Search results for: drug addiction

Authors: Mumuni Sumaila, Viness Pillay, Yahya E. Choonara, Pradeep Kumar, Pierre P. Kondiah

Abstract:

Tuberculosis (TB) remains a serious challenge to public health globally, despite every effort put together to curb the disease. Current TB therapeutics available have proven to be inefficient due to a multitude of drawbacks that range from serious adverse effects/drug toxicity to inconsistent bioavailability, which ultimately contributes to the emergence of drug-resistant TB. An effective ‘cargo’ system designed to cleverly deliver therapeutic doses of anti-TB drugs to infection sites and in a sustained-release manner may provide a better therapeutic choice towards winning the war against TB. In the current study, we investigated mannose-functionalized lipopolysaccharide hybrid nanoparticles for safety and efficacy towards macrophage-targeted simultaneous delivery of the two first-line anti-TB drugs, rifampicin (RF) and isoniazid (IS). RF-IS-loaded lipopolysaccharide hybrid nanoparticles were fabricated using the solvent injection technique (SIT), incorporating soy lecithin (SL) and low molecular weight chitosan (CS) as the lipid and polysaccharide components, respectively. Surface-functionalized nanoparticles were obtained through the reaction of the aldehyde group of mannose with free amine functionality present at the surface of the nanoparticles. The functionalized nanocarriers were spherical with average particle size and surface charge of 107.83 nm and +21.77 mV, respectively, and entrapment efficiencies (EE) were 53.52% and 69.80% for RF and IS, respectively. FTIR spectrum revealed high-intensity bands between 1663 cm⁻¹ and 1408 cm⁻¹ wavenumbers (absent in non-functionalized nanoparticles), which could be attributed to the C=N stretching vibration produced by the formation of Schiff’s base (–N=CH–) during the mannosylation reaction. In vitro release studies showed a sustained-release profile for RF and IS, with less than half of the total payload released over a 48-hour period. The nanocarriers were biocompatible and safe, with more than 80% cell viability achieved when incubated with RAW 264.7 cells at concentrations 30 to 500 μg/mL over a 24-hour period. Cellular uptake studies (after a 24-hour incubation period with the murine macrophage cells, RAW 264.7) revealed a 13- and a 9-fold increase in intracellular accumulation of RF and IS, respectively, when compared with the unformulated RF+IS solution. A 6- and a 3-fold increase in intracellular accumulation of RF and IS, respectively, were observed when compared with the non-functionalized nanoparticles. Furthermore, fluorescent microscopy images showed nanoparticle internalization and accumulation within the RAW 264.7 cells, which was more significant in the mannose-functionalized system compared to the non-functionalized nanoparticles. The overall results suggested that the fabricated mannose-functionalized lipopolysaccharide nanoparticles are a safe and promising platform for macrophage-targeted delivery of anti-TB therapeutics. However, in vivo pharmacokinetic/pharmacodynamics studies are required to further substantiate the therapeutic efficacy of the nanosystem.

Keywords: anti-tuberculosis therapeutics, hybrid nanosystem, lipopolysaccharide nanoparticles, macrophage-targeted delivery

Procedia PDF Downloads 157

Authors: Heiko Jessen, Laura Tanus, Slobodan Ruzicic

Abstract:

Objectives: The efficacy of Stribild®, an integrase strand transfer inhibitor (INSTI) -based STR, has been evaluated in randomized clinical trials and it has demonstrated durable capability in terms of achieving sustained suppression of HIV-1 RNA-levels. However, differences in monitoring frequency, existing selection bias and profile of patients enrolled in the trials, may all result in divergent efficacy of this regimen in routine clinical settings. The aim of this study was to assess the virologic outcomes, safety and tolerability profile of Stribild® in a routine clinical setting. Methods: This was a retrospective monocentric analysis on HIV-1-infected patients, who started with or were switched to Stribild®. Virological failure (VF) was defined as confirmed HIV-RNA>50 copies/ml. The minimum time of follow-up was 24 weeks. The percentage of patients remaining free of therapeutic failure was estimated using the time-to-loss-of-virologic-response (TLOVR) algorithm, by intent-to-treat analysis. Results: We analyzed the data of 197 patients (56 ART-naïve and 141 treatment-experienced patients), who fulfilled the inclusion criteria. Majority (95.9%) of patients were male. The median time of HIV-infection at baseline was 2 months in treatment-naïve and 70 months in treatment-experienced patients. Median time [IQR] under ART in treatment-experienced patients was 37 months. Among the treatment-experienced patients 27.0% had already been treated with a regimen consisting of two NRTIs and one INSTI, whereas 18.4% of them experienced a VF. The median time [IQR] of virological suppression prior to therapy with Stribild® in the treatment-experienced patients was 10 months [0-27]. At the end of follow-up (median 33 months), 87.3% (95% CI, 83.5-91.2) of treatment-naïve and 80.3% (95% CI, 75.8-84.8) of treatment-experienced patients remained free of therapeutic failure. Considering only treatment-experienced patients with baseline VL<50 copies/ml, 83.0% (95% CI, 78.5-87.5) remained free of therapeutic failure. A total of 17 patients stopped treatment with Stribild®, 5.4% (3/56) of them were treatment-naïve and 9.9% (14/141) were treatment-experienced patients. The Stribild® therapy was discontinued in 2 (1.0%) because of VF, loss to follow-up in 4 (2.0%), and drug-drug interactions in 2 (1.0%) patients. Adverse events were in 7 (3.6%) patients the reason to switch from therapy with Stribild® and further 2 (1.0%) patients decided personally to switch. The most frequently observed adverse events were gastrointestinal side effects (20.0%), headache (8%), rash events (7%) and dizziness (6%). In two patients we observed an emergence of novel resistances in integrase-gene. The N155H evolved in one patient and resulted in VF. In another patient S119R evolved either during or shortly upon switch from therapy with Stribild®. In one further patient with VF two novel mutations in the RT-gene were observed when compared to historical genotypic test result (V106I/M and M184V), whereby it is not clear whether they evolved during or already before the switch to Stribild®. Conclusions: Effectiveness of Stribild® for treatment-naïve patients was consistent with data obtained in clinical trials. The safety and tolerability profile as well as resistance development confirmed clinical efficacy of Stribild® in a daily practice setting.

Keywords: ART, HIV, integrase inhibitor, stribild

Procedia PDF Downloads 268

Authors: Sophio Kobauri, Vladimir P. Torchilin, David Tugushi, Ramaz Katsarava

Abstract:

Nanotherapy is an actual newest mode of treatment numerous diseases using nanoparticles (NPs) loading with different pharmaceuticals. NPs of biodegradable polymeric micelles (PMs) are gaining increased attention for their numerous and attractive abilities to be used in a variety of applications in the various fields of medicine. The present paper deals with the synthesis of a class of biodegradable micelle-forming polymers, namely ABA triblock-copolymer in which A-blocks represent amino-poly(ethylene glycol) (H₂N-PEG) and B-block is biodegradable amino acid-based poly(ester amide) constituted of α-amino acid – L-phenylalanine. The obtained copolymer formed micelles of 70±4 nm size at 10 mg/mL concentration.

Keywords: amino acids, biodegradable poly (ester amide), amphiphilic triblock-copolymer, micelles

Procedia PDF Downloads 176

Authors: M. Sai Veerendra

Abstract:

Today, money laundering (ML) poses a serious threat not only to financial institutions but also to the nation. This criminal activity is becoming more and more sophisticated and seems to have moved from the cliché of drug trafficking to financing terrorism and surely not forgetting personal gain. Most of the financial institutions internationally have been implementing anti-money laundering solutions (AML) to fight investment fraud activities. However, traditional investigative techniques consume numerous man-hours. Recently, data mining approaches have been developed and are considered as well-suited techniques for detecting ML activities. Within the scope of a collaboration project on developing a new data mining solution for AML Units in an international investment bank in Ireland, we survey recent data mining approaches for AML. In this paper, we present not only these approaches but also give an overview on the important factors in building data mining solutions for AML activities.

Keywords: data mining, clustering, money laundering, anti-money laundering solutions

Procedia PDF Downloads 524

Authors: Kevin William Taylor

Abstract:

This work draws upon research in the fields of games development and mental health treatments to assess the influence that interactive entertainment has on the populous, and the potential of technology to affect areas of psychiatric assessment and treatment. It will use studies to establish the evolving direction of interactive media in the development of ‘digital self-identity,’ and how this can be incorporated into treatment to the benefit of psychiatry. It will determine that this approach will require collaborative production between developers and psychiatrists in order to ensure precise goals are met, improving the success of serious gaming for psychiatric assessment and treatment. Analysis documents the reach of video games across a growing global community of gamers, highlighting cases of the positives and negatives of video game usage. The games industry is largely oblivious to the psychological negatives, with psychiatrists encountering new conditions such as gaming addiction, which is now recognized by the World Health Organization. With an increasing amount of gamers worldwide, and an additional time per day invested in online gaming and character development, the concept of virtual identity as a means of expressing the id needs further study to ensure successful treatment. In conclusion, the assessment and treatment of game-related conditions are currently reactionary, and while some mental health professionals have begun utilizing interactive technologies to assist with the assessment and treatment of conditions, this study will determine how the success of these products can be enhanced. This will include collaboration between software developers and psychiatrists, allowing new avenues of skill-sharing in interactive design and development. Outlining how to innovate approaches to engagement will reap greater rewards in future interactive products developed for psychiatric assessment and treatment.

Keywords: virtual reality, virtual identity, interactivity, psychiatry

Procedia PDF Downloads 132

Authors: Sumeet Dwivedi, Shweta Shriwas, Raghvendra Dubey

Abstract:

Madhya Pradesh, a Central State of India is rich in natural heritage due to tribal impact. Herbal harmony present either cultivated or by naturally being used by the tribes of the state in the treatment of several human and animal disorders. Diseases of ear, nose and throat (ENT) often have serious consequences including hearing impairment, and emotional strain that lower the quality of life of patients. Traditional phytotherapy have now been found to be instrumental in improving chances of discovering plants with antimicrobial activity in new drug development. The present paper enumerates the uses of ten herbs viz., garlic, eucalyptus, marigold, tulsi, euphorbia, lemon grass, haldi, bhringraj, ginger and ajwain. An attempt has also been made to reveal the method of preparation, dose, duration possible MOA of these herbs used for ENT disorders.

Keywords: ENT, traditional phytotherapy, herbs, Madhya Pradesh

Procedia PDF Downloads 240

Authors: Khalida Boutemak, Nasssima Benali, Nadji Moulai-Mostefa

Abstract:

Effect of enzyme on the yield and chemical composition of Artemisia campestris essential oil is reported in the present study. It was demonstrated that enzyme facilitated the extraction of essential oil with increase in oil yield and did not affect any noticeable change in flavour profile of the volatile oil. Essential oil was tested for antibacterial activity using Escherichia coli; which was extremely sensitive against control with the largest inhibition (29mm), whereas Staphylococcus aureus was the most sensitive against essential oil obtained from enzymatic pre-treatment with the largest inhibition zone (25mm). The antioxidant activity of the essential oil with hemicellulase pre-treatment (EO2) and control sample (EO1) was determined through reducing power. It was significantly lower than the standard drug (vitamin C) in this order: vitamin C˃EO2˃EO1.

Keywords: Artemisia campestris, enzyme pre-treatment, hemicellulase, antibacterial activity, antioxidant activity

Procedia PDF Downloads 310

Authors: Ibrahim Magaji

Abstract:

WhatsApp messaging platform brings about new opportunities for users to participate in unique storytelling experiences and audience engagement, particularly to Students of Mass communication who receive training to report events and issues accurately and objectively in accordance with official controls. Also, the complex nature of society today made it possible to use the WhatsApp platform that revolutionizes the means of sharing information, ideas, and experiences. This paper examined the WhatsApp messaging platform and how it influenced the academic performance of students in the Department of Mass Communication, Abdu Gusau Polytechnic, Talata Mafara. It used in-depth interview techniques and focus group discussion with students, as well as the use of published materials as well as unpublished materials to gather related and relevant data. Also, the paper used procedures involved to analyze long interview content. This procedure includes observation of a useful utterance, development of expanded observation, the examination of the interconnection of observed comments, collective scrutiny of observation for patterns and themes, and review and analysis of the themes across all interviews for development of the thesis. The result revealed that the majority of students used WhatsApp messenger for making friends and chatting. Also, the students experienced negative effects such as poor grammar and spelling, less study time, and poor academic performance because of active participation in the use of WhatsApp messaging platform. Surprisingly, there was a high addiction rate among students in the usage of WhatsApp messenger. However, other students experienced an improvement in their readings skills as a result of participation in the use of the platform. Also, students shared ideas, discussed, and shared examination questions among themselves on WhatsApp messenger.

Keywords: WhatsApp messenger, students, participation, group

Procedia PDF Downloads 113

Authors: Abubakar Ahmed, Zainab Mohammed, Hadiza D. Nuhu, Hamisu Ibrahim

Abstract:

Introduction: The plant Tacazzea apiculata Oliv (Periplocaceae) is widely distributed in tropical West Africa. It is claimed to have multiple uses in traditional medicine among which are its use to treat hemorrhoids, inflammations and cancers. Methods: Ethno-botanical survey through interview and using show-and-tell method of data collection were conducted among Hausa and Fulani tribes of northern Nigeria with the view to document useful information on the numerous claims by the local people on the plant. Results: The results revealed that the plant T. apiculata has relative popularity among the herbalist (38.2 %), nomads (14.8 %) and fishermen (16.0%). The most important uses of the plant in traditional medicine are inflammation (Fedelity level: 25.7 %) and Haemorrhoids (Fedelity level: 17.1 %) Conclusion: These results suggest the relevance of T. apiculata in traditional medicine and as a good candidate for drug Development.

Keywords: ethno-botany, periplocaceae, Tacazzea apiculata, traditional medicine

Procedia PDF Downloads 494

Authors: Sun Tao, Lou Liang, Tan Xing Haw Marvin, Gu Yuandong Alex

Abstract:

Patients with blood clots in their brains can experience problems with their vision or speech, seizures and general weakness. To treat blood clots, clinicians presently have two options. The first involves drug therapy to thin the blood and thus reduce the clot. The second choice is to invasively remove the clot using a plastic tube called a catheter. Both approaches carry a high risk of bleeding, and invasive procedures, such as catheter intervention, can also damage the blood vessel wall and cause infection. Ultrasonic treatment as a potential alternative therapy to break down clots is attracting growing interests due to the reduced adverse effects. To demonstrate the concept, in this investigation a microfabricated ultrasonic device was electrically packaged with printed circuit board to treat healthy human blood. The red blood cells could be broken down after 3-hour ultrasonic treatment.

Keywords: microfabrication, blood clot, ultrasonic thrombolysis device, ultrasonic device

Procedia PDF Downloads 436

Authors: Patcharawalai Jaisamut, Kamonthip Wiwattanawongsa, Ruedeekorn Wiwattanapatapee

Abstract:

Supersaturation of drugs in the gastrointestinal tract is one approach to increase the absorption of poorly water-soluble drugs. The stabilization of a supersaturated state was achieved by adding precipitation inhibitors that may act through a variety of mechanisms.In this study, the effect of the natural gums, acacia, gelatin, pectin and tragacanth on curcumin supersaturation in simulated gastric fluid (SGF) (pH 1.2), fasted state simulated gastric fluid (FaSSGF) (pH 1.6), and simulated intestinal fluid (SIF) (pH 6.8)was investigated. The results indicated that all natural gums significantly increased the curcum insolubility (about 1.2-6-fold)when compared to the absence of gum, and assisted in maintaining the supersaturated drug solution. Among the tested gums, pectin at 3% w/w was the best precipitation inhibitor with a significant increase in the degree of supersaturation about 3-fold in SGF, 2.4-fold in FaSSGF and 2-fold in SIF.

Keywords: curcumin, solubility, supersaturation, precipitation inhibitor

Procedia PDF Downloads 335

Authors: N. Naga Subrahmanyeswara Rao, Parag Arvind Deshpande

Abstract:

Understanding nucleotide synthesis reaction of any organism is beneficial to know the growth of it as in Mycobacterium tuberculosis to design anti TB drug. One of the reactions of de novo pathway which takes place in all organisms was considered. The reaction takes places between phosphoribosyl pyrophosphate and orotate catalyzed by orotate phosphoribosyl transferase and divalent metal ion gives orotdine monophosphate, a nucleotide. All the reaction steps of three experimentally proposed mechanisms for this reaction were considered to develop kinetic rate expression. The model was validated using the data for four organisms. This model could successfully describe the kinetics for the reported data. The developed model can serve as a reliable model to describe the kinetics in new organisms without the need of mechanistic determination. So an organism-independent model was developed.

Keywords: mechanism, nucleotide, organism, tuberculosis

Procedia PDF Downloads 317

Authors: Mebruka Mohammed, Daniel Bisrat, Asfaw Debella, Tarekegn Birhanu

Abstract:

Lack of quality control standards for medicinal plants and their preparations is considered major barrier to their integration in to effective primary health care in Ethiopia. Poor quality herbal preparations led to countless adverse reactions extending to death. Denial of penetration for the Ethiopian medicinal plants in to the world’s booming herbal market is also another significant loss resulting from absence of herbal quality control system. Thus, in the present study, Gnidia stenophylla Gilg (popular antimalarial plant of south eastern Ethiopia), is standardized and a full monograph is produced that can serve as a guideline in quality control of the crude drug. Morphologically, the roots are found to be cylindrical and tapering towards the end. It has a hard, corky and friable touch with saddle brown color externally and it is relatively smooth and pale brown internally. It has got characteristic pungent odor and very bitter taste. Microscopically it has showed lignified xylem vessels, wider medullary rays with some calcium oxalate crystals, reddish brown secondary metabolite contents and slender shaped long fibres. Physicochemical standards quantified and resulted: foreign matter (5.25%), moisture content (6.69%), total ash (40.80%), acid insoluble ash (8.00%), water soluble ash (2.30%), alcohol soluble extractive (15.27%), water soluble extractive (10.98%), foaming index (100.01 ml/g), swelling index (7.60 ml/g). Phytochemically: Phenols, flavonoids, steroids, tannins and saponins were detected in the root extract; TLC and HPLC fingerprints were produced and an analytical marker was also tentatively characterized as 3-(3,4-dihydro-3,5-dihydroxy-2-(4-hydroxy-5-methylhex-1-en-2-yl)-7-methoxy-4-oxo-2H-chromen-8-yl)-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one. Residue wise pesticides (i.e. DDT, DDE, g-BHC) and radiochemical levels fall below the WHO limit while Heavy metals (i.e. Co, Ni, Cr, Pb, and Cu), total aerobic count and fungal load lie way above the WHO limit. In conclusion, the result can be taken as signal that employing non standardized medicinal plants could cause many health risks of the Ethiopian people and Africans’ at large (as 80% of inhabitants in the continent depends on it for primary health care). Therefore, following a more universal approach to herbal quality by adopting the WHO guidelines and developing monographs using the various quality parameters is inevitable to minimize quality breach and promote effective herbal drug usage.

Keywords: Gnidia stenophylla Gilg, standardization/monograph, pharmacognostic, residue/impurity, quality

Procedia PDF Downloads 264

Authors: Raquel C. A. G. Mota, Livia R. Menezes, Emerson O. da Silva

Abstract:

Both silver nanoparticles and titanium dioxide have been extensively used in tissue engineering since they’ve been approved by the Food and Drug Administration (FDA), and present a bactericide effect when added to a polymeric matrix. In this work, the focus is on fabricating binary systems with both nanoparticles so that the synergistic effect can be investigated. The systems were tested by Nuclear Magnetic Resonance (NMR), Thermogravimetric Analysis (TGA), Fourier-Transformed Infrared (FTIR), and Differential Scanning Calorimetry (DSC), and X-ray Diffraction (XRD), and had both their bioactivity and bactericide effect tested. The binary systems presented different properties than the individual systems, enhancing both the thermal and biological properties as was to be expected. The crystallinity was also affected, as indicated by the finding of the DSC and XDR techniques, and the NMR showed a good dispersion of both nanoparticles in the polymer matrix. These findings indicate the potential of combining TiO₂ and silver nanoparticles in biomedicine.

Keywords: metallic nanoparticles, nanotechnology, polymer nanocomposites, polymer science

Procedia PDF Downloads 118

Authors: R. Fegas, S. Zerkout, S. Taberkokt, M. Righezza

Abstract:

The present work demonstrate the potential of Betacyclodextrine (BCD) for the chiral analysis of a drug .Various separation mechanisms were applied and several parameters affecting the separation were studied, including the type and concentration of chiral selector, and pH of buffer. A simple and sensitive high-performance liquid chromatography (HPLC) method was developed as an assay for fexofenadine enantiomers in pharmaceutical preparation. Fexofenadine enantiomers were separated using a mobile phase of 0.25mM NaH2PO4–acetonitrile (65:35, v/v) – Betacyclodextrine on achiral phenyl-urea column at a flow rate of 1ml/min and measurement at 220nm. The chiral mechanism of separation was mainly based on specific interaction between the solute and the stationary phase. The retention was directly controlled by mobile phase composition but not the selectivity which results of the two mechanisms, electrostatic interactions and partition mechanism.

Keywords: fexofenadine enantiomer, HPLC, achiral phenyl-urea column

Procedia PDF Downloads 445

Authors: Theo Welch

Abstract:

Background: Gamma-hydroxybutyrate (GHB) is a depressant of the central nervous system with euphoric effects. It is being increasingly used recreationally in the United Kingdom (UK) despite associated morbidity and mortality. Due to the lack of evidence, healthcare professionals remain unsure as to the optimum management of GHB acute toxicity. Methods: A literature review was undertaken of its pharmacology and the emergency management of its acute toxicity.Findings: GHB is inexpensive and readily available over the Internet. Treatment of GHB acute toxicity is supportive. Clinicians should pay particular attention to the airway as emesis is common. Intubation is required in a minority of cases. Polydrug use is common and worsens prognosis. Conclusion: An inexpensive and readily available drug, GHB acute toxicity can be difficult to identify and treat. GHB acute toxicity is generally treated conservatively. Further research is needed to ascertain the indications, benefits, and risks of intubating patients with GHB acute toxicity. instructions give you guidelines for preparing papers for the conference.

Keywords: GHB, gamma-hydroxybutyrate, prehospital, emergency, toxicity, management

Procedia PDF Downloads 181

Authors: D. Ravinder

Abstract:

Nickel ferrites and Ni doped Lithium nano ferrites [Li0.5Fe0.5]1-xNixFe2O4 with x= 0.8 and 1.0 synthesized by citrate-gel auto combustion method. The broad peaks in the X-ray diffraction pattern (XRD) indicate a crystalline behavior of the prepared samples. Low temperature magnetization studies i,e Field Cooled (FC) and Zero Field Cooled (ZFC) magnetic studies of the investigated samples are measured by using vibrating sample magnetometer (VSM). The magnetization of the prepared samples as a function of an applied magnetic field 10 T was measured at two different temperatures 5 K and 310 K. Field Cooled (FC) and Zero Field Cooled (ZFC) magnetization measurements under an applied field of 100 Oe and 1000 Oe in the temperature range of 5–375 K were carried out.

Keywords: ferro-spinels, field cooled (FC), Zero Field Cooled (ZFC) and blocking temperature, superpara magnetism, drug delivery applications

Procedia PDF Downloads 536

Authors: Ferjani Hanen, El Arem Amira, Boussema Ayed Imen, Bacha Hassen

Abstract:

Tacrolimus (TAC), a calcineurin inhibitor, is clinically used as an immunosuppressive agent in the transplant recipient, but its use associated-hepatotoxicity. Mycophenolate mofetil (MMF), an anti-metabolite, is a potent immunosuppressive drug. MMF is not hepatotoxic and is the most common adjunctive immunosuppressant for TAC. The effects of TAC and MMF combination in the liver is still not well understood. This work aimed to investigate their combined effect against in liver in rats Wistar after 24 h. The oral median lethal doses (LD50) of TAC and MMF alone were evaluated in rats are 240 mg/kg and 500 mg/kg respectively. Oral administration of the MMF at 50 mg/kg to male Wistar intoxicated with TAC at 60 mg/kg, demonstrated a significant protective effect by lowering the levels of hepatic markers enzymes (AST, ALT) in the serum rat. MMF attenuated oxidative stress by restoring the activities of SOD, CAT and by reducing the malondialdehyde (MDA) and protein carbonyl levels liver. This study provided evidence that MMF protects rat liver from TAC-induced injury and suggests a most combination use for organ transplantation.

Keywords: tacrolimus, mycophenolate mofetil, combination, liver, rat

Procedia PDF Downloads 320

Authors: A. N.Ukwuani, A. K. Abdulfatah

Abstract:

G. crenata is used locally for the treatment of fractured bones, wound healing and inflammatory conditions. In vitro and in vivo antioxidant activity of hydromethanolic extracts of the leaves of G. crenata were assessed. The phytochemical analysis shows the presence of phenols, flavonoids, saponins, cardiac glycosides and tannins. An in vitro quantitative analysis of phenols, flavonoids and tannins respectively were (164±1.20, 199±0.88 and 88.67±0.88 mg/100g FW). In vivo studies of hydromethanolic extract demonstrated a dose dependent increase in hepatic superoxide dismutase (1.14±0.14, 2.13±0.11, 2.55±0.11 U/mg Protein) with improvement in hepatic glutathione (6.98±0.42, 8.91±0.37, 11.07±0.46 µM/mg Protein) and Catalase (4.47±0.05, 6.24±0.02, 7.17±0.04 U/mg Protein) and Total protein (6.18±0.08, 6.69±0.18, 7.27±0.16 mg/ml) respectively at 100-300mg/kg body weight Grewia crenata leaves when compared to the control and standard drug. It can be concluded from the present findings of that G. crenata leaves possess antioxidant potential.

Keywords: Grewia crenata, antioxidant, hydromethanolic extract, in vivo, in vitro

Procedia PDF Downloads 521

Authors: A. Nusrath Unissa, Sameer Hassan, Luke Elizabeth Hanna

Abstract:

Altered drug binding may be an important factor in isoniazid (INH) resistance, rather than major changes in the enzyme’s activity as a catalase or peroxidase (KatG). The identification of structural or functional defects in the mutant KatGs responsible for INH resistance remains as an area to be explored. In this connection, the differences in the binding affinity between wild-type (WT) and mutants of KatG were investigated, through the generation of three mutants of KatG, Ser315Thr [S315T], Ser315Asn [S315N], Ser315Arg [S315R] and a WT [S315]) with the help of software-MODELLER. The mutants were docked with INH using the software-GOLD. The affinity is lower for WT than mutant, suggesting the tight binding of INH with the mutant protein compared to WT type. These models provide the in silico evidence for the binding interaction of KatG with INH and implicate the basis for rationalization of INH resistance in naturally occurring KatG mutant strains of Mycobacterium tuberculosis.

Keywords: Mycobacterium tuberculosis, KatG, INH resistance, mutants, modelling, docking

Procedia PDF Downloads 306

Authors: Milu T. Cherian, Sergio C. Chai, Morgan A. Casal, Taosheng Chen

Abstract:

This study aims to use CINPA1, a recently discovered small-molecule inhibitor of the xenobiotic receptor CAR (constitutive androstane receptor) for understanding the binding modes of CAR and to guide CAR-mediated gene expression profiling studies in human primary hepatocytes. CAR and PXR are xenobiotic sensors that respond to drugs and endobiotics by modulating the expression of metabolic genes that enhance detoxification and elimination. Elevated levels of drug metabolizing enzymes and efflux transporters resulting from CAR activation promote the elimination of chemotherapeutic agents leading to reduced therapeutic effectiveness. Multidrug resistance in tumors after chemotherapy could be associated with errant CAR activity, as shown in the case of neuroblastoma. CAR inhibitors used in combination with existing chemotherapeutics could be utilized to attenuate multidrug resistance and resensitize chemo-resistant cancer cells. CAR and PXR have many overlapping modulating ligands as well as many overlapping target genes which confounded attempts to understand and regulate receptor-specific activity. Through a directed screening approach we previously identified a new CAR inhibitor, CINPA1, which is novel in its ability to inhibit CAR function without activating PXR. The cellular mechanisms by which CINPA1 inhibits CAR function were also extensively examined along with its pharmacokinetic properties. CINPA1 binding was shown to change CAR-coregulator interactions as well as modify CAR recruitment at DNA response elements of regulated genes. CINPA1 was shown to be broken down in the liver to form two, mostly inactive, metabolites. The structure-activity differences of CINPA1 and its metabolites were used to guide computational modeling using the CAR-LBD structure. To rationalize how ligand binding may lead to different CAR pharmacology, an analysis of the docked poses of human CAR bound to CITCO (a CAR activator) vs. CINPA1 or the metabolites was conducted. From our modeling, strong hydrogen bonding of CINPA1 with N165 and H203 in the CAR-LBD was predicted. These residues were validated to be important for CINPA1 binding using single amino-acid CAR mutants in a CAR-mediated functional reporter assay. Also predicted were residues making key hydrophobic interactions with CINPA1 but not the inactive metabolites. Some of these hydrophobic amino acids were also identified and additionally, the differential coregulator interactions of these mutants were determined in mammalian two-hybrid systems. CINPA1 represents an excellent starting point for future optimization into highly relevant probe molecules to study the function of the CAR receptor in normal- and pathophysiology, and possible development of therapeutics (for e.g. use for resensitizing chemoresistant neuroblastoma cells).

Keywords: antagonist, chemoresistance, constitutive androstane receptor (CAR), multi-drug resistance, structure activity relationship (SAR), xenobiotic resistance

Procedia PDF Downloads 267

Authors: Ren-Jy Ben, Jo-Chi Jao, Chiu-Ya Liao, Ya-Ru Tsai, Lain-Chyr Hwang, Po-Chou Chen

Abstract:

Cancer is still one of the serious diseases threatening the lives of human beings. How to have an early diagnosis and effective treatment for tumors is a very important issue. The animal carcinoma model can provide a simulation tool for the study of pathogenesis, biological characteristics and therapeutic effects. Recently, drug delivery systems have been rapidly developed to effectively improve the therapeutic effects. Liposome plays an increasingly important role in clinical diagnosis and therapy for delivering a pharmaceutic or contrast agent to the targeted sites. Liposome can be absorbed and excreted by the human body, and is well known that no harm to the human body. This study aimed to compare the therapeutic effects between encapsulated (doxorubicin liposomal, LipoDox) and un-encapsulated (doxorubicin, Dox) anti-tumor drugs using Magnetic Resonance Imaging (MRI). Twenty-four New Zealand rabbits implanted with VX2 carcinoma at left thigh were classified into three groups: control group (untreated), Dox-treated group and LipoDox-treated group, 8 rabbits for each group. MRI scans were performed three days after tumor implantation. A 1.5T GE Signa HDxt whole body MRI scanner with a high resolution knee coil was used in this study. After a 3-plane localizer scan was performed, Three-Dimensional (3D) Fast Spin Echo (FSE) T2-Weighted Images (T2WI) was used for tumor volumetric quantification. And Two-Dimensional (2D) spoiled gradient recalled echo (SPGR) dynamic Contrast-enhanced (DCE) MRI was used for tumor perfusion evaluation. DCE-MRI was designed to acquire four baseline images, followed by contrast agent Gd-DOTA injection through the ear vein of rabbits. Afterwards, a series of 32 images were acquired to observe the signals change over time in the tumor and muscle. The MRI scanning was scheduled on a weekly basis for a period of four weeks to observe the tumor progression longitudinally. The Dox and LipoDox treatments were prescribed 3 times in the first week immediately after VX2 tumor implantation. ImageJ was used to quantitate tumor volume and time course signal enhancement on DCE images. The changes of tumor size showed that the growth of VX2 tumors was effectively inhibited for both LipoDox-treated and Dox-treated groups. Furthermore, the tumor volume of LipoDox-treated group was significantly lower than that of Dox-treated group, which implies that LipoDox has better therapeutic effect than Dox. The signal intensity of LipoDox-treated group is significantly lower than that of the other two groups, which implies that targeted therapeutic drug remained in the tumor tissue. This study provides a radiation-free and non-invasive MRI method for therapeutic monitoring of targeted liposome on an animal tumor model.

Keywords: doxorubicin, dynamic contrast-enhanced MRI, lipodox, magnetic resonance imaging, VX2 tumor model

Procedia PDF Downloads 445

Authors: Sudhanshu Sharma

Abstract:

Lisinopril, 1-[N-{(s)-I-carboxy-3 phenyl propyl}-L-proline dehydrate is a lysine analog of enalaprilat, the active metabolite of enalapril. It is long-acting, non-sulhydryl angiotensin-converting enzyme (ACE) inhibitor that is used for the treatment of hypertension and congestive heart failure in daily dosage 10-80 mg. Pharmacological activity of lisinopril has been proved in various experimental and clinical studies. Owing to its importance and widespread use, efforts have been made towards the development of simple and reliable analytical methods. As per our literature survey, lisinopril in pharmaceutical formulations has been determined by various analytical methodologies like polaragraphy, potentiometry, and spectrophotometry, but most of these analytical methods are not too suitable for the Identification of lisinopril from clinical samples because of the interferences caused by the amino acids and amino groups containing metabolites present in biological samples. This report is an attempt in the direction of developing a simple and reliable method for on plate identification and quantification of lisinopril in pharmaceutical formulations as well as from human urine samples using silica gel H layers developed with a new mobile phase comprising of micellar solutions of N-cetyl-N, N, N-trimethylammonium bromide (CTAB). Micellar solutions have found numerous practical applications in many areas of separation science. Micellar liquid chromatography (MLC) has gained immense popularity and wider applicability due to operational simplicity, cost effectiveness, relatively non-toxicity and enhanced separation efficiency, low aggressiveness. Incorporation of aqueous micellar solutions as mobile phase was pioneered by Armstrong and Terrill as they accentuated the importance of TLC where simultaneous separation of ionic or non-ionic species in a variety of matrices is required. A peculiarity of the micellar mobile phases (MMPs) is that they have no macroscopic analogues, as a result the typical separations can be easily achieved by using MMPs than aqueous organic mobile phases. Previously MMPs were successfully employed in TLC based critical separations of aromatic hydrocarbons, nucleotides, vitamin K1 and K5, o-, m- and p- aminophenol, amino acids, separation of penicillins. The human urine analysis for identification of selected drugs and their metabolites has emerged as an important investigation tool in forensic drug analysis. Among all chromatographic methods available only thin layer chromatography (TLC) enables a simple fast and effective separation of the complex mixtures present in various biological samples and is recommended as an approved testing for forensic drug analysis by federal Law. TLC proved its applicability during successful separation of bio-active amines, carbohydrates, enzymes, porphyrins, and their precursors, alkaloid and drugs from urine samples.

Keywords: lisnopril, surfactant, chromatography, micellar solutions

Procedia PDF Downloads 345

Authors: Ana Flavia Belchior De Andrade

Abstract:

Forensic laboratories all over the world face a great challenge to overcame waiting time and backlog in many different areas. Many aspects contribute to this situation, such as an increase in drug complexity, increment in the number of exams requested and cuts in funding limiting laboratories hiring capacity. Altogether, those facts pose an essential challenge for forensic chemistry laboratories to keep both quality and time of response within an acceptable period. In this paper we will analyze how the backlog affects test results and, in the end, the whole judicial system. In this study data from marijuana samples seized by the Federal District Civil Police in Brazil between the years 2013 and 2017 were tabulated and the results analyzed and discussed. In the last five years, the number of petitioned exams increased from 822 in February 2013 to 1358 in March 2018, representing an increase of 32% in 5 years, a rise of more than 6% per year. Meanwhile, our data shows that the number of performed exams did not grow at the same rate. Product numbers are stationed as using the actual technology scenario and analyses routine the laboratory is running in full capacity. Marijuana detection is the most prevalence exam required, representing almost 70% of all exams. In this study, data from 7,110 (seven thousand one hundred and ten) marijuana samples were analyzed. Regarding waiting time, most of the exams were performed not later than 60 days after receipt (77%). Although some samples waited up to 30 months before being examined (0,65%). When marijuana´s exam is delayed we notice the enlargement of inconclusive results using thin-layer chromatography (TLC). Our data shows that if a marijuana sample is stored for more than 18 months, inconclusive results rise from 2% to 7% and when if storage exceeds 30 months, inconclusive rates increase to 13%. This is probably because Cannabis plants and preparations undergo oxidation under storage resulting in a decrease in the content of Δ9-tetrahydrocannabinol ( Δ9-THC). An inconclusive result triggers other procedures that require at least two more working hours of our analysts (e.g., GC/MS analysis) and the report would be delayed at least one day. Those new procedures increase considerably the running cost of a forensic drug laboratory especially when the backlog is significant as inconclusive results tend to increase with waiting time. Financial aspects are not the only ones to be observed regarding backlog cases; there are also social issues as legal procedures can be delayed and prosecution of serious crimes can be unsuccessful. Delays may slow investigations and endanger public safety by giving criminals more time on the street to re-offend. This situation also implies a considerable cost to society as at some point, if the exam takes a long time to be performed, an inconclusive can turn into a negative result and a criminal can be absolved by flawed expert evidence.

Keywords: backlog, forensic laboratory, quality management, accreditation

Procedia PDF Downloads 105

Authors: Stavros Poulopoulos, Aphrodite Tetorou, Constantine Philippopoulos

Abstract:

Day after day more pharmaceutical compounds that are not efficiently removed by conventional treatment methods are found in treated wastewaters and drinking waters. Due to their refractory nature, they escape conventional wastewater treatment facilities, and thus advanced oxidation processes have to be utilized to effectively eliminate them. In the present study, the removal of Ibuprofen from aqueous solutions containing the commercial drug Algofren (non-steroidal, anti-inflammatory) using UV irradiation, hydrogen peroxide, titanium dioxide and ferric ions was examined. All experiments were conducted in a batch photoreactor operated for 120 min. The main target was to select the most effective operating conditions for the mineralization of the solutions treated. The combination of Fe(III)/ H₂O₂/UV proved to be very efficient in terms of total organic carbon removal and ibuprofen conversion. For solutions containing 5 mg/L ibuprofen and initial total carbon 51.1 mg/L, complete mineralization was achieved by means of 2.2 ppm Fe(III) and 333 mg/L H₂O₂.

Keywords: pharmaceuticals, photocatalytic, photo-Fenton, TiO₂

Procedia PDF Downloads 130

Authors: Navid Kaboudi, Ali Shayanfar

Abstract:

Introduction: Feeding infants with safe milk from the beginning of their life is an important issue. Drugs which are used by mothers can affect the composition of milk in a way that is not only unsuitable, but also toxic for infants. Consuming permeable drugs during that sensitive period by mother could lead to serious side effects to the infant. Due to the ethical restrictions of drug testing on humans, especially women, during their lactation period, computational approaches based on structural parameters could be useful. The aim of this study is to develop mechanistic models to predict the M/P ratio of drugs during breastfeeding period based on their structural descriptors. Methods: Two hundred and nine different chemicals with their M/P ratio were used in this study. All drugs were categorized into two groups based on their M/P value as Malone classification: 1: Drugs with M/P>1, which are considered as high risk 2: Drugs with M/P>1, which are considered as low risk Thirty eight chemical descriptors were calculated by ACD/labs 6.00 and Data warrior software in order to assess the penetration during breastfeeding period. Later on, four specific models based on the number of hydrogen bond acceptors, polar surface area, total surface area, and number of acidic oxygen were established for the prediction. The mentioned descriptors can predict the penetration with an acceptable accuracy. For the remaining compounds (N= 147, 158, 160, and 174 for models 1 to 4, respectively) of each model binary regression with SPSS 21 was done in order to give us a model to predict the penetration ratio of compounds. Only structural descriptors with p-value<0.1 remained in the final model. Results and discussion: Four different models based on the number of hydrogen bond acceptors, polar surface area, and total surface area were obtained in order to predict the penetration of drugs into human milk during breastfeeding period About 3-4% of milk consists of lipids, and the amount of lipid after parturition increases. Lipid soluble drugs diffuse alongside with fats from plasma to mammary glands. lipophilicity plays a vital role in predicting the penetration class of drugs during lactation period. It was shown in the logistic regression models that compounds with number of hydrogen bond acceptors, PSA and TSA above 5, 90 and 25 respectively, are less permeable to milk because they are less soluble in the amount of fats in milk. The pH of milk is acidic and due to that, basic compounds tend to be concentrated in milk than plasma while acidic compounds may consist lower concentrations in milk than plasma. Conclusion: In this study, we developed four regression-based models to predict the penetration class of drugs during the lactation period. The obtained models can lead to a higher speed in drug development process, saving energy, and costs. Milk/plasma ratio assessment of drugs requires multiple steps of animal testing, which has its own ethical issues. QSAR modeling could help scientist to reduce the amount of animal testing, and our models are also eligible to do that.

Keywords: logistic regression, breastfeeding, descriptors, penetration

Procedia PDF Downloads 54

Authors: Temesgen Geremew

Abstract:

Functionalized nanoparticles have emerged as a revolutionary class of materials with immense potential in various biomedical applications. These engineered nanoparticles possess unique properties tailored to interact with biological systems, offering unprecedented opportunities in drug delivery, imaging, diagnostics, and therapy. This research delves into the design, synthesis, and characterization of functionalized nanoparticles for targeted biomedical applications. The primary focus lies on developing nanoparticles with precisely controlled size, surface chemistry, and biocompatibility for specific medical purposes. The research will also explore the crucial interaction of these nanoparticles with biological systems, encompassing cellular uptake, biodistribution, and potential toxicity evaluation. The successful development of functionalized nanoparticles holds the promise to revolutionize various aspects of healthcare. This research aspires to contribute significantly to this advancement by providing valuable insights into the design and application of these versatile materials within the ever-evolving field of biomedicine.

Keywords: nanoparticles, biomedicals, cancer, biocompatibility

Procedia PDF Downloads 47

Authors: Tuji Jemal Ahmed

Abstract:

Food quality and safety challenges are prevalent in Ethiopia's food processing industry, which can have adverse effects on consumers' health and wellbeing. The country is known for its diverse range of agricultural products, which are essential to its economy. However, poor food quality and safety policies and management systems in the food processing industry have led to several health problems, foodborne illnesses, and economic losses. This paper aims to highlight the causes and effects of food safety and quality issues in the food processing industry of Ethiopia and discuss potential solutions to address these issues. One of the main causes of poor food quality and safety in Ethiopia's food processing industry is the lack of adequate regulations and enforcement mechanisms. The absence of comprehensive food safety and quality policies and guidelines has led to substandard practices in the food manufacturing process. Moreover, the lack of monitoring and enforcement of existing regulations has created a conducive environment for unscrupulous businesses to engage in unsafe practices that endanger the public's health. The effects of poor food quality and safety are significant, ranging from the loss of human lives, increased healthcare costs, and loss of consumer confidence in the food processing industry. Foodborne illnesses, such as diarrhea, typhoid fever, and cholera, are prevalent in Ethiopia, and poor food quality and safety practices contribute significantly to their prevalence. Additionally, food recalls due to contamination or mislabeling often result in significant economic losses for businesses in the food processing industry. To address these challenges, the Ethiopian government has begun to take steps to improve food quality and safety in the food processing industry. One of the most notable initiatives is the Ethiopian Food and Drug Administration (EFDA), which was established in 2010 to regulate and monitor the quality and safety of food and drug products in the country. The EFDA has implemented several measures to enhance food safety, such as conducting routine inspections, monitoring the importation of food products, and enforcing strict labeling requirements. Another potential solution to improve food quality and safety in Ethiopia's food processing industry is the implementation of food safety management systems (FSMS). An FSMS is a set of procedures and policies designed to identify, assess, and control food safety hazards throughout the food manufacturing process. Implementing an FSMS can help businesses in the food processing industry identify and address potential hazards before they cause harm to consumers. Additionally, the implementation of an FSMS can help businesses comply with existing food safety regulations and guidelines. In conclusion, improving food quality and safety policies and management systems in Ethiopia's food processing industry is critical to protecting public health and enhancing the country's economy. Addressing the root causes of poor food quality and safety and implementing effective solutions, such as the establishment of regulatory agencies and the implementation of food safety management systems, can help to improve the overall safety and quality of the country's food supply.

Keywords: food quality, food safety, policy, management system, food processing industry

Procedia PDF Downloads 64

Authors: Luphumlo Ncanywa, Paul Watts

Abstract:

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

Procedia PDF Downloads 181

Authors: Kalsoom Rani

Abstract:

Tobacco contains nicotine, which causes addiction to many toxic chemicals. In the world, people consume it in the form of smoke, chew, and sniffing, smoke of it is composed of almost 7000 active chemicals, which are very harmful to human health as well as for eye health, inhalation of tobacco smoke and fumes can accelerate and cause many blinding eye diseases. Dry eye and smoking have not been covered extensively in researches; more studies are required to unveil the relationship between smoking and dry eye. This study was conducted to determine the quantity and quality of tears in smokers. 60 subjects participated in the study, which was divided into two groups on the basis of consumption of cigarettes per day with age matched non smokers of 15-50 years. All participants have gone through a study based questioner, eye examination, and diagnostic 'Dry Eye Tests' for evaporative tears evaluation and measurement of basal tear secretion. Subjects were included in the criteria of 10 cigarettes per day with a minimum duration of 1 year; passive smokers for control groups were excluded. The study was carried out in a Medina Teaching Hospital, Faisalabad, Pakistan, ophthalmology department for the duration of 8 months. Mean values for tear break up time (TBUT), was reported 10sec with SD of +3.74 in controlled group, 5sec with SD + 2.32 in smokers and 4sec SD +3.77 heavy smokers in right eye (RE) and left eye (LE) 10.35sec with SD of +3.88 in controlled 5sec with SD + 2.3 in smokers and much reduced TBUT in heavy smokers was 3.85sec SD+2.20. Smoking has a very strong association with TRUT with a significance of P=.00 both eyes. Mean Schirmer-I value of the subjects was reported 12.6mm with SD + 8.37 in RE and 12.59mm with SD + 8.96 LE. The mean Schirmer-II test value was reported in the right, and left eye with a mean value for control was 20.23mm with SD + 8.93, 20.75mm with SD + 8.84 respectively, and in Smokers 9.90mm with SD + 5.74, and 10.07mm with SD + 6.98, and in heavy smokers 7.7mm, SD + 3.22 and 6.9, SD + 3.50 mm, association with smoking showed p=.001 in RE and .003 in LE. Smoking has deteriorated effect on both evaporative tear and aqueous tear secretion and causing symptoms of dry eye burning, itching, redness, and watering with epithelial cell damage.

Keywords: tear break-up time, basal tear secretion, smokers, dry eye

Procedia PDF Downloads 115