to injectable drugs on the market and among close friends influenced the time lag between first regular drug use and first injecting—which took an average of 4.5 years. By the age of 24, at least 81.6% (95.7% for females and 78.4% for males) had transitioned into injecting. Over 84.8% shared injecting equipment during their first injection, 47.2% started injecting because a close friend was already injecting, 26.4% desired to achieve a greater “high” (26.4%) which could reflect drug-tolerance, and 12% out of curiosity.

Keywords: People who Use Drugs, transition, injection drug use, Uganda

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Authors: K. R. Thabethe, G. A. Adefolaju, M. J. Hosie

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Cervical cancer is the third most commonly diagnosed cancer globally and it is one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs and has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. The aim of this study was to investigate the relationship between cervical cancer and HAART. This was achieved by studying the expression of two signalling molecules expressed in cervical cancer; MUC1 and P65. Following the 24 hour treatment of a cervical cancer cell line, HCS-2, with drugs which are commonly used as part of HAART at their clinical plasma concentrations, real-time qPCR and immunofluorescence were used in order to study gene and protein expression. A one way ANOVA followed by a Tukey Kramer Post Hoc test was conducted using JMP 11 software on both sets of data. The drug classified as a protease inhibitor (PI) (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other drug tested. PIs are known to play a significant role in cell death, therefore the cells were thought to be more susceptible to cell death following treatment with PIs. In conclusion, the drugs used, especially the PI showed some anticancer effects by facilitating cell death through decreased gene and protein expression of MUC1 and P65 and present promising agents for cancer treatment.

Keywords: cervical cancer, haart, MUC1, P65

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Authors: Yogesh Karunakar, Praveen Kandaswamy

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Mother’s milk provides the most superior source of nutrition to a child. There is no other substitute to the mother’s milk. Postpartum secretions like breast milk can be analyzed on the go for testing the presence of any harmful pathogen before a mother can feed the child or donate the milk for the milk bank. Since breast feeding is one of the main causes for transmission of diseases to the newborn, it is mandatory to test the secretions. In this paper, we describe the detection of pathogens like E-coli, Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), Hepatitis C (HCV), Cytomegalovirus (CMV), Zika and Ebola virus through an innovative method, in which we are developing a unique chip for testing the mother’s milk sample. The chip will contain an antibody specific to the target pathogen that will show a color change if there are enough pathogens present in the fluid that will be considered dangerous. A smart-phone camera will then be acquiring the image of the strip and using various image processing techniques we will detect the color development due to antigen antibody interaction within 5 minutes, thereby not adding to any delay, before the newborn is fed or prior to the collection of the milk for the milk bank. If the target pathogen comes positive through this method, then the health care provider can provide adequate treatment to bring down the number of pathogens. This will reduce the postpartum related mortality and morbidity which arises due to feeding infectious breast milk to own child.

Keywords: postpartum, fluids, camera, HIV, HCV, CMV, Zika, Ebola, smart-phones, breast milk, pathogens, image processing techniques

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Authors: Monika Szpringer, Aneta Pawlinska

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Adverse childhood experiences are linked to various types of health and adapt problems at different stages of life. They include various types of abuse, neglect, and dysfunctional environment. They have an unfavorable impact on the development of a child and his future functioning in society. Adolescents who were exposed to bad treatment may suffer from health problems during adulthood, like chronic diseases, psychological disorders, drug addiction, and suicide attempts. Objective: The aim of the project is to assess the relationship between adverse childhood experiences and the sense of efficacy and coping with emotions among teenagers aged 16-18 taking drugs. Material And Methods: The research was carried out in the period from March to December 2018 in Mazowieckie, Świętokrzyskie, Łódzkie, and Lubelskie Voivodship. The group consisted of 600 people aged 16-18 (M=16,58; SD=0, 78), men (63,2%) aged 16-18 (M=16,60;SD= 0,78) and women (35,5%) aged 16-18 (M16,55;SD=0,79). Participants included residents from Youth Educational Centers and Youth Sociotherapy Centers. Each participant filled in Author's Questionnaire, Adverse Childhood Questionnaire, then Courtland Emotional Control Scale-CECS and Generalized Self Efficacy Scale-GSES. Results and conclusions: The most common adverse experiences, according to teenagers, were family abuse, divorce/separation/parent's death, overuse of alcohol or drugs by an inmate, and emotional neglect. Adolescents who suffered from five to twelve adverse experiences had a higher level of depression's control. Adverse childhood experiences have an importance for the level of anger and depression's control among teenagers taking drugs. The greatest importance of the level of anger's control has emotional neglect. A higher level of emotional neglect is linked to a lower ability to control anger. The greatest importance of the level of depression's control has physical abuse and emotional neglect. The higher physical abuse during childhood, and the higher frequency of emotional neglect, the bigger the depression's control. The sense of efficacy in the group of people who suffered from one to four adverse experiences is close to the sense of efficacy that suffered people from five to twelve adverse experiences. The most important factor lowering the sense of one's efficacy was the intensification of sexual abuse. It was confirmed that the intensification and frequency of adverse childhood experiences were higher among women than men. Women also characterized lower anger control and greater depression's control. The authors’ own analyses confirmed the relationship between adverse childhood experiences and the sense of efficacy and coping with emotions among teenagers aged 16-18 taking drugs.

Keywords: adolescences, adverse childhood experiences, coping with emotions, drugs

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Authors: Nicholas Fletcher, Zachary Houston, Yongmei Zhao, Christopher Howard, Kristofer Thurecht

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One promising approach to enhance nanomedicine therapeutic efficacy is to include a targeting agent, such as an antibody, to increase accumulation at the tumor site. However, the application of such targeted nanomedicines remains limited, in part due to difficulties involved with biomolecule conjugation to synthetic nanomaterials. One approach recently developed to overcome this has been to engineer bispecific antibodies (BsAbs) with dual specificity, whereby one portion binds to methoxy polyethyleneglycol (mPEG) epitopes present on synthetic nanomedicines, while the other binds to molecular disease markers of interest. In this way, noncovalent complexes of nanomedicine core, comprising a hyperbranched polymer (HBP) of primarily mPEG, decorated with targeting ligands are able to be produced by simple mixing. Further work in this area has now demonstrated such complexes targeting the breast cancer marker epidermal growth factor receptor (EGFR) to show enhanced binding to tumor cells both in vitro and in vivo. Indeed the enhanced accumulation at the tumor site resulted in improved therapeutic outcomes compared to untargeted nanomedicines and free chemotherapeutics. The current work on these BsAb-HBP conjugates focuses on further probing antibody-nanomaterial interactions and demonstrating broad applicability to a range of cancer types. Herein are reported BsAb-HBP materials targeted towards prostate-specific membrane antigen (PSMA) and study of their behavior in vivo using ⁸⁹Zr positron emission tomography (PET) in a dual-tumor prostate cancer xenograft model. In this model mice bearing both PSMA+ and PSMA- tumors allow for PET imaging to discriminate between nonspecific and targeted uptake in tumors, and better quantify the increased accumulation following BsAb conjugation. Also examined is the potential for formation of these targeted complexes in situ following injection of individual components? The aim of this approach being to avoid undesirable clearance of proteinaceous complexes upon injection limiting available therapeutic. Ultimately these results demonstrate BsAb functionalized nanomaterials as a powerful and versatile approach for producing targeted nanomedicines for a variety of cancers.

Keywords: bioengineering, cancer, nanomedicine, polymer chemistry

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Authors: S. Roy, R. Rekha, K. Sriram, G. Subhadra, R. Johana

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Cardiovascular disease remains a leading cause of death in most industrialized countries. Many chemical drugs are available in the market which targets different receptor proteins related to cardiovascular diseases. Of late the traditional herbal drugs are safer when compared to chemical drugs because of its side effects. However, many herbal remedies used in treating cardiovascular diseases have not undergone scientific assessment to prove its pharmacological activities. There are many natural compounds, nature derived and Natural product mimic compounds are available which are in the market as approved drug. In the most of the cases drug activity at the molecular level are not known. Here we have categorized those compounds with our experimental compounds in different classes based on the structural similarity and physicochemical properties, using a tool, Chemmine and has attempted to understand the mechanism of the action of a experimental compound, which are clustered with Simvastatin, Lovastatin, Mevastatin and Pravastatin. Target protein molecule for Simvastatin, Lovastatin, Mevastatin and Pravastatin is HMG-CoA reductase, so we concluded that the experimental compound may be able to bind to the same target. Molecular docking and atomic interaction studies with simvastatin and our experimental compound were compared. A pharmacophore modeling was done based on the experimental compound and HMG-CoA reductase inhibitor.

Keywords: molecular docking, physicochemical properties, pharmacophore modeling structural similarity, pravastatin

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Authors: Huafeng Wei

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Dementia in Alzheimer’s Disease (AD) is the number one cause of dementia internationally, without effective treatments. Increasing evidence suggest that disruption of intracellular calcium homeostasis, primarily pathological elevation of cytosol and mitochondria but reduction of endoplasmic reticulum (ER) calcium concentrations, play critical upstream roles on multiple pathologies and associated neurodegeneration, impaired neurogenesis, synapse, and cognitive dysfunction in various AD preclinical studies. The last federal drug agency (FDA) approved drug for AD dementia treatment, memantine, exert its therapeutic effects by ameliorating N-methyl-D-aspartate (NMDA) glutamate receptor overactivation and subsequent calcium dysregulation. More research works are needed to develop other drugs targeting calcium dysregulation at multiple pharmacological acting sites for future effective AD dementia treatment. Particularly, calcium channel blockers for the treatment of hypertension and dantrolene for the treatment of muscle spasm and malignant hyperthermia can be repurposed for this purpose. In our own research work, intranasal administration of dantrolene significantly increased its brain concentrations and durations, rendering it a more effective therapeutic drug with less side effects for chronic AD dementia treatment. This review summarizesthe progress of various studies repurposing drugs targeting calcium dysregulation for future effective AD dementia treatment as potentially disease-modifying drugs.

Keywords: alzheimer, calcium, cognitive dysfunction, dementia, neurodegeneration, neurogenesis

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Authors: Sidra Shaw, Sarenna Shaw, Chae Joon Lee, Irimpan Mathews, Eric Koehn

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One of the biggest public health concerns of our time is increasing antimicrobial resistance. As of 2019, the CDC has documented more than 2.8 million serious antibiotic resistant infections in the United States. Currently, antibiotic resistant infections are directly implicated in over 750,000 deaths per year globally. On our current trajectory, British economist Jim O’Neill predicts that by 2050, an additional 10 million people (about half the population of New York) will die annually due to drug resistant infections. As a result, new biochemical pathways must be targeted to generate next generation antibiotic drugs that will be effective against drug resistant bacteria. One enticing target is the biosynthesis of DNA within bacteria, as few drugs interrupt this essential life process. Thymidylate synthase enzymes are essential for life as they catalyze the synthesis of a DNA building block, 2′-deoxythymidine-5′-monophosphate (dTMP). In humans, the thymidylate synthase enzyme (TSase) has been shown to be distinct from the flavin-dependent thymidylate synthase (FDTS) produced by many pathogenic bacteria. TSase and FDTS have distinct structures and mechanisms of catalysis, which should allow selective inhibition of FDTS over human TSase. Currently, C. diff is one of the most antibiotic resistant bacteria, and no drugs that target thymine biosynthesis exist for C. diff. Here we present the initial biochemical characterization of FDTS from C. diff. Specifically, we examine enzyme kinetics and binding features of this enzyme to determine the nature of interaction with ligands/inhibitors and understand the molecular mechanism of catalysis. This research will provide more insight into the targetability of the C. diff FDTS enzyme for novel antibiotic drugs.

Keywords: flavin-dependent thymidylate synthase, FDTS, clostridioides difficile, C. diff, antibiotic resistance, DNA synthesis, enzyme kinetics, binding features

Procedia PDF Downloads 74