Search results for: adverse drug reactions

Authors: Jianuo Sun, Jinghan Wang, Sirui Zhang, Chenhan Xu, Hongxia Hao, Hong Zhou

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In recent years, the diversification and industrialization of drug-related crimes have posed significant threats to public health and safety globally. The widespread and increasingly younger demographics of drug users and the persistence of drug-impaired driving incidents underscore the urgency of this issue. Drug detection, a specialized forensic activity, is pivotal in identifying and analyzing substances involved in drug crimes. It relies on pharmacological and chemical knowledge and employs analytical chemistry and modern detection techniques. However, current drug detection methods are limited by their inability to perform semi-quantitative, real-time field analyses. They require extensive, complex laboratory-based preprocessing, expensive equipment, and specialized personnel and are hindered by long processing times. This study introduces an alternative approach using nucleic acid aptamers and Aggregation-Induced Emission (AIE) technology. Nucleic acid aptamers, selected artificially for their specific binding to target molecules and stable spatial structures, represent a new generation of biosensors following antibodies. Rapid advancements in AIE technology, particularly in tetraphenyl ethene-based luminous, offer simplicity in synthesis and versatility in modifications, making them ideal for fluorescence analysis. This work successfully synthesized, isolated, and purified an AIE molecule and constructed a probe comprising the AIE molecule, nucleic acid aptamers, and exonuclease for cocaine detection. The probe demonstrated significant relative fluorescence intensity changes and selectivity towards cocaine over other drugs. Using 4-Butoxytriethylammonium Bromide Tetraphenylethene (TPE-TTA) as the fluorescent probe, the aptamer as the recognition unit, and Exo I as an auxiliary, the system achieved rapid detection of cocaine within 5 mins in aqueous and urine, with detection limits of 1.0 and 5.0 µmol/L respectively. The probe-maintained stability and interference resistance in urine, enabling quantitative cocaine detection within a certain concentration range. This fluorescent sensor significantly reduces sample preprocessing time, offers a basis for rapid onsite cocaine detection, and promises potential for miniaturized testing setups.

Keywords: drug detection, aggregation-induced emission (AIE), nucleic acid aptamer, exonuclease, cocaine

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Authors: Sinead Creedon, Anna Trace

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Nurses were the most exposed of all frontline healthcare workers during the COVID-19 pandemic. Mainly female nurses working in the acute hospital sector formed the frontline defence in the Irish health service. They faced it with resilience and courage despite exposure to risk of burnout and threats to their mental health and wellbeing. Gaining an understanding of the nurses’ journey in adapting to this harsh climate could inform positive psychology interventions and / or support staff such as senior hospital managers in an adverse work situation. Furthermore, it would strengthen our insight and theoretical understanding on the use of positive psychology interventions in adverse work conditions. An interpretative phenomenological analysis was carried out to gain insight into how nurses adapted to the changing work environment during the pandemic. Online semi-structured interviews were done with six experienced female nurses who were all redeployed to the frontline from their own roles. The three themes representing the nurses’ journey were the Protection of Sacrificial Self, The Fortifying Effect of Us, and Critical Turning Points & Growth. Nurses revitalised themselves by creating a sense of ‘us’ to help them face a harsh climate against others, which enabled additional critical turning points. This study further enriches our understanding of personal growth and trauma in adverse work conditions by including an exploration of what sacrificial commitment adds to our understanding of physical and moral courage.

Keywords: COVID-19, nurses, positive psychology, resilience, sacrificial commitment, supports

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Authors: Vatsal M. Patel, Navin B. Patel

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The present studies deal with the developing a series bearing a diphenyl ethers nucleus using structure-based drug design concept. A newer series of diphenyl ether based azetidinone namely N-(3-chloro-2-oxo-4-(3-phenoxyphenyl)azetidin-1-yl)-2-(substituted amino)acetamide (2a-j) have been synthesized by condensation of m-phenoxybenzaldehyde with 2-(substituted-phenylamino)acetohydrazide followed by the cyclisation of resulting Schiff base (1a-j) by conventional method as well as microwave heating approach as a part of an environmentally benign synthetic protocol. All the synthesized compounds were characterized by spectral analysis and were screened for in vitro antimicrobial, antitubercular and antiprotozoal activity. The compound 2f was found to be most active M. tuberculosis (6.25 µM) MIC value in the primary screening as well as this same derivative has been found potency against L. mexicana and T. cruzi with MIC value 2.09 and 6.69 µM comparable to the reference drug Miltefosina and Nifurtimox. To provide understandable evidence to predict binding mode and approximate binding energy of a compound to a target in the terms of ligand-protein interaction, all synthesized compounds were docked against an enoyl-[acyl-carrier-protein] reductase of M. tuberculosis (PDB ID: 4u0j). The computational studies revealed that azetidinone derivatives have a high affinity for the active site of enzyme which provides a strong platform for new structure-based design efforts. The Lipinski’s parameters showed good drug-like properties and can be developed as an oral drug candidate.

Keywords: antimycobacterial, antiprotozoal, azetidinone, diphenylether, docking, microwave

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Authors: Michalina Aniola, Andrzej Katrusiak

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4,4-Bipyridine is an important compound often used in chemical practice and more recently frequently applied for designing new metal organic framework (MoFs). Here we present a systematic high-pressure study of its hydrobromide salt. 4,4-Bipyridine hydrobromide monohydrate, 44biPyHBrH₂O, at ambient-pressure is orthorhombic, space group P212121 (phase a). Its hydrostatic compression shows that it is stable to 1.32 GPa at least. However, the recrystallization above 0.55 GPa reveals a new hidden b-phase (monoclinic, P21/c). Moreover, when the 44biPyHBrH2O is heated to high temperature the chemical reactions of this compound in methanol solution can be observed. High-pressure experiments were performed using a Merrill-Bassett diamond-anvil cell (DAC), modified by mounting the anvils directly on the steel supports, and X-ray diffraction measurements were carried out on a KUMA and Excalibur diffractometer equipped with an EOS CCD detector. At elevated pressure, the crystal of 44biPyHBrH₂O exhibits several striking and unexpected features. No signs of instability of phase a were detected to 1.32 GPa, while phase b becomes stable at above 0.55 GPa, as evidenced by its recrystallizations. Phases a and b of 44biPyHBrH2O are partly isostructural: their unit-cell dimensions and the arrangement of ions and water molecules are similar. In phase b the HOH-Br- chains double the frequency of their zigzag motifs, compared to phase a, and the 44biPyH+ cations change their conformation. Like in all monosalts of 44biPy determined so far, in phase a the pyridine rings are twisted by about 30 degrees about bond C4-C4 and in phase b they assume energy-unfavorable planar conformation. Another unusual feature of 44biPyHBrH2O is that all unit-cell parameters become longer on the transition from phase a to phase b. Thus the volume drop on the transition to high-pressure phase b totally depends on the shear strain of the lattice. Higher temperature triggers chemical reactions of 44biPyHBrH2O with methanol. When the saturated methanol solution compound precipitated at 0.1 GPa and temperature of 423 K was required to dissolve all the sample, the subsequent slow recrystallization at isochoric conditions resulted in disalt 4,4-bipyridinium dibromide. For the 44biPyHBrH2O sample sealed in the DAC at 0.35 GPa, then dissolved at isochoric conditions at 473 K and recrystallized by slow controlled cooling, a reaction of N,N-dimethylation took place. It is characteristic that in both high-pressure reactions of 44biPyHBrH₂O the unsolvated disalt products were formed and that free base 44biPy and H₂O remained in the solution. The observed reactions indicate that high pressure destabilized ambient-pressure salts and favors new products. Further studies on pressure-induced reactions are carried out in order to better understand the structural preferences induced by pressure.

Keywords: conformation, high-pressure, negative area compressibility, polymorphism

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Authors: Durata Haciu, Ozgur Birer

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Zinc acetate solution is sonicated at high power in water and in ethanol in the absence and presence of various peroxides. In the absence of peroxides, the products are zinc oxide and layered hydroxy zinc acetate in water and in ethanol, respectively. Layered basic zinc acetate are prepared for the first time using sonochemical methods. The addition of peroxides alters the reaction mechanisms. In water, insoluble peroxides produce zinc oxides while the water soluble peroxide, i.e.hydrogen peroxide, completely destroyed the structure and casted a doubt on the accepted peroxide initiated mechanism of reactions. In ethanol,peroxide addition caused the reaction mechanism to change and some oxide formation is observed. The reaction mechanism is sensitive to water/ethanol amounts as well as the peroxide to zinc ion mole ratio.Thin zinc oxide wafers (ca. 30 nm) with band gaps of 3.24 eV were obtained.

Keywords: ultrasound, zinc oxide, hydroxy zinc acetate, fenton, peroxide initiation

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Authors: Bharti Jain, Rajeev Jain, Abuzar Kabir, Torki Zughaibi, Shweta Sharma

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Drug-facilitated crimes (DFCs) entail the use of a single drug or a mixture of drugs to render a victim unable. Traditionally, biological samples have been gathered from victims and conducted analysis to establish evidence of drug administration. Nevertheless, the rapid metabolism of various drugs and delays in analysis can impede the identification of such substances. For this, the present article describes a rapid, sustainable, highly efficient and miniaturized protocol for the identification and quantification of three sedative-hypnotic drugs, namely diazepam, chlordiazepoxide and ketamine in alcoholic beverages and complex food samples (cream of biscuit, flavored milk, juice, cake, tea, sweets and chocolate). The methodology involves utilizing fabric phase sorptive extraction (FPSE) to extract diazepam (DZ), chlordiazepoxide (CDP), and ketamine (KET). Subsequently, the extracted samples are subjected to analysis using gas chromatography-mass spectrometry (GC-MS). Several parameters, including the type of membrane, pH, agitation time and speed, ionic strength, sample volume, elution volume and time, and type of elution solvent, were screened and thoroughly optimized. Sol-gel Carbowax 20M (CW-20M) has demonstrated the most effective extraction efficiency for the target analytes among all evaluated membranes. Under optimal conditions, the method displayed linearity within the range of 0.3–10 µg mL–¹ (or µg g–¹), exhibiting a coefficient of determination (R2) ranging from 0.996–0.999. The limits of detection (LODs) and limits of quantification (LOQs) for liquid samples range between 0.020-0.069 µg mL-¹ and 0.066-0.22 µg mL-¹, respectively. Correspondingly, the LODs for solid samples ranged from 0.056-0.090 µg g-¹, while the LOQs ranged from 0.18-0.29 µg g-¹. Notably, the method showcased better precision, with repeatability and reproducibility both below 5% and 10%, respectively. Furthermore, the FPSE-GC-MS method proved effective in determining diazepam (DZ) in forensic food samples connected to drug-facilitated crimes (DFCs). Additionally, the proposed method underwent evaluation for its whiteness using the RGB12 algorithm.

Keywords: drug facilitated crime, fabric phase sorptive extraction, food forensics, white analytical chemistry

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Authors: Daniel C. Bonzo

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Practical considerations lead to the use of unit of analysis within subjects, e.g., bleeding episodes or treatment-related adverse events, in rare disease settings. This is coupled with data augmentation techniques such as extrapolation to enlarge the subject base. In general, one can think about extrapolation of data as extending information and conclusions from one estimand to another estimand. This approach induces hierarchichal clustered data with varying cluster sizes. Extrapolation of clinical trial data is being accepted increasingly by regulatory agencies as a means of generating data in diverse situations during drug development process. Under certain circumstances, data can be extrapolated to a different population, a different but related indication, and different but similar product. We consider here the problem of estimation (point and interval) using a mixed-models approach under an extrapolation. It is proposed that estimators (point and interval) be constructed using weighting schemes for the clusters, e.g., equally weighted and with weights proportional to cluster size. Simulated data generated under varying scenarios are then used to evaluate the performance of this approach. In conclusion, the evaluation result showed that the approach is a useful means for improving statistical inference in rare disease settings and thus aids not only signal detection but risk-benefit evaluation as well.

Keywords: clustered data, estimand, extrapolation, mixed model

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Authors: Anshu Gupta, Charu Gupta

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Background: Punjab, a border state in India has achieved notoriety world over for its drug abuse problem. People right from school kids to elderly are hooked to drugs. This pattern of substance abuse is prevalent in both cities and villages alike. Excess of younger population in India has further aggravated the situation. It is feared that the benefits of India’s economic growth may well be negated by the rising substance abuse especially in this part of the country. It is quite evident that the pattern of substance abuse tends to change over time which is an impediment in the formulation of effective strategies to tackle this issue. Aim: Purpose of the study was to ascertain the change in the pattern of drug abuse for two consecutive years in the out patient department (OPD) population. Method: The study population comprised of all the patients reporting for deaddiction to the psychiatry outpatient department over a period of twelve months for two consecutive years. All the patients were evaluated by the International Classification of Diseases; 10 criteria for substance abuse/dependence. Results: A considerably high prevalence of substance abuse was present in the Indian population. In general, there was an increase in prevalence from first to the second year, especially among the female population. Increase in prevalence of substance abuse appeared to be more prominent among the younger age group of both the sexes. A significant increase in intravenous drug abuse was observed. Peer pressure and parental imitation were the major factors fueling substance abuse. Precipitation or fear of withdrawal symptoms was the major factor preventing abstinence. Substance abuse had a significant effect on the health and interpersonal relations of these patients. Summary/Conclusion: Drug abuse and addiction are on the rise throughout India. Changing cultural values, increasing economic stress and dwindling supportive bonds appear to be leading to initiation of substance abuse. Need of the hour is to formulate a comprehensive strategy to bring about an overall reduction in the use of drugs.

Keywords: deaddiction, peer pressure, parental imitation, substance abuse/dependance

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Authors: Melaku Takele Abate, Abbi Lemma Wodajo, Adula Bekele Hunde

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This study aimed at exploring mathematics teachers' reactions, learning, school leaders’ support, and use of the Lesson Study for Transformative Assessment (LSforTA) program ideas in practice. The LSforTA program was new, and therefore, a local and grounded approach was needed to examine teachers’ knowledge and skills acquired using LSforTA. So, a design-based research approach was selected to evaluate and refine the LSforTA approach. The results showed that LSforTA increased teachers' knowledge and use of different levels of mathematics assessment tasks. The program positively affected teachers' practices of transformative assessment and enhanced their knowledge and skills in assessing students in a transformative way. The paper concludes how the LSforTA procedures were adapted in response to this evaluation and provides suggestions for future development and research.

Keywords: classroom assessment, feedback practices, lesson study, mathematics, design-based research

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Authors: Mirko Ante, Şeniz Sörgel, Andreas Bund

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Li-S- (Lithium-Sulfur-) battery systems provide very high specific gravimetric energy (2600 Wh/kg) and volumetric energy density (2800Wh/l). Hence, Li-S batteries are one of the key technologies for both the upcoming electromobility and stationary applications. Furthermore, the Li-S battery system is potentially cheap and environmentally benign. However, the technical implementation suffers from cycling stability, low charge and discharge rates and incomplete understanding of the complex polysulfide reaction mechanism. The aim of this work is to develop an effective electrocatalyst for the polysulfide reactions so that the electrode kinetics of the sulfur half-cell will be improved. Accordingly, the overvoltage will be decreased, and the efficiency of the cell will be increased. An enhanced electroactive surface additionally improves the charge and discharge rates. To reach this goal, functionalized electrocatalytic coatings are investigated to accelerate the kinetics of the polysulfide reactions. In order to determine a suitable electrocatalyst, apparent exchange current densities of a variety of materials (Ni, Co, Pt, Cr, Al, Cu, ITO, stainless steel) have been evaluated in a polysulfide containing electrolyte by potentiodynamic measurements and a Butler-Volmer fit including diffusion limitation. The samples have been examined by Scanning Electron Microscopy (SEM) after the potentiodynamic measurements. Up to now, our work shows that cobalt is a promising material with good electrocatalytic properties for the polysulfide reactions and good chemical stability in the system. Furthermore, an electrodeposition from a modified Watt’s nickel electrolyte with a sulfur source seems to provide an autocatalytic effect, but the electrocatalytic behavior decreases after several cycles of the current-potential-curve.

Keywords: electrocatalyst, energy storage, lithium sulfur battery, sulfur electrode materials

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Authors: Simona Dostalova, Dita Munzova, Ana Maria Jimenez Jimenez, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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The boom of nanomedicine in recent years has led to the development of numerous new nanomaterials that can be used as nanocarriers in the drug delivery. These nanocarriers can either be synthetic or natural-based. The disadvantage of many synthetic nanocarriers is their toxicity in patient’s body. Protein cages that can naturally be found in human body do not exhibit such disadvantage. However, the release of cargo from some protein cages in target cells can be problematic. As a special type of protein cages can serve the capsid of many viruses, including phage. Phages infect bacterial cells; therefore they are not harmful to human cells. The targeting of phage particles to cancer cells can be solved by producing of empty phage capsids during which the targeting moieties (e.g. peptides) can be cloned into genes of phage capsid to decorate its surface. Moreover, the produced capsids do not contain viral nucleic acid and are therefore not infectious to beneficial bacteria in the patient’s body. The protein cage composed of viral capsid is larger than other frequently used apoferritin cage but its size is still small enough to benefit from passive targeting by Enhanced Permeability and Retention effect. In this work, bacteriophage λ was used, both whole and its empty capsid for delivery of different cytotoxic drugs (cisplatin, carboplatin, oxaliplatin, etoposide and doxorubicin). Large quantities of phage λ were obtained from phage λ-producing strain of E. coli cultivated in medium with 0.2 % maltose. After killing of E. coli with chloroform and its removal by centrifugation, the phage was concentrated by ultracentrifugation at 130 000 g and 4 °C for 3 h. The encapsulation of the drugs was performed by infusion method and four different concentrations of the drugs were encapsulated (200; 100; 50; 25 µg/ml). Free molecules of drugs were removed by dialysis. The encapsulation was verified using spectrophotometric and electrochemical methods. The amount of encapsulated drug linearly increased with the amount of applied drug (determination coefficient R2=0.8013). 76% of applied drug was encapsulated in phage λ particles (concentration of 10 µg/ml), even with the highest applied concentration of drugs, 200 µg/ml. Only 1% of encapsulated drug was detected in phage DNA. Similar results were obtained with encapsulation in phage empty capsid. Therefore, it can be concluded that the encapsulation of drugs into phage particles is efficient and mostly occurs by interaction of drugs with protein capsid.

Keywords: cytostatics, drug delivery, nanocarriers, phage capsid

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Authors: Shahab Azimi, Siamak Arzanpour, Anahita Sayyar

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Asthma and Chronic obstructive pulmonary disease (COPD) are common lung diseases that have a significant global impact. Pressurized metered dose inhalers (pMDIs) are widely used for treatment, but they can have limitations such as high medication release speed resulting in drug deposition in the mouth or oral cavity and difficulty achieving proper synchronization with inhalation by users. Spacers are add-on devices that improve the efficiency of pMDIs by reducing the release speed and providing space for aerosol particle breakup to have finer and medically effective medication. The aim of this study is to optimize the size and cylindrical shape of spacers to enhance their drug delivery performance. The study was based on fluid dynamics theory and employed Ansys software for simulation and optimization. Results showed that optimization of the spacer's geometry greatly influenced its performance and improved drug delivery. This study provides a foundation for future research on enhancing the efficiency of inhalation therapy for lung diseases.

Keywords: asthma, COPD, pressurized metered dose inhalers, spacers, CFD, shape optimization

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Authors: Yasser Gaber, Mohamed Ismail, Serena Bisagni, Mohamad Takwa, Rajni Hatti-Kaul

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Enzymes are safe and selective catalysts. They skillfully catalyze chemical reactions; however, the native form is not usually suitable for industrial applications. Enzymes are therefore engineered by several techniques to meet the required catalytic task. Clopidogrel is recorded among the five best selling pharmaceutical in 2010 under the brand name Plavix. The commonly used route for production of the drug on an industrial scale is the synthesis of the racemic mixture followed by diastereomeric resolution to obtain the pure S isomer. The process consumes a lot of solvents and chemicals. We have evaluated a biocatalytic cleaner approach for asymmetric hydrolysis of racemic clopidogrel. Initial screening of a selected number of hydrolases showed only one enzyme EST to exhibit activity and selectivity towards the desired stereoisomer. As the crude EST is a mixture of several isoenzymes, a homology model of EST-1 was used in molecular dynamic simulations to study the interaction of the enzyme with R and S isomers of clopidogrel. Analysis of the geometric hindrances of the tetrahedral intermediates revealed a potential site for mutagenesis in order to improve the activity and the selectivity. Single point mutation showed dramatic increase in activity and inversion of the enantioselectivity (400 fold change in E value).

Keywords: biocatalysis, biotechnology, enzyme, protein engineering, molecular modeling

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Authors: Yasin I. Tayem, Jamil Ahmed, Mahmood Bahzad, Abdullah Alnama, Fahad Al Asfoor, Mahmood A. Jalil, Mohammed Radhi, Ahmed Alenezi, Khalid A. J. Al-Khaja

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Drug-drug interactions (DDIs) represent a significant cause of patient’s morbidity and mortality. The rate of DDIs is rapidly increasing worldwide with the increasing proportion of ageing population and frequent requirement of polypharmacy-prescription of multiple drugs to treat comorbidities. Prescribing physicians are responsible for checking their prescriptions for the presence and severity of DDIs. However, since a large number of new drugs are approved and marketed every year, new interactions between medications are increasingly reported. Consequently, it is no longer practical for physicians to rely only upon their previous knowledge of medicine to avoid potential DDIs. The aim of this study was to explore the perceptions of physicians working at primary healthcare centers in Bahrain towards DDIs and how they manage them during their practice. Methodology: In this cross-sectional study, physicians working at all governmental primary healthcare centers in Bahrain were invited to voluntarily, privately and anonymously respond to a self-administered questionnaire. The questionnaire aims to assess their self-reported knowledge of DDIs and how they check for them in their practice. The participants were requested to provide socio demographic data and information related to their attitudes towards DDIs including strategies they employ for detecting and managing them, and their awareness of drugs which commonly cause DDIs. At the end of the questionnaire, an open-ended item was added to allow participants to further add any comment. Findings and Conclusions: The study is going on currently, and the results and conclusions will be presented at the conference.

Keywords: awareness, drug interactions, health centres, physicians

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Authors: M. Helen

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Chemical graph serves as a convenient model for any real or abstract chemical system. Dendrimers are novel three dimensional hyper branched globular nanopolymeric architectures. Drug delivery scientists are especially enthusiastic about possible utility of dendrimers as drug delivery tool. Dendrimers like poly L lysine (PLL), poly-propylene imine (PPI) and poly-amidoamine (PAMAM), etc., are used as gene carrier in drug delivery system because of their chemical characteristics. These characteristics of chemical compounds are analysed using topological indices (invariants under graph isomorphism) such as Wiener index, Zagreb index, etc., Prof. V. R. Kulli motivated by the application of Zagreb indices in finding the total π energy and derived Gourava indices which is an improved version over Zagreb indices. In this paper, we study the structure of PLL-Dendrimer that has the following applications: reduction in toxicity, colon delivery, and topical delivery. Also, we determine first and second Gourava indices, first and second hyper Gourava indices, product and sum connectivity Gourava indices for PLL-Dendrimer. Gourava Indices have found applications in Quantitative Structure-Property Relationship (QSPR)/ Quantitative Structure-Activity Relationship (QSAR) studies.

Keywords: connectivity Gourava indices, dendrimer, Gourava indices, hyper GouravaG indices

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Authors: Rajni Kant Panik

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The aim of the present study was to develop and evaluate mupirocin loaded nanoparticle incorporated into hydrogel as an infected wound healer. Incorporated Nanoparticle in hydrogel provides a barrier that effectively prevents the contamination of the wound and further progression of infection to deeper tissues. Hydrogel creates moist healing environment on wound space with good fluid absorbance. Nanoparticles were prepared by double emulsion solvent evaporation method using different ratios of PLGA polymer and the hydrogels was developed using sodium alginate and gelatin. Further prepared nanoparticles were then incorporated into the hydrogels. The formulations were characterized by FT-IR and DSC for drug and polymer compatibility and surface morphology was studied by TEM. Nanoparticle hydrogel were evaluated for their size, shape, encapsulation efficiency and for in vitro studies. The FT-IR and DSC confirmed the absence of any drug polymer interaction. The average size of Nanoparticle was found to be in range of 208.21-412.33 nm and shape was found to be spherical. The maximum encapsulation efficiency was found to be 69.03%. The in vitro release profile of Nanoparticle incorporated hydrogel formulation was found to give sustained release of drug. Antimicrobial activity testing confirmed that encapsulated drug preserve its effectiveness. The stability study confirmed that the formulation prepared were stable. Present study complements our finding that mupirocin loaded Nanoparticle incorporated into hydrogel has the potential to be an effective and safe novel addition for the release of mupirocin in sustained manner, which may be a better option for the management of wound. These finding also supports the progression of antibiotic via hydrogel delivery system is a novel topical dosage form for the management of wound.

Keywords: hydrogel, nanoparticle, PLGA, wound healing

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Authors: Arpita Roy, Navneeta Bharadvaja

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Cancer is an uncontrolled growth of abnormal cells in the body. It is one of the most serious diseases on which extensive research work has been going on all over the world. Structure-based drug designing is a computational approach which helps in the identification of potential leads that can be used for the development of a drug. Plumbagin is a naphthoquinone derivative from Plumbago zeylanica roots and belongs to one of the largest and diverse groups of plant metabolites. Anticancer and antiproliferative activities of plumbagin have been observed in animal models as well as in cell cultures. Plumbagin shows inhibitory effects on multiple cancer-signaling proteins; however, the binding mode and the molecular interactions have not yet been elucidated for most of these protein targets. In this investigation, an attempt to provide structural insights into the binding mode of plumbagin against four cancer receptors using molecular docking was performed. Plumbagin showed minimal energy against targeted cancer receptors, therefore suggested its stability and potential towards different cancers. The least binding energies of plumbagin with COX-2, TACE, and CDK6 are -5.39, -4.93, -and 4.81 kcal/mol, respectively. Comparison studies of plumbagin with different receptors showed that it is a promising compound for cancer treatment. It was also found that plumbagin obeys the Lipinski’s Rule of 5 and computed ADMET properties which showed drug likeliness and improved bioavailability. Since plumbagin is from a natural source, it has reduced side effects, and these results would be useful for cancer treatment.

Keywords: cancer, receptor, plumbagin, docking

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Authors: Aasaithambi Kalaiselvi, Michael Gabriel Paulraj, Ekambaram Nakkeeran

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Emergences of mosquito vector-borne diseases are considered as a perpetual problem globally in tropical countries. The outbreak of several diseases such as chikungunya, zika virus infection and dengue fever has created a massive threat towards the living population. Frequent usage of synthetic insecticides like Dichloro Diphenyl Trichloroethane (DDT) eventually had its adverse harmful effects on humans as well as the environment. Since there are no perennial vaccines, prevention, treatment or drugs available for these pathogenic vectors, WHO is more concerned in eradicating their breeding sites effectively without any side effects on humans and environment by approaching plant-derived natural eco-friendly bio-insecticides. The aim of this study is to investigate the larvicidal potency of Cinnamomum verum essential oil (CEO) loaded niosomes. Cholesterol and surfactant variants of Span 20, 60 and 80 were used in synthesizing CEO loaded niosomes using Transmembrane pH gradient method. The synthesized CEO loaded niosomes were characterized by Zeta potential, particle size, Fourier Transform Infrared Spectroscopy (FT-IR), GC-MS and SEM analysis to evaluate charge, size, functional properties, the composition of secondary metabolites and morphology. The Z-average size of the formed niosomes was 1870.84 nm and had good stability with zeta potential -85.3 meV. The entrapment efficiency of the CEO loaded niosomes was determined by UV-Visible Spectrophotometry. The bio-potency of CEO loaded niosomes was treated and assessed against gram-positive (Bacillus subtilis) and gram-negative (Escherichia coli) bacteria and fungi (Aspergillus fumigatus and Candida albicans) at various concentrations. The larvicidal activity was evaluated against II to IV instar larvae of Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus at various concentrations for 24 h. The mortality rate of LC₅₀ and LC₉₀ values were calculated. The results exhibited that CEO loaded niosomes have greater efficiency against mosquito larvicidal activity. The results suggest that niosomes could be used in various applications of biotechnology and drug delivery systems with greater stability by altering the drug of interest.

Keywords: Cinnamomum verum, niosomes, entrapment efficiency, bactericidal and fungicidal, mosquito larvicidal activity

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Authors: Swapnila V. Vanshiv, Hemant P. Joshi, Atul B. Aware

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Current study illustrates the formulation of floating microspheres for purpose of gastroretention of Dipyridamole which shows pH dependent solubility, with the highest solubility in acidic pH. The formulation involved hollow microsphere preparation by using solvent evaporation technique. Concentrations of rate controlling polymer, hydrophilic polymer, internal phase ratio, stirring speed were optimized to get desired responses, namely release of Dipyridamole, buoyancy of microspheres, entrapment efficiency of microspheres. In the formulation, the floating microspheres were prepared by using ethyl cellulose as release retardant and HPMC as a low density hydrophilic swellable polymer. Formulated microspheres were evaluated for their physical properties such as particle size and surface morphology by optical microscopy and SEM. Entrapment efficiency, floating behavior and drug release study as well the formulation was evaluated for in vivo gastroretention in rabbits using gamma scintigraphy. Formulation showed 75% drug release up to 10 hr with entrapment efficiency of 91% and 88% buoyancy till 10 hr. Gamma scintigraphic studies revealed that the optimized system was retained in the gastric region (stomach) for a prolonged period i.e. more than 5 hr.

Keywords: Dipyridamole microspheres, gastroretention, HPMC, optimization method

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Authors: Sandipika Gupta

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Objective: Due to admirably low 30-day mortality rates for paediatric cardiac surgery, it is now pertinent to turn towards more intermediate-length outcomes such as morbidities closely associated with these surgeries. One such morbidity, major adverse events (MAE) comprises a group of adverse outcomes associated with paediatric cardiac surgery (e.g. cardiac arrest, major haemorrhage). Methods: This is a retrospective study that analysed the incidence and impact of MAE which was the primary outcome in the UK population. The data was collected in 5 centres between October 2015 and June 2017, amassing 3090 surgical episodes. The incidence and risk factors for MAE, were assessed through descriptive statistical analyses and multivariate logistic regression. The secondary outcomes of life status at 6 months and the length of hospital stay were also evaluated to understand the impact of MAE on patients. Results: Out of 3090 episodes, 134 (4.3%) had a postoperative MAE. The majority of the episodes were in: neonates (47%, P<0.001), high-risk cardiac diagnosis groups (20.1%, P<0.001), episodes with longer 5mes on the bypass (72.4%, P<0.001) and urgent surgeries (57.9%, P<0.001). Episodes reporting MAE also reported longer lengths of stay in hospital (29 days vs 9 days, P<0.001). Furthermore, patients experiencing MAE were at a higher risk of mortality at the 6-month life status check (mortality rates: 29.2% vs 2%, P<0.001).Conclusions: Key risk factors were identified. An important negative impact of MAE was found for patients. The identified risk factors could be used to profile and flag at-risk patients. Monitoring of MAE rates and closer investigation into the care pathway before and after individual MAEs in children’s heart units may lead to a reduction in these terrible events.

Keywords:

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Authors: Norma Binti Alias, Che Rahim Che The, Norfarizan Mohd Said, Sakinah Abdul Hanan, Akhtar Ali

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This paper discusses on the transportation of magnetic drug targeting through blood within vessels, tissues and cells. There are three integrated mathematical models to be discussed and analyze the concentration of drug and blood flow through magnetic nanoparticles. The cell therapy brought advancement in the field of nanotechnology to fight against the tumors. The systematic therapeutic effect of Single Cells can reduce the growth of cancer tissue. The process of this nanoscale phenomena system is able to measure and to model, by identifying some parameters and applying fundamental principles of mathematical modeling and simulation. The mathematical modeling of single cell growth depends on three types of cell densities such as proliferative, quiescent and necrotic cells. The aim of this paper is to enhance the simulation of three types of models. The first model represents the transport of drugs by coupled partial differential equations (PDEs) with 3D parabolic type in a cylindrical coordinate system. This model is integrated by Non-Newtonian flow equations, leading to blood liquid flow as the medium for transportation system and the magnetic force on the magnetic nanoparticles. The interaction between the magnetic force on drug with magnetic properties produces induced currents and the applied magnetic field yields forces with tend to move slowly the movement of blood and bring the drug to the cancer cells. The devices of nanoscale allow the drug to discharge the blood vessels and even spread out through the tissue and access to the cancer cells. The second model is the transport of drug nanoparticles from the vascular system to a single cell. The treatment of the vascular system encounters some parameter identification such as magnetic nanoparticle targeted delivery, blood flow, momentum transport, density and viscosity for drug and blood medium, intensity of magnetic fields and the radius of the capillary. Based on two discretization techniques, finite difference method (FDM) and finite element method (FEM), the set of integrated models are transformed into a series of grid points to get a large system of equations. The third model is a single cell density model involving the three sets of first order PDEs equations for proliferating, quiescent and necrotic cells change over time and space in Cartesian coordinate which regulates under different rates of nutrients consumptions. The model presents the proliferative and quiescent cell growth depends on some parameter changes and the necrotic cells emerged as the tumor core. Some numerical schemes for solving the system of equations are compared and analyzed. Simulation and computation of the discretized model are supported by Matlab and C programming languages on a single processing unit. Some numerical results and analysis of the algorithms are presented in terms of informative presentation of tables, multiple graph and multidimensional visualization. As a conclusion, the integrated of three types mathematical modeling and the comparison of numerical performance indicates that the superior tool and analysis for solving the complete set of magnetic drug delivery system which give significant effects on the growth of the targeted cancer cell.

Keywords: mathematical modeling, visualization, PDE models, magnetic nanoparticle drug delivery model, drug release model, single cell effects, avascular tumor growth, numerical analysis

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Authors: Kalyan Koganti

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Background: In India, platelet transfusions are given to large no. of patients suffering from dengue due to the fear of bleeding especially when the platelet counts are low. Though many patients do not bleed when the platelet count falls to less than 20,000, certain patients bleed even if the platelet counts are more than 20,000 without any comorbid condition (like gastrointestinal ulcer) in the past. This fear has led to huge amounts of unnecessary platelet transfusions which cause significant economic burden to low and middle-income countries like India and also sometimes these transfusions end with transfusion-related adverse reactions. Objective: To identify the role of Activated Partial Thromboplastin Time (APTT) in comparison with thrombocytoenia as an indicator to assess the real need of platelet transfusions. Method: A prospective study was conducted at a hospital in South India which included 176 admitted cases of dengue confirmed by immunochromatography. APTT was performed in all these patients along with platelet count. Cut off values of > 60 seconds for APTT and < 20,000 for platelet count were considered to assess the bleeding manifestations. Results: Among the total 176 patients, 56 patients had bleeding manifestations like malena, hematuria, bleeding gums etc. APTT > 60 seconds had a sensitivity and specificity of 93% and 90% respectively in identifying bleeding manifestations where as platelet count of < 20,000 had a sensitivity and specificity of 64% and 73% respectively. Conclusion: Elevated APTT levels can be considered as an indicator to assess the need of platelet transfusion in dengue. As there is a significant variation among patients who bleed with respect to platelet count, APTT can be considered to avoid unnecessary transfusions.

Keywords: activated partial thromboplastin time, dengue, platelet transfusion, thrombocytopenia

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Authors: Johannes J. Schneider, Mathias S. Weyland, Peter Eggenberger Hotz, William D. Jamieson, Oliver Castell, Alessia Faggian, Rudolf M. Füchslin

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In the description of the origin of life, there are still some open gaps, e.g., the formation of macromolecules cannot be fully explained so far. The Kauffman model proposes the existence of autocatalytic sets of macromolecules which mutually catalyze reactions leading to each other’s formation. Usually, this model is simulated in one well-stirred pot only, with a continuous inflow of small building blocks, from which larger molecules are created by a set of catalyzed ligation and cleavage reactions. This approach represents the picture of the primordial soup. However, the conditions on the early Earth must have differed geographically, leading to spatially different outcomes whether a specific reaction could be performed or not. Guided by this picture, the Kauffman model is simulated in a large number of containers in parallel, with neighboring containers being connected by diffusion. In each container, only a subset of the overall reaction set can be performed. Under specific conditions, this approach leads to a larger probability for the existence of an autocatalytic metabolism than in the original Kauffman model.

Keywords: agglomeration, autocatalytic set, differential equation, Kauffman model

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Authors: Anushka Naidoo, Veron Ramsuran, Maxwell Chirehwa, Paolo Denti, Kogieleum Naidoo, Helen McIlleron, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ngcapu, Nesri Padayatachi

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Background: Despite efforts to introduce new drugs and shorter drug regimens for drug-susceptible tuberculosis (TB), the standard first-line treatment has not changed in over 50 years. Rifampicin, isoniazid, and pyrazinamide are critical components of the current standard treatment regimens. Some studies suggest that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic (PK) variability independent of adherence to treatment. Wide between-patient pharmacokinetic variability for rifampin, isoniazid, and pyrazinamide has been reported in prior studies. There may be several reasons for this variability. However, genetic variability in genes coding for drug metabolizing and transporter enzymes have been shown to be a contributing factor for variable tuberculosis drug exposures. Objective: We describe the pharmacokinetics of first-line TB drugs rifampicin, isoniazid, and pyrazinamide and assess the effect of genetic variability in relevant selected drug metabolizing and transporter enzymes on pharmacokinetic parameters of isoniazid and rifampicin. Methods: We conducted the randomized-controlled Improving retreatment success TB trial in Durban, South Africa. The drug regimen included rifampicin, isoniazid, and pyrazinamide. Drug concentrations were measured in plasma, and concentration-time data were analysed using nonlinear-mixed-effects models to quantify the effects of relevant covariates and single nucleotide polymorphisms (SNP’s) of drug metabolizing and transporter genes on rifampicin, isoniazid and pyrazinamide exposure. A total of 25 SNP’s: four NAT2 (used to determine acetylator status), four SLCO1B1, three Pregnane X receptor (NR1), six ABCB1 and eight UGT1A, were selected for analysis in this study. Genotypes were determined for each of the SNP’s using a TaqMan® Genotyping OpenArray™. Results: Among fifty-eight patients studied; 41 (70.7%) were male, 97% black African, 42 (72.4%) HIV co-infected and 40 (95%) on efavirenz-based ART. Median weight, fat-free mass (FFM), and age at baseline were 56.9 kg (interquartile range, IQR: 51.1-65.2), 46.8 kg (IQR: 42.5-50.3) and 37 years (IQR: 31-42), respectively. The pharmacokinetics of rifampicin and pyrazinamide was best described using one-compartment models with first-order absorption and elimination, while for isoniazid two-compartment disposition was used. The median (interquartile range: IQR) AUC (h·mg/L) and Cmax (mg/L) for rifampicin, isoniazid, and pyrazinamide were; 25.62 (23.01-28.53) and 4.85 (4.36-5.40), 10.62 (9.20-12.25) and 2.79 (2.61-2.97), 345.74 (312.03-383.10) and 28.06 (25.01-31.52), respectively. Eighteen percent of patients were classified as rapid acetylators, and 34% and 43% as slow and intermediate acetylators, respectively. Rapid and intermediate acetylator status based on NAT 2 genotype resulted in 2.3 and 1.6 times higher isoniazid clearance than slow acetylators. We found no effects of the SLCO1B1 genotypes on rifampicin pharmacokinetics. Conclusion: Plasma concentrations of rifampicin, isoniazid, and pyrazinamide were low overall in our patients. Isoniazid clearance was high overall and as expected higher in rapid and intermediate acetylators resulting in lower drug exposures. In contrast to reports from previous South African or Ugandan studies, we did not find any effects of the SLCO1B1 or other genotypes tested on rifampicin PK. However, our findings are in keeping with more recent studies from Malawi and India emphasizing the need for geographically diverse and adequately powered studies. The clinical relevance of the low tuberculosis drug concentrations warrants further investigation.

Keywords: rifampicin, isoniazid pharmacokinetics, genetics, NAT2, SLCO1B1, tuberculosis

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Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar

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The need for investigations protecting against toxic impurities though seems to be a primary requirement; the impurities which may prove non - toxic can be explored for their therapeutic potential if any to assist advanced drug discovery. The essential role of pharmaceutical analysis can thus be extended effectively to achieve it. The present study successfully achieved these objectives with characterization of major degradation products as impurities for Zileuton which has been used for to treat asthma since years. The forced degradation studies were performed to identify the potential degradation products using Ultra-fine Liquid-chromatography. Liquid-chromatography-Mass spectrometry (Time of Flight) and Proton Nuclear Magnetic Resonance Studies were utilized effectively to characterize the drug along with five major oxidative and hydrolytic degradation products (DP’s). The mass fragments were identified for Zileuton and path for the degradation was investigated. The characterized DP’s were subjected to In-Silico studies as XP Molecular Docking to compare the gain or loss in binding affinity with 5-Lipooxygenase enzyme. One of the impurity of was found to have the binding affinity more than the drug itself indicating for its potential to be more bioactive as better Antiasthmatic. The close structural resemblance has the ability to potentiate or reduce bioactivity and or toxicity. The chances of being active biologically at other sites cannot be denied and the same is achieved to some extent by predictions for probability of being active with Prediction of Activity Spectrum for Substances (PASS) The impurities found to be bio-active as Antineoplastic, Antiallergic, and inhibitors of Complement Factor D. The toxicological abilities as Ames-Mutagenicity, Carcinogenicity, Developmental Toxicity and Skin Irritancy were evaluated using Toxicity Prediction by Komputer Assisted Technology (TOPKAT). Two of the impurities were found to be non-toxic as compared to original drug Zileuton. As the drugs are purposed and repurposed effectively the impurities can also be; as they can have more binding affinity; less toxicity and better ability to be bio-active at other biological targets.

Keywords: UFLC, LC-MS-TOF, NMR, Zileuton, impurities, toxicity, bio-activity

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Authors: Yogeeta O. Agrawal, Hitendra S. Mahajan, Sanjay J. Surana

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Methotrexate is effective in controlling recalcitrant psoriasis when administered by the oral or parenteral route long-term. However, the systematic use of this drug may provoke any of a number of side effects, notably hepatotoxic effects. To reduce these effects, clinical studies have been done with topical MTx. It is useful in treating a number of cutaneous conditions, including psoriasis. A major problem in topical administration of MTx currently available in market is that the drug is hydrosoluble and is mostly in the dissociated form at physiological pH. Its capacity for passive diffusion is thus limited. Localization of MTx in effected layers of skin is likely to improve the role of topical dosage form of the drug as a supplementary to oral therapy for treatment of psoriasis. One of the possibilities for increasing the penetration of drugs through the skin is the use of Nanostructured lipid Carriers. The objective of the present study was to formulate and characterize Methotrexate loaded Nanostructured Lipid Carriers (MtxNLCs), to understand in vitro drug release and evaluate the role of the developed gel in the topical treatment of psoriasis. MtxNLCs were prepared by solvent diffusion technique using 3(2) full factorial design.The mean diameter and surface morphology of MtxNLC was evaluated. MtxNLCs were lyophilized and crystallinity of NLC was characterized by Differential Scanning Calorimtery (DSC) and powder X-Ray Diffraction (XRD). The NLCs were incorporated in 1% w/w Carbopol 934 P gel base and in vitro skin deposition studies in Human Cadaver Skin were conducted. The optimized MtxNLCs were spherical in shape, with average particle size of 253(±9.92)nm, zeta potential of -30.4 (±0.86) mV and EE of 53.12(±1.54)%. DSC and XRD data confirmed the formation of NLCs. Significantly higher deposition of Methotrexate was found in human cadaver skin from MtxNLC gel (71.52 ±1.23%) as compared to Mtx plain gel (54.28±1.02%). Findings of the studies suggest that there is significant improvement in therapeutic index in treatment of psoriasis by MTx-NLCs incorporated gel base developed in this investigation over plain drug gel currently available in the market.

Keywords: methotrexate, psoriasis, NLCs, hepatotoxic effects

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Authors: Mandy Wilson, Emma Vieira, Jocelyn Jones, Alice V. Brown, Lindey Andrews, Louise Southalan, Jackie Oakley, Dorothy Bagshaw, Patrick Egan, Laura Dent, Duc Dau, Lucy Spanswick

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Alcohol and drug dependency are pertinent issues for those experiencing homelessness. This includes Aboriginal and Torres Strait Islander people, Australia’s traditional owners, living in Perth, Western Australia (WA). Societal narratives around the drivers behind drug and alcohol dependency in Aboriginal communities, particularly those experiencing homelessness, have been biased and unchanging, with little regard for complexity. This can include the idea that Aboriginal people have ‘chosen’ to use alcohol or other drugs without consideration for intergenerational trauma and the trauma of homelessness that may influence their choices. These narratives have flow-on impacts on policies and services that directly impact Aboriginal people experiencing homelessness. In 2021, we commenced a project which aimed to listen to and elevate the voices of 70-90 Aboriginal people experiencing homelessness in Perth. The project is community-driven, led by an Aboriginal Community Controlled Organisation in partnership with a university research institute. A community-ownership group of Aboriginal Elders endorsed the project’s methods, chosen to ensure their suitability for the Aboriginal community. In this paper, we detail these methods, including semi-structured interviews influenced by an Aboriginal yarning approach – an important style of conversation for Aboriginal people which follows cultural protocols; and photovoice – supporting people to share their stories through photography. Through these engagements, we detail the reasons Aboriginal people in Perth shared for using alcohol or other drugs while experiencing homelessness. These included supporting their survival on the streets, managing their mental health, and coping while on the journey to finding support. We also detail why they sought to discontinue alcohol and other drug use, including wanting to reconnect with family and changing priorities. Finally, we share how Aboriginal people experiencing homelessness have said they are impacted by their family’s alcohol and other drug use, including feeling uncomfortable living with a family who is drug and alcohol-dependent and having to care for grandchildren despite their own homelessness. These findings provide a richer understanding of alcohol and drug use for Aboriginal people experiencing homelessness in Perth, shedding light on potential changes to targeted policy and service approaches.

Keywords: Aboriginal and Torres Strait Islander peoples, alcohol and other drugs, homelessness, community-led research

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Authors: Amy Halseth, Kevin Shan, Kye Gilder, John Buse

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The study assessed the effect of prolonged-release naltrexone 32 mg/bupropion 360 mg (NB) on cardiovascular (CV) events in overweight/obese participants at elevated CV risk. Participants must lose ≥ 2% body weight at 16 wks, without a sustained increase in blood pressure, to continue drug. The study was terminated early after second interim analysis with 50% of all CV events. Data on CV endpoints has been published. Current analyses focus on weight change. Intent-to-treat (ITT) population (placebo [PBO] N=4450, NB N=4455) was 54.5% female, 83.5% white, mean age 61 yrs, mean BMI 37.3 kg/m2; 85.2% had type 2 diabetes, 32.1% had CV disease, 17.4% had both. At 52 wks, ITT-LOCF analysis showed greater least squares mean percent change in weight (LSM%ΔBW) with NB (-3.1%; 95% CI -4.8, -1.4) vs PBO (-0.3%; 95% CI -1.9, 1.4). Both groups demonstrated greater weight loss while on-treatment (NB [-7.3%], PBO [-3.9%]). Odds ratios of 5% and 10% weight loss were 3.3 and 4.1 (ITT-LOCF), respectively, in NB over PBO. At 104 wks, on-treatment LSM%ΔBW was -6.3% with NB (n=1137) vs -3.5% with PBO (n=741). Major reasons for NB withdrawal were adverse events (AE, 29%) and patient decision (21%), with GI disorders being the most common. Weight loss with NB in this study, in an older population predominantly with diabetes and elevated CV risk, was somewhat lower than that observed in overweight/obese participants without diabetes and similar to participants with diabetes in Phase 3 studies.

Keywords: contrave, mysimba, obesity, pharmacotherapy, weight loss

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Authors: Abdul Matin, Muhammad Ajmal, Uzma Yunus, Noaman-ul Haq, Hafiz M. Shohaib, Ambreen G. Muazzam

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Carbon nanoparticles (CNPs) have unique properties that are useful for the diagnosis and treatment of cancer due to their precise properties like small size (ideal for delivery within the body) stability in solvent and tunable surface chemistry for targeted delivery. Here, highly fluorescent, monodispersed and water-soluble CNPs were synthesized directly from a suitable carbohydrate source (glucose and sucrose) by one-step acid assisted ultrasonic treatment at 35 KHz for 4 hours. This method is green, simple, rapid and economical and can be used for large scale production and applications. The average particle sizes of CNPs are less than 10nm and they emit bright and colorful green-blue fluorescence under the irradiation of UV-light at 365nm. The CNPs were characterized by scanning electron microscopy, fluorescent spectrophotometry, Fourier transform infrared spectrophotometry, ultraviolet-visible spectrophotometry and TGA analysis. Fluorescent CNPs were used as fluorescent probe and nano-carriers for anticancer drug. Functionalized CNPs (with ethylene diamine) were attached with anticancer drug-Methotrexate. In vitro bioactivity and biocompatibility of CNPs-drug conjugates was evaluated by LDH assay and Sulforhodamine B assay using human lung carcinoma cell lines (H157). Our results reveled that CNPs showed biocompatibility and CNPs-anticancer drug conjugates have shown potent cytotoxic effects and high antitumor activities in lung cancer cell lines. CNPs are proved to be excellent substitute for conventional drug delivery cargo systems and anticancer therapeutics in vitro. Our future studies will be more focused on using the same nanoparticles in vivo model system.

Keywords: carbon nanoparticles, carbon nanoparticles-methotrexate conjugates, human lung carcinoma cell lines, lactate dehydrogenase, methotrexate

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Authors: Mandy W. M. Chan, Samantha Y. N. Shek, Chi K. Yeung, Taro Kono, Henry H. L. Chan

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Fractional radiofrequency devices have shown to improve skin texture such as smoothness, rhytides, brightness as well as atrophic acne scars by increasing dermal thickness, dermal collagen content and dermal fibrillin content. The objective of the study is to assess the efficacy and adverse effects of this device on Asian patients with skin textural changes. In this study, 20 Chinese patients (ranging from 21-60 years old) with irregularities of skin texture, rhytides and acne scars were recruited. Patients received six treatments at 2-4 week intervals. Treatment was initiated with maximum energy tolerated and was adjustable during treatment if patients felt excessive discomfort. A total of two passes were delivered at each session. Physician assessment and standardized photographs were taken at baseline, all treatment visits and at one, two, and six month after final treatment. As a result, 17 patients were recruited and completed the study according to the study protocol. One patient withdrew after the first treatment due to reaction to local anesthesia and two patients were lost to follow-up. At six months follow-up, 71% of the patients were satisfied and 24% were very satisfied, while treatment physician reported various degrees of improvement based on the global assessment scale in 60% of the subjects. Anticipated side effects including erythema, edema, pinpoint bleeding, scabs formation and flare of acne were recorded, but there were no serious adverse effects noted. Conclude up, the use of fractional radiofrequency improves skin texture and appears to be safe in Asian patients. No long-term serious adverse effect was noted.

Keywords: Asian, fractional radiogrequency, skin, texture

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