Search results for: and immunomodulatory drugs

Authors: Siti Salina Abdullah

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Drug abuse is a global problem that affects individuals everywhere. The onset of drug use is usually during adolescence. The use of most drugs has been found to be more prevalent among adolescents than among adults. Drug abuse among adolescents is receiving more attention from parents, friends, communities, and policymakers. Adolescent drug use has been linked to higher rates of physical and mental illness, as well as decreased overall health and well-being. Furthermore, adolescents who use drugs are more susceptible to addiction. The increasing trend of drug use among young generations, particularly in Malaysia, is causing significant concerns. Adolescent drug use is commonly linked to peers, environment, and families. The National Anti-Drugs Agency (NADA) is the main agency in Malaysia that works with the Ministry of Home Affairs to prevent drug and substance abuse. NADA operates by providing preventive drug education, enforcement and security measures, treatment, medical rehabilitation, and international relations. The objective of this study is to examine the involvement of parents living in high-risk drug environments in drug prevention programs. It also discusses the difficulties they face when participating in drug prevention programs. This study was conducted in high-risk areas identified by National Anti-Drug Agencies (Malaysia). A total of 515 drug-free parents were interviewed in this study. The findings showed that B40 families were the majority among families living in high-risk drug environments. The study shows that drug prevention programs have a low participation rate among respondents. Previous research has demonstrated that drug prevention programs have a low rate of participation. The NADA campaign 'Prevention Start from Home' requires that this issue is addressed. To ensure that this campaign works, families, especially those at risk, should be empowered to participate in drug prevention programs. To fight drug problems among teenagers, it is crucial for families to take the first step in conducting prevention measures. To ensure that families with young children are equipped with drug prevention information, more advocacy programs are required. In addition, the drug prevention program should be accessible and reachable to families.

Keywords: drug prevention program, drug abuse, family, malaysia

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Authors: Shirin Jalili, Hadi Shirzad, Samaneh Nabavi, Somayeh Khanjani

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Forensic entomology is the science of study and analysis of insects evidences to aid in criminal investigation. Being aware of the distribution, biology, ecology and behavior of insects, which are founded at crime scene can provide information about when, where and how the crime has been committed. It has many application in criminal investigations. Its main use is estimation of the minimum time after death in suspicious death. The close association between insects and corpses and the use of insects in criminal investigations is the subject of forensic entomology. Because insects attack to the decomposing corpse and spawning on it from the initial stages. Forensic scientists can estimate the postmortem index by studying the insects population and the developing larval stages.In addition, toxicological and molecular studies of these insects can reveal the cause of death or even the identity of a victim. It also be used to detect drugs and poisons, and determination of incident location. Gathering robust entomological evidences is made possible for experts by recent Techniques. They can provide vital information about death, corpse movement or burial, submersion interval, time of decapitation, identification of specific sites of trauma, post-mortem artefacts on the body, use of drugs, linking a suspect to the scene of a crime, sexual molestations and the identification of suspects.

Keywords: Forensic entomology, post mortem interval, insects, larvae

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Authors: Donna L. Roberts

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Heroin has appeared on the drug scene before. Yet the current opioid crisis differs in significant ways. In order to address the grave challenges, this epidemic poses, the unique precipitating and sustaining conditions must be thoroughly examined. This research explored the various aspects of the political, economic, and social conditions that created a 'perfect storm' for the evolution and maintenance of the current opioid crisis. Specifically, the epidemiology, demographics, and progression of addiction inherent in the current crisis were compared to the patterns of past opioid use. Additionally, the role of pharmaceutical companies and prescribing physicians, the nature and pharmaceutical properties of the available substances and the changing socioeconomic climate were considered. Results indicated that the current crisis differs significantly with respect to its evolution, magnitude, prevalence, and widespread societal effects. Precipitated by a proliferation of prescription medication and sustained by the availability of cheaper, more potent street drugs, including new versions of synthetic opioids, the current crisis presents unprecedented challenges affecting a wider and more diverse segment of society. The unique aspects of this epidemic demand unique approaches to addressing the problem. Understanding these differences is a key step in working toward a practical and enduring solution.

Keywords: addiction, drug abuse, opioids, opioid crisis

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Authors: Liya Abraham

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Medicinal plants are globally valuable sources of herbal products, either as lifesaving or life maintaining medicines. Studies reveal that more than 25% of modern drugs in the world are derived from plants. The Horn of Africa as a world hotspot; it has more than 1500 endemic plants. Eritrea, a country located in the Horn of Africa, is blessed with medicinal flora and fauna and marine and terrestrial biodiversity. Previous studies of flora of Ethiopia and Eritrea, incomplete species lists, indicate figures ranging between 6000 and 7000 species, with levels of endemism between 12–20%. In the past two decades, there has been growing interest in natural remedy herbal medicines owing to, but not limited to; resistance to antimicrobials, intolerance of side effects of modern drugs, and rise in chronic diseases like diabetes, hypertension, cancer, etc. Hence, owing to the rising demand for nature based health solutions, deforestation, construction purposes, grazing, and agricultural expansion; several medicinal plants in general and the endemic ones, in particular, are in the verge of extinction. Therefore, conservation strategies of endangered and endemic medicinal plants, especially those located in hot spot regions, must be promoted at global level. Thus, the author aims to share certain information regarding the endemic medicinal plants in Eritrea with the international scientific world.

Keywords: endemic, eritrea, horn of Africa, medicinal plants, species

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Authors: Fabiola Xavier Leal, Lara Campanharo, Sueli Aparecida Rodrigues Lucas

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The phenomenon of judicialization in health policy brings with it a great deal of problematization, but in general, it means that some issues that were previously solved by traditional political bodies are being decided by the Judiciary bodies. It is, therefore, a controversial topic that has generated many reflections both in the academic and political fields, considering that not only a dispute of public funds is at stake, but also the debate on access to social rights provided for in the Brazilian Federal Constitution of 1988 and in the various public policies, such as healthcare. With regard to the phenomenon in the Mental Health Policy focusing on people who use drugs, the disputes that permeate this scenario are evident: moral, cultural, sanitary, economic, psychological aspects. There are also the individual and collective dimensions of suffering. And in this process, we all question: What is the role of the Brazilian State in this matter? In this context, another question that needs to be answered is the amount spent on this procedure in the state of Espírito Santo (ES), Brazil (in the last 04 years, around R$121,978,591.44 were paid only for compulsory hospitalization of individuals) in the field in question, which is the financing of the services of the Psychosocial Care Network (RAPS). Therefore, this article aims to problematize the phenomenon of judicialization in Mental Health Policy through the compulsory hospitalization of people who use drugs in Espírito Santo (ES). We proposed a study that sought to understand how this has been occurring and making an impact on the provision of RAPS services in the Espírito Santo scenario. Therefore, the general objective of this study is to analyze the expenses with compulsory hospitalizations for drug use carried out by the State Health Department (SESA) between 2014 and 2019, in which we will seek to identify its destination and the impact of these actions on public health policy. For the purposes of this article, we will present the preliminary data of this study, such as the amount spent by the state and the receiving institutions. For data collection, the following data sources were used: documents available publicly on the Transparency Portal (payments made per year, institutions that received, subjects hospitalized, period and the amount of the daily rates paid); as well as the processes generated by SESA through its own system - ONBASE. For qualitative analysis, content analysis was used; and for quantitative analysis, descriptive statistics was used. Thus, we seek to problematize the issue of judicialization for compulsory hospitalizations, considering the current situation in which this resource has been widely requested to legitimize the war on drugs. This scenario highlights the moral-legal discourse, pointing out strategies through the control of bodies and through faith as an alternative.

Keywords: compulsory hospitalization, drugs, judicialization, mental health

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Authors: J. B. Minari, O. B. Oloyede, A. A. Odutuga

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Myeloperoxidase is the most abundant enzyme found in the polymorphonuclear neutrophil and is known to play a central role in the host defense system of the leukocyte. The enzyme has been reported to interact with some drugs to generate free radical which inhibits its activity. This study investigated the effects of artesunate on the activity of the enzyme and the subsequent effect on the host immune system. In investigating the effects of the drugs on myeloperoxidase, the influence of concentration, pH, partition ratio estimation and kinetics of inhibition were studied. This study showed that artesunate is concentration-dependent inhibitor of myeloperoxidase with an IC50 of 0.078mM. Partition ratio estimation showed that 60 enzymatic turnover cycles are required for complete inhibition of myeloperoxidase in the presence of artesunate. The influence of pH on the effect of artesunate on the enzyme showed least activity of myeloperoxidase at physiological pH. The kinetic inhibition studies showed that artesunate caused a competitive inhibition with an increase in the Km value from 0.12mM to 0.26mM and no effect on the Vmax value. The Ki value was estimated to be 2.5mM. The results obtained from this study show that artesunate is a potent inhibitor of myeloperoxidase and it is capable of inactivating the enzyme. It is considered that the inhibition of myeloperoxidase in the presence of artesunate as revealed in this study may partly explain the impairment of polymorphonuclear neutrophil and consequent reduction of the strength of the host defense system against secondary infections.

Keywords: myeloperoxidase, artesunate, inhibition, nuetrophill

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Authors: Ashish Jain, Satish Nayak

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Transdermal iontophoretic drug delivery system is viable drug delivery platform technology and has a strong market worldwide. Transdermal drug delivery system is particularly desirable for therapeutic agents that need prolonged administration at controlled plasma level. This makes appropriateness to antihypertensive and anti-diabetic agents for their transdermal development. Controlled zero order absorption, easily termination of drug delivery and easy to administration also support for popularity of transdermal delivery. In this current research iontophoretic delivery of various anti diabetic agents like glipizide, glibenclamide and glimepiride were carried out. The experiments were carried out at different drug concentrations and different current densities using cathodal iontophoresis. Diffusion cell for iontophoretic permeation study was modified according to Glikfield Design. Pig skin was used for in vitro permeation study and for the in-vivo study New Zealand rabbits were used. At all concentration level iontophoresis showed enhanced permeation rate compared to passive controls. Iontophoretic transports of selected drugs were found to be increased with the current densities. Results showed that target permeation rate for selected drugs could be achieved with the aid of iontophoresis by increasing the area in an appreciable range.

Keywords: transdermal, iontophoresis, pig skin, rabbits, glipizide, glibeclamide

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Authors: Seydou Drabo

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This paper examines how traditional contraceptives and abortion practices challenges the use of modern contraceptives in Burkina Faso. It demonstrates how fears and ‘superstitions’ interact with knowledge about modern contraceptives methods to determine use in a context where other way of controlling fertility (traditional contraceptives, abortion) are available to women in the public, private and traditional health sectors. Furthermore, these issues come at the time when Burkina Faso is among countries with a high fertility rate which (6.0 in 2010) and a very low used of contraceptives as only 16% of married women of childbearing age were using a contraceptive method in 2010. The country also has a young population since 33 % of the population is between 10-24 years old and this number is expected to increase by 2050, generating fears that a growing population of youth will put excessive pressure on available resources, including access to education, health services, and employment. Despite over two decades of dedicated policy attention, 24% of women of reproductive age (15-49) was estimated to have an unmet need for contraception in 2010. This paper draws on ethnographic fieldwork conducted since march 2016 (The research is still in progress) in Burkina Faso. Data were collected from 25 women (users and non-users of modern contraceptives and /or traditional contraceptives, post abortion care patients), 4 street drugs vendors and 3 traditional healers through formal and informal interviews, as well as direct observation. The findings show that a variety of contraceptives methods and abortion drugs or methods, both traditional and modern circulate and are available to women. Traditional contraceptives called African contraceptives by some of our participants refer to several birth control method including plants decoction, magical ring, waist necklace, a ritual done with a mixture of lay coming from termite mound and menses. Abortion is a practice that is done in secret through the use of abortion drugs or through intra uterine manoeuvres. Modern contraceptives include Oral contraceptive, implants, injectable. Stereotypes about modern contraceptives, having regular menstrual cycles and adopt of natural birth control methods, bad experience with modern contraceptives methods, the side effect of modern contraceptives, irregularity of sexual activities and the availability of emergency contraceptives are among factors that limit their use among women. In addition, a negative perception is built around modern contraceptives seen as the drug of ‘white people’. In general, the information on these drugs circulates in women’s social network (first line of information on contraceptive). Some women prefer using what they call African contraceptives or inducing an abortion over modern contraceptives because of their side effect. Furthermore, the findings show that women practices and attitudes in controlling birth varies throughout different phases of their lives. Beyond global discourses and technical solution, the issue of Family planning is all about social practices.

Keywords: abortion, Burkina Faso, contraception, culture, women

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Authors: Deepak Kakde, Steve Howdle, Derek Irvine, Cameron Alexander

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The poor aqueous solubility is one of the major obstacles in the formulation development of many drugs. Around 70% of drugs are poorly soluble in aqueous media. In the last few decades, micelles have emerged as one of the major tools for solubilization of hydrophobic drugs. Micelles are nanosized structures (10-100nm) obtained by self-assembly of amphiphilic molecules into the water. The hydrophobic part of the micelle forms core which is surrounded by a hydrophilic outer shell called corona. These core-shell structures have been used as a drug delivery vehicle for many years. Although, the utility of micelles have been reduced due to the lack of sustainable materials. In the present study, a novel methoxy poly(ethylene glycol)-b-poly(ε-decalactone) (mPEG-b-PεDL) copolymer was synthesized by ring opening polymerization (ROP) of renewable ε-decalactone (ε-DL) monomers on methoxy poly(ethylene glycol) (mPEG) initiator using 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as a organocatalyst. All the reactions were conducted in bulk to avoid the use of toxic organic solvents. The copolymer was characterized by nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography (GPC) and differential scanning calorimetry (DSC).The mPEG-b-PεDL block copolymeric micelles containing indomethacin (IND) were prepared by nanoprecipitation method and evaluated as drug delivery vehicle. The size of the micelles was less than 40nm with narrow polydispersity pattern. TEM image showed uniform distribution of spherical micelles defined by clear surface boundary. The indomethacin loading was 7.4% for copolymer with molecular weight of 13000 and drug/polymer weight ratio of 4/50. The higher drug/polymer ratio decreased the drug loading. The drug release study in PBS (pH7.4) showed a sustained release of drug over a period of 24hr. In conclusion, we have developed a new sustainable polymeric material for IND delivery by combining the green synthetic approach with the use of renewable monomer for sustainable development of polymeric nanomedicine.

Keywords: dopolymer, ε-decalactone, indomethacin, micelles

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Authors: Hulya Tuba Kiyan, Nilgun Ozturk

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Gentiana, a member of Gentianaceae, is represented by approximately 400 species in the world and 12 species in Turkey. Flavonoids, iridoids, triterpenoids and also xanthones are the major compounds of this genus, have been previously reported to have antiinflammatory, antimicrobial, antioxidant, hepatoprotective, hypotensive, hypoglycaemic, DNA repair and immunomodulatory properties. The methanolic extract of the aerial parts of Gentiana brachyphylla Vill. from Turkey was evaluated for its biological activities and its total phenolic content in the present study. According to the antioxidant activity results, G. brachyphylla methanolic extract showed very strong anti-DNA damage antioxidant activity with an inhibition of 81.82%. It showed weak ferric-reducing power with a EC50 value of 0.65 when compared to BHT (EC50 = 0.2). Also, at 0.5 mg/ml concentration, the methanolic extract inhibited ABTS radical cation activity with an inhibition of 20.13% when compared to Trolox (79.01%). Chelating ability of G. brachyphylla was 44.71% whereas EDTA showed 78.87% chelating activity at 0.2 mg/ml. Also G. brachyphylla showed weak 27.21% AChE, 20.23% BChE, strong 67.86% MAO-A and moderate 50.06% MAO-B, weak 19.14% COX-1, 29.11% COX-2 inhibitory activities at 0.25 mg/ml. The total phenolic content of G. brachyphylla was 156.23 ± 2.73 mg gallic acid equivalent/100 g extract.

Keywords: antioxidant activity, cholinesterase inhibitory activity, Gentiana brachyphylla Vill., total phenolic content

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Authors: Asma Temagoult, Bariza Zitouni, Yassin Noui

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Cactus fruit contains different nutritional and functional components, which are used because of their benefits to human health, such as flavonoids, phenolic compounds, carotenoids and vitamins C. It has hypoglycemic and hypolipidemic action, and antioxidant properties related to anticarcinogenic, antiulcerogenic and immunomodulatory effects. The antioxidant and nutritional properties have been characterized in cactus prickly pear (Opuntia ficus-indica Mill.), cultivar yellow, grown in Arris area; Eastern of Algeria. The antioxidant properties of this cactus cultivar were higher than the others cactus cultivar in the world. The amount of fruit phenolic compounds revealed contents between 20.65 and 45.70 mg / 100 g of FW for total polyphenols and 0.519 - 0.591 mg / 100 g of FW for the flavonoids. The antioxidant activity was evaluated by DPPH radical scavenging and FRAP (ferric reducing antioxidant power) methods. The average recorded to the potassium content is about 1070 mg / 100 g of the fresh weight; sodium is 60.7 mg / 100 g of the fresh weight and 80 mg / 100g for the calcium. According to the high value of this cactus, it was considered as a good nutrient and important pharmaceutical resource. It could be used as a natural additive or substituted food supplement in many foodstuffs production, to benefit from these benefits.

Keywords: antioxidant properties, DPPH, FRAP, nutritional properties, Opuntia ficus indica

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Authors: Firman Riyudha, Endrik Mifta Shaiful

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The spread of drug users is one kind of behavioral epidemiology that becomes a threat to every country in the world. This problem caused various crisis simultaneously, including financial or economic crisis, social, health, until human crisis. Most drug users are teenagers at school age. A new deterministic model would be constructed to determine the dynamics of the spread of drug users by considering level of education in a susceptible population. Based on the analytical model, two equilibria points were obtained; there were E₀ (zero user) and E₁ (endemic equilibrium). Existence of equilibrium and local stability of equilibria depended on the Basic Reproduction Ratio (R₀). This parameter was defined as the expected rate of secondary prevalence and primary prevalence in virgin population along spreading primary prevalence. The zero-victim equilibrium would be locally asymptotically stable if R₀ < 1 while if R₀ > 1 the endemic equilibrium would be locally asymptotically stable. The result showed that R₀ was proportional to the rate of interaction of each susceptible population based on educational level with the users' population. It is concluded that there was a need to be given a control in interaction, so that drug users population could be minimized. Numerical simulations were also provided to support analytical results.

Keywords: drugs users, level education, mathematical model, stability

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Authors: Zuhrotun Ulya, Muchammad Syamsulhadi, Debree Septiawan

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Patients with bipolar disorder are three times more likely to suffer cardiovascular disorders than the general population, which will influence their level of morbidity and rate of mortality. Bipolar disorder also affects the pulmonary system. The choice of long term-monotherapy and other combinative therapies have clinical impacts on patients. This study investigates the case of a woman who has been suffering from bipolar disorder for 16 years, and who has a history of Steven Johnson Syndrome. At present she is suffering also from cardiovascular and pulmonary disorder. An analysis of the results of this study suggests that there is a relationship between cardiovascular disorder, drug therapies, Steven Johnson Syndrome and mood stabilizer obtained from the PubMed, Cochrane, Medline, and ProQuest (publications between 2005 and 2015). Combination therapy with mood stabilizer is recommended for patients who do not have side effect histories from these drugs. The replacement drugs and combinations may be applied, especially for those with bipolar disorders, and the combination between atypical antipsychotic groups and mood stabilizers is often made. Clinicians, however, should be careful with the patients’ physical and metabolic changes, especially those who have experienced long-term therapy and who showed a history of Steven Johnson Syndrome (for which clinicians probably prescribed one type of medicine).

Keywords: cardiopulmonary disease, bipolar disorder, SJS, therapy

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Authors: Muhammad Mustaqeem, Musa Kaleem Baloch, Irfan Ullah, Ammarah Luqman, Afshan Ahmad

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Flurbiprofen is one of the most potent nonsteroidal anti-inflammatory drugs. It is widely used for relief of pain in patients suffering from rheumatic diseases, migraine, sore throat and primary dysmenorrhea. However, its aqueous solubility is very low and hinders the skin permeation. Thus, it is imperative to develop such a drug delivery systems which can improve its aqueous solubility and hence improve the skin permeation and therapeutic compliance. Microemulsions have been also proven to increase the cutaneous absorption of lipophilic drugs as compared to conventional vehicles. Micro-emulsion is thermodynamically stable emulsion that has the capacity to ‘hide/solubilize’ water-insoluble molecules within a continuous oil phase. Therefore, flurbiprofen was converted to Easters through chemical reactions with alcohols such as methanol, ethanol, propanol and butanol. The product was further treated with hydrazine to get hydrazide. The solubility of the parent drug Flurbiprofen and the products were solubilized in microemulsions formed using various surfactants like ionic, non-ionic and zwitterions. It has been concluded that the product was more soluble than the parent compound. The biological activities of these were also investigated. The outcome was very promising and the product was more active than the parent compound. It, therefore, concluded that in this way, we can not only enhance the solubility of the drug and increase its bioactivity, but also reduce the risk of stomach cancer.

Keywords: Flurbiprofen, microemulsion, surfactants, hyrazides

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Authors: Zerihun Tesfaye Nigusse

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Objective: This study evaluates the antileishmanial activity of the methanolic extract of Aloe otallensis (A. otallensis) on the promastigote stage of Leishmaniadonovani (L. donovani) as compared to standard drugs and to screen its phytochemical constituents. Methods: Phytochemical screening was done by using the method mentioned by Evans and Trease on methanolic extract of the exudates of Aloe otallensis leaves. The extract was also evaluated for in vitro antileishmanial activity against L. donavani, which is found in the Parasitology Unit of Black Lion Hospital. The result was compared to standard drugs of sodium stibogluconate, milfostin and paramomycin. Results: The extract has good antileishmanial activity with an IC50 of 0.123 0 μg/mL on L. donovani (AM 563). The experimental data showed that relatively, it had better activity than paramomycin and milfostin but less activity than sodium stibogluconate. The data analyses were done by GraphPad Prism version 5 software after it was read by an ELISA reader at the wavelength of 650 nm. The phytochemical screening of the exudates of A. otallensis showed the presence of phenol, alkaloid and saponin. Conclusions: The methanol extract of the exudates of A.otallensishas a good anti- leishmaniasis activity and this may be attributed to phenol, alkaloid and saponin present in the plant. But it needs further analysis for the conformation of which constituent presents in high concentration to know which one has the strongest effect.

Keywords: anti leshimaniasis, aloe otallensis, leshimania ethiopica, IC50

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Authors: M. Mirmohammadi, S. Taghdisi, F. Anali

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Gossypol is a yellow anti-nutritional compound found in the cotton plant. This substance exists in the cottonseed and other parts of the cotton plant, such as bark, leaves, and stems. Chemically, gossypol is a very active polyphenolic aldehyde compound, and due to this polyphenolic structure, it has antioxidant and therapeutic properties. On the other hand, this compound, especially in free form, has many toxic effects, that its excessive consumption can be very dangerous for humans and animals. In this study, gossypol was extracted as a derivative compound of gossypol acetic acid from cottonseed using the n-hexane solvent with an efficiency of 0.84 ± 0.04, which compared to the Gossypol extracted from cottonseed oil with the same method (cold press) showed a significant difference with its efficiency of 1.14 ± 0.06. Therefore, it can be suggested to use cottonseed oil to extract this valuable compound. In the other part of this research, cottonseed extracts and cotton bolls extracts were obtained by two methods of soaking and Soxhlet with hydroalcoholic solvent taken with a ratio of (25:75), then by using extracts and corn starch powder, four herbal medicine code was created and after receiving the code of ethics (IR.SSU.REC.1398.136) the therapeutic effect of each one on the Cutaneous leishmaniasis resistant to drugs (caused by the leishmaniasis parasite) was investigated in real patients and its results was compared with the common drug glucantime (local ampoule) (n = 36). Statistical studies showed that the use of herbal medicines prepared with cottonseed extract and cotton bolls extract has a significant positive effect on the treatment of the disease’s wounds (p-value > 0.05) compared to the control group (only ethanol). Also, by comparing the average diameter of the wounds after a two-month treatment period, no significant difference was found between the use of ointment containing extracts and local glucantime ampoules (p-value < 0.05). Bolls extract extracted with the Soxhlet method showed the best therapeutic effects, although there was no significant difference between them (p-value < 0.05). Therefore, there is acceptable reliability to recommend this medicine for the treatment of Cutaneous leishmaniasis resistant to drugs without the side effects of the chemical drug glucantime and the pain of injecting the ampoule.

Keywords: cottonseed oil, gossypol, cotton boll, cutaneous leishmaniasis

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Authors: R. H. Bustos, L. Martinez, J. García, F. Suárez

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MRP1 (Multi-drug resistance associated protein 1) and MRP2 (Multi-drug resistance associated protein 2) are two proteins belonging to the transporters of ABC (ATP-Binding Cassette). These transporter proteins are involved in the efflux of several biological drugs and xenobiotic and also in multiple physiological, pathological and pharmacological processes. Evidence has been found that there is a correlation among different polymorphisms found and their clinical implication in the resistance to antiepileptic, chemotherapy and anti-infectious drugs. In our study, exonic regions of MRP1/ABCC1 y MRP2/ABCC2 were studied in the Colombian population, specifically in the region of the central Savannah (Cundinamarca) to determinate SNP (Single Nucleotide Polymorphisms) and determinate its allele frequency and its genomics frequency. Results showed that for our population, SNP are found that have been previously reported for MRP1/ABCC1 (rs200647436, rs200624910, rs150214567) as well as for MRP2/ABCC2 (rs2273697, rs3740066, rs142573385, rs17216212). In addition, 13 new SNP were identified. Evidences show an important clinic correlation for polymorphisms rs3740066 and rs2273697. The study object population displays genetic variability as compared to the one reported in other populations.

Keywords: ATP-binding cassette (ABCC), Colombian population, multidrug-resistance protein (MRP), pharmacogenetic, single nucleotide polymorphism (SNP)

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Authors: Muzaffar Iqbal, Essam Ezzeldin, Khalid A. Al-Rashood

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Pomalidomide is a second generation oral immunomodulatory agent, being used for the treatment of multiple myeloma in patients with disease refractory to lenalidomide and bortezomib. In this study, a sensitive UPLC-MS/MS assay was developed and validated for high-throughput determination of pomalidomide in rat plasma using celecoxib as an internal standard (IS). Liquid liquid extraction using dichloromethane as extracting agent was employed to extract pomalidomide and IS from 200 µL of plasma. Chromatographic separation was carried on Acquity BEHTM C18 column (50 × 2.1 mm, 1.7 µm) using an isocratic mobile phase of acetonitrile:10 mM ammonium acetate (80:20, v/v), at a flow rate of 0.250 mL/min. Both pomalidomide and IS were eluted at 0.66 ± 0.03 and 0.80 ± 0.03 min, respectively with a total run time of 1.5 min only. Detection was performed on a triple quadrupole tandem mass spectrometer using electrospray ionization in negative mode. The precursor to product ion transitions of m/z 272.01 → 160.89 for pomalidomide and m/z 380.08 → 316.01 for IS were used to quantify them respectively, using multiple reaction monitoring mode. The developed method was validated according to regulatory guideline for bioanalytical method validation. The linearity in plasma sample was achieved in the concentration range of 0.47–400 ng/mL (r2 ≥ 0.997). The intra and inter-day precision values were ≤ 11.1% (RSD, %) whereas accuracy values ranged from - 6.8 – 8.5% (RE, %). In addition, other validation results were within the acceptance criteria and the method was successfully applied in a pharmacokinetic study of pomalidomide in rats.

Keywords: pomalidomide, pharmacokinetics, LC-MS/MS, celecoxib

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Authors: Gulsharat A. Baigonakova, Ekaterina S. Marchenko, Venera R. Luchsheva

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The preferred materials for bone grafting are titanium-nickel alloys. They have a porous, permeable structure similar to that of bone tissue, can withstand long-term physiological stress in the body, and retain the scaffolding function for bone tissue ingrowth. Despite the excellent functional properties of these alloys, there is a possibility of post-operative infectious complications that prevent the newly formed bone tissue from filling the spaces created in a timely manner and prolong the rehabilitation period of patients. In order to minimise such consequences, it is necessary to use biocompatible materials capable of simultaneously fulfilling the function of a long-term functioning implant and an osteoreplacement carrier saturated with drugs. Methods to modify the surface by saturation with bioactive substances, in particular macrocyclic compounds, for the controlled release of drugs, biologically active substances, and cells are becoming increasingly important. This work is dedicated to the functionalisation of the surface of porous titanium nickelide by the deposition of macrocyclic compounds in order to provide titanium nickelide with antibacterial activity and accelerated osteogenesis. The paper evaluates the effect of macrocyclic compound deposition methods on the continuity, structure, and cytocompatibility of the surface properties of porous titanium nickelide. Macrocyclic compounds were deposited on the porous surface of titanium nickelide under the influence of various physical effects. Structural research methods have allowed the evaluation of the surface morphology of titanium nickelide and the nature of the distribution of these compounds. The method of surface functionalisation of titanium nickelide influences the size of the deposited bioactive molecules and the nature of their distribution. The surface functionalisation method developed has enabled titanium nickelide to be deposited uniformly on the inner and outer surfaces of the pores, which will subsequently enable the material to be uniformly saturated with various drugs, including antibiotics and inhibitors. The surface-modified porous titanium nickelide showed high biocompatibility and low cytotoxicity in in vitro studies. The research was carried out with financial support from the Russian Science Foundation under Grant No. 22-72-10037.

Keywords: biocompatibility, NiTi, surface, porous structure

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Authors: Aijing Luo, Zirui Xin, Yifeng Yuan

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Background: With the rapid development of the online health community, more and more patients or families are seeking health information on the Internet. Objective: This study aimed to discuss how to fully reveal the health information needs expressed by hypertensive patients in their questions in the online environment. Methods: This study randomly selected 1,000 text records from the question data of hypertensive patients from 2008 to 2018 collected from the website www.haodf.com and constructed a classification system through literature research and content analysis. This paper identified the background characteristics and questioning the intention of each hypertensive patient based on the patient’s question and used co-occurrence network analysis to explore the features of the health information needs of hypertensive patients. Results: The classification system for health information needs of patients with hypertension is composed of 9 parts: 355 kinds of drugs, 395 kinds of symptoms and signs, 545 kinds of tests and examinations , 526 kinds of demographic data, 80 kinds of diseases, 37 kinds of risk factors, 43 kinds of emotions, 6 kinds of lifestyles, 49 kinds of questions. The characteristics of the explored online health information needs of the hypertensive patients include: i)more than 49% of patients describe the features such as drugs, symptoms and signs, tests and examinations, demographic data, diseases, etc. ii) these groups are most concerned about treatment (77.8%), followed by diagnosis (32.3%); iii) 65.8% of hypertensive patients will ask doctors online several questions at the same time. 28.3% of the patients are very concerned about how to adjust the medication, and they will ask other treatment-related questions at the same time, including drug side effects, whether to take drugs, how to treat a disease, etc.; secondly, 17.6% of the patients will consult the doctors online about the causes of the clinical findings, including the relationship between the clinical findings and a disease, the treatment of a disease, medication, and examinations. Conclusion: In the online environment, the health information needs expressed by Chinese hypertensive patients to doctors are personalized; that is, patients with different background features express their questioning intentions to doctors. The classification system constructed in this study can guide health information service providers in the construction of online health resources, to help solve the problem of information asymmetry in communication between doctors and patients.

Keywords: online health community, health information needs, hypertensive patients, doctor-patient communication

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Authors: Fakhreldin O. Suliman, Alia H. Al-Battashi

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This work explored the interaction of three different imidazoline drugs, naphazoline nitrate (NPH), oxymetazoline hydrochloride (OXY) and xylometazoline hydrochloride (XYL) with two different synthesized cucurbit[n]urils CB[n], cucurbit[7]uril (CB[7]) and cucuribit[8]uril (CB[8]). Three binary inclusion complexes have been investigated in solution and in the solid state. The solid complexes were obtained by lyophilization, whereas the physical mixtures of guests and hosts at a stoichiometric ratio of 1:1 were obtained for each drug. 1HNMR, electrospray ionization mass spectrometry (ESI-MS), and matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry was used to study the complexes prepared in aqueous media. The lyophilized solid complexes were characterized by Fourier transform-infrared spectroscopy (FT-IR), powder X-ray diffractometry (PXRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). MS, FT-IR and PXRD experimental results established in this work reveal that NPH, OXY and XYL molecules form stable inclusion complexes with the two hosts. The TGA and DSC confirmed the enhancement of the thermal stability of each drug and the production of a thermally stable solid complex. The 1HNMR has shown that the protons of the guests faced shifting in ppm and broadening of their peaks upon the formation of inclusion complexes with the selected CB[n]. The aromatic protons of the guest exhibited the highest changes in the chemical shifts and shape of the NMR peaks, suggesting their inclusion into the cavity of the CB[n]. The diffusion coefficients (D), developed from the diffusion-controlled NMR Spectroscopy (DOSY) measurements, for the complexation of the selected imidazoline drugs with CB[7] and CB[8], were decreased in the presence of hosts compared to the free guests indicating the formation of the guest-host adduct. Furthermore, we conducted molecular dynamic simulations and quantum mechanics calculations on these complexes. The results of the theoretical study corroborate the experimental findings and have also shed light on the mechanism of inclusion of the guests into the two hosts. This study generates initial data for potential drug delivery or drug formulation systems for these three selected imidazoline drug compounds based on their inclusion into the CB[n] cavities.

Keywords: cucurbit[n]urils, imidazoline, inclusion complexes, molecular dynamics, DFT calculations, mass spectrometry

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Authors: Trapti Pathak

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Fishes can change their body colour according to their surroundings by. They do so by either aggregation or dispersion of melanosomes within the skin. These movements can regulate by means of sympathetic nerves with the help of cytoskeleton. Employing the melanophores on isolated scales of the fingerling of teleost fish, it is attempted to characterise the concerned nerves and the receptors located on melenocytes along with implication of microtubules a part of cytoskeleton in the pigmentary translocation in the fish. The scales from dorso-lateral trunk of the fish represented the sympathetic– neuromelanophore preparations which were stimulated by chemical means, such as adrenergic agonist, antagonist and the microtubule-disrupting drugs such as yuhombine, dopamine, colchicine etc. Adrenaline is an adrenergic agonist which is strongly induced the dorse-dependent concentration of pigment in innervated melanophores while Yohimbine is an adrenergic antagonist which is known to block effectively the α2-adrenoceptors inhibited the action of adrenaline. Colchicine effectively interferes with melanosome aggregating action of adrenaline. From these results it is concluded that the chromatic fibres of adrenergic nature innervate the melanophores and these cells do possess α2-adrenoceptors which mediate the melanosome aggregation and the movements of pigment granules through microtubules means of transport within the cell. These movements of pigment are linked to paling or darkening achieved of teleost fish respectively when they approach to their background.

Keywords: melenophores, agonists, antagonist, colour change

Procedia PDF Downloads 78

Authors: Taruna Katyal Arora, Geeta Kumari, Hari Shankar, Neelima Mishra

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Substandard and counterfeit antimalarials is a major problem in malaria endemic areas. The availability of counterfeit/ substandard medicines is not only decreasing the efficacy in patients, but it is also one of the contributing factors for developing antimalarial drug resistance. Owing to this, a pilot study was conducted to survey quality of drugs collected from different malaria endemic areas of India. Artesunate+Sulphadoxine-Pyrimethamine (AS+SP), Artemether-Lumefantrine (AL), Chloroquine (CQ) tablets were randomly picked from public health facilities in selected states of India. The quality of antimalarial drugs from these areas was assessed by using Global Pharma Health Fund Minilab test kit. This includes physical/visual inspection and disintegration test. Thin-layer chromatography (TLC) was carried out for semi-quantitative assessment of active pharmaceutical ingredients. A total of 45 brands, out of which 21 were for CQ, 14 for AL and 10 for AS+SP were tested from Uttar Pradesh (U.P.), Mizoram, Meghalaya and Gujrat states. One out of 45 samples showed variable disintegration and retension factor. The variable disintegration and retention factor which would have been due to substandard quality or other factors including storage. However, HPLC analysis confirms standard active pharmaceutical ingredient, but may be due to humid temperature and moisture in storage may account for the observed result.

Keywords: antimalarial medicines, counterfeit, substandard, TLC

Procedia PDF Downloads 322

Authors: Kazunari Ozaki, Mitsuru Kageyama, Kenki Miyazawa, Yoshio Nakamura

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Background: Kampo (Japanese Traditional medicine) is a medicine traditionally practiced in Japan, based on ancient Chinese medicine. Most Kampo doctors have used decoction of crude drug pieces for treatment. 93% of the Kampo drugs sold in Japan are Kampo products nowadays. Of all Kampo products, 81% of them are Kampo extract formulations for prescription, which is prepared in powdered or granulated form from medicinal crude drug extracts mixed with appropriate excipient. Physicians with medical license for Western medicine prescribe these Kampo extract formulations for prescription in Japan. Objectives: Our study aims at presenting a brief history of Kampo extract formulations for prescription in Japan. Methods: Systematic searches for relevant studies were conducted using not only printed journals but also electronic journals from the bibliographic databases, such as PubMed/Medline, Ichushi-Web, and university/institutional websites, as well as search engines, such as Google and Google Scholar. Results: The first commercialization of Kampo extract formulations for general use (or OTC (over-the-counter) Kampo extract formulation) was achieved after 1957. The number of drugs has been subsequentially increased, reaching 148 Kampo extract formulation for prescription currently. Conclusion: We provide a history of Kampo extract formulations for prescription in Japan. The originality of this research is that it analyzes the background history of Kampo in parallel with relevant transitions in the government and insurance systems.

Keywords: health insurance system, history, Kampo, Kampo extract formulation for prescription, OTC Kampo extract formulation, pattern corresponding prescription (Ho-sho-so-tai) system

Procedia PDF Downloads 286

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

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Hydrophobic / hydrophilically modified functional polymers are of high interest in modern biomedicine due to their ability to solubilize water-insoluble / poorly soluble (hydrophobic) drugs. Among the many approaches that are being developed in this direction, one of the most effective methods is the use of polymeric micelles (PMs) (micelles formed by amphiphilic block-copolymers) for solubilization of hydrophobic biologicals. For therapeutic purposes, PMs are required to be stable and biodegradable, although quite a few amphiphilic block-copolymers are described capable of forming stable micelles with good solubilization properties. For obtaining micelle-forming block-copolymers, polyethylene glycol (PEG) derivatives are desirable to use as hydrophilic shell because it represents the most popular biocompatible hydrophilic block and various hydrophobic blocks (polymers) can be attached to it. Although the construction of the hydrophobic core, due to the complex requirements and micelles structure development, is the very actual and the main problem for nanobioengineers. Considering the above, our research goal was obtaining biodegradable micelles for the solubilization of hydrophobic drugs and biologicals. For this purpose, we used biodegradable polymers– pseudo-proteins (PPs)(synthesized with naturally occurring amino acids and other non-toxic building blocks, such as fatty diols and dicarboxylic acids) as hydrophobic core since these polymers showed reasonable biodegradation rates and excellent biocompatibility. In the present study, we used the hydrophobic amino acid – L-phenylalanine (MW 4000-8000Da) instead of L-leucine. Amino-PEG (MW 2000Da) was used as hydrophilic fragments for constructing the suitable micelles. The molecular weight of PP (the hydrophobic core of micelle) was regulated by variation of used monomers ratios. Micelles were obtained by dissolving of synthesized amphiphilic polymer in water. The micelle-forming property was tested using dynamic light scattering (Malvern zetasizer NanoZSZEN3600). The study showed that obtaining amphiphilic block-copolymer form stable neutral micelles 100 ± 7 nm in size at 10mg/mL concentration, which is considered as an optimal range for pharmaceutical micelles. The obtained preliminary data allow us to conclude that the obtained micelles are suitable for the delivery of poorly water-soluble drugs and biologicals.

Keywords: amino acid – L-phenylalanine, pseudo-proteins, amphiphilic block-copolymers, biodegradable micelles

Procedia PDF Downloads 137

Authors: Yuan Yang, Mickey Lam

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Oral dissolvable films have been considered as a unique alternative approach to conventional oral dosage forms. The films could be administrated via the gastrointestinal tract as conventional dosages or through sublingual/buccal mucosa membranes, which could enhance drug bioavailability by avoiding the first-pass effect and improving permeability due to high blood flow and lymphatic circulation. This work has described a state-of-art technic using nano-emulsion/nano-suspension as a precursor for the film to enhance the bioavailability of BCS class II drugs. The drug molecules are consequentially processed through the emulsification, gelation, and film-casting processes. The gelation process is critical to stabilizing the nano-emulsion for the film-casting as well as controlling the drug release process. Furthermore, the size of the nanoparticle on the film has a strong correlation with the size of the micelles in the precursor and the condition of the gelation process. It has been discovered that nanoparticle from 200 nm to 300 nm has shown the highest permeability for sublingual administration. In one example shown in work, the bioavailability of a low solubilize drug has been increased from 10% to 24% via sublingual administration of the film. The increasing of the bioavailability was thought to be associated with the enhancement of the diffusion process of the drug in the saliva layer above the mucosa membrane and the fact that the presents of the emulsifier help lose the rigid junction of the mucosa cells.

Keywords: oral dissolvable film, nano-suspension, nano-emulsion, bioavailability

Procedia PDF Downloads 186

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

Procedia PDF Downloads 71

Authors: Dada Kolawole Segun

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Transdermal drug delivery has gained popularity as a non-invasive method for controlled drug release compared to traditional delivery routes. Dissolvable transdermal patches have emerged as a promising platform for delivering a variety of drugs due to their ease of use. The objective of this research was to create and characterize dissolvable transdermal patches using various compositions and ratios of hyaluronic acid and zinc oxide nanoparticles. A micromolding technique was utilized to fabricate the patches, which were subsequently characterized using scanning electron microscopy, atomic force microscopy, and tensile strength testing. In vitro drug release studies were conducted to evaluate the drug release kinetics of the patches. The study found that the mechanical strength and dissolution properties of the patches were influenced by the hyaluronic acid and zinc oxide nanoparticle ratios used in the fabrication process. Moreover, the patches demonstrated controlled delivery of model drugs through the skin, highlighting their potential for transdermal drug delivery applications. The results suggest that dissolvable transdermal patches can be tailored to meet specific requirements for drug delivery applications using different compositions and ratios of hyaluronic acid and zinc oxide nanoparticles. This development has the potential to improve treatment outcomes and patient compliance in various therapeutic areas.

Keywords: transdermal drug delivery, characterization, skin permeation, biodegradable materials

Procedia PDF Downloads 91

Authors: Thomas Geninatti, Bruno Giacomo, Alessandro Grattoni

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Nanofluidic devices have been investigated for over a decade as promising platforms for the controlled release of therapeutics. The nanochannel drug delivery system (nDS), a membrane fabricated with high precision silicon techniques, capable of zero-order release of drugs by exploiting diffusion transport at the nanoscale originated from the interactions between molecules with nanochannel surfaces, showed the flexibility of the sustained release in vitro and in vivo, over periods of time ranging from weeks to months. To improve the implantable bio nanotechnology, in order to create a system that possesses the key features for achieve the suitable release of therapeutics, the next generation of nDS has been created. Platinum electrodes are integrated by e-beam deposition onto both surfaces of the membrane allowing low voltage (<2 V) and active temporal control of drug release through modulation of electrostatic potentials at the inlet and outlet of the membrane’s fluidic channels. Hence, a tunable administration of drugs is ensured from the nanochannel drug delivery system. The membrane will be incorporated into a peek implantable capsule, which will include drug reservoir, control hardware and RF system to allow suitable therapeutic regimens in real-time. Therefore, this new nanotechnology offers tremendous potential solutions to manage chronic disease such as cancer, heart disease, circadian dysfunction, pain and stress.

Keywords: nanochannel membrane, drug delivery, tunable release, personalized administration, nanoscale transport, biomems

Procedia PDF Downloads 315

Authors: Rafael Mineiro, André Furtado, Isabel Gonçalves, Cecília Santos, Telma Quintela

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The choroid plexus (CP) epithelial cells form the blood-cerebrospinal fluid barrier. This barrier is highly important for brain protection by physically separating the blood from the cerebrospinal fluid, controlling the trafficking of molecules, including therapeutic drugs, from blood to the brain. The control is achieved by tight junctions between epithelial cells, membrane receptors and transport proteins from the solute carrier and ATP-binding cassette superfamily on the choroid plexus epithelial cells membrane. Previous research of our group showed a functional molecular clock in the CP. The key findings included a rhythmic expression of Bmal1, Per2, and Cry2 in female rat CP. and a rhythmic expression of Cry2 and Per2 in male rat CP. Furthermore, in cultured rat CP epithelial cells we already showed that 17β-estradiol upregulates the expression of Bmal1 and Per1, where the Per1 and Per2 upregulation was abrogated in the presence of the estrogen receptors antagonist ICI. These findings, together with the fact that the CP produces robust rhythms, prompt us to understand the impact of sex hormones and circadian rhythms in CP drug transporters expression, which is a step towards the development and optimization of therapeutic strategies for efficiently delivering drugs to the brain. For that, we analyzed the circadian rhythmicity of the Abcb1, Abcc2, Abcc4 Abcg2, and Oat3 drug transporters at the CP of male and female rats. This analysis was performed by accessing the gene expression of the mentioned transporters at 4 time points by RT-qPCR and the presence of rhythms was evaluated by the CircWave software. Our findings showed a rhythmic expression of Abcc1 in the CP of male rats, of Abcg2 in female rats, and of Abcc4 and Oat3 in both male and female rats with an almost antiphasic pattern between male and female rats for Abcc4. In conclusion, these findings translated to a functional point of view may account for daily variations in brain permeability for several therapeutic drugs, making our findings important data for the future establishment and development of therapeutic strategies according to daytime.

Keywords: choroid plexus, circadian rhythm, membrane transporters, sex hormones

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